Ovize M, Przyklenk K, Hale S L, Kloner R A
Heart Institute Research, Hospital of the Good Samaritan, Los Angeles, CA 90017.
Circulation. 1992 Jun;85(6):2247-54. doi: 10.1161/01.cir.85.6.2247.
Despite numerous reports that one or more episodes of brief coronary artery occlusion preconditions the myocardium and dramatically reduces myocardial infarct size produced by a subsequent prolonged ischemia, we recently demonstrated that preconditioning does not attenuate contractile dysfunction in the peri-infarct tissue. However, the specific effects of preconditioning on myocardium in which wall motion has not been compromised by the preconditioning regimen per se and is further submitted to a short ischemic insult (that is, not confounded by necrosis) remain unknown.
We addressed these issues in the canine model of myocardial stunning. Eighteen anesthetized dogs underwent 15 minutes of coronary occlusion followed by 3 hours of reperfusion. Before the 15-minute coronary occlusion, each dog received one of three treatments: no intervention (control group, n = 6), one episode of 5-minute coronary occlusion/5-minute reperfusion (PC5 group, n = 6), or one episode of 2.5-minute coronary occlusion/5-minute reperfusion (PC2.5 group, n = 6). Segment shortening (SS) in the ischemic/reperfused midmyocardium was monitored by sonomicrometry, and myocardial blood flow was assessed by injection of radiolabeled microspheres. All three groups were equally ischemic during the 15-minute coronary occlusion: Midmyocardial blood flow averaged 0.05 +/- 0.02, 0.07 +/- 0.04, and 0.08 +/- 0.03 ml/min/g in control, PC2.5, and PC5 groups, respectively. Before the 15-minute coronary occlusion, PC5 dogs exhibited significant stunning (SS = 55% baseline; p less than 0.01 versus control), whereas PC2.5 dogs did not (SS = 91% baseline; p = NS versus control). However, segment shortening during the subsequent 15-minute coronary occlusion was equally depressed at -25% to -42% of baseline values among the three groups. Furthermore, all three groups demonstrated a similar degree of stunning after reperfusion: SS at 3 hours after reflow averaged 24 +/- 12%, 34 +/- 16%, and 48 +/- 12% of baseline in control, PC2.5, and PC5 groups, respectively (p = NS). The degree of recovery of function after reperfusion correlated with the amount of midmyocardial blood flow during coronary artery occlusion. However, this relation was not different among the three groups: Specifically, for any given collateral flow during ischemia, preconditioning did not reduce the degree of stunning.
Preconditioning neither preserves contractile function during a reversible ischemic insult nor prevents myocardial stunning during the initial hours of reflow.
尽管有大量报道称,一次或多次短暂冠状动脉闭塞可使心肌产生预处理,并显著减小随后长时间缺血所导致的心肌梗死面积,但我们最近证明,预处理并不能减轻梗死周边组织的收缩功能障碍。然而,预处理对心肌的具体影响仍不清楚,在这些心肌中,壁运动本身并未因预处理方案而受损,并且进一步遭受短暂缺血性损伤(即不受坏死影响)。
我们在犬心肌顿抑模型中研究了这些问题。18只麻醉犬接受15分钟冠状动脉闭塞,随后再灌注3小时。在15分钟冠状动脉闭塞前,每只犬接受三种处理之一:不干预(对照组,n = 6)、一次5分钟冠状动脉闭塞/5分钟再灌注(PC5组,n = 6)或一次2.5分钟冠状动脉闭塞/5分钟再灌注(PC2.5组,n = 6)。通过超声心动图监测缺血/再灌注心肌中层的节段缩短(SS),并通过注射放射性微球评估心肌血流量。在15分钟冠状动脉闭塞期间,三组的缺血程度相同:对照组、PC2.5组和PC5组心肌中层血流量分别平均为0.05±0.02、0.07±0.04和0.08±0.03 ml/min/g。在15分钟冠状动脉闭塞前,PC5组犬表现出明显的顿抑(SS = 基线的55%;与对照组相比,p < 0.01),而PC2.5组犬则没有(SS = 基线的91%;与对照组相比,p = 无显著差异)。然而,在随后的15分钟冠状动脉闭塞期间,三组节段缩短均同样降低至基线值的 -25%至 -42%。此外,三组在再灌注后均表现出相似程度的顿抑:再灌注3小时时的SS在对照组、PC2.5组和PC5组分别平均为基线的24±12%、34±16%和48±12%(p = 无显著差异)。再灌注后功能恢复程度与冠状动脉闭塞期间心肌中层血流量相关。然而,三组之间这种关系并无差异:具体而言,对于缺血期间任何给定的侧支血流量,预处理均未降低顿抑程度。
预处理既不能在可逆性缺血损伤期间保留收缩功能,也不能在再灌注最初数小时预防心肌顿抑。