Weselcouch E O, Baird A J, Sleph P G, Dzwonczyk S, Murray H N, Grover G J
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4000.
Cardiovasc Res. 1995 Jan;29(1):126-32.
The mechanism of the protective effect of ischaemic preconditioning in the myocardium is not yet known. The aim of this study was to test the hypothesis that endogenous myocardial catecholamines may be mediators of preconditioning.
To test whether endogenous catecholamines are involved in preconditioning, experiments were performed in hearts from rats which had been catecholamine depleted with either reserpine or 6-hydroxydopamine. Experiments were also done to determine if noradrenaline can mimic preconditioning.
Catecholamine depletion with either reserpine or 6-hydroxydopamine had no effect on preischaemic coronary flow or cardiac function. Ischaemic preconditioning (four episodes of 5 min global ischaemia and 5 min reperfusion) resulted in a significant increase in postischaemic cardiac function and a 50% decrease in lactate dehydrogenase (LDH) release following 30 min ischaemia and 30 min reperfusion compared with non-preconditioned hearts. Reserpine pretreatment did not affect the response to ischaemia or to preconditioning, although LDH release tended to be greater than in normal hearts, especially in the non-preconditioned group. Although 6-hydroxydopamine significantly increased postischaemic cardiac function in the preconditioned group, no other index of ischaemic damage (for example, LDH release, left ventricular end diastolic pressure) was affected. Further studies showed that 10 nmol.min-1 noradrenaline did not affect the severity of ischaemia, indicating that it does not mimic preconditioning.
Endogenous catecholamines are not necessary for ischaemic preconditioning in isolated rat hearts and play little or no role in the functional responses to ischaemia.
缺血预处理对心肌的保护作用机制尚不清楚。本研究旨在验证内源性心肌儿茶酚胺可能是预处理介质这一假说。
为检测内源性儿茶酚胺是否参与预处理，对用利血平或6-羟基多巴胺使儿茶酚胺耗竭的大鼠心脏进行实验。还进行了实验以确定去甲肾上腺素是否能模拟预处理。
利血平或6-羟基多巴胺使儿茶酚胺耗竭对缺血前冠脉血流或心功能无影响。与未预处理的心脏相比，缺血预处理（4次5分钟全心缺血和5分钟再灌注）导致缺血后心功能显著增加，且在30分钟缺血和30分钟再灌注后乳酸脱氢酶（LDH）释放减少50%。利血平预处理不影响对缺血或预处理的反应，尽管LDH释放往往比正常心脏更大，尤其是在未预处理组。虽然6-羟基多巴胺显著增加了预处理组缺血后的心功能，但缺血损伤的其他指标（如LDH释放、左心室舒张末期压力）均未受影响。进一步研究表明，10 nmol·min-1去甲肾上腺素不影响缺血严重程度，表明它不能模拟预处理。
内源性儿茶酚胺对离体大鼠心脏的缺血预处理并非必需，且在对缺血的功能反应中作用很小或无作用。
