OPIOID HIBERNATION FACTORS FOR MYOCARDIAL PROTECTION

描述：(改编自调查人员摘要) 许多患者患有晚期心脏病，需要复杂的 心脏手术或移植。在心脏手术期间，包括 移植后，心脏变得缺血；血液流向心脏 心脏停止，要么接受手术，要么运送 器官，目前限制在4-6小时内。为了病人的利益 从体外循环中移除并恢复活动， 心脏手术后心脏必须有良好的功能。任何增强功能 在保存心肌能量时会增加阳性细胞的数量 改善患者的预后，提高患者护理的质量。 有趣的是，冬眠的动物可以保存高达90%的能量 在正常的常温新陈代谢过程中需要。这其中的机制是 冬眠期间的能量保存目前尚不清楚；然而， 许多研究指出了一种阿片类“触发”分子，它已经被 称为冬眠诱导触发或击打。安眠药的鸦片性质 HIT是公认的，因为HIT可以被鸦片逆转或延缓 对抗者。证据表明，HIT启动了它的潜力 通过特定的膜阿片受体发挥代谢抑制作用 尤其是三角洲受体。三角洲阿片类药物已经在许多 模型和调查人员的初步结果产生深刻的影响 行为、生理和代谢抑制作用有利于 在整个动物、器官和细胞水平上存活。这个 拟议的研究将调查三角洲的作用机制。 器官和亚细胞水平的阿片类药物。这些研究可能 延长安全心脏缺血时间，具有潜在的应用价值 心脏手术和心脏移植。在这些建议中 隔离心脏研究，研究人员将确定Delta是否 阿片类药物在缺血期间提供增强的心肌保护。这个 研究人员还将试图阐明细胞内的机制 三角洲阿片类药物通过这种方式保护缺血心肌。一种能力 三角洲阿片类药物对心肌的保护作用表明 这些分子的使用在许多临床方案中可能是有价值的 导致脑缺血。

DESCRIPTION: (Adapted from investigator's abstract) Many patients have advanced cardiac disease, necessitating complicated cardiac surgery or transplantation. During cardiac surgery, including transplantation, the heart is rendered ischemic; and blood flow to the heart is stopped either to undertake the surgery or to transport the organ, which is currently limited to 4-6 hours. In order for the patient to be removed from cardiopulmonary bypass and return to activity, the heart has to function well following cardiac surgery. Any enhancement in myocardial energy preservation will increase the number of positive outcomes for patients and improve the quality of patient care. Interestingly, hibernating animals can preserve up to 90% of the energy required during normal euthermic metabolism. The mechanism of this energy preservation during hibernation is currently unknown; however, many studies point to an opioid "trigger" molecule, which has been termed the hibernation induction trigger or HIT. The opiate nature of HIT is well established, as HIT can be reversed or retarded by opiate antagonists. Evidence indicates that HIT initiates its potential metabolic inhibitory effects through specific membrane opioid receptors, particularly delta receptors. Delta opioids have been shown in many models and the investigators' preliminary results to produce profound behavioral, physiological and metabolic inhibitory effects favoring survival at the whole animal, the organ and the cellular level. The proposed study will investigate the mechanisms of action of delta opioids at both the organ and subcellular levels. These studies could result in extended safe cardiac ischemic time with potential application to cardiac surgery and cardiac transplantation. In these proposed isolated heart studies, the investigators will determine if delta opioids provide enhanced myocardial protection during ischemia. The investigators will also seek to elucidate the intracellular mechanism by which the delta opioids protect the ischemic myocardium. The ability of the delta opioids to effect myocardial protection suggests that the use of these molecules may be valuable in many clinical scenarios resulting in ischemia.