Loucks E B, Qayumi A K, Godin D V, English J C, Lim S P, Al Mahmeed T, Gul S
University of British Columbia, Vancouver Hospital and Health Sciences Centre, Vancouver, Canada.
Can J Cardiol. 2000 Apr;16(4):497-504.
Antagonists of platelet-activating factor (PAF) reduce myocardial postischemia reperfusion injury when given before the onset of ischemia. However, the effects of PAF antagonists when administered at a clinically modelled time (during ischemia but before reperfusion) are controversial. Moreover, the extended survival (eight day) and the characteristics of scar formation after treatment with PAF antagonists have not been investigated.
To determine the therapeutic potential of PAF antagonist TCV-309 for the treatment of regional myocardial ischemia-reperfusion injury; and to determine the effects of TCV-309 on cardiovascular recovery, evolution of scar formation and survival eight days after a myocardial infarction treated with reperfusion.
Swine underwent regional myocardial ischemia for 60 mins by ligation of the left anterior descending coronary artery, followed by reperfusion for eight days. The treated group (n=7) received PAF antagonist TCV-309 (0.1 mg/kg) 45 mins after ligation; the untreated group (n=7) received vehicle only.
Untreated animals experienced significantly (P<0.001) lower systemic arterial blood pressure during the reperfusion period than animals treated with TCV-309. Furthermore, untreated animals required significantly more (P<0.01) antiarrhythmic and inotropic support. Only two of seven animals in the untreated group survived, which was significantly different (P<0.05) from the six of seven treated animals that survived for eight days. Morphometric analyses did not show differences between groups in the characteristics of scar formation following reperfusion for eight days.
PAF antagonist TCV-309 improves survival and reduces cardiovascular dysfunctions associated with regional myocardial ischemia reperfusion injury when administered at a clinically modelled time.
血小板活化因子（PAF）拮抗剂在缺血发作前给药可减轻心肌缺血再灌注损伤。然而，在临床模拟时间（缺血期间但再灌注前）给予PAF拮抗剂的效果存在争议。此外，PAF拮抗剂治疗后的延长生存期（八天）以及瘢痕形成特征尚未得到研究。
确定PAF拮抗剂TCV - 309对治疗局部心肌缺血再灌注损伤的治疗潜力；并确定TCV - 309对再灌注治疗的心肌梗死后八天心血管恢复、瘢痕形成演变和生存期的影响。
猪通过结扎左冠状动脉前降支进行局部心肌缺血60分钟，随后再灌注八天。治疗组（n = 7）在结扎后45分钟接受PAF拮抗剂TCV - 309（0.1 mg/kg）；未治疗组（n = 7）仅接受赋形剂。
与接受TCV - 309治疗的动物相比，未治疗动物在再灌注期间的体循环动脉血压显著降低（P < 0.001）。此外，未治疗动物需要显著更多（P < 0.01）的抗心律失常和正性肌力支持。未治疗组七只动物中仅两只存活，这与接受治疗的七只动物中有六只存活八天有显著差异（P < 0.05）。形态计量分析未显示两组在再灌注八天后瘢痕形成特征方面存在差异。
PAF拮抗剂TCV - 309在临床模拟时间给药时可提高生存率，并减少与局部心肌缺血再灌注损伤相关的心血管功能障碍。
