Wainwright C L, Parratt J R, Bigaud M
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland, U.K.
Eur Heart J. 1989 Mar;10(3):235-43. doi: 10.1093/oxfordjournals.eurheartj.a059471.
The aim of the study was to examine a possible role for platelet activating factor (PAF) in experimental myocardial ischaemia and reperfusion. Anaesthetized open-chest greyhounds were subjected to 40 min of coronary artery (LAD) occlusion followed by reperfusion. Blood samples for platelet counting were obtained from a local coronary vein draining the ischaemic region. Pretreatment with PAF antagonists BN52021 (5 mg kg-1 i.v.) or SRI63441 (10 mg kg-1 i.v.), 15 min prior to occlusion reduced the ventricular ectopic count during the ischaemic period from 614 +/- 82 (controls) to 296 +/- 145 (BN52021) and 474 +/- 200 (SRI63441). Both drugs also reduced the incidence of ventricular fibrillation (VF) (during ischaemia and reperfusion) from 90% (controls), to 50% (BN52021) and 43% (SRI63441). Ischaemia was accompanied by a 32 +/- 7% reduction in coronary venous platelets; this was attenuated by both BN52021 (-2 +/- 6%) and SRI63441) (-1 +/- 5%). These results suggest that PAF may contribute to ischaemia and reperfusion-induced arrhythmias by activating platelets.
本研究的目的是探讨血小板活化因子(PAF)在实验性心肌缺血及再灌注过程中可能发挥的作用。对麻醉开胸的灵缇犬进行40分钟的冠状动脉(左前降支)闭塞,随后再灌注。从引流缺血区域的局部冠状静脉采集用于血小板计数的血样。在闭塞前15分钟,用PAF拮抗剂BN52021(5毫克/千克静脉注射)或SRI63441(10毫克/千克静脉注射)预处理,可使缺血期室性异位搏动次数从614±82(对照组)降至296±145(BN52021组)和474±200(SRI63441组)。两种药物还使(缺血和再灌注期间)室颤(VF)发生率从90%(对照组)降至50%(BN52021组)和43%(SRI63441组)。缺血伴随着冠状静脉血小板减少32±7%;BN52021(-2±6%)和SRI63441(-1±5%)均可减轻这种减少。这些结果表明,PAF可能通过激活血小板导致缺血和再灌注诱导的心律失常。