冠状微循环障碍和过氧亚硝酸生成在心肌顿抑发生中的作用
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摘要
研究目的 顿抑心肌中氧自由基生成增加，氧自由基抑制心肌收缩
功能，这两点是明确的。但氧自由基是靠直接的细胞毒作用还是通过形
成其它产物来引起心肌顿抑，目前仍未明了。最近研究提示，一氧化氮
（NO）与超氧阴离子（·O_2~-）反应生成的过氧亚硝酸阴离子（ONOO~-）
在·O_2~-启动的细胞损害中起着重要作用。此外，顿抑心肌是否存在微
循环障碍，这是一个尚未解决的问题。本研究的目的是：1.探讨顿抑心
肌微循环改变及机制；2.探讨NO和ONOO~-在心肌顿抑发生中的作用
及机制；3.观察NO合成酶抑制剂和云芝多糖（PSK）对顿抑心肌结构、
功能及微循环的影响。
材料和方法 39只雄性杂种犬随机分入6组。1.短时间缺血顿抑
（MSS）组：左前降支冠脉（LAD）结扎15min、再灌注120min；2.长
时间缺血顿抑（MSL）组：LAD结扎60min、再灌注120min；3.N~ω-硝
基-左旋精氨酸甲酯（NAME）组：MSL加NAME干预；4.氨基胍（AMD）
组：MSL加AMD干预；5.云芝多糖（PSK）组：MSL加PSK干预；6.
假手术（SHAO）组。全过程监测血流动力学和心电图。在不同观察时
间点静脉注射含全氟丙烷声振白蛋白微泡造影剂，采用二次谐波成像和
间歇发射技术行心肌声学造影（MCE）。由主动脉根部分别注射乙酰胆
碱（ACH）和硝酸甘油（NG）后即刻重复MCE以检测冠脉舒张功能。
每次MCE后行超声心功能测定。相应时间点冠状静脉窦抽血测定血浆
乳酸、NO和丙二醛浓度。心肌标本行病理检查。
以MCE心肌视频密度峰值（PVI）表示心肌血流灌注，顿抑区与正
常区PVI比值（PVIR）表示顿抑区相对血流灌注。MCE曲线上升斜率
和曲线早期下降斜率分别代表心肌血流灌注速度和排空速度。以注射
ACH或NG后、前顿抑心肌PVI比值分别表示心肌微血管内皮依赖性
舒张（EDR）功能和非EDR功能，以注射ACH或NG后、前顿抑心肌
PVIR比值分别表示相对性EDR功能和相对性非EDR功能。
结果1．血流动力学改变：除NAME组再灌注期心率减慢、平均
主动脉压升高外，其余各组心率和平均主动脉压无显著变化；MSS组、
MSL组和NAME组再灌注前和再灌注早期左室舒张压显著升高，AMD
组和PSK组仅再灌注前左室舒张压升高。2．心肌血流和微血管舒张功
能改变：MSS组和MSL组再灌注早期心肌充血，血流灌注速度和排空
速度加快；微血管EDR和非EDR功能减弱，其恢复速度与原缺血时间
长短有关：＊＊＊E显著减慢再灌注期心肌血流灌注速度和排空速度，
引起心肌缺血，加重微血管EDR和非EDR功能损害：AMD和PSK减
轻再灌注期心肌充血程度，使再灌注期加快的血流灌注速度和排空速度
．减慢，促进微血管EDR和非EDR功能的恢复。3．心功能改变：MSS
组和MSL组再灌注期心肌节段收缩期增厚百分率和左室射血分数显著
下降，随着再灌注时间的延长心功能呈进行性改善；NAME加重心功
能损害；AMD和 PSK促进再灌注期心肌功能的恢复。4．血生化指标变
化：＊）乳酸：MSS组再灌注早期乳酸浓度显著升高，至再灌注120min
恢复正常；MSL组和NAME组再灌注前乳酸浓度即明显升高，再灌注
早期进一步升高，至再灌注120min尚未恢复正常；AMD组和PSK组
再灌注前和再灌注早期乳酸浓度升高，至再灌注 120min恢复正常。
口）NO：MSS组和 MSL组再灌注期NO浓度明显升高，至再灌注 120min
尚未恢复正常：＊＊＊E组整个再灌注期＊O浓度明显减低；＊＊D组和
PSK组再灌注期NO浓度轻度升高，但与结扎前相比，除PSK组再灌
注30min时差异有统计学意义外，其余均无统计学意义。（3）丙H醛：MSS
组、MSL组和 NAME组再灌注期丙二醛浓度明显升高，至再灌注 120min
尚未恢复至结扎前水平。AMD组和PSK组再灌注早期丙二醛浓度升高，
但恢复较快。5．顿抑心肌病理改变：MSS组心肌细胞除偶见线粒体轻
度脱颗粒外，未见其它超微结构改变。MSL组心肌组织水肿，毛细血
管内皮细胞稍肿胀，内皮细胞间连接间隙稍增宽；心肌细胞部分肌丝断
．裂，收缩带溶解，线粒体肿胀、脱颗粒，胞质水肿。NAME组心肌组
织水肿，毛细血管内皮细胞显著肿胀，内皮细胞间连接间隙明显增宽，
基底膜电于密度减低；心肌细胞肌丝断裂，收缩带溶解、变模糊或消失，
线粒体明显肿胀、脱颗粒，线粒体脊断裂，胞质水肿：心肌细胞间连接
间隙增宽，闰盘结构变模糊。AMD组和PSK组心肌组织轻微水肿，毛
．－仁
细血管和内皮细胞结构未见明显改变，心肌细胞除偶见胞质轻微水肿、
线粒体肿胀和脱颗粒外，未见其它明显异常改变。硝基酪氨酸免疫组化
检查发现，MSS组顿抑心肌组织见较强阳性染色的心肌细胞灶；MSL
组顿抑心肌组织见心肌细胞强阳性染色，主要是胞浆尤其横纹处染色较
深，阳性染色的心肌细胞呈灶性分布，而且阳性灶较大、较多：＊＊＊E
组顿抑心肌组织中偶见单个心肌细胞局部弱阳性染色；AMD组和pSK
组顿抑心肌组织偶见心肌细胞较弱阳性染?
Mechanisms of the pathogenesis of myocardial stunning are not fully
understood. It has been known that reactive oxygen species(ROS) production
increases in myocardial stunning and ROS depress myocardial function. But
it is unclear whether ROS impair myocardium directly or through the
formation of other substances. Recently, it has been demonstrated that
ischemialreperfusion(I/R) leads to the activation of nitric oxide synthase
(NOS) and nitric oxide(NO) participates in the regulation of hemodynamic
and microcirculatory changes in organic hR. The dual role of NO as a
cytoprotective or a cytotoxic free radical gas has been noted in various types
of pathophysiological conditions. However, It is controversial whether NO is
protective or deleterious against myocardial hR injury? Recent studies
suggest that peroxynitrite(ONOO ) formed by the reaction of NO with
superoxide plays an important role in the cell damages caused by superoxide.
Additionally, there is a continuing debate as to the effects of inhibitors of
NOS on myocardial hR injury. Finally, whether intramyocardial
microcirculatory dysfunction occurs in stunned myoeardiurn is an unresolved
issue. The purposes of this study were (1) to research the intramyocardial
microcirculatory derangement and its mechanism during myocardial stunning,
(2) to study the roles of NO and ONOO in the pathogenesis of myocardial
stunning and their mechanisms, (3) to evaluate the effects of a nonselective
NOS inhibitor, N -nitro-L-arginine methyl ester(NAME), a selective
inducible NOS(iNOS) inhibitor, aminoguanidine (AMD), and an antioxidant,
polysaccharide krestin(PSK), on microcireulatory changes, myocardial
performance and structural damages after myocardial stunning.
Methods
Thirty-nine adult mongrel dogs of male, weighing 13-18 kg, anesthetized
with sodium pentobarbital, were randomly assigned to six groups.
(I )Myocardial stunning after a short-time ischemia(MSS) group: dogs
underwent 15 mm of left anterior descending coronary artery(LAD)
occlusion, followed by 120 mm reperfusion. (2)Myocardial stunning after a
long-time ischemia(MSL) group: dogs underwent 60 mm of LAD occlusion,
followed by 120 mm reperfusion. (3)NAME group: dogs underwent the same
hR as MSL group, received NAME(lOmg/kg). One-third of NAME dose was
given intravenously 10 mm prior to LAD occlusion, and the rest was infused
continuously intravenously from 10 mm before reperfusion to the end of
reperfusion. (4)AMD group: dogs were subjected to the same I/R as MSL
group, received AMD(l0Omg/kg). AMD was given by the same way as
NAME. (5)PSK group: animals were subjected to the same J/R, received
PSK. which was administered orally, at a dose of 150mg/kg once daily for
two day抯 before thoracotomy. (6)Sham operation(SHAO) group. Myocardial
contrast echocardiography (MCE) was performed using intravenous
perfluoropropane-exposed sonicated dextrose albumin(0.Olml/kg) at baseline,
during coronary occlusion, and at 5,30,60.90.and 120 mm after reperfusion.
At baseline. 5.60,and 120 mm after reperfusion. acetylcholine (ACH, 10 1-?
g/kg) and nitroglycerin(NG. 10 p g/kg) were given from aortic root injections
after resting MCE, respectively, and MCE was repeated immediately,
respectively. Electrocardiogram-gated end-systolic images in short axis were
acquired in harmonic mode and digitized on-line. Left ventricular function
was evaluated by?echocardiography using an echocardiogram at the above
time points. Hemodynamics was measured by
功能，这两点是明确的。但氧自由基是靠直接的细胞毒作用还是通过形
成其它产物来引起心肌顿抑，目前仍未明了。最近研究提示，一氧化氮
（NO）与超氧阴离子（·O_2~-）反应生成的过氧亚硝酸阴离子（ONOO~-）
在·O_2~-启动的细胞损害中起着重要作用。此外，顿抑心肌是否存在微
循环障碍，这是一个尚未解决的问题。本研究的目的是：1.探讨顿抑心
肌微循环改变及机制；2.探讨NO和ONOO~-在心肌顿抑发生中的作用
及机制；3.观察NO合成酶抑制剂和云芝多糖（PSK）对顿抑心肌结构、
功能及微循环的影响。
材料和方法 39只雄性杂种犬随机分入6组。1.短时间缺血顿抑
（MSS）组：左前降支冠脉（LAD）结扎15min、再灌注120min；2.长
时间缺血顿抑（MSL）组：LAD结扎60min、再灌注120min；3.N~ω-硝
基-左旋精氨酸甲酯（NAME）组：MSL加NAME干预；4.氨基胍（AMD）
组：MSL加AMD干预；5.云芝多糖（PSK）组：MSL加PSK干预；6.
假手术（SHAO）组。全过程监测血流动力学和心电图。在不同观察时
间点静脉注射含全氟丙烷声振白蛋白微泡造影剂，采用二次谐波成像和
间歇发射技术行心肌声学造影（MCE）。由主动脉根部分别注射乙酰胆
碱（ACH）和硝酸甘油（NG）后即刻重复MCE以检测冠脉舒张功能。
每次MCE后行超声心功能测定。相应时间点冠状静脉窦抽血测定血浆
乳酸、NO和丙二醛浓度。心肌标本行病理检查。
以MCE心肌视频密度峰值（PVI）表示心肌血流灌注，顿抑区与正
常区PVI比值（PVIR）表示顿抑区相对血流灌注。MCE曲线上升斜率
和曲线早期下降斜率分别代表心肌血流灌注速度和排空速度。以注射
ACH或NG后、前顿抑心肌PVI比值分别表示心肌微血管内皮依赖性
舒张（EDR）功能和非EDR功能，以注射ACH或NG后、前顿抑心肌
PVIR比值分别表示相对性EDR功能和相对性非EDR功能。
结果1．血流动力学改变：除NAME组再灌注期心率减慢、平均
主动脉压升高外，其余各组心率和平均主动脉压无显著变化；MSS组、
MSL组和NAME组再灌注前和再灌注早期左室舒张压显著升高，AMD
组和PSK组仅再灌注前左室舒张压升高。2．心肌血流和微血管舒张功
能改变：MSS组和MSL组再灌注早期心肌充血，血流灌注速度和排空
速度加快；微血管EDR和非EDR功能减弱，其恢复速度与原缺血时间
长短有关：＊＊＊E显著减慢再灌注期心肌血流灌注速度和排空速度，
引起心肌缺血，加重微血管EDR和非EDR功能损害：AMD和PSK减
轻再灌注期心肌充血程度，使再灌注期加快的血流灌注速度和排空速度
．减慢，促进微血管EDR和非EDR功能的恢复。3．心功能改变：MSS
组和MSL组再灌注期心肌节段收缩期增厚百分率和左室射血分数显著
下降，随着再灌注时间的延长心功能呈进行性改善；NAME加重心功
能损害；AMD和 PSK促进再灌注期心肌功能的恢复。4．血生化指标变
化：＊）乳酸：MSS组再灌注早期乳酸浓度显著升高，至再灌注120min
恢复正常；MSL组和NAME组再灌注前乳酸浓度即明显升高，再灌注
早期进一步升高，至再灌注120min尚未恢复正常；AMD组和PSK组
再灌注前和再灌注早期乳酸浓度升高，至再灌注 120min恢复正常。
口）NO：MSS组和 MSL组再灌注期NO浓度明显升高，至再灌注 120min
尚未恢复正常：＊＊＊E组整个再灌注期＊O浓度明显减低；＊＊D组和
PSK组再灌注期NO浓度轻度升高，但与结扎前相比，除PSK组再灌
注30min时差异有统计学意义外，其余均无统计学意义。（3）丙H醛：MSS
组、MSL组和 NAME组再灌注期丙二醛浓度明显升高，至再灌注 120min
尚未恢复至结扎前水平。AMD组和PSK组再灌注早期丙二醛浓度升高，
但恢复较快。5．顿抑心肌病理改变：MSS组心肌细胞除偶见线粒体轻
度脱颗粒外，未见其它超微结构改变。MSL组心肌组织水肿，毛细血
管内皮细胞稍肿胀，内皮细胞间连接间隙稍增宽；心肌细胞部分肌丝断
．裂，收缩带溶解，线粒体肿胀、脱颗粒，胞质水肿。NAME组心肌组
织水肿，毛细血管内皮细胞显著肿胀，内皮细胞间连接间隙明显增宽，
基底膜电于密度减低；心肌细胞肌丝断裂，收缩带溶解、变模糊或消失，
线粒体明显肿胀、脱颗粒，线粒体脊断裂，胞质水肿：心肌细胞间连接
间隙增宽，闰盘结构变模糊。AMD组和PSK组心肌组织轻微水肿，毛
．－仁
细血管和内皮细胞结构未见明显改变，心肌细胞除偶见胞质轻微水肿、
线粒体肿胀和脱颗粒外，未见其它明显异常改变。硝基酪氨酸免疫组化
检查发现，MSS组顿抑心肌组织见较强阳性染色的心肌细胞灶；MSL
组顿抑心肌组织见心肌细胞强阳性染色，主要是胞浆尤其横纹处染色较
深，阳性染色的心肌细胞呈灶性分布，而且阳性灶较大、较多：＊＊＊E
组顿抑心肌组织中偶见单个心肌细胞局部弱阳性染色；AMD组和pSK
组顿抑心肌组织偶见心肌细胞较弱阳性染?
Mechanisms of the pathogenesis of myocardial stunning are not fully
understood. It has been known that reactive oxygen species(ROS) production
increases in myocardial stunning and ROS depress myocardial function. But
it is unclear whether ROS impair myocardium directly or through the
formation of other substances. Recently, it has been demonstrated that
ischemialreperfusion(I/R) leads to the activation of nitric oxide synthase
(NOS) and nitric oxide(NO) participates in the regulation of hemodynamic
and microcirculatory changes in organic hR. The dual role of NO as a
cytoprotective or a cytotoxic free radical gas has been noted in various types
of pathophysiological conditions. However, It is controversial whether NO is
protective or deleterious against myocardial hR injury? Recent studies
suggest that peroxynitrite(ONOO ) formed by the reaction of NO with
superoxide plays an important role in the cell damages caused by superoxide.
Additionally, there is a continuing debate as to the effects of inhibitors of
NOS on myocardial hR injury. Finally, whether intramyocardial
microcirculatory dysfunction occurs in stunned myoeardiurn is an unresolved
issue. The purposes of this study were (1) to research the intramyocardial
microcirculatory derangement and its mechanism during myocardial stunning,
(2) to study the roles of NO and ONOO in the pathogenesis of myocardial
stunning and their mechanisms, (3) to evaluate the effects of a nonselective
NOS inhibitor, N -nitro-L-arginine methyl ester(NAME), a selective
inducible NOS(iNOS) inhibitor, aminoguanidine (AMD), and an antioxidant,
polysaccharide krestin(PSK), on microcireulatory changes, myocardial
performance and structural damages after myocardial stunning.
Methods
Thirty-nine adult mongrel dogs of male, weighing 13-18 kg, anesthetized
with sodium pentobarbital, were randomly assigned to six groups.
(I )Myocardial stunning after a short-time ischemia(MSS) group: dogs
underwent 15 mm of left anterior descending coronary artery(LAD)
occlusion, followed by 120 mm reperfusion. (2)Myocardial stunning after a
long-time ischemia(MSL) group: dogs underwent 60 mm of LAD occlusion,
followed by 120 mm reperfusion. (3)NAME group: dogs underwent the same
hR as MSL group, received NAME(lOmg/kg). One-third of NAME dose was
given intravenously 10 mm prior to LAD occlusion, and the rest was infused
continuously intravenously from 10 mm before reperfusion to the end of
reperfusion. (4)AMD group: dogs were subjected to the same I/R as MSL
group, received AMD(l0Omg/kg). AMD was given by the same way as
NAME. (5)PSK group: animals were subjected to the same J/R, received
PSK. which was administered orally, at a dose of 150mg/kg once daily for
two day抯 before thoracotomy. (6)Sham operation(SHAO) group. Myocardial
contrast echocardiography (MCE) was performed using intravenous
perfluoropropane-exposed sonicated dextrose albumin(0.Olml/kg) at baseline,
during coronary occlusion, and at 5,30,60.90.and 120 mm after reperfusion.
At baseline. 5.60,and 120 mm after reperfusion. acetylcholine (ACH, 10 1-?
g/kg) and nitroglycerin(NG. 10 p g/kg) were given from aortic root injections
after resting MCE, respectively, and MCE was repeated immediately,
respectively. Electrocardiogram-gated end-systolic images in short axis were
acquired in harmonic mode and digitized on-line. Left ventricular function
was evaluated by?echocardiography using an echocardiogram at the above
time points. Hemodynamics was measured by
引文
1.Braunwald E, Kloner RA. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulaiion, 1982,66:1146-1149.
2.Bolli R. Mechanism of myocardial "stunning". Circulation, 1990,82:723-738.
3.Bolli R. Myocardial 'stunning' in man. Circulaiion, 1992,86:1671-1691.
4.Bolli R. Basic and clinical aspects of myocardial stunning. Prog Cardiovasc Dis, 1998,40:477-516.
5.Kloner RA, Bolli R Marban E, et al. Medical and cellular implications of stunning, hibemaiion, and preconditioning. An NHLBI workshop. Circulation, 1998,97:1848-1867.
6.Tennant T, Wiggers CT. Effect of coronary occlusion on myocardial contraction. Am J Physiol,1935,112:351.
7.Heynddckx GR Millard RW, McRitchie RJ, et al. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest,1975,56:978-985.
8.Bolli R. Oxygen-derived free radicals and postischemic myocardial dysfunction("stunned myocardium"). J Am Coll Cardiol, 1988,12:239-249.
9.Kloner PA, Przyklenk K, Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Circulation, 1989,80:1115-1127.
10.Bolli R Jeroudi MO, Patel BS, et al. Marked reduction of free radical generation and contractile disfunction by antioxidant therapy begun at the time of reperfusion: Evidence that myocardial"stunning" is a manifestation of reperfusion injury. Circ Res, 1989,65:607-622.
11.Bolli R Patel BS, Jeroudi MO, et al. Demonstration of free radical generation in "stunned"myocardium of intact dogs with the use of the spin trap α_phenyl N-tert-butyl nitronc. J Clin Invest,1988,82:476-485.
12.Bolli R, Jeroudi MO, Patel BS, et al. Direct evidence that oxygen-derived free radicals contribute to postischemic myocardial dysfunction in the intact dog. Proc Nail AcM Sci USA,1989,86:4695-4699.
13．田英平，李星海，陶桂华．一氧化氮对于心肌功能的影响．心血管病学进展，1996，17：296-297
14.Brady AJB, Warren JB, Poole-Wilson PA, et al. Nitric oxide attenuates cardiac myocyte contraction. Am J Physiol, 1993,265:H176-H182.
15.Gulick T, Pieper SJ, Murphy MA, et al. A new method for assessment of culture cardiac myocyte contractility detects immune factor-mediaied inhibition of β-adrenergic responses. Circulation,1991,84:313-321.
16.Paulus WJ, Vantrimpont PJ, Shah AM. Acute effects of nitric oxide on left ventricular relaxation and diastolic distensibility in humans. Assessment by coronary sodium nitroprusside infusion.Circulation, 1994,89:2070-2078.
17.Balligand J-L, Kelly PA, Maraden PA, et al. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc Nail Acad Sci USA,1993,90:347-351.
18.Hare JM, Keaney JF, Kelly RA, et al. Inhibition of nitric oxide synthase potentiates the positive inotropic response to β-adrenergic stimulation in normal dogs. Circulation, 1993,88(abstr):I-1905.
19.Winlaw DS, Sm}the GA, Keogh AM, et al. Increased nitric oxide production in heart failure.Lancet, 1994,344:373-374.
20． Levine B, Kalman J, Mayer L, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990,323:236-241．
21． Lipton SA, Choi YB, Pan ZH, et al. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature, 1993,364:626-632．
22． Vinten-Johansen J, Sato H. Zhao ZQ. The role of nitric oxide and NO-donor agents in myocardial protection from surgical ischemic-reperfusion injury. Int J Cardiol, 1995,50:273-281
23． Lefer DJ, Nakanishi K, Johonston WE, et al. Antineutrophil and myocardial protecting actions of a novel nitric oxide donor after acute myocardial ischemia and reperfusion in dogs. Circulation, 1993,88:2337．
24． Weyrich AS, Ma XL, Lefer AM. The role of L-arginine in ameliorating reperfusion injury after myocardial ischermia in the cat. Circulation, 1992,86:279-288．
25． Beresewicz A. Karwatowska-Prokopczuk E, Lewartowski B. et al. A protective role of nitric oxide in isolated ischaemic reperfused rat heart. Cardiovasc Res,1995． 30:1001-1008
26． Li XS, Uriuda Y, Wang QD. et al. Role of L-arginine in preventing myocardial and endothelial injury following ischaemia/reperfusion in the rat isolated heart. Acta Physiol Scand. 1996,156:37-44
27． Hasebe N, Shen Y-T, Vatner SF. Inhibition of endothelium-derived relaxing factor enhances myocardial stunning in conscious dogs. Circulation. 1993,88:2862-2871．
28． Williams MW. Taft CS. Ramnauth S. et al. Endogenous nitric oxide (NO) protects against ischaemia-reperfusion injury in the rabbit. Cardiovasc Res.1995． 30:79-86．
29． Takeuchi K. McGowan FX. Danh HC, et al. Direct detrimental effect of L-Arginine upon ischemia-reperfusion injury to myocardium. J Mol Cell Cardiol, 1995,27:1405-1414．
30． Mori E. Haramaki N. Ikeda H, et al. Intra-coronary administration of L-arginine aggravates myocardial stunning through production of peroxynitrite in dogs. Cardiovasc Res. 1998, 40:113-123．
31． Morita K, Ihnken K, Buchberg GD. et al. Role of controlled cardiac reoxygenation in reducing nitric oxide production and cardiac oxidant damage in cyanotic infantile hearts. J Clin Invest, 1994． 93:2658-2662．
32． Wang P, Zweier JL. Measurement of nitric oxide and peroxynitrite generation in the postischemic heart. J Biol Chem. 1996,271:29223-29230
33． Schulz R, Wambolt R. Inhibition of nitric oxide synthesis protects the isolated working rabbit heart from ischemia-reperfusion injury. Cardiovasc Res, 1995,30:432-439
34． Naseem SA, Kontos MC, Rao PS, et al. Sustained inhibition of nitric oxide by NG-nitro-L-arginine improves myocardial function following ischemia/reperfusion in isolated perfused rat heart. J Mol Cell Card, 1995,27:419-426
35． Tsao PS, Aoki N, Lefer DJ, et al. Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the rat. Circulation, 1990,82:1402-1412
36． Balligand J-L, Ungureanu-Longrois D, Simmons WW, et al. Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. J Biol Chem, 1994,269:27580-27588
37． Tsujino M, Hirata Y, Imai T, et al. Induction of nitric oxide synthase gene by interleukin 1β in cultured rat cardiocytcs. Circulation, 1994,90:375-383
38． LaPointe MC, Sitkins JR. Mechanisms of interleukin 1β regulation of nitric oxide synthase in cardiac myocytes. Hypertension, 1996,27:709-714
39． Birdsall HH, Green DM, Trial J, et al. Complement C5a, TGF-β1, and MCP-1, in sequence, induce migration of monocytes into ischemic canine myocardium within the first one to five hours after
reperfusion. Circulation, 1997,95:684-692
40.Cheng XS, Shimokawa H, Momii H, et al. Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo. Circulation, 1997,96(Suppl):1605.
41.Bechman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad. and the ugly. Am J Physiol,1996,271(cell Physiol 40):C1424-1437.
42.Xia Y, Dawson VL, Dawson TM. et al. Nitric oxide synthase generates superoxide and nitric oxide in arginine depleted cells leading to peroxynitrite mediated cellular injury. Proc Natl Acad Sci USA,1996,93:6770-6774.
43．周玫，陈瑗．体内一氧化氮和过氧亚硝酸的生成及其生物学效应．中国动脉硬化杂志，1998，6：178-181．
44.Seo HG, Tannenbaum SR. Identification of a stress-inducible protein containing nitrotyrosine in RAW264.7 cells activated by IFN-γ and LPS. Proceedings of the 5th international meeting on the biology of nitric oxide.Jpn J Pharmacol, 1997.75(Suppl 1):105.
45.Beckman JS. Peroxynitrite versus hydroxyl radical: The role of nitric oxide in superoxide-dependent cerebral injury. Ann NY Acad Sci. 1994.738:69-75
46.Liu P, Hock CE, Nagele R. et al. Formation of nitric oxide, superoxide, and peroxynitrite in myocardial ischemia-reperfusion injury in rats. Am J Physiol, 1997. 272(5 Pt 2): H2327-2336
47.Zingarelli B. Cuzzocrea S. Zsengeller Z, et al. Protection against myocardial ischemia and reperfusion injury by 3-aminobenzamide. an inhibitor of poly (ADP-ribose) synthetase. Cardiovasc Res. 1997,36:205-215
48.Ma XL, Lopez BL, Liu GL. et al. Peroxynitrite aggravates myocardial reperfusion injury in the isolated perfused rat heart. Cardiovasc Res, 1997,36:195-204
49.Ischiropoulos H, Duran D, HorwitzJ. Peroxynitrite-mediated inhibition of DOPA synthesis in PC12 cells. J Neurochem, 1995,65:2366-2372
50.Sharpe MA, Cooper CE. Reactions of nitric oxide with mitochondrial cytochrome c: a novel mechanism for the formation of nitroxyl anion and peroxynitrite. Biochem J. 1998.332(Pt1): 9-19
51.Oyama Ji, Shimokawa H, Momii H, et al. Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in clogs in vivo. J Clin Invest. 1998,101:2207-2214
52.Misko TP, Moore WM, Kasten TP, et al. Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. Eur J Pharmacol, 1993,233: 119-125
53.Becket LC. Is stunned myocardium ischemic on a microvaseular level? Basic Res Cardiol, 1995,90:282-284.
54.Bolli R, Triana JF, Jeroudi MO.. Prolonged impairment of coronary vasodilation after reversible ischemia. Evidence for microvascular "stunning". Circ Res, 1990,67:332-343.
55.Tillmanns H, Neumann FJ, Tiefenbacher C, et al. Activation of neutrophils in the microvasculature of the ischaemic and repeffused myocardium. Eur Heart J.1993,14(Suppl 1)82-86.
56.Duncker DJ, McFalls EO, Krams R, et al. Pressure-maximal coronary flow relationship in regionally stunned porcine myoeardium. Am J Physiol, 1992,262:H1744-H1751.
57.Jeremy RW, Stahl L, Gillinov M, et al. Preservation of coronary, flow reserve in stunned myocardium. Am J Physiol, 1989,256:H1301-H1310.
58.McFalls EO, Duncker DJ, Krams R, et al. Endothelium dependent vasodilatation following brief ischemia and reperfusion in anaesthetized swine. Cardiovasc Res, 1991,25:659-665.
59.Stahl LD, Aversano TR, Becher LC. Selective enhancement of function of stunned myocardium by increased flow. Circulation, 1986,74:843-851.
60.Stahl LD, Weiss HR, Becher LC. Myocardial oxygen consumption, oxygen supply/demand heterogeneity and microvascular patency in regionally stunned myocardium. Circulation,1988,77:865-872.
61.Nicklas JM, Gips S. Decreased coronary flow reserve after transient myocardial ischemia in dogs.J Am Coil Cardiol, 1989,13:195-199.
62.Bolli R, Triana .JF, Jeroudi MO.. Prolonged impairment of coronary vasodilation after reversible ischemia. Evidence for microvascular "stunning". Circ Res, 1990,67:332-343.
63．徐成斌．对缺血后心肌功能障碍的新认识——心肌击昏与心肌冬眠的临床意义．心血管病学进展，1992，13：137-142．
64.Becher LC, Levine JH, Dipaula AF, et al. Reversal of dysfunction in postiscemic stunned myocardium by epinephrine and postextrasystolic potentiation. J AM Coll Cardiol, 1986,7:580-589.
65.Pierard LA, De Landsheere CM, Berthe C, et al. Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography. J Am Coil Cardiol, 1990,15: 1021-1031.
66.Dilsizian V, Bonow RO. Current diagnostic techniques of assessing myocardial viability in hibernating and stunned myocardium. Circulation, 1993,87:1-20.
67.Ferrari R,La Canna G, Giubbini R, et al. Stunned and hibernating myocardium: possibility of intervention. J Cardiovasc Pharmacol, 1992,20(Suppl 5):S5-S13.
68.Cheirif J, Narkiewicz-jodko JB, Bravenec JS, et al. Myocardial contrast echocardiograhy: relation between online and off-line assessment of myocardial perfusion. Echocardiography, 1993,10:471.
69．刘伊丽．心肌声学造影——一种评价冠状动脉微循环的新技术．中华心血管病杂志，1997，25：76-78．
70.Feinstein SB, et al. Two-dimensional contrast echocardiography: 1. In vitro development and quantitative analysis of echo contrast agents. JACC, 1984,3:14-20.
71.Kaul S, et al. Relation between anterograde blood flow through a coronary artery and the size of the perfusion bed it supplies: Experimental and clinical implications. JACC, 1992,17:1403.
72.Xie F, Porter TR. Acute myocardial ischemia and reperfusion can be visually identified non-invasively with intravenous perfluropropane exposed sonicated dextrose albumin ultrasound contrast.Circulation, 1994,91:1-555.
73.Porter TR., Xie F. Visually discernible myocardial echocardiographic contrast after intravenous injection of sonicated dextrose albumin microbubbles containing high molecular weight less soluble gasses. JACC, 1995,25:509-515.
74.Dittrich HC, et al. Myocardial contrast echocardiography in experimental coronary artery occlusion with a new intravenously administered contrast agent. J Am Soc Echocardiogr,1995,8:465.
75．谢峰，勒斌，李澎，等．新型声学造影剂非损伤性估价正常心肌血流灌注的实验研究．中华超声医学杂志，1996，12：1-6．
76.Porter TR, Xie F, Kricsfeld A, et al. Myocardial perfusion abnormalities during low-dose dobutamine after coronary reperfusion can be demonstrated with intravenous perfluorocarbon-exposed sonicated dextrose albumin ultrasound contrast. Am Heart J. 1996.131 :1079-1087.
77.Desir RM, Cheirif J, Bolli R, et al. Assessment of regional myocardial perfusion with myocardial contrast echocardiography in a canine model of varying degrees of coronary stenosis. Am Heart J,1994, 127:56-63.
78.Porter TIC D'Sa A, Turner C, et al. Myocardial contrast echocardiography for the assessment of coronary blood flow reserve: Validation in humans. JACC, 1993,21:349-355.
79．邵波，钱蕴秋，张军，等．心肌造影超声心动图评估心肌缺血程度的实验研究．中华超声影像学杂志，1997，6：40-42．
80．张洁．心肌对比超声评价冠状动脉微循环的应用研究现状．心血管病学进展，1996，17：285-286．
81．王新明，牟善初．经静脉心肌造影超声显像评价冠状动脉微循环的研究现状．军医进修学院学报，1997，18：295-297．
82.Kaul S, Jayaweera AR. Myocardial contrast echocardiography has the potential for the assessment of coronary microvascular reserve. JACC, 1993,21:356-358.
83.Lou N, Zhou M, Chen Y. Inhibitory effect of polysaccharide Krestin on foam cell formation and necrosis of murine peritoneal macrophage caused by oxidized low density lipopmtein. Med Sci Res,1996, 24: 49-51.
84.Chen Y, Zhou M, Li J, et al. Injurious effect of reactive oxygen species on macrophage and its prevention by PSK. J Clin Lab Immunol, 1994, 43:99-115.
85.Zhou M, Chen Y, Liu SX, et al. Elevation of macrophage SeGSHPx gene expression and prevention of foam cell formation. In: Eds By Lester Pacher, Proceedings of the international Symposium on Natural antioxidants: Molecuar Mechanisms and Health Effects. Maret G Traber.AOCS Press, Champaign, Illinois, USA, 1996:339-351.
86．庞战军，陈瑷，周玫．云芝多糖对小鼠腹腔巨噬细胞锰超氧化物歧化酶基因表达的调控．中国动脉硬化杂志，1999，7：106-109．
87.Porter TR., Xie F, Kricsfeld A, et al. Noninvasive identification of acute myocardial ischemia and reperfusion with contrast ultrasound using intravenous perfluoropmpane-exposed sonicated dextrose albumin. J Am Coll Cardi?l,1995,26:33-40.
88.Agati L. Microvascular integrity after reperfusion therapy. Am Heart J, 1999,138(2 Pt 2):s76-s78.
89.Hasdai D, Holmes DR Jr, Higano ST, et al. Prevalence of coronary blood flow reserve abnormalities among patients with nonobstmctive coronary artery disease and chest pain. Mayo Clin Proc, 1998, 73:1133-1140.
90.Koglin J, yon Scheidt W. Isolated defect of adenosine-mediated coronary vasodilation: functional evidence for a new microangiopathic entity. J Am Coil Cardiol, 1997, 30:103-107.
91.Knecht M, Burkhoff D, Yi GH, et al. Coronary endothelial dysfunction precedes heart failure and reduction of coronary reserve in awake dogs. J Mol Cell Cardiol, 1997, 29:217-227.
92.Hasdai D, Holmes DR Jr, Higano ST, et al. Effect of basal epicardial tone on endothelium-independent coronary flow reserve measurement. Cathet Cardiovasc Diagn, 1998, 44:392-396.
93.Hartmann A, Lahoda T, Burger W, et al.,Endothelium-dependent and endothelium-independent flow regulation in coronary vascular regions supplied by arterial and venous bypass grafts.Cardiology, 1997, 88:425-432.
94.Murakami H, Urabe K, Nishimura M. Inappropriate microvascular constriction produced transientST-segment elevation in patients with syndrome X. J Am Coll Cardiol, 1998, 32:1287-1294.
95.Hasdai D, Gibbons RJ, Holmes DR Jr, et al. Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects. Circulation, 1997, 96:3390-3395.
96.Tiefenbacher CP, Tillmanns H. Niroomand F, et al. Adaptation of myocardial blood flow to increased metabolic demand is not dependent on endothelial vasodilators in the rat heart. Heart,1997, 77:147-153.
97.Loke KE, Woodman OL.Preconditioning improves myocardial function and reflow, but not vasodilator reactivity, after ischaemia and reperfusion in anaesthetized dogs. Clin Exp Pharmacol Physiol, 1998, 25:552-558.
98.Hartmann A, Reuss W, Burger W. et al. Endothelium-dependent and endothelium-independent flow reserve in vascular regions supplied by the internal mammary artery before and after bypass grafting.Eur J Cardiothorac Surg. 1998, 13:410-415.
99.Weis M, Hartmann A, Olbrich HG. et al. Prognostic significance of coronary flow reserve on left ventricular ejection fraction in cardiac transplant recipients. Transplantation, 1998, 65:103-108.
100.Lerman A, Burnett JC Jr, Higano ST, ct al. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation, 1998.97:2123-2128.
101.Lerman A, Cannan CR. Higano SH. et al. Coronary vascular remodeling in association with endothelial dysfunction. Am J Cardiol. 1998, 81:1105-1109.
102.Tio RA. Van Gelder IC. Boonstra PW, et al. Myocardial bridging in a survivor of sudden cardiac near-death: role of intracoronary doppler flow measurements and angiography during dobutamine stress in the clinical evaluation. Heart. 1997, 77:280-282.
103.Wildhirt SM, Weis M, Schulze C, et al. Endothelium-dependent microvascular vasomotion and its correlation with vasoactivc mediators early after cardiac transplantation in humans. Transpl Int,1998, 11(Suppl 1):S519-S524.
104.Weis M, Hartmann A, Scheuermann EH, et al. Soluble interleukin-2-receptor levels as a marker of coronary microvascular dysfunction after heart transplantation. J Heart Lung Transplant, 1998.17:294-298.
105.Drexler H. Endothelial dysfunction: clinical implications. Prog Cardiovasc Dis, 1997,39:287-234.
106.Kaul S. Assessment of coronary microcirculation with myocardial contrast echocardiography:current and future clinical applications. Br Heart J,1995, 75:490-495.
107.Senior R, Lahiri A, Ravai U, et al. Detection of coronary artery disease using myocardial contrast echocardiography: comparison with 99m-Tc-Sestamibi Single Photon Emission Tomography.Circulation, 1996, 94(suppl 1):1-140.
108.Galiuto L, DeMaria AN, May Newman K, et al. Evaluation of dynamic changes in microvascular flow during ischemia-rcperfusion by myocardial contrast echocardiography. J Am Coll Cardiol, 1998,32:1096-11O1.
109.Wu CC. Feldman MD, Mill JD, et al. Myocardial contrast echocardiography can be used to quantify intramyocardial blood volume: new insights into structural mechanisms of coronary autorcgulation. Circulation, 1997,96: 1004-1011.
110.Fici GJ, Althaus JS, Von Voigtlander PF. Effects of lazaroids and a peroxynitrite scavenger in a cell model of peroxynitritc toxicity. Frec Rad Biol Mod, 1997,22:223-228.
111．李祈．心肌缺血再灌注损伤中的冠状微循环障碍．国外医学心血管病分册，1998，25：262-265．
112.Pryor WA, Squadrito GL.The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol, 1995,268:L699-L722
113.Ishid H, lchimori K, Hirota Y. et al. Peroxynitrite-induced cardiac myocyte injury. Free Rad Biol Med, 1996, 20:343-350
114． 李中言,赵连友．一氧化氮与心血管疾病．中华心血管病杂志，1996． 24：73-76
115． Herbertson MJ, Werner HA. Walley KR. Nitric oxide synthase inhibition partially prevents decreased LV contractility during endotoxemia. Am J Physiol. 1996,270:H1979-H1984
116． Sampson JB, Rosen H. Beckman JS. Peroxynitrite dependent tyrosine nitration catalyzed by superoxide dismutase, myeloperoxidase and horseradish peroxidase. Methods Enzymol, 1996,269:210-218
117． Pearse DB, Wagner EM, Permutt S. Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs. J Appl Physiol. 1999, 86:123-132．
118． Harris NR, Langlois KW. Age-dependent responses of the mesenteric vasculature to ischemia-reperfusion. Am J Physiol. 1998,274(5 Pt 2) :H1509-1515．
119． Borsch DM, Cilento EV. Reilly FD. Role for nitric oxide but not prostaglandins in acetylcholine-induced relaxation of rat cremaster third-order arterioles in 5-hour ischemia-reperfusion control rats. Chin J Physiol 1999 Mar: 42:9-16．
120． Altug S. Demiry AT, Cakici I. et al. The beneficial effects of peroxynitrite on ischaemia-reperfusion arrhythmias in rat isolated hearts. Eur J Pharmacol. 1999． 384:157-162．
121． Zweier JL. Samouilov A, Kuppusamy P. Non-enzymatic nitric oxide synthesis in biological systems. Biochim Biophys Acta. 1999． 1411:250-262．
122． Masini E. Salvemini D. Ndisang JF, et al. Cardioprotective activity of endogenous and exogenous nitric oxide on ischaemia reperfusion injury in isolated guinea pig hearts. Inflamm Res, 1999,48:561-568．
123． Hotta Y. Otsuka Murakami H. Fujita M, et al. Protective role of nitric oxide synthase against ischemia-reperfusion injury in guinea pig myocardial mitochondria. Eur J Pharmacol, 1999,380:37-48．
124． Haklar G, Ulukaya Durakbasa C. Ysel M, et al. Oxygen radicals and nitric oxide in rat mesenteric ischaemia-reperfusion: modulation by L-arginine and NG-nitro-L-arginine methyl ester. Clin Exp Pharmacol Physiol, 1998,25:908-912．
125． Mashiach E. Sela S, Winaver J. et al. Renal ischemia-reperfusion injury: contribution of nitric oxide and renal blood flow. Nephron.1998． 80:458-467．
126． Abe K, Hayashi N, Terada H. Effect of endogenous nitric oxide on energy metabolism of rat heart mitochondria during ischemia and reperfusion. Free Radic Biol Med ,1999,26:379-387．
127． Node K, Kitakaze M, Kosaka H, et al. Role of Ca2+-activated K+ channels in the protective effect of ACE inhibition against ischemic myocardial injury. Hypertension, 1998,31:1290-1298．
128． Humphreys SA, Koss MC. Role of nitric oxide in post-ischemic cerebral hyperemia in anesthetized rats. Eur J Pharmacol, 1998,347:223-229．
129． Kren T, Inal M. The effect of nitric oxide on ischemia-reperfusion injury in rat liver. Clin Chim Acta, 1999, 288:55-62．
130． Wang Y, Lawson JA, Jaeschke H. Differential effect of 2-aminoethyl-isothiourea, an inhibitor of the inducible nitric oxide synthase, on microvascular blood flow and organ injury in models of hepatic ischemia-reperfusion and endotoxemia. Shock, 1998, 10:20-25．
131． Vega VL, Maldonado M, Mardones L, et al. Inhibition of nitric oxide synthesis aggravates hepatic oxidative stress and enhances superoxide dismutase inactivation in rats subjected to tourniquet shock. Shock, 1998,9:320-328．
132． Weight SC, Furness PN, Nicholson ML. Nitric oxide generation is increased in experimental renal warm ischaemia-reperfusion injury. Br J Surg, 1998,85:1663-1668．
133． Liu P, Yin K, Nagele R, et al. Inhibition of nitric oxide synthase attenuates peroxynitrite generation, but augments neutrophil accumulation in hepatic ischemia-reperfusion in rats. J Pharmacol Exp Ther,1998,284:1139-1146．
134． Ockaili R, Emani VR, Okubo S, et at. Opening of mitochondrial KATP channel induces early and delayed cardioprotective effect: role of nitric oxide. Am J Physiol,1999,277(6 Pt 2) :H2425-H2434．
135． Pudupakkam S, Harris KA, Jamieson WG, et al. Ischemic tolerance in skeletal muscle: role of nitric oxide. Am J Physiol, 1998,275(1 Pt 2) :H94-H99．
136． Yoshida K, Mizukami Y, Kitakaze M. Nitric oxide mediates protein kinase C isoform translocation in rat heart during postischentic reperfusion. Biochim Biophys Acta, 1999, 1453:230-238．
137． Maczewski M, Beresewicz A. The role of adenosine and ATP-sensitive potassium channels in the protection afforded by ischemic preconditioning against the post-ischemic endothelial dysfunction in guinea-pig hearts. J Mol Cell Cardiol, 1998,30:1735-1747．
138． Kis A, Verb A, Papp J, et al. Pacing-induced delayed protection against arrhythmias is attenuated by aminoguanidine, an inhibitor of nitric oxide synthase. Br J Pharmacol, 1999,127:1545-1550．
139． Lo CC, Chen JC, Chen HM, et al. Aminoguanidine attenuates hemodynamic and microcirculatory derangement in rat intestinal ischemia and reperfusion. J Trauma, 1999,47:1108-1113．
140． Takizawa S, Fukuyama N, Hirabayashi H, et al. Dynamics of nitrotyrosine formation and decay in rat brain during focal ischemia-reperfusion. J Cereb Blood Flow Metab, 1999, 19:667-672．
141． Wildhirt SM, Schulze C, Conrad N, et al. Aminoguanidine inhibits inducible NOS and reverses cardiac dysfunction late after ischemia and reperfusion-implications for iNOS-mediated myocardial stunning. Thorac Cardiovasc Surg, 1999,47:137-143．
142． Richard V, Danielou E, Kaeffer N, et al. Delayed endothelial protective effects of monophosphoryl lipid A after myocardial ischemia and reperfusion in rats. J Mol Cell Cardiol,1999, 31:1117-1123．
143． Wildhirt SM, Weismueller S, Schulze C, et al. Inducible nitric oxide synthase activation after ischemia/reperfusion contributes to myocardial dysfunction and extent of infarct size in rabbits: evidence for a late phase of nitric oxide-mediated reperfusion injury. Cardiovasc Res, 1999, 43:698-711．
144． Isobe M, Katsuramaki T, Hirata K, et al. Beneficial effects of inducible nitric oxide synthase inhibitor on reperfusion injury in the pig liver. Transplantation, 1999,68:803-813．
145． Tsuji M, Higuchi Y, Shiraishi K, et al. Protective effect of aminoguanidine on hypoxic-ischemic brain damage and temporal profile of brain nitric oxide in neonatal rat. Pediatr Res, 2000,47:79-83．
146． Matoba S, Tatsumi T, Keira N, et al,. Cardioprotective effect of angiotensin-converting enzyme inhibition against hypoxia/reoxygenation injury in cultured rat cardiac myocytes. Circulation, 1999, 99:817-822．
147． Das DK, Kalfin R, Maulik N, ct al. Coordinated role of vasoactive intestinal peptide and nitric oxide in cardioprotection. Ann N Y Acad Sci,1998,865:297-308．
148． Cottart CH, Do L, Blanc MC, et al. Hepatoprotective effect of endogenous nitric oxide during ischemia-reperfusion in the rat. Hepatology, 1999,29:809-813．
149． Takano H, Manchikalapudi S, Tang XL, etal. Nitric oxide synthase is the mediator of late preconditioning against myocardial infarction in conscious rabbits. Circulation, 1998,98:441-449
150． Imagawa J, Yellon DM, Baxter GF. Pharmacological evidence that inducible nitric oxide
synthase is a mediator of delayed preconditioning. Br J Pharmacol, 1999, 126:701-708.
151.Zhou M, Chen Y, Ouyang Q, et al. The effect of teft-butyl hydroperoxide on peritoneal macrophages and the protective effect of protein-bound polysaccharide administered intraperitoneally and orally. Am J Chin Med, 1998,26:301-310.
152．庞战军，陈瑷，周玫．腹腔注射云芝多糖对小鼠腹腔巨噬细胞一氧化氮产生的影响．中国动脉硬化杂志，1999，7：155—157．
153.Pang ZJ, Zhou M, Chen Y, et al. A protein-bound polysaccharide synergistic with lipopolysaccharide induces nitric oxide release and antioxidant enzyme activities in mouse peritoneal macrophages. Am J Chin Med, 1998, 26:133-141.
154．魏文树，谭建权，陈海生．云芝多糖对小鼠肝脏超氧化物歧化酶活力和脂质过氧化的影响．中国药理学与毒理学杂志，1996,10：307-308．
155．欧阳谦，刘翠华，陈瑷，等．云芝多糖提高实验性动脉粥样硬化家兔抗氧化能力和减轻主动脉粥样硬化斑块．第一军医大学学报，1998,18：8-11．
156.Matsunaga K, Morita I, Oguchi Y, et al. Restoration of immune responsiveness by a biological response modifier, PSK, in aged mice bearing syngeneic transplantable tumor. J Clin Lab Immunol, 1987,24:143-149.
157．刘尚喜；周玫；陈瑗．云芝多糖对叔丁基脂氢过氧化物所致腹腔巨噬细胞损伤的保护作用的特点．第一军医大学学报，1998,18：15-17．
2.Bolli R. Mechanism of myocardial "stunning". Circulation, 1990,82:723-738.
3.Bolli R. Myocardial 'stunning' in man. Circulaiion, 1992,86:1671-1691.
4.Bolli R. Basic and clinical aspects of myocardial stunning. Prog Cardiovasc Dis, 1998,40:477-516.
5.Kloner RA, Bolli R Marban E, et al. Medical and cellular implications of stunning, hibemaiion, and preconditioning. An NHLBI workshop. Circulation, 1998,97:1848-1867.
6.Tennant T, Wiggers CT. Effect of coronary occlusion on myocardial contraction. Am J Physiol,1935,112:351.
7.Heynddckx GR Millard RW, McRitchie RJ, et al. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest,1975,56:978-985.
8.Bolli R. Oxygen-derived free radicals and postischemic myocardial dysfunction("stunned myocardium"). J Am Coll Cardiol, 1988,12:239-249.
9.Kloner PA, Przyklenk K, Whittaker P. Deleterious effects of oxygen radicals in ischemia/reperfusion. Circulation, 1989,80:1115-1127.
10.Bolli R Jeroudi MO, Patel BS, et al. Marked reduction of free radical generation and contractile disfunction by antioxidant therapy begun at the time of reperfusion: Evidence that myocardial"stunning" is a manifestation of reperfusion injury. Circ Res, 1989,65:607-622.
11.Bolli R Patel BS, Jeroudi MO, et al. Demonstration of free radical generation in "stunned"myocardium of intact dogs with the use of the spin trap α_phenyl N-tert-butyl nitronc. J Clin Invest,1988,82:476-485.
12.Bolli R, Jeroudi MO, Patel BS, et al. Direct evidence that oxygen-derived free radicals contribute to postischemic myocardial dysfunction in the intact dog. Proc Nail AcM Sci USA,1989,86:4695-4699.
13．田英平，李星海，陶桂华．一氧化氮对于心肌功能的影响．心血管病学进展，1996，17：296-297
14.Brady AJB, Warren JB, Poole-Wilson PA, et al. Nitric oxide attenuates cardiac myocyte contraction. Am J Physiol, 1993,265:H176-H182.
15.Gulick T, Pieper SJ, Murphy MA, et al. A new method for assessment of culture cardiac myocyte contractility detects immune factor-mediaied inhibition of β-adrenergic responses. Circulation,1991,84:313-321.
16.Paulus WJ, Vantrimpont PJ, Shah AM. Acute effects of nitric oxide on left ventricular relaxation and diastolic distensibility in humans. Assessment by coronary sodium nitroprusside infusion.Circulation, 1994,89:2070-2078.
17.Balligand J-L, Kelly PA, Maraden PA, et al. Control of cardiac muscle cell function by an endogenous nitric oxide signaling system. Proc Nail Acad Sci USA,1993,90:347-351.
18.Hare JM, Keaney JF, Kelly RA, et al. Inhibition of nitric oxide synthase potentiates the positive inotropic response to β-adrenergic stimulation in normal dogs. Circulation, 1993,88(abstr):I-1905.
19.Winlaw DS, Sm}the GA, Keogh AM, et al. Increased nitric oxide production in heart failure.Lancet, 1994,344:373-374.
20． Levine B, Kalman J, Mayer L, et al. Elevated circulating levels of tumor necrosis factor in severe chronic heart failure. N Engl J Med 1990,323:236-241．
21． Lipton SA, Choi YB, Pan ZH, et al. A redox-based mechanism for the neuroprotective and neurodestructive effects of nitric oxide and related nitroso-compounds. Nature, 1993,364:626-632．
22． Vinten-Johansen J, Sato H. Zhao ZQ. The role of nitric oxide and NO-donor agents in myocardial protection from surgical ischemic-reperfusion injury. Int J Cardiol, 1995,50:273-281
23． Lefer DJ, Nakanishi K, Johonston WE, et al. Antineutrophil and myocardial protecting actions of a novel nitric oxide donor after acute myocardial ischemia and reperfusion in dogs. Circulation, 1993,88:2337．
24． Weyrich AS, Ma XL, Lefer AM. The role of L-arginine in ameliorating reperfusion injury after myocardial ischermia in the cat. Circulation, 1992,86:279-288．
25． Beresewicz A. Karwatowska-Prokopczuk E, Lewartowski B. et al. A protective role of nitric oxide in isolated ischaemic reperfused rat heart. Cardiovasc Res,1995． 30:1001-1008
26． Li XS, Uriuda Y, Wang QD. et al. Role of L-arginine in preventing myocardial and endothelial injury following ischaemia/reperfusion in the rat isolated heart. Acta Physiol Scand. 1996,156:37-44
27． Hasebe N, Shen Y-T, Vatner SF. Inhibition of endothelium-derived relaxing factor enhances myocardial stunning in conscious dogs. Circulation. 1993,88:2862-2871．
28． Williams MW. Taft CS. Ramnauth S. et al. Endogenous nitric oxide (NO) protects against ischaemia-reperfusion injury in the rabbit. Cardiovasc Res.1995． 30:79-86．
29． Takeuchi K. McGowan FX. Danh HC, et al. Direct detrimental effect of L-Arginine upon ischemia-reperfusion injury to myocardium. J Mol Cell Cardiol, 1995,27:1405-1414．
30． Mori E. Haramaki N. Ikeda H, et al. Intra-coronary administration of L-arginine aggravates myocardial stunning through production of peroxynitrite in dogs. Cardiovasc Res. 1998, 40:113-123．
31． Morita K, Ihnken K, Buchberg GD. et al. Role of controlled cardiac reoxygenation in reducing nitric oxide production and cardiac oxidant damage in cyanotic infantile hearts. J Clin Invest, 1994． 93:2658-2662．
32． Wang P, Zweier JL. Measurement of nitric oxide and peroxynitrite generation in the postischemic heart. J Biol Chem. 1996,271:29223-29230
33． Schulz R, Wambolt R. Inhibition of nitric oxide synthesis protects the isolated working rabbit heart from ischemia-reperfusion injury. Cardiovasc Res, 1995,30:432-439
34． Naseem SA, Kontos MC, Rao PS, et al. Sustained inhibition of nitric oxide by NG-nitro-L-arginine improves myocardial function following ischemia/reperfusion in isolated perfused rat heart. J Mol Cell Card, 1995,27:419-426
35． Tsao PS, Aoki N, Lefer DJ, et al. Time course of endothelial dysfunction and myocardial injury during myocardial ischemia and reperfusion in the rat. Circulation, 1990,82:1402-1412
36． Balligand J-L, Ungureanu-Longrois D, Simmons WW, et al. Cytokine-inducible nitric oxide synthase (iNOS) expression in cardiac myocytes. J Biol Chem, 1994,269:27580-27588
37． Tsujino M, Hirata Y, Imai T, et al. Induction of nitric oxide synthase gene by interleukin 1β in cultured rat cardiocytcs. Circulation, 1994,90:375-383
38． LaPointe MC, Sitkins JR. Mechanisms of interleukin 1β regulation of nitric oxide synthase in cardiac myocytes. Hypertension, 1996,27:709-714
39． Birdsall HH, Green DM, Trial J, et al. Complement C5a, TGF-β1, and MCP-1, in sequence, induce migration of monocytes into ischemic canine myocardium within the first one to five hours after
reperfusion. Circulation, 1997,95:684-692
40.Cheng XS, Shimokawa H, Momii H, et al. Role of superoxide anion in the pathogenesis of cytokine-induced myocardial dysfunction in dogs in vivo. Circulation, 1997,96(Suppl):1605.
41.Bechman JS, Koppenol WH. Nitric oxide, superoxide, and peroxynitrite: the good, the bad. and the ugly. Am J Physiol,1996,271(cell Physiol 40):C1424-1437.
42.Xia Y, Dawson VL, Dawson TM. et al. Nitric oxide synthase generates superoxide and nitric oxide in arginine depleted cells leading to peroxynitrite mediated cellular injury. Proc Natl Acad Sci USA,1996,93:6770-6774.
43．周玫，陈瑗．体内一氧化氮和过氧亚硝酸的生成及其生物学效应．中国动脉硬化杂志，1998，6：178-181．
44.Seo HG, Tannenbaum SR. Identification of a stress-inducible protein containing nitrotyrosine in RAW264.7 cells activated by IFN-γ and LPS. Proceedings of the 5th international meeting on the biology of nitric oxide.Jpn J Pharmacol, 1997.75(Suppl 1):105.
45.Beckman JS. Peroxynitrite versus hydroxyl radical: The role of nitric oxide in superoxide-dependent cerebral injury. Ann NY Acad Sci. 1994.738:69-75
46.Liu P, Hock CE, Nagele R. et al. Formation of nitric oxide, superoxide, and peroxynitrite in myocardial ischemia-reperfusion injury in rats. Am J Physiol, 1997. 272(5 Pt 2): H2327-2336
47.Zingarelli B. Cuzzocrea S. Zsengeller Z, et al. Protection against myocardial ischemia and reperfusion injury by 3-aminobenzamide. an inhibitor of poly (ADP-ribose) synthetase. Cardiovasc Res. 1997,36:205-215
48.Ma XL, Lopez BL, Liu GL. et al. Peroxynitrite aggravates myocardial reperfusion injury in the isolated perfused rat heart. Cardiovasc Res, 1997,36:195-204
49.Ischiropoulos H, Duran D, HorwitzJ. Peroxynitrite-mediated inhibition of DOPA synthesis in PC12 cells. J Neurochem, 1995,65:2366-2372
50.Sharpe MA, Cooper CE. Reactions of nitric oxide with mitochondrial cytochrome c: a novel mechanism for the formation of nitroxyl anion and peroxynitrite. Biochem J. 1998.332(Pt1): 9-19
51.Oyama Ji, Shimokawa H, Momii H, et al. Role of nitric oxide and peroxynitrite in the cytokine-induced sustained myocardial dysfunction in clogs in vivo. J Clin Invest. 1998,101:2207-2214
52.Misko TP, Moore WM, Kasten TP, et al. Selective inhibition of the inducible nitric oxide synthase by aminoguanidine. Eur J Pharmacol, 1993,233: 119-125
53.Becket LC. Is stunned myocardium ischemic on a microvaseular level? Basic Res Cardiol, 1995,90:282-284.
54.Bolli R, Triana JF, Jeroudi MO.. Prolonged impairment of coronary vasodilation after reversible ischemia. Evidence for microvascular "stunning". Circ Res, 1990,67:332-343.
55.Tillmanns H, Neumann FJ, Tiefenbacher C, et al. Activation of neutrophils in the microvasculature of the ischaemic and repeffused myocardium. Eur Heart J.1993,14(Suppl 1)82-86.
56.Duncker DJ, McFalls EO, Krams R, et al. Pressure-maximal coronary flow relationship in regionally stunned porcine myoeardium. Am J Physiol, 1992,262:H1744-H1751.
57.Jeremy RW, Stahl L, Gillinov M, et al. Preservation of coronary, flow reserve in stunned myocardium. Am J Physiol, 1989,256:H1301-H1310.
58.McFalls EO, Duncker DJ, Krams R, et al. Endothelium dependent vasodilatation following brief ischemia and reperfusion in anaesthetized swine. Cardiovasc Res, 1991,25:659-665.
59.Stahl LD, Aversano TR, Becher LC. Selective enhancement of function of stunned myocardium by increased flow. Circulation, 1986,74:843-851.
60.Stahl LD, Weiss HR, Becher LC. Myocardial oxygen consumption, oxygen supply/demand heterogeneity and microvascular patency in regionally stunned myocardium. Circulation,1988,77:865-872.
61.Nicklas JM, Gips S. Decreased coronary flow reserve after transient myocardial ischemia in dogs.J Am Coil Cardiol, 1989,13:195-199.
62.Bolli R, Triana .JF, Jeroudi MO.. Prolonged impairment of coronary vasodilation after reversible ischemia. Evidence for microvascular "stunning". Circ Res, 1990,67:332-343.
63．徐成斌．对缺血后心肌功能障碍的新认识——心肌击昏与心肌冬眠的临床意义．心血管病学进展，1992，13：137-142．
64.Becher LC, Levine JH, Dipaula AF, et al. Reversal of dysfunction in postiscemic stunned myocardium by epinephrine and postextrasystolic potentiation. J AM Coll Cardiol, 1986,7:580-589.
65.Pierard LA, De Landsheere CM, Berthe C, et al. Identification of viable myocardium by echocardiography during dobutamine infusion in patients with myocardial infarction after thrombolytic therapy: comparison with positron emission tomography. J Am Coil Cardiol, 1990,15: 1021-1031.
66.Dilsizian V, Bonow RO. Current diagnostic techniques of assessing myocardial viability in hibernating and stunned myocardium. Circulation, 1993,87:1-20.
67.Ferrari R,La Canna G, Giubbini R, et al. Stunned and hibernating myocardium: possibility of intervention. J Cardiovasc Pharmacol, 1992,20(Suppl 5):S5-S13.
68.Cheirif J, Narkiewicz-jodko JB, Bravenec JS, et al. Myocardial contrast echocardiograhy: relation between online and off-line assessment of myocardial perfusion. Echocardiography, 1993,10:471.
69．刘伊丽．心肌声学造影——一种评价冠状动脉微循环的新技术．中华心血管病杂志，1997，25：76-78．
70.Feinstein SB, et al. Two-dimensional contrast echocardiography: 1. In vitro development and quantitative analysis of echo contrast agents. JACC, 1984,3:14-20.
71.Kaul S, et al. Relation between anterograde blood flow through a coronary artery and the size of the perfusion bed it supplies: Experimental and clinical implications. JACC, 1992,17:1403.
72.Xie F, Porter TR. Acute myocardial ischemia and reperfusion can be visually identified non-invasively with intravenous perfluropropane exposed sonicated dextrose albumin ultrasound contrast.Circulation, 1994,91:1-555.
73.Porter TR., Xie F. Visually discernible myocardial echocardiographic contrast after intravenous injection of sonicated dextrose albumin microbubbles containing high molecular weight less soluble gasses. JACC, 1995,25:509-515.
74.Dittrich HC, et al. Myocardial contrast echocardiography in experimental coronary artery occlusion with a new intravenously administered contrast agent. J Am Soc Echocardiogr,1995,8:465.
75．谢峰，勒斌，李澎，等．新型声学造影剂非损伤性估价正常心肌血流灌注的实验研究．中华超声医学杂志，1996，12：1-6．
76.Porter TR, Xie F, Kricsfeld A, et al. Myocardial perfusion abnormalities during low-dose dobutamine after coronary reperfusion can be demonstrated with intravenous perfluorocarbon-exposed sonicated dextrose albumin ultrasound contrast. Am Heart J. 1996.131 :1079-1087.
77.Desir RM, Cheirif J, Bolli R, et al. Assessment of regional myocardial perfusion with myocardial contrast echocardiography in a canine model of varying degrees of coronary stenosis. Am Heart J,1994, 127:56-63.
78.Porter TIC D'Sa A, Turner C, et al. Myocardial contrast echocardiography for the assessment of coronary blood flow reserve: Validation in humans. JACC, 1993,21:349-355.
79．邵波，钱蕴秋，张军，等．心肌造影超声心动图评估心肌缺血程度的实验研究．中华超声影像学杂志，1997，6：40-42．
80．张洁．心肌对比超声评价冠状动脉微循环的应用研究现状．心血管病学进展，1996，17：285-286．
81．王新明，牟善初．经静脉心肌造影超声显像评价冠状动脉微循环的研究现状．军医进修学院学报，1997，18：295-297．
82.Kaul S, Jayaweera AR. Myocardial contrast echocardiography has the potential for the assessment of coronary microvascular reserve. JACC, 1993,21:356-358.
83.Lou N, Zhou M, Chen Y. Inhibitory effect of polysaccharide Krestin on foam cell formation and necrosis of murine peritoneal macrophage caused by oxidized low density lipopmtein. Med Sci Res,1996, 24: 49-51.
84.Chen Y, Zhou M, Li J, et al. Injurious effect of reactive oxygen species on macrophage and its prevention by PSK. J Clin Lab Immunol, 1994, 43:99-115.
85.Zhou M, Chen Y, Liu SX, et al. Elevation of macrophage SeGSHPx gene expression and prevention of foam cell formation. In: Eds By Lester Pacher, Proceedings of the international Symposium on Natural antioxidants: Molecuar Mechanisms and Health Effects. Maret G Traber.AOCS Press, Champaign, Illinois, USA, 1996:339-351.
86．庞战军，陈瑷，周玫．云芝多糖对小鼠腹腔巨噬细胞锰超氧化物歧化酶基因表达的调控．中国动脉硬化杂志，1999，7：106-109．
87.Porter TR., Xie F, Kricsfeld A, et al. Noninvasive identification of acute myocardial ischemia and reperfusion with contrast ultrasound using intravenous perfluoropmpane-exposed sonicated dextrose albumin. J Am Coll Cardi?l,1995,26:33-40.
88.Agati L. Microvascular integrity after reperfusion therapy. Am Heart J, 1999,138(2 Pt 2):s76-s78.
89.Hasdai D, Holmes DR Jr, Higano ST, et al. Prevalence of coronary blood flow reserve abnormalities among patients with nonobstmctive coronary artery disease and chest pain. Mayo Clin Proc, 1998, 73:1133-1140.
90.Koglin J, yon Scheidt W. Isolated defect of adenosine-mediated coronary vasodilation: functional evidence for a new microangiopathic entity. J Am Coil Cardiol, 1997, 30:103-107.
91.Knecht M, Burkhoff D, Yi GH, et al. Coronary endothelial dysfunction precedes heart failure and reduction of coronary reserve in awake dogs. J Mol Cell Cardiol, 1997, 29:217-227.
92.Hasdai D, Holmes DR Jr, Higano ST, et al. Effect of basal epicardial tone on endothelium-independent coronary flow reserve measurement. Cathet Cardiovasc Diagn, 1998, 44:392-396.
93.Hartmann A, Lahoda T, Burger W, et al.,Endothelium-dependent and endothelium-independent flow regulation in coronary vascular regions supplied by arterial and venous bypass grafts.Cardiology, 1997, 88:425-432.
94.Murakami H, Urabe K, Nishimura M. Inappropriate microvascular constriction produced transientST-segment elevation in patients with syndrome X. J Am Coll Cardiol, 1998, 32:1287-1294.
95.Hasdai D, Gibbons RJ, Holmes DR Jr, et al. Coronary endothelial dysfunction in humans is associated with myocardial perfusion defects. Circulation, 1997, 96:3390-3395.
96.Tiefenbacher CP, Tillmanns H. Niroomand F, et al. Adaptation of myocardial blood flow to increased metabolic demand is not dependent on endothelial vasodilators in the rat heart. Heart,1997, 77:147-153.
97.Loke KE, Woodman OL.Preconditioning improves myocardial function and reflow, but not vasodilator reactivity, after ischaemia and reperfusion in anaesthetized dogs. Clin Exp Pharmacol Physiol, 1998, 25:552-558.
98.Hartmann A, Reuss W, Burger W. et al. Endothelium-dependent and endothelium-independent flow reserve in vascular regions supplied by the internal mammary artery before and after bypass grafting.Eur J Cardiothorac Surg. 1998, 13:410-415.
99.Weis M, Hartmann A, Olbrich HG. et al. Prognostic significance of coronary flow reserve on left ventricular ejection fraction in cardiac transplant recipients. Transplantation, 1998, 65:103-108.
100.Lerman A, Burnett JC Jr, Higano ST, ct al. Long-term L-arginine supplementation improves small-vessel coronary endothelial function in humans. Circulation, 1998.97:2123-2128.
101.Lerman A, Cannan CR. Higano SH. et al. Coronary vascular remodeling in association with endothelial dysfunction. Am J Cardiol. 1998, 81:1105-1109.
102.Tio RA. Van Gelder IC. Boonstra PW, et al. Myocardial bridging in a survivor of sudden cardiac near-death: role of intracoronary doppler flow measurements and angiography during dobutamine stress in the clinical evaluation. Heart. 1997, 77:280-282.
103.Wildhirt SM, Weis M, Schulze C, et al. Endothelium-dependent microvascular vasomotion and its correlation with vasoactivc mediators early after cardiac transplantation in humans. Transpl Int,1998, 11(Suppl 1):S519-S524.
104.Weis M, Hartmann A, Scheuermann EH, et al. Soluble interleukin-2-receptor levels as a marker of coronary microvascular dysfunction after heart transplantation. J Heart Lung Transplant, 1998.17:294-298.
105.Drexler H. Endothelial dysfunction: clinical implications. Prog Cardiovasc Dis, 1997,39:287-234.
106.Kaul S. Assessment of coronary microcirculation with myocardial contrast echocardiography:current and future clinical applications. Br Heart J,1995, 75:490-495.
107.Senior R, Lahiri A, Ravai U, et al. Detection of coronary artery disease using myocardial contrast echocardiography: comparison with 99m-Tc-Sestamibi Single Photon Emission Tomography.Circulation, 1996, 94(suppl 1):1-140.
108.Galiuto L, DeMaria AN, May Newman K, et al. Evaluation of dynamic changes in microvascular flow during ischemia-rcperfusion by myocardial contrast echocardiography. J Am Coll Cardiol, 1998,32:1096-11O1.
109.Wu CC. Feldman MD, Mill JD, et al. Myocardial contrast echocardiography can be used to quantify intramyocardial blood volume: new insights into structural mechanisms of coronary autorcgulation. Circulation, 1997,96: 1004-1011.
110.Fici GJ, Althaus JS, Von Voigtlander PF. Effects of lazaroids and a peroxynitrite scavenger in a cell model of peroxynitritc toxicity. Frec Rad Biol Mod, 1997,22:223-228.
111．李祈．心肌缺血再灌注损伤中的冠状微循环障碍．国外医学心血管病分册，1998，25：262-265．
112.Pryor WA, Squadrito GL.The chemistry of peroxynitrite: a product from the reaction of nitric oxide with superoxide. Am J Physiol, 1995,268:L699-L722
113.Ishid H, lchimori K, Hirota Y. et al. Peroxynitrite-induced cardiac myocyte injury. Free Rad Biol Med, 1996, 20:343-350
114． 李中言,赵连友．一氧化氮与心血管疾病．中华心血管病杂志，1996． 24：73-76
115． Herbertson MJ, Werner HA. Walley KR. Nitric oxide synthase inhibition partially prevents decreased LV contractility during endotoxemia. Am J Physiol. 1996,270:H1979-H1984
116． Sampson JB, Rosen H. Beckman JS. Peroxynitrite dependent tyrosine nitration catalyzed by superoxide dismutase, myeloperoxidase and horseradish peroxidase. Methods Enzymol, 1996,269:210-218
117． Pearse DB, Wagner EM, Permutt S. Effect of ventilation on vascular permeability and cyclic nucleotide concentrations in ischemic sheep lungs. J Appl Physiol. 1999, 86:123-132．
118． Harris NR, Langlois KW. Age-dependent responses of the mesenteric vasculature to ischemia-reperfusion. Am J Physiol. 1998,274(5 Pt 2) :H1509-1515．
119． Borsch DM, Cilento EV. Reilly FD. Role for nitric oxide but not prostaglandins in acetylcholine-induced relaxation of rat cremaster third-order arterioles in 5-hour ischemia-reperfusion control rats. Chin J Physiol 1999 Mar: 42:9-16．
120． Altug S. Demiry AT, Cakici I. et al. The beneficial effects of peroxynitrite on ischaemia-reperfusion arrhythmias in rat isolated hearts. Eur J Pharmacol. 1999． 384:157-162．
121． Zweier JL. Samouilov A, Kuppusamy P. Non-enzymatic nitric oxide synthesis in biological systems. Biochim Biophys Acta. 1999． 1411:250-262．
122． Masini E. Salvemini D. Ndisang JF, et al. Cardioprotective activity of endogenous and exogenous nitric oxide on ischaemia reperfusion injury in isolated guinea pig hearts. Inflamm Res, 1999,48:561-568．
123． Hotta Y. Otsuka Murakami H. Fujita M, et al. Protective role of nitric oxide synthase against ischemia-reperfusion injury in guinea pig myocardial mitochondria. Eur J Pharmacol, 1999,380:37-48．
124． Haklar G, Ulukaya Durakbasa C. Ysel M, et al. Oxygen radicals and nitric oxide in rat mesenteric ischaemia-reperfusion: modulation by L-arginine and NG-nitro-L-arginine methyl ester. Clin Exp Pharmacol Physiol, 1998,25:908-912．
125． Mashiach E. Sela S, Winaver J. et al. Renal ischemia-reperfusion injury: contribution of nitric oxide and renal blood flow. Nephron.1998． 80:458-467．
126． Abe K, Hayashi N, Terada H. Effect of endogenous nitric oxide on energy metabolism of rat heart mitochondria during ischemia and reperfusion. Free Radic Biol Med ,1999,26:379-387．
127． Node K, Kitakaze M, Kosaka H, et al. Role of Ca2+-activated K+ channels in the protective effect of ACE inhibition against ischemic myocardial injury. Hypertension, 1998,31:1290-1298．
128． Humphreys SA, Koss MC. Role of nitric oxide in post-ischemic cerebral hyperemia in anesthetized rats. Eur J Pharmacol, 1998,347:223-229．
129． Kren T, Inal M. The effect of nitric oxide on ischemia-reperfusion injury in rat liver. Clin Chim Acta, 1999, 288:55-62．
130． Wang Y, Lawson JA, Jaeschke H. Differential effect of 2-aminoethyl-isothiourea, an inhibitor of the inducible nitric oxide synthase, on microvascular blood flow and organ injury in models of hepatic ischemia-reperfusion and endotoxemia. Shock, 1998, 10:20-25．
131． Vega VL, Maldonado M, Mardones L, et al. Inhibition of nitric oxide synthesis aggravates hepatic oxidative stress and enhances superoxide dismutase inactivation in rats subjected to tourniquet shock. Shock, 1998,9:320-328．
132． Weight SC, Furness PN, Nicholson ML. Nitric oxide generation is increased in experimental renal warm ischaemia-reperfusion injury. Br J Surg, 1998,85:1663-1668．
133． Liu P, Yin K, Nagele R, et al. Inhibition of nitric oxide synthase attenuates peroxynitrite generation, but augments neutrophil accumulation in hepatic ischemia-reperfusion in rats. J Pharmacol Exp Ther,1998,284:1139-1146．
134． Ockaili R, Emani VR, Okubo S, et at. Opening of mitochondrial KATP channel induces early and delayed cardioprotective effect: role of nitric oxide. Am J Physiol,1999,277(6 Pt 2) :H2425-H2434．
135． Pudupakkam S, Harris KA, Jamieson WG, et al. Ischemic tolerance in skeletal muscle: role of nitric oxide. Am J Physiol, 1998,275(1 Pt 2) :H94-H99．
136． Yoshida K, Mizukami Y, Kitakaze M. Nitric oxide mediates protein kinase C isoform translocation in rat heart during postischentic reperfusion. Biochim Biophys Acta, 1999, 1453:230-238．
137． Maczewski M, Beresewicz A. The role of adenosine and ATP-sensitive potassium channels in the protection afforded by ischemic preconditioning against the post-ischemic endothelial dysfunction in guinea-pig hearts. J Mol Cell Cardiol, 1998,30:1735-1747．
138． Kis A, Verb A, Papp J, et al. Pacing-induced delayed protection against arrhythmias is attenuated by aminoguanidine, an inhibitor of nitric oxide synthase. Br J Pharmacol, 1999,127:1545-1550．
139． Lo CC, Chen JC, Chen HM, et al. Aminoguanidine attenuates hemodynamic and microcirculatory derangement in rat intestinal ischemia and reperfusion. J Trauma, 1999,47:1108-1113．
140． Takizawa S, Fukuyama N, Hirabayashi H, et al. Dynamics of nitrotyrosine formation and decay in rat brain during focal ischemia-reperfusion. J Cereb Blood Flow Metab, 1999, 19:667-672．
141． Wildhirt SM, Schulze C, Conrad N, et al. Aminoguanidine inhibits inducible NOS and reverses cardiac dysfunction late after ischemia and reperfusion-implications for iNOS-mediated myocardial stunning. Thorac Cardiovasc Surg, 1999,47:137-143．
142． Richard V, Danielou E, Kaeffer N, et al. Delayed endothelial protective effects of monophosphoryl lipid A after myocardial ischemia and reperfusion in rats. J Mol Cell Cardiol,1999, 31:1117-1123．
143． Wildhirt SM, Weismueller S, Schulze C, et al. Inducible nitric oxide synthase activation after ischemia/reperfusion contributes to myocardial dysfunction and extent of infarct size in rabbits: evidence for a late phase of nitric oxide-mediated reperfusion injury. Cardiovasc Res, 1999, 43:698-711．
144． Isobe M, Katsuramaki T, Hirata K, et al. Beneficial effects of inducible nitric oxide synthase inhibitor on reperfusion injury in the pig liver. Transplantation, 1999,68:803-813．
145． Tsuji M, Higuchi Y, Shiraishi K, et al. Protective effect of aminoguanidine on hypoxic-ischemic brain damage and temporal profile of brain nitric oxide in neonatal rat. Pediatr Res, 2000,47:79-83．
146． Matoba S, Tatsumi T, Keira N, et al,. Cardioprotective effect of angiotensin-converting enzyme inhibition against hypoxia/reoxygenation injury in cultured rat cardiac myocytes. Circulation, 1999, 99:817-822．
147． Das DK, Kalfin R, Maulik N, ct al. Coordinated role of vasoactive intestinal peptide and nitric oxide in cardioprotection. Ann N Y Acad Sci,1998,865:297-308．
148． Cottart CH, Do L, Blanc MC, et al. Hepatoprotective effect of endogenous nitric oxide during ischemia-reperfusion in the rat. Hepatology, 1999,29:809-813．
149． Takano H, Manchikalapudi S, Tang XL, etal. Nitric oxide synthase is the mediator of late preconditioning against myocardial infarction in conscious rabbits. Circulation, 1998,98:441-449
150． Imagawa J, Yellon DM, Baxter GF. Pharmacological evidence that inducible nitric oxide
synthase is a mediator of delayed preconditioning. Br J Pharmacol, 1999, 126:701-708.
151.Zhou M, Chen Y, Ouyang Q, et al. The effect of teft-butyl hydroperoxide on peritoneal macrophages and the protective effect of protein-bound polysaccharide administered intraperitoneally and orally. Am J Chin Med, 1998,26:301-310.
152．庞战军，陈瑷，周玫．腹腔注射云芝多糖对小鼠腹腔巨噬细胞一氧化氮产生的影响．中国动脉硬化杂志，1999，7：155—157．
153.Pang ZJ, Zhou M, Chen Y, et al. A protein-bound polysaccharide synergistic with lipopolysaccharide induces nitric oxide release and antioxidant enzyme activities in mouse peritoneal macrophages. Am J Chin Med, 1998, 26:133-141.
154．魏文树，谭建权，陈海生．云芝多糖对小鼠肝脏超氧化物歧化酶活力和脂质过氧化的影响．中国药理学与毒理学杂志，1996,10：307-308．
155．欧阳谦，刘翠华，陈瑷，等．云芝多糖提高实验性动脉粥样硬化家兔抗氧化能力和减轻主动脉粥样硬化斑块．第一军医大学学报，1998,18：8-11．
156.Matsunaga K, Morita I, Oguchi Y, et al. Restoration of immune responsiveness by a biological response modifier, PSK, in aged mice bearing syngeneic transplantable tumor. J Clin Lab Immunol, 1987,24:143-149.
157．刘尚喜；周玫；陈瑗．云芝多糖对叔丁基脂氢过氧化物所致腹腔巨噬细胞损伤的保护作用的特点．第一军医大学学报，1998,18：15-17．