三维标测系统射频消融去肾交感神经术对高血压犬模型血压和心脏功能的影响
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摘要
目的:研究三维标测系统指导下射频消融去肾交感神经术(renal sympathetic denervation,RSD)对高血压犬模型血压和心脏功能的影响。方法:10只合格的比格犬适应性喂养1周后随机分为手术组和假手术组(n=5),均造成高血压模型犬,造模后手术组在CARTO三维标测系统指导下实施RSD术,假手术组仅行双肾动脉造影术。获取比格犬血压监测数据,术前(造模后12周)、术后2周行超声心动图检查,测定心脏功能指标,同时采集血清标本测定血管紧张素II(angiotensin II,AngII)、丙二醛(malondialdehyde,MDA)、一氧化氮(nitric oxide,NO)浓度。结果:两组比格犬造模前、造模后12周收缩压(systolic blood pressure,SBP)、舒张压(diastolic blood pressure,DBP)及平均动脉压(mean arterial pressure,MAP)比较无统计学意义(P>0.05);与造模后12周比较,手术组术后2,4,8周SBP,DBP及MBP水平显著下降(P<0.05);与假手术组比较,手术组术后2,4,8周时SBP,DBP及MAP水平显著降低(P<0.05)。术后手术组左室收缩末期内径(left ventricular end-systolicdiameter,LVESD)、左室舒张末期内径(leftventricularend-diastolicdiameter,LVEDD)、心输出量(cardiacoutput,CO)、心脏指数(cardiacindex,CI)及左室射血分数(leftventricularejectionfraction,LVEF)显著改善,且LVESD,LVEDD明显低于假手术组,CO,CI,LVEF明显高于假手术组(P<0.05)。术后手术组血清Ang II,MDA,NO水平显著改善,且Ang II和MDA水平明显低于假手术组,NO水平明显高于假手术组(P<0.05)。结论:三维标测系统指导下RSD可有效降低高血压犬模型血压及改善心脏功能,可能与其抑制肾素血管紧张素系统、减轻氧化应激反应及改善血管内皮功能有关。
Objective: To investigate the effect of three-dimensional mapping-guided radiofrequency ablation of renal sympathetic denervation(RSD) on the blood pressure and cardiac function in hypertensive canine models. Methods: Ten qualified beagle dogs were randomly divided into the operation group and the sham operation group with 5 dogs in each group after 10 weeks of adaptive feeding. All of them were used for hypertensive canine models. The operation group was treated by RSD under the guidance of CARTO 3 D mapping system after modeling while the sham operation group was given bilateral renal arteriography. The blood pressure monitoring data were obtained. Echocardiography was performed before operation(12 weeks after modeling) and 2 weeks after operation to determine the cardiac function parameters. Serum samples were collected to determine the levels of angiotensin II(AngII), malondialdehyde(MDA) and nitric oxide(NO). Results: There was no statistically significant difference in the systolic blood pressure(SBP), diastolic blood pressure(DBP) or mean arterial pressure(MAP) in the two groups before modeling and at 12 weeks after modeling(P>0.05). The SBP, DBP and MBP in the operation group at 2, 4 and 8 weeks after operation were significantly lower than those at 12 weeks after modeling(P<0.05), and those in the sham operation group(P<0.05). The left ventricular endsystolic diameter(LVESD), left ventricular end-diastolic diameter(LVEDD), cardiac output(CO), cardiac index(CI) and left ventricular ejection fraction(LVEF) in the operation groups were significantly improved after operation. The LVESD and LVEDD were significantly smaller than those in the sham operation group, while CO, CI and LVEF were significantly larger than those in the sham operation group(P<0.05). The levels of serum AngII, MDA and NO in the operation group were significantly improved after operation, and the levels of AngII and MDA were significantly lower than those in the sham operation group while the level of NO was significantly higher than that in the sham operation group(P<0.05). Conclusion: The three-dimensional mapping system guided RSD can effectively decrease the blood pressure and improve the cardiac function in hypertensive canine models, which may be related to inhibiting the renin-angiotensin system, reducing oxidative stress response and improving endothelial function.
Objective: To investigate the effect of three-dimensional mapping-guided radiofrequency ablation of renal sympathetic denervation(RSD) on the blood pressure and cardiac function in hypertensive canine models. Methods: Ten qualified beagle dogs were randomly divided into the operation group and the sham operation group with 5 dogs in each group after 10 weeks of adaptive feeding. All of them were used for hypertensive canine models. The operation group was treated by RSD under the guidance of CARTO 3 D mapping system after modeling while the sham operation group was given bilateral renal arteriography. The blood pressure monitoring data were obtained. Echocardiography was performed before operation(12 weeks after modeling) and 2 weeks after operation to determine the cardiac function parameters. Serum samples were collected to determine the levels of angiotensin II(AngII), malondialdehyde(MDA) and nitric oxide(NO). Results: There was no statistically significant difference in the systolic blood pressure(SBP), diastolic blood pressure(DBP) or mean arterial pressure(MAP) in the two groups before modeling and at 12 weeks after modeling(P>0.05). The SBP, DBP and MBP in the operation group at 2, 4 and 8 weeks after operation were significantly lower than those at 12 weeks after modeling(P<0.05), and those in the sham operation group(P<0.05). The left ventricular endsystolic diameter(LVESD), left ventricular end-diastolic diameter(LVEDD), cardiac output(CO), cardiac index(CI) and left ventricular ejection fraction(LVEF) in the operation groups were significantly improved after operation. The LVESD and LVEDD were significantly smaller than those in the sham operation group, while CO, CI and LVEF were significantly larger than those in the sham operation group(P<0.05). The levels of serum AngII, MDA and NO in the operation group were significantly improved after operation, and the levels of AngII and MDA were significantly lower than those in the sham operation group while the level of NO was significantly higher than that in the sham operation group(P<0.05). Conclusion: The three-dimensional mapping system guided RSD can effectively decrease the blood pressure and improve the cardiac function in hypertensive canine models, which may be related to inhibiting the renin-angiotensin system, reducing oxidative stress response and improving endothelial function.
引文
1.刘玉祥,富路.经皮导管射频消融去肾脏交感神经术治疗顽固性高血压的研究进展[J].中华老年心脑血管病杂志,2015,17(8):878-881.LIU Yuxiang,FU Lu.Advances in percutaneous transcatheter radiofrequenc y ablation renal sympathectomy for refractor y hypertension[J].Chinese Journal of Geriatric Cardiovascular and Cerebrovascular Diseases,2015,17(8):878-881.
2.Bakris GL,Townsend RR,Flack JM,等.经皮经导管射频消融去肾交感神经术对难治性高血压患者1年时血压的影响[J].中华高血压杂志,2015,23(6):586-588.Bakris GL,Townsend RR,Flack JM,et al.Effect of percutaneous transcatheter radiofrequency ablation renal sympathectomy on blood pressure in patients with refractory hypertension at 1 year[J].Chinese Journal of Hypertension,2015,23(6):586-588.
3.柴文静,刘德敏,崔炜.经导管射频消融去肾交感神经术治疗难治性高血压的相关器械及研究[J].中华高血压杂志,2016,24(7):685-688.CHAI Wenjing,LIU Demin,CUI Wei.Related equipment and research of transcatheter radiofrequency ablation renal sympathectomy in the treatment of refractory hypertension[J].Chinese Journal of Hypertension,2016,24(7):685-688.
4.Gosse P,Cremer A,Pereira H,等.24h动态血压监测预测和评估经皮经导管射频消融去肾交感神经术的降压作用[J].中华高血压杂志,2017,25(4):382-383.Gosse P,Cremer A,Pereira H,et al.Twenty-four-hour blood pressure monitoring to predict and access impact of renal denervation:the DENERHTN study(renal denervation for hypertension)[J].Chinese Journal of Hypertension,2017,25(4):382-383.
5.黄达民,侯舒心,罗晓菡,等.肾交感神经去除术对心力衰竭犬心功能的影响[J].心血管康复医学杂志,2016,25(2):161-166.HUANG Damin,HOU Shuxin,LUO Xiaohan,et al.Influence of renal sympathetic denervation on cardiac function of dogs with heart failure[J].Chinese Journal of Cardiovascular Rehabilitation Medicine,2016,25(2):161-166.
6.肖宜超,刘启明.经皮经导管射频消融去肾交感神经术治疗高血压法国专家共识(节译)[J].中华高血压杂志,2013,21(5):488-490.XIAO Yichao,LIU Qiming.French expert consensus to hypertension treatmentwith percutaneous transcatheter radiofrequency ablation renal sympathectomy(brief translation)[J].Chinese Journal of Hypertension,2013,21(5):488-490.
7.林海龙.经皮经导管射频消融去肾交感神经术治疗难治性高血压:有应用必要吗?[J].中华高血压杂志,2017,25(4):312-318.LIN Hailong.Percutaneous transcatheter radiofrequency ablation renal sympathetic nerve therapy for refractory hypertension:Is it necessary for application?[J].Chinese Journal of Hypertension,2017,25(4):312-318.
8.Investigators SH.Catheter-based renal sympathetic denervation for resistant hypertension:durability of blood pressure reduction out to 24months[J].Hypertension,2011,57(5):911-917.
9.Guo X,Zhai F,Nan Q.The temperature f ield simulation of radiofrequency catheter-based renal sympathetic denervation for resistant hypertension.[J].Biomed Mater Eng,2014,24(1):315-321.
10.Esler M.Illusions of truths in the symplicity HTN-3 trial:generic design strengths but neuroscience failings[J].J Am Soc Hypertens,2014,8(8):593-598.
11.Bhatt DL,Kandzari DE,O’Neill WW,et al.A controlled trial of renal denervation for resistant hypertension[J].N Engl J Med,2014,370(15):1393-1401.
12.Epstein M,de Marchena E.Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the"end of the road"for renal denervation?[J].J Am Soc Hypertens,2015,9(2):140-149.
13.Zaman S,Pouliopoulos J,Al R aisi S,et al.Novel use of NavXthree-dimensional mapping to guide renal artery denervation[J].EuroIntervention,2013,9(6):687-693.
14.谭洪文,郭志福,陈翔,等.EnSite-NavX三维标测系统指导下去肾交感神经术的实验研究[J].第二军医大学学报,2016,37(6):750-753.TAN Hongwen,GUO Zhifu,CHEN Xiang,et al.EnSite-NavX threedimensional mapping-guided renal sympathetic denervation:an experimental study[J].Academic Journal of Second Military Medical University,2016,37(6):750-753.
15.刘莉,叶鹏,Tsioufis C,等.多电极经导管去肾交感神经射频消融术对难治性高血压伴心肌肥厚患者的心脏及神经体液功能适应性的影响[J].中华高血压杂志,2014,22(11):1003-1003.LIU Li,YE Peng,Tsioufis C,et al.Effect of multi-electrode transcatheter renal sympathectomy radiofrequency ablation on cardiac and neurohumoral functional adaptation in patients with refractory hypertension and cardiac hypertrophy[J].Chinese Journal of Hypertension,2014,22(11):1003-1003.
16.王彬,王海昌,薛玉生,等.肾脏去交感神经对肥胖型高血压家兔血压及相关神经体液因子的影响[J].山西医科大学学报,2016,47(8):703-705.WANG Bin,WANG Haichang,XUE Yusheng,et al.Effects of renal sympathetic denervation on obesity-associated hypertension and related neurohormonal factors in rabbits[J].Journal of Shanxi Medical University,2016,47(8):703-705.
17.江凤林,张志辉,李慧,等.经导管射频消融去肾交感神经术对犬高血压降压机制的探讨[J].临床心血管病杂志,2015,31(1):106-110.JIANG Fenglin,ZHANG Zhihui,LI Hui,et al.Potential mechanism of antihypertensive effect of catheter-based renal sympathetic denervation on hypertension in Canine[J].Journal of Clinical Cardiology,2015,31(1):106-110.
18.Kayhan FE,Koldemir M,Cagatay P,et al.Prevalence of endothelial nitric oxide synthase E298D polymorphism in Turkish patients with essential hypertension[J].Diabetes Metab Syndr,2013,7(1):12-16.
2.Bakris GL,Townsend RR,Flack JM,等.经皮经导管射频消融去肾交感神经术对难治性高血压患者1年时血压的影响[J].中华高血压杂志,2015,23(6):586-588.Bakris GL,Townsend RR,Flack JM,et al.Effect of percutaneous transcatheter radiofrequency ablation renal sympathectomy on blood pressure in patients with refractory hypertension at 1 year[J].Chinese Journal of Hypertension,2015,23(6):586-588.
3.柴文静,刘德敏,崔炜.经导管射频消融去肾交感神经术治疗难治性高血压的相关器械及研究[J].中华高血压杂志,2016,24(7):685-688.CHAI Wenjing,LIU Demin,CUI Wei.Related equipment and research of transcatheter radiofrequency ablation renal sympathectomy in the treatment of refractory hypertension[J].Chinese Journal of Hypertension,2016,24(7):685-688.
4.Gosse P,Cremer A,Pereira H,等.24h动态血压监测预测和评估经皮经导管射频消融去肾交感神经术的降压作用[J].中华高血压杂志,2017,25(4):382-383.Gosse P,Cremer A,Pereira H,et al.Twenty-four-hour blood pressure monitoring to predict and access impact of renal denervation:the DENERHTN study(renal denervation for hypertension)[J].Chinese Journal of Hypertension,2017,25(4):382-383.
5.黄达民,侯舒心,罗晓菡,等.肾交感神经去除术对心力衰竭犬心功能的影响[J].心血管康复医学杂志,2016,25(2):161-166.HUANG Damin,HOU Shuxin,LUO Xiaohan,et al.Influence of renal sympathetic denervation on cardiac function of dogs with heart failure[J].Chinese Journal of Cardiovascular Rehabilitation Medicine,2016,25(2):161-166.
6.肖宜超,刘启明.经皮经导管射频消融去肾交感神经术治疗高血压法国专家共识(节译)[J].中华高血压杂志,2013,21(5):488-490.XIAO Yichao,LIU Qiming.French expert consensus to hypertension treatmentwith percutaneous transcatheter radiofrequency ablation renal sympathectomy(brief translation)[J].Chinese Journal of Hypertension,2013,21(5):488-490.
7.林海龙.经皮经导管射频消融去肾交感神经术治疗难治性高血压:有应用必要吗?[J].中华高血压杂志,2017,25(4):312-318.LIN Hailong.Percutaneous transcatheter radiofrequency ablation renal sympathetic nerve therapy for refractory hypertension:Is it necessary for application?[J].Chinese Journal of Hypertension,2017,25(4):312-318.
8.Investigators SH.Catheter-based renal sympathetic denervation for resistant hypertension:durability of blood pressure reduction out to 24months[J].Hypertension,2011,57(5):911-917.
9.Guo X,Zhai F,Nan Q.The temperature f ield simulation of radiofrequency catheter-based renal sympathetic denervation for resistant hypertension.[J].Biomed Mater Eng,2014,24(1):315-321.
10.Esler M.Illusions of truths in the symplicity HTN-3 trial:generic design strengths but neuroscience failings[J].J Am Soc Hypertens,2014,8(8):593-598.
11.Bhatt DL,Kandzari DE,O’Neill WW,et al.A controlled trial of renal denervation for resistant hypertension[J].N Engl J Med,2014,370(15):1393-1401.
12.Epstein M,de Marchena E.Is the failure of SYMPLICITY HTN-3 trial to meet its efficacy endpoint the"end of the road"for renal denervation?[J].J Am Soc Hypertens,2015,9(2):140-149.
13.Zaman S,Pouliopoulos J,Al R aisi S,et al.Novel use of NavXthree-dimensional mapping to guide renal artery denervation[J].EuroIntervention,2013,9(6):687-693.
14.谭洪文,郭志福,陈翔,等.EnSite-NavX三维标测系统指导下去肾交感神经术的实验研究[J].第二军医大学学报,2016,37(6):750-753.TAN Hongwen,GUO Zhifu,CHEN Xiang,et al.EnSite-NavX threedimensional mapping-guided renal sympathetic denervation:an experimental study[J].Academic Journal of Second Military Medical University,2016,37(6):750-753.
15.刘莉,叶鹏,Tsioufis C,等.多电极经导管去肾交感神经射频消融术对难治性高血压伴心肌肥厚患者的心脏及神经体液功能适应性的影响[J].中华高血压杂志,2014,22(11):1003-1003.LIU Li,YE Peng,Tsioufis C,et al.Effect of multi-electrode transcatheter renal sympathectomy radiofrequency ablation on cardiac and neurohumoral functional adaptation in patients with refractory hypertension and cardiac hypertrophy[J].Chinese Journal of Hypertension,2014,22(11):1003-1003.
16.王彬,王海昌,薛玉生,等.肾脏去交感神经对肥胖型高血压家兔血压及相关神经体液因子的影响[J].山西医科大学学报,2016,47(8):703-705.WANG Bin,WANG Haichang,XUE Yusheng,et al.Effects of renal sympathetic denervation on obesity-associated hypertension and related neurohormonal factors in rabbits[J].Journal of Shanxi Medical University,2016,47(8):703-705.
17.江凤林,张志辉,李慧,等.经导管射频消融去肾交感神经术对犬高血压降压机制的探讨[J].临床心血管病杂志,2015,31(1):106-110.JIANG Fenglin,ZHANG Zhihui,LI Hui,et al.Potential mechanism of antihypertensive effect of catheter-based renal sympathetic denervation on hypertension in Canine[J].Journal of Clinical Cardiology,2015,31(1):106-110.
18.Kayhan FE,Koldemir M,Cagatay P,et al.Prevalence of endothelial nitric oxide synthase E298D polymorphism in Turkish patients with essential hypertension[J].Diabetes Metab Syndr,2013,7(1):12-16.