ENERGETIC SUPPORT OF POST-ISCHEMIC CARDIAC PERFORMANCE

收缩功能在可逆性收缩中被长时间抑制， 相对短暂的冠状动脉粥样硬化性心脏病 闭塞。 虽然被认为是一个重要的临床问题， 这种心肌“顿抑”的病理生理机制是 争议 我们已经开发并表征了一种孤立的工作 豚鼠心脏模型的惊人。 在这些心脏中， 底物丙酮酸盐产生显著的平行增强心室肌的 性能和肌细胞能量水平（胞浆ATP磷酸化 ATP水解的势能和吉布斯自由能）。 的总目标 这项研究是为了描述亚细胞机制， 这些与能量相关的功能性改进。 心肌功能是 控制在很大程度上由Ca 2+泵活性的 肌浆网Ca ~（2+）ATP酶。 我们的初步调查结果显示 结论：牛磺酸能增强肌浆网Ca ~（2+）_（2+）浓度， 非缺血性心脏中的转运。 一号计划将检验 胞浆钙离子刺激肌浆钙离子摄取， 缺血后“顿抑”心肌中的网状结构。 胞质能级 在“休克”的豚鼠心脏中， 或通过β-肾上腺素能刺激， 异丙肾上腺素、Ca 2+摄取和Ca 2 + ATP酶活性， 在从停止冷冻的心脏分离的肌浆网中定量。 项目二将测试的假设，基板增强的 肌浆网功能源于受磷蛋白增加 磷酸化，β-肾上腺素能的一种充分表征的机制， 心脏变力性的刺激。 为了实现心脏的放射性标记， 磷蛋白，肌细胞内高能磷酸盐池将被 用[32 P]无机磷酸盐灌注标记;在无示踪剂期间 洗脱期，心肌变力性将增加 或通过用异丙肾上腺素刺激β-肾上腺素能。 蛋白 分离的肌浆网将通过电泳分离，并且 通过放射自显影检测并定量32 P掺入， 闪烁计数 这项调查将描绘生物能源机制， 观察到收缩性和 常氧心肌尤其是“顿抑”心肌的胞质能量水平 在没有肾上腺素刺激的情况下。 具有特殊的临床意义， 丙酮酸盐可有效逆转缺血后 肌浆网Ca ~（2+）转运障碍。 因为丙酮酸， 不像儿茶酚胺，增加胞质能量水平， 研究表明，丙酮酸可能是一种有价值 在能量耗竭的临床情况下的心脏保护性干预 心

Contractile function is depressed for prolonged periods in reversibly injured, viable myocardium following relatively brief coronary occlusions. Although recognized as an important clinical problem, the pathophysiological mechanisms of this myocardial 'stunning' are controversial. We have developed and characterized an isolated working guinea-pig heart model of stunning. In these hearts, the energy-yielding substrate pyruvate produces marked, parallel enhancements of ventricular performance and myocytic energy level (cytosolic ATP phosphorylation potential and Gibbs free energy of ATP hydrolysis). The overall goal of this research is to delineate the subcellular mechanisms responsible for these energy-linked functional improvements. Myocardial function is controlled in large measure by the Ca2+ pumping activity of the sarcoplasmic reticulum Ca2+ ATPase. Our preliminary findings indicate that pyruvate-energization enhances sarcoplasmic reticulum Ca2+_ transport in non-ischemic heart. Project one will test the hypothesis that cytosolic energization stimulates Ca2+ uptake by sarcoplasmic reticulum in post-ischemic 'stunned' myocardium. Cytosolic energy level in 'stunned' guinea-pig hearts will be varied by altering substrate composition of perfusion media or by beta-adrenergic stimulation with isoproterenol, and Ca2+ uptake and Ca2+ ATPase activity will be quantitated in sarcoplasmic reticulum isolated from stop-frozen hearts. Project two will test the hypothesis that substrate-enhancement of sarcoplasmic reticular function stems from increased phospholamban phosphorylation, a well-characterized mechanism for beta-adrenergic stimulation of cardiac inotropism. To effect radiolabelling of cardiac phosphoproteins, intramyocytic high-energy phosphate pools will be labelled by perfusion with [32P]inorganic phosphate; during tracer-free washout, cardiac inotropism will be increased by pyruvate-energization or by beta-adrenergic stimulation with isoproterenol. Proteins in isolated sarcoplasmic reticulum will be separated by electrophoresis, and 32P incorporation detected and quantitated by autoradiography and scintillation counting. This investigation will delineate the bioenergetic mechanisms for the observed highly significant relationship between contractility and cytosolic energy level in normoxic and especially 'stunned' myocardium in the absence of adrenergic stimulation. Of special clinical interest, pyruvate energization may be effective in reversing postischemic impairment of sarcoplasmic reticulum Ca2+ transport. Since pyruvate, unlike catecholamines, increases cytosolic energy level, this investigation may indicate that pyruvate could be a valuable cardioprotective intervention in clinical situations of energy-depleted heart.