摘要
目的：本研究测定左室舒张功能障碍的患者血浆BNP浓度，旨在探讨BNP在左室舒张功能障碍中的变化规律，了解左室舒张功能障碍的病理生理，为早期诊断左室舒张功能障碍提供依据。
方法：1.正常对照组
20例。其中男11例，女9例。平均年龄57±15岁，选自河北医科大学第三医院2002年12月至2003年6月的健康查体者，行心电图、超声心动图、胸部X线等系统检查排除心、脑、肝、肾、肺等疾病。
2.左室舒张功能障碍组
入选条件：①有易致舒张功能障碍的基础病，如高血压病、冠心病、肥厚性心肌病等②超声心动图舒张指标异常，收缩指标正常。
51例符合条件的患者（其中男27例，女24例,平均年龄为62±11岁, 原发性高血压34例，高血压病合并冠心病12例，冠心病4例，肥厚性心肌病1例）定为左室舒张功能障碍组。
3.舒张性心力衰竭组
符合第六届全国心力衰竭学术会（2001年5月，无锡）修订的左室舒张障碍性心力衰竭的诊断标准。（14例，其中男8例，女6例，平均年龄65±10岁, 原发性高血压4例，高血压病合并冠心病9例，肥厚性心肌病1例）。
所有患者均选自河北医科大学第三医院2002年12月至2003年6月住院患者。排除继发性高血压、心脏瓣膜病、肾功能衰竭、肝硬化、淀粉样变、甲状腺疾病、循环中糖皮质激素过多、慢性肺部疾病等。
本研究采用固相免疫放射分析法检测血浆BNP浓度。BNP试剂盒由法国CIS公司生产,天津新四方科技有限公司提供。
超声心动图指标由超声室专业人员统一检测，采用美国HP5500彩色多普勒超声诊断仪，探头频率为2.5HZ。患者左侧卧位，平静呼吸。①利用2D超声于左室长轴切面测量舒张期主动脉瓣瓣口(AO)内径、左房（LA）内径、左室（LV）内径、室间隔（IVS）、左室后壁（LVPW）的厚度、左室射血分数（EF%）。②利用脉冲多普勒测定二尖瓣舒张早期最大血流速度（E峰）、舒张晚期的最大血流速度（A峰）并算出E/A的比值。③采用组织多普勒速度成像技术（TDI）于心尖四腔心切面，取样框位于二尖瓣瓣环水平间隔处心肌、侧壁处心肌分别测量舒张早期、舒张晚期的速度峰值（Em间,Am间；Em侧,Am侧）并计算得出Em/Am值（Em/Am间;Em/Am侧）；于心尖两腔心切面取样框位于二尖瓣瓣环水平前壁处心肌、下壁处心肌，分别测量舒张早期、舒张晚期的速度峰值（Em前，Am前；Em下,Am下），分别计算得出Em/Am值(Em/Am前；Em/Am下)（注：脚注间代表左室间隔，侧代表左室侧壁，前代表左室前壁，下代表左室下壁）。
所有数据均输入计算机，用SPSS11.0统计软件包进行处理。p<0.05为差异显著性标准。
结果：1.左室舒张功能障碍组血浆BNP浓度比正常对
照组（27.01±32.97pg/ml V 13.33±15.93pg/ml）升高（p<0.05）,有显著差异,具有统计学意义；舒张性心力衰竭组血浆BNP浓度比正常对照组升高（98.61±109.69pg/ml V 13.33±15.93pg/ml）（p<0.001）,有显著差异,具有统计学意义；舒张性心力衰竭组与左室舒张功能障碍组比较（98.61±109.69pg/ml V 27.01±32.97pg/ml），血浆BNP浓度升高（p<0.001）,有显著差异,具有统计学意义。
2.左室舒张功能障碍组血浆BNP浓度分别与年龄(r=0.32,p=0.02)、 脉压(r=0.32,p<0.01)成正相关，与舒张压成负相关（r=-0.28,p=0.05）。
3.舒张性心力衰竭组血浆BNP浓度与Em间(r=-0.82,p<0.001)、Em/Am间(r=-0.70,p<0.01)、Em前(r=-0.60,p<0.05)、Em/Am前(r=-0.61,p=0.02)、Em下(r=-0.63,p<0.05)、Am下(r=-0.59,p<0.05)、Em/Am下(r=-0.53,p=0.05)成负相关。
结 论：1.左室舒张末压升高、室壁张力的增大、动脉顺应性减低、局部心肌舒张功能减退均可促进BNP的释放。
2.左室舒张功能障碍的患者血浆BNP浓度升高，且随着疾病程度加重而升高越明显。BNP可作为左室舒张功能障碍的诊断标准,其升高程度可提示疾病的严重性。
3.随着年龄的增长, 血浆BNP浓度也随之升高。随着脉压升高，血浆BNP浓度也升高。随着舒张压降低,血浆BNP浓度反而增加。
4.血浆BNP浓度比超声心动图更早期预测左室舒张功能障碍。组织多普勒（TDI）比超声多普勒敏感，能早期检测出局部心肌组织的舒张功能受损情况。
Objective: The purpose of our research is to understand the regularity of the variation of the plasma BNP in the patients of left ventricular diastolic dysfunction and failure, therefore,we can explore the pathophysiology of left ventricular diastolic dysfunction and search for an evidence to diagnose them earlierly.
Methods: 1.The control group
From December 2002 to July 2003,20 persons who had been proved to be healthy through health examination in the third hospital of Hebei medical university were selected as a control group(11 men,9 women, average 57±15 years).
2. Left ventricular diastolic dysfunction group(LVDD)
The selected criteria are①There are basic diseases lead to left ventricular diastolic dysfunction,such as essential hyper- tension,coronary heart disease or hypertrophic cardiomyopathy②There are some abnormal parameters of diastolic function in the echocardiography,while systolic parameters is normal.
51 patients were selected( 27 men,24 women,average 62±11 years,34 essential hypertension,12 essential hypertension combined with coronary heart disease,4 coronary heart disease,1 hypertrophic cardiomyopathy)as a group of LVDD.
3. Diastolic heart failure group
The patients correspond to the diagnostic criteria of the left ventricular diastolic heart failure,which was passed by the National sixth heart failure conference(2001 year,Wuxi) (8 men,6 women,average 65±10 years,4 essential hypertension,9 essential hypertension combined with coronary heart disease, 1 hypertrophic cardiomyopathy).
All patients were hospitalized the third hospital of Hebei medical university.
All patients had been excluded secondary hypertension﹑valvular heart disease,renal failure,hepatic cirrhosis,thyroid disease,excessive circulating glucocorticoid and chronic pulmonary disease et al.
The plasma BNP was determined by solid-phase immunoradiometric assay.BNP reagent box was produced by CIS company in France and was bought from Tianjin XinSiFang company.
M-mode,two-dimensional, and pulsed wave Doppler echocardiographic examinations were performed by only one person. HP5500 echocardiography(made in USA) equipped with 2.5MHz was used.Arterial dimension,left atrial dimension,left ventricular chamber dimension,left ventricular septal and posterior wall thickness,left ventricular ejetion fraction,peak early transmitral filling velocity(E wave),peak atrial filling velocity(A wave),ratio of peak early and atrial filling velocity(E/A) were measured.Furthermore, tissue
Doppler imaging technique was used to measure the diastolic function of myocardial segments.In the apical four-chamber view, peak velocity of the early diastolic wave(Em) and peak velocity of the late diastolic wave(Am) of the septal and lateral myocardial segment were measured at the mitral annulus.In the apical two-chamber view, peak velocity of the early diastolic wave(Em) and peak velocity of the late diastolic wave(Am) of the anterior and inferior myocardial segment were measured at the mitral annulus.Em/Am was calculated respectively.
All data were inputted into computer and statistically analyse with Software pakage of SPSS Ver 11.0.A value of p<0.05 was considered statistically significanct.
Result: 1.Compared with the control group,the plasma BNP of LVDD group was increased(27.01±32.97pg/ml versus 13.33±15.93pg/ml) (p<0.05);the plasma BNP of the diastolic heart failure group was increased too(98.61±109.69pg/ml versus 13.33±15.93pg/ml)(p<0.001);furthermore the plasma BNP of diastolic heart failure group was higher than LVDD group(p<0.001).
2.The plasma BNP of left ventricular dysfunction group was positive correlation with age(r=0.32,p=0.02)、pulse pressure(r=0.32,p<0.01),was negative correlation with diastolic blood pressure(r=-0.28,p<0.05).
3.The plasma BNP of diastolic heart failure group was negative correlation with Em间(r=-0.84,p<0.001),Em/Am间(r=-0.70,p<0.01),Em前(r=-0.60,p<0.05),Em前(r=-0.61,p=0.02),
Em下(r=-0.63,p<0.05),Am下(r=-0.59,p<0.05) and Em/Am下(r=-0.53,p=0.05).
Conclusion:1.It can stimulate BNP s
引文
Sudoh T,Kanga K,Minamnio N,et al. A new natriuretic peptide in poreine brain. Nature, 1988,332:78~81
Cheung BMY,Kumana CR. Natriuretic peptide-relevance in cardio vascular disease. JAMA,1994,90:195~203
Hama N,Itoh H,Shirajami G,et al. Rapid ventricular induction of brain natriuretic peptide gene expression in experimental acute myocardial infarction. Circulation,1995,76:230~235
Yasue H,Yoshimura M,Sumidan H,et al. Localization and mechanism of secretion of B-type natriuretic peptide in
nomal subjects and patients with heart falure. Circulation, 1994,90:195~203
Allan D,Stuthers. Ten years of natriuretic peptide research:a new dawn for their diagnostic and therapeutic use? BMJ, 1994, 308:18
Tsutamoto T, Wado A, Maeda K, et al. Attenuation of compensation of endogenous cardiac natriuretic peptide system in chronic heart failure. Circulation, 1997, 96: 509~516
de Bold AJ,Bruneau BG,de Bold MLK. Mechanical and neauroendocrine regulation of the endocrine heart. Cardiovasc Res, 1996,31:7~18
Magga J,Vuolteenaho O,Tokola H,et al. Involvement of transcriptional and posttranscriptional mechanism in cardiac overload-induced increased of B-type natriuretic peptide gene expression. Cir Res,1997,694~702
Clerico A,Ry SD,Giannessi d. Measurement of cardiac natriu -retic homones(atrial natriuretic peptide,brain natriuretic peptide,and related peptides) in clinical practice:the need for a new generation of immunoassay methods. Clin Chemistry, 2000,46:1529~1534
Lainchbury JG,Nicholls MG,Espiner EA, et al. Regional plasma levels of cardiac peptides and their response to acute neutal endopeptidase inhibition in man. Clin Sci, 1998, 95:547~555
Yoshimur M,Yasue H,Morita E,et al. Hemodynamic and
responses to brain natriuretic peptide infusion in patients with congestive hert failure. Circulation, 1991, 84:1581~ 1588
Marcus LS,Hart D,Paker M,et al. Hemodynmic and renal excretory effect of human brain natriuretic peptide infusion in patients with congextive heart failure. Circulation, 1994, 3184~3189
Kato H, Yasue H, Yoshimura M, et al. Suppression of hyperventilation-induced attacks with infusion of B-type (brain) natiuretic peptide in patients with vatiant angina. Am Heart J, 1994,128:1098~1104
Koch A,Singer H. Normal values of B type natiuretic peptide in infants children and adolescents. Heart, 2003,89(8): 875~878
Redfied MM,Rodeheffer RJ,Jacobsen SJ,et al. Plasma brain natriuretic peptide concentraction:impact of age nd gender. J Am Coll Cardiol, 2002,40:976~982
Missouris CG,Grouzmann E,Bukley MG,et al. How does treatment influence endocrine mechanisms in acute sever heart failure?Effects on cardiac natriuretic peptides,the rennin system,neuropeptide Y and catecholamines. Clin Sci, 1998,94:591~599
MoNairy M,Gardetto N,Clopton P,et al. Stability of B-type natriuretic peptide levels during exercise in patients with congestive heart failure implications for outpatient monitoring with B-type natriuretic peptide. Am Heart J,
2002,143(3):406~411
Matsumoto A,Hirata Y,Momomura S,et al. Effects of exercise on plasma level of brain natriuretic peptide in congestive heart failure with and without left ventricular dysfunction. Am Heart J, 1995;129:139~145
Fisher Y, Filamaier K, Stiegler H, et al. Evaluation of a new,rapid bedside test for quantitative determination of B-type natriuretic peptide. Clin Chemistry, 2001, 47: 591~ 594
Vogeser M,Jacob K. B-type natriuretic peptide (BNP) -validationof an immediate response assy. Clin Lab, 2001, 47:29~33
Cowie MR,Jourdain P,Maisel A,et al. Clinical applications of B-type natriuretic peptide testing. Eur Heart J, 2003, 24(19): 1710~1718
Value of natriuretic peptide in assessment patients with possible new heart failure in primry care. Lacet, 1997, 350: 1349~1353
Dao Q,Krishnaswamy P,Kazanegrar,et al. Utility of B-type natriuretic peptide in the diagnosis of congestive hert failure in an urengent-care setting. J Am Coll Cardiol, 2001, 37:379~385
Wieczorek SJ,Wu AH,Christenson R,et al. B-type natriuretic peptide assay accurately dignoses left ventricular dysfunction and heart failure:a multicenter evaluation. Am Heart J, 2002,144(5):834~839
Mc Cullough PA,Nowak RM,Mc Cord J, et al. B-type natriuretic peptide and clinical judgememt in emergency diagnosis of heart failure:analysia from Breathing Not Porperly(BNP)Mutinational study. Circulation, 2002, 106(4): 416~422
Mitka M. Peptides prove predictive for heart failure patients. JAMA, 2002,287:1928~1929
Task Force for the Diagnosis and Treatment of Chronic Heart Failure. Eur Heart J, 2001,22:1527~1560
吴振国，许瑞吉，黄承等。无症状左室功能不全患者血浆脑钠素浓度的测定。金陵医学报，1995，8（4）:302~305
Omland T,Aakvaag A,Vik-Mo H. Plasma cardiac natriuretic peptide determination as screening test for the detection of patients with mild left ventricular impairment. Heart, 1996, 76:232~237
Maeda K,Takayoshi T,Wada A,et al. Plasma brain natriuretic peptide as abiochemical marker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction. Am Heart J,1998,135:825~832
Groenning BA,Nilsson JC,Sondergaard l,et al. Evaluation of impaired ventricular ejection fraction and increased dimensions by multiple neurohormonal plasma concen- trations. Eur J Heart Failure, 2001,3:699~708
林杰，郑德林，李庭富。心力衰竭患者血浆脑钠素浓度与心功能的关系。临床心血管杂志 2001，17（10）：454~ 455
Lang CC,Prasad N,McAlpine HM,et al. Increased plasma levels of brain natriuretic peptide in patients with isolated diastolic dysfunction. Am Heart J,1994,127:1635~1636
Fruhwald F.M,Fahrleitner A,Watizinger N,et al. Natriuretic peptide in patients with diastolic dysfunction due to idiopathic dilated cardiomyopathy. Eur Heart J, 1999, 20:1415~1423
Cheung BM. Plasma concentration of brain natriuretic peptide is related to diastolic function in hypertention. Clin Exp Pharmacol Physiol, 1997,24(12):966~968
Yamamoto K,Burnett JC Jr,Jougasaki M,et al. Superiority of brain natriuretic peptide as a hormonal marker of ventricular systolic and diastolic dysfunction and ventricular hypertrophy. Hypertension,1996,28(6):988-94.Comment in: Hypertension, 1997,30(2 Pt1):305~306
Maisel AS,Koon J,Krishnaswamy P,et al. Utility of B-type natriuretic peptide as a rapid,point-of-care test for screening patients undergoing echocardiography to determine left ventricular dysfunction. Am Heart J, 2001,141:367~374
Lubien E,DeMaria A,Krishnaswamy P,et al. Utility of B-natriuretic peptide in detecting diastolic dysfunction comparision with Doppler Velocity recordings. Circultion, 2002,105(5):595~601
Horio T,Shimada K,Kohno M,et al. Serial changes in atrial and brain natriuretic peptides in patients with acute myocardial infarction treated with early coronary angilplasty.
Am Heart J, 1993,126:293~299
Moria E,Yasue H,Yoshimura M,et al. Increased plasma levels of brain natriuretic peptide in patients with myocardial infarction. Circulation,1993,88:82~91
Choy A-MJ, Darbar D, Lang cc, et al. Detection of left ventricular dysfunction after acute myocardial infarction: comparision of clinical, echocardiographic,and neurohor- monal methods. Br Heart J, 1994, 72: 16~22
Nagaya N,Goto Y,Nishikimi T,et al. Sustained elevation of plasma brain natriuretic peptide levels associated with progressive ventricular remodeling after acute myocardial infarction. Clin Sci, 1999,96:129~136
Omland T,Aakvaag A,Bonarjiee VVS,et al. Plasma brain natriuretic peptide as an indicator of left ventricular systolic dysfunction and long-term survial after acute myocardial infarction.Comparision with plasma atrial natriuretic peptide and N-terminal proatrial natriuretic peptides.Circulation, 1996,93;1963~1969
McClure SJ,Oaruana L,Davie AP,et al.Corhort study of plasma natriuretic peptides for identifying left ventricular systolic dysfunction in primary care. BMJ, 1998,317:516 ~519
Tsutamoto T,Wada A,Maeda K,et al. Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction.Eur Heart J, 1999, 20:1799~1807
Cowie MR,Fox KF,Wood DA,et al. N-terminal Pro-BNP predicts prognosis in patients presenting with heart failure for the first time better than does N-terminal Pro-ANP or BNP. Circulation, 2000,102:274~281
Sagnell G.A. Measurement and significance of circulating natriuretic peptides in cardiovascular disease. Clin Sci, 1998,95:519~529
Berger R,Huelsman M,Strecker K,et al. B-type natriuretic peptide predicts sudden death in patients with chronic heart failure. Circulation 2002,105:2392~2397
Isnard R,Pousset F,Chafirovskia O,et al. Combination of B-type matriuretic peptide and peak oxygen consumption improves risk stratification in outpatients with chronic heart failure. Am Heart J 2003,146(4):729~735
Richards AM, Nicholls MG, Yandle TG, et al. Plasma N-terminal pro-brain natriuretic peptide and adsrenomedulin: New neurohormonal predictors of left ventricular function and prognosis after myocardial infarction. Circulation, 1998, 97: 1921~1929
Richard AM,Nicholls MG,Yandle TG,et al. Neuroendocrine prediction of left ventricular function and heart failure after acute myocardial infarction. Heart 1999,81:114~120
McDonagh T, Cunningham AD, Morrison CE, et al. Left ventricular dysfunction,natriuretic peptides and mortality in an urban population. Heart 2001,86:21~26
Richards AM,Espine EA,et al. B-type natriuretic peptides and ejection fraction for prognosis after myocardial infarction.Circulation, 2003,107(22):2786~2792
Murdoch DR,McDonagh TA,Byrne J,et al. Titration of
vosodilator therapy in chronic heart failure according to plasma brain natriuretic peptide concentraction:Randomized comparision of the hemodynamic and neuroendocrine effects of tailored versus empirical therapy. Am Heart J, 1999, 138:1126~1132
Richards A.M, Nicholls MG, Macmahon S, et al. Neurohum- oral prediction of benefit from carvedilol in ischemic left ventricular dysfunction. Circulation, 1999, 99: 786~792
Kohno M,Horio T,Yokokawa K,et al. Brain natriuretic peptide as a marker for hypertensive left ventricular hypertrophy: changes during 1-year antihypertensive therapy with angiotensin-converting enzyme inhibitor. Am J Med, 1995,98(3):257~265
Marcus LS,Hart D,Pacher M,et al.Hemodynamic and renal excrectory effects of parients with congestive heart failure:A double-blind,placebo-controlled,randomizes crossover trail. Circulation, 1996,94:3184~3189
Pubication committee for VMAC investigator:Intravenous nesiritide vs nitroglycerin for treatment of decompensted congestive heart failure.JAMA, 2002,287:1531~1540
Clarkson P.B.M,Wheeldon NM,MacFadyen RJ,et al. Effects of brain natriuretic peptide on exercise hemodynamics and neurohormones in isolated diastolic heart failure.Circulation, 1996,93:2037~2042
Northridge DB,Newby DE,Rooney E,et al. Comparision of the short-term effects of candoxatril,an orally active neautal endopeptidase inhibitor,and frusemide in the treatment of patients with chronic heart failure. Am Heart J,1999,138: 149 ~157