CHRONIC CORONARY ARTERY OCCLUSION--EFFECTS OF EXERCISE TRAINING

缺血性心脏病（IHD）仍然是最常见的严重健康问题。 当代西方社会的问题。 然而，IHD患者 参加运动康复计划的人 死亡率和运动训练似乎是关键因素。 参与培训有益效果的机制并不完全 明白 这项建议将集中于运动对冠状动脉的影响 慢性冠状动脉闭塞实验模型中的训练 和侧支灌注。 血管平滑肌的体外分析 (VSM)正常冠状动脉内皮功能比较 动脉和离冠状动脉闭塞远端的动脉 （侧支依赖性心肌区域）。 我们的初步研究 表明α-肾上腺素能血管收缩反应增强， 内皮介导的冠状动脉舒张功能受损， 依赖脉管系统。 另一方面，运动训练减少 α-肾上腺素能血管收缩和增强内皮介导的 冠状血管舒张 我们的总体假设是，锻炼 对暴露于慢性冠状动脉闭塞的动物进行训练， 冠状动脉VSM和内皮功能的有益适应性反应; 功能改变取决于血管部位（正常对， 侧支依赖性心肌）和动脉大小（导管，近， 阻力，阻力动脉）。 当前项目的具体目标 包括体外评价1）激动剂（去甲肾上腺素，血管加压素， 内皮素介导的VSM收缩机制和细胞内Ca ~（2+） （[Ca]i）调节; 2）内皮依赖性（缓激肽，ADP，物质 P，血流）和内皮非依赖性（硝普钠，腺苷） 舒张反应; 3）改变内皮依赖性的机制 松弛包括EDRF/一氧化氮的合成/释放， 血管活性前列腺素类; 4）血管反应性，在存在 灌注液氧张力降低;和5） 体内侧支依赖性心肌。 体外终点为 测量包括：等长收缩和舒张;血管腔 直径（视频跟踪成像技术）;放射性同位素通量（42 K） 和[Ca]i（Fura-2显微荧光测定法）。 我们预计， 训练将对VSM的内在功能产生有益的影响， 冠状动脉闭塞心脏的内皮细胞， 血管收缩剂/血管舒张剂对血管舒张增加的影响， 优化心肌血流至侧支依赖性心肌。

Ischemic heart disease (IHD) remains the most common serious health problem of contemporary western society. However, patients with IHD enrolled in exercise-based rehabilitation programs experience lower mortality rates, and exercise training appears to be the key ingredient. Mechanisms involved in the beneficial effects of training are not fully understood. This proposal will focus on coronary effects of exercise training in an experimental model of chronic coronary artery occlusion and collateral perfusion. In vitro analyses of vascular smooth muscle (VSM) and endothelium function will be compared in normal coronary arteries and in arteries isolated distal to the coronary occlusion (collateral-dependent myocardial region). Our preliminary studies suggest that alpha-adrenergic vasoconstrictor responses are enhanced and endothelium-mediated coronary relaxation is impaired in collateral- dependent vasculature. On the other hand, exercise training decreases alpha-adrenergic vasoconstriction and enhances endothelium-mediated coronary vasorelaxation. Our overall hypothesis is that exercise training of animals exposed to chronic coronary artery occlusion produces beneficial adaptive responses of coronary VSM and endothelium function; functional alterations are dependent upon vascular site (normal vs. collateral-dependent myocardium) and on artery size (conduit, near- resistance, resistance arteries). Specific aims of the current project involve in vitro evaluation of 1) agonist (norepinephrine, vasopressin, endothelin)-mediated VSM contractile mechanisms and intracellular Ca2+ ([Ca]i) regulation; 2) endothelium-dependent (bradykinin, ADP, substance P, flow) and endothelium-independent (nitroprusside, adenosine) relaxation responses; 3) mechanisms of altered endothelium-dependent relaxation including synthesis/release of EDRF/nitric oxide and vasoactive prostanoids; 4) vasomotor responsiveness in the presence of reduced perfusate oxygen tension; and 5) blood flow responses of collateral-dependent myocardium in vivo. In vitro end points to be measured include: isometric contraction and relaxation; vessel luminal diameter (videotracking imaging techniques); radioisotope fluxes (42K) and [Ca]i (fura-2 microfluorometry). We anticipate that exercise training will have a beneficial effect upon intrinsic function of VSM and endothelium in coronary-occluded hearts, shifting the balance of vasoconstrictor/vasodilator influence toward increased vasorelaxation and optimization of myocardial blood flow to collateral dependent myocardium.