经心肌血管重建以增强心肌血管生成和血流动力学功能。

Transmyocardial revascularization to enhance myocardial vasculogenesis and hemodynamic function.

作者信息

Atluri Pavan, Panlilio Corinna M, Liao George P, Suarez Eric E, McCormick Ryan C, Hiesinger William, Cohen Jeffrey E, Smith Maximilian J, Patel Abha B, Feng Wei, Woo Y Joseph

机构信息

Division of Cardiovascular Surgery, Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

出版信息

J Thorac Cardiovasc Surg. 2008 Feb;135(2):283-91, 291.e1; discussion 291. doi: 10.1016/j.jtcvs.2007.09.043. Epub 2008 Jan 11.

DOI:10.1016/j.jtcvs.2007.09.043

PMID:18242252

Abstract

OBJECTIVE

A significant number of patients have coronary artery disease that is not amenable to traditional revascularization. Prospective, randomized clinical trials have demonstrated therapeutic benefits with transmyocardial laser revascularization in this cohort. The molecular mechanisms underlying this therapy, however, are poorly understood. The focus of this study was evaluation of the proposed vasculogenic mechanisms involved in transmyocardial laser revascularization.

METHODS

Male Yorkshire pigs (30-35 kg, n = 25) underwent left thoracotomy and placement of ameroid constrictors around the proximal left circumflex coronary artery. During the next 4 weeks, a well-defined region of myocardial ischemia developed, and the animals underwent a redo left thoracotomy. The animals were randomly assigned to sham treatment (thoracotomy only, control, n = 11) or transmyocardial laser revascularization of hibernating myocardium with a holmium:yttrium-aluminum-garnet laser (n = 14). After an additional 4 weeks, the animals underwent median sternotomy, echocardiographic analysis of wall motion, and hemodynamic analysis with an ascending aortic flow probe and pulmonary artery catheter. The hearts were explanted for molecular analysis.

RESULTS

Molecular analysis demonstrated statistically significant increases in the proangiogenic proteins nuclear factor kappaB (42 +/- 27 intensity units vs 591 +/- 383 intensity units, P = .03) and angiopoietin 1 (0 +/- 0 intensity units vs 241 +/- 87 intensity units, P = .003) relative to sham control values with transmyocardial laser revascularization within the ischemic myocardium. There were also increases in vasculogenesis (18.8 +/- 8.7 vessels/high-power field vs 31.4 +/- 10.2 vessels/high-power field, P = .02), and perfusion (0.028 +/- 0.009 microm3 blood/microm3 tissue vs 0.044 +/- 0.004 microm3 blood/microm3 tissue, P = .01). Enhanced myocardial viability was demonstrated by increased myofilament density (40.7 +/- 8.5 cardiomyocytes/high-power field vs 50.8 +/- 7.5 cardiomyocytes/high-power field, P = .03). Regional myocardial function within the treated territory demonstrated augmented contractility. Global hemodynamic function was significantly improved relative to the control group with transmyocardial laser revascularization (cardiac output 2.1 +/- 0.2 L/min vs 2.7 +/- 0.2 L/min, P = .007, mixed venous oxygen saturation 64.7% +/- 3.6% vs 76.1% +/- 3.4%, P = .008).

CONCLUSION

Transmyocardial laser revascularization with the holmium-YAG laser enhances perfusion, with resultant improvement in myocardial contractility.

摘要

目的

大量患者患有无法进行传统血运重建的冠状动脉疾病。前瞻性随机临床试验已证明经心肌激光血运重建术对该队列患者具有治疗益处。然而，这种治疗的分子机制尚不清楚。本研究的重点是评估经心肌激光血运重建术中涉及的血管生成机制。

方法

雄性约克夏猪（30 - 35千克，n = 25）接受左胸切开术，并在左回旋支冠状动脉近端放置阿梅洛依德缩窄环。在接下来的4周内，形成明确的心肌缺血区域，然后动物接受再次左胸切开术。将动物随机分为假治疗组（仅开胸，对照组，n = 11）或用钬：钇铝石榴石激光对冬眠心肌进行经心肌激光血运重建术组（n = 14）。再过4周后，动物接受正中胸骨切开术、壁运动的超声心动图分析以及使用升主动脉血流探头和肺动脉导管进行血流动力学分析。取出心脏进行分子分析。

结果

分子分析显示，与假手术对照组相比，经心肌激光血运重建术后缺血心肌中的促血管生成蛋白核因子κB（强度单位42±27 vs 591±383，P = 0.03）和血管生成素1（强度单位0±0 vs 241±87，P = 0.003）有统计学意义的增加。血管生成（每高倍视野18.8±8.7条血管 vs 31.4±10.2条血管，P = 0.02）和灌注（每立方微米组织0.028±0.009立方微米血液 vs 0.044±（此处原文有误，应为0.004）0.004立方微米血液，P = 0.01）也有所增加。肌丝密度增加（每高倍视野40.7±8.5个心肌细胞 vs 50.8±7.5个心肌细胞，P = 0.03）证明心肌活力增强。治疗区域内的局部心肌功能显示收缩力增强。与对照组相比，经心肌激光血运重建术使整体血流动力学功能显著改善（心输出量2.1±0.2升/分钟 vs 2.7±0.2升/分钟，P = 0.007，混合静脉血氧饱和度64.7%±3.6% vs 76.1%±3.4%，P = 0.008）。