Vander Heide R S, Reimer K A
Department of Pathology, Duke University Medical Center, Durham, NC 27710, USA.
Cardiovasc Res. 1996 May;31(5):711-8. doi: 10.1016/0008-6363(95)00235-9.
The concept of lethal reperfusion injury in ischemic myocardium has been the subject of controversy. Adenosine administered during reperfusion has been reported to limit lethal reperfusion injury in several studies. On the contrary, it has been reported that cardioprotection may not be achieved with adenosine alone but may occur if adenosine is co-administered with lidocaine. Still other investigators have reported no beneficial effect of adenosine, given with or without lidocaine. If the positive reports are reproducible, they are important both because they provide evidence for the existence of reperfusion injury and establish a rationale for preventing it. Thus, the present study was done to determine if adenosine could limit lethal reperfusion injury in a canine model of regional myocardial ischemia and reperfusion, carefully controlled for baseline predictors of infarct size.
Dogs (n = 37) of either sex were subjected to 90 min of coronary occlusion followed by 3 h of reperfusion. Two groups of dogs received adenosine (150 micrograms/kg/min) intravenously for 155 min starting 5 min prior to the reperfusion. One treated group received adenosine only and a second group received adenosine plus lidocaine (2 mg/kg). Control dogs received a saline infusion. After 3 h of reflow, hearts were excised and infarct size was measured and expressed as a percentage of the ischemic area at risk (AAR). To control for variation in infarct size due to variation in collateral blood flow (CBF), infarct size among groups was compared using ANCOVA, using CBF as the independent variable and infarct size as the dependent variable.
Transmural collateral blood flow and AAR were not significantly different between any of the groups. Mean infarct size (adjusted by ANCOVA) in control dogs (n = 9) was 38.1 +/- 5.3% of the AAR. Neither adenosine (n = 9) nor adenosine plus lidocaine (n = 7) significantly limited infarct size (35.6 +/- 5.6% AAR and 38.1 +/- 7.7% AAR, respectively; both P = NS).
Intravenous adenosine therapy (150 micrograms/kg/min) during reperfusion, whether administered alone or in dogs previously treated with lidocaine, did not limit infarct size after 90 min of regional ischemia in canine myocardium.
缺血心肌中致死性再灌注损伤的概念一直存在争议。在多项研究中，已报道在再灌注期间给予腺苷可限制致死性再灌注损伤。相反，有报道称单独使用腺苷可能无法实现心脏保护作用，但如果腺苷与利多卡因联合使用则可能发生心脏保护作用。还有其他研究者报道，无论是否联合利多卡因，腺苷均无有益作用。如果这些阳性报道具有可重复性，那么它们很重要，因为它们既为再灌注损伤的存在提供了证据，也为预防再灌注损伤建立了理论依据。因此，本研究旨在确定在区域心肌缺血和再灌注的犬模型中，腺苷是否能限制致死性再灌注损伤，并对梗死面积的基线预测因素进行了仔细控制。
对37只雌雄不限的犬进行90分钟的冠状动脉闭塞，随后进行3小时的再灌注。两组犬在再灌注前5分钟开始静脉注射腺苷（150微克/千克/分钟），持续155分钟。一个治疗组仅接受腺苷，另一组接受腺苷加利多卡因（2毫克/千克）。对照犬接受生理盐水输注。再灌注3小时后，取出心脏并测量梗死面积，以危险缺血区（AAR）的百分比表示。为了控制由于侧支血流（CBF）变化导致的梗死面积差异，使用协方差分析（ANCOVA）比较各组间的梗死面积，以CBF作为自变量，梗死面积作为因变量。
各组间的透壁侧支血流和AAR无显著差异。对照犬（n = 9）经ANCOVA调整后的平均梗死面积为AAR的38.1±5.3%。腺苷组（n = 9）和腺苷加利多卡因组（n = 7）均未显著限制梗死面积（分别为35.6±5.6% AAR和38.1±7.7% AAR；P均=无统计学意义）。
在犬心肌局部缺血90分钟后的再灌注期间，静脉注射腺苷治疗（150微克/千克/分钟），无论单独给药还是在先前用利多卡因治疗的犬中给药，均未限制梗死面积。
