Flores N A, Goulielmos N V, Seghatchian M J, Sheridan D J
Academic Cardiology Unit, St Mary's Hospital Medical School, London, United Kingdom.
Cardiovasc Res. 1994 Nov;28(11):1662-71. doi: 10.1093/cvr/28.11.1662.
The aim was to investigate how platelet activation during myocardial ischaemia can induce electrophysiological and arrhythmogenic effects, and examine the involvement of different platelet membrane receptors in producing these effects.
Transmembrane action potentials and electrograms were recorded from isolated, Langendorff perfused guinea pig hearts during normal perfusion, global myocardial ischaemia, and reperfusion during infusion of human platelets. Platelet reactivity was altered by treating platelets with forskolin, aspirin, the platelet activating factor (PAF) receptor antagonist BN 52021, the thromboxane A2 (TP) receptor antagonist GR 32191B, and the alpha 2 adrenoceptor antagonist yohimbine. Myocardial catecholamine depletion was induced by treatment with 6-hydroxydopamine.
Platelet infusion had no electrophysiological effects during normal perfusion, but during ischaemia it enhanced the reduction in action potential duration at 95% repolarisation [APD95, 110(SEM 3) ms v 121(5) ms, p < 0.05, at 15 min] and increased the incidence of ventricular arrhythmias (from 56% to 94%, p = 0.04) compared to hearts receiving buffer but no platelets. The reductions in APD95 and the arrhythmogenic effects were attenuated when forskolin treated, aspirin treated or GR 32191B treated platelets were infused (VF: 50% v 94%, p = 0.03; 50% v 94%, p = 0.02; 22% v 94%, p < 0.001, respectively). Similar results were obtained when normal platelets were infused into catecholamine depleted hearts (VF: 60% v 94%, p = 0.0549). These differences were associated with inhibited aggregatory responses to thrombin (for forskolin treated platelets) and the thromboxane mimetic U44069 (for GR 32191B treated platelets). Yohimbine was antiarrhythmic in the presence and absence of platelets, suggesting direct myocardial effects, but BN 52021 had no antiarrhythmic effects.
Myocardial ischaemia causes platelet activation resulting in electrophysiological and arrhythmogenic effects. PAF receptor antagonism does not prevent these effects, but inhibition of platelet reactivity, platelet thromboxane receptor antagonism, and myocardial catecholamine depletion are effective. These findings suggest that the arrhythmogenic effects of platelet activation during myocardial ischaemia are principally mediated by a thromboxane dependent mechanism, while catecholamine release has a contributory role.
旨在研究心肌缺血期间血小板活化如何诱发电生理和致心律失常作用，并探讨不同血小板膜受体在产生这些作用中的参与情况。
在正常灌注、全心肌缺血以及输注人血小板期间再灌注过程中，从离体的、经Langendorff灌注的豚鼠心脏记录跨膜动作电位和心电图。通过用福斯高林、阿司匹林、血小板活化因子（PAF）受体拮抗剂BN 52021、血栓素A2（TP）受体拮抗剂GR 32191B以及α2肾上腺素能受体拮抗剂育亨宾处理血小板来改变血小板反应性。用6-羟基多巴胺处理诱导心肌儿茶酚胺耗竭。
在正常灌注期间，血小板输注无电生理作用，但在缺血期间，与接受缓冲液但未输注血小板的心脏相比，它增强了95%复极化时动作电位时程的缩短[APD95，15分钟时为110（标准误3）毫秒对121（5）毫秒，p<0.05]，并增加了室性心律失常的发生率（从56%增至94%，p = 0.04）。当输注经福斯高林处理、阿司匹林处理或GR 32191B处理的血小板时，APD95的缩短和致心律失常作用减弱（室颤：分别为50%对94%，p = 0.03；50%对94%，p = 0.02；22%对94%，p<0.001）。当将正常血小板输注到儿茶酚胺耗竭的心脏中时，也得到了类似结果（室颤：60%对94%，p = 0.0549）。这些差异与对凝血酶（对于经福斯高林处理的血小板）和血栓素模拟物U44069（对于经GR 32191B处理的血小板）的聚集反应受抑制有关。育亨宾在有和无血小板存在时均具有抗心律失常作用，提示其对心肌有直接作用，但BN 52021无抗心律失常作用。
心肌缺血导致血小板活化，从而产生电生理和致心律失常作用。PAF受体拮抗不能预防这些作用，但抑制血小板反应性、血小板血栓素受体拮抗以及心肌儿茶酚胺耗竭是有效的。这些发现提示，心肌缺血期间血小板活化的致心律失常作用主要由血栓素依赖性机制介导，而儿茶酚胺释放起辅助作用。
