de Jong J W, Cargnoni A, Bradamante S, Curello S, Janssen M, Pasini E, Ceconi C, Bünger R, Ferrari R
Cardiochemical Laboratory, Thoraxcenter, Erasmus University Rotterdam, The Netherlands.
J Mol Cell Cardiol. 1995 Jan;27(1):659-71. doi: 10.1016/s0022-2828(08)80058-2.
Myocardium tolerates intermittent ischemia followed by short reperfusions better than continuous ischemia of the same duration. We attempted to delineate the differential mechanism(s) involved in intermittent v continuous ischemia. Isolated, paced rabbit hearts were perfused at 22 ml/min. Coronary flow was stopped intermittently 12 x for 2 or 4 min, with 3-min reperfusions (total reperfusion period: 36 min). In two other groups, flow was stopped continuously for 24 or 36 min followed by a flat 36-min reperfusion. Following the first intermittent 2-min ischemia, adenosine efflux increased ninefold; in all subsequent ischemia/reperfusion cycles, adenosine and total purine releases were substantially less despite identical heart rates, coronary flows and ischemic periods. The rate-pressure product prior to the intermittent ischemias exhibited exponential correlations with total purine efflux during the 3 min of reperfusion. When intermittent ischemia was extended to 4 min, the initial attenuation of ATP breakdown during the prior 2-min occlusions was overcome, but during subsequent 4-min ischemia/reperfusion cycles, ATP breakdown was again attenuated relative to the first 4-min ischemia. After the prolonged continuous ischemias, purine efflux was up to 6 x higher than with intermittent ischemias of the same total time of zero flow. Lactate release and hence cellular H+ export after intermittent ischemias remained consistently elevated, but following the continuous ischemia of 36 min, release of lactate, and thus H+, was subsequentially decreased. Glycogen mobilization occurred regardless of the ischemia's nature, but it was markedly enhanced during continuous ischemias, where no fall in proglycogen levels occurred. Similarly, myocardial norepinephrine release increased substantially only during the prolonged continuous ischemias. Thus short intermittent ischemia attenuates cardiac adenylate degradation and glycogen mobilization; such ischemic insult also provides for better lactate and H+ washouts immediately upon reperfusion. Another beneficial effect of intermittent ischemia was the near-complete absence of free interstitial norepinephrine, which exacerbates myocardial ischemic insults. In addition, the exponential correlations between preischemic rate-pressure product and postischemic purine release suggest that preischemic energy demand may determine ATP breakdown in ischemic rabbit myocardium.
心肌对间歇性缺血后短时间再灌注的耐受性优于相同持续时间的持续性缺血。我们试图阐明间歇性与持续性缺血所涉及的不同机制。将离体的、起搏的兔心脏以22毫升/分钟的速度灌注。冠状动脉血流间歇性停止12次，每次2或4分钟，再灌注3分钟（总再灌注期：36分钟）。在另外两组中，血流持续停止24或36分钟，随后进行36分钟的平稳再灌注。在第一次间歇性2分钟缺血后，腺苷流出增加了9倍；在所有随后的缺血/再灌注周期中，尽管心率、冠状动脉血流和缺血期相同，但腺苷和总嘌呤释放量明显减少。间歇性缺血前的心率-压力乘积与再灌注3分钟期间的总嘌呤流出呈指数相关。当间歇性缺血延长至4分钟时，先前2分钟闭塞期间ATP分解的初始衰减被克服，但在随后的4分钟缺血/再灌注周期中，相对于第一次4分钟缺血，ATP分解再次减弱。在长时间持续性缺血后，嘌呤流出比相同总零流量时间的间歇性缺血高6倍。间歇性缺血后乳酸释放以及因此细胞H+输出持续升高，但在36分钟的持续性缺血后，乳酸以及因此H+的释放随后减少。糖原动员无论缺血性质如何都会发生，但在持续性缺血期间显著增强，此时前糖原水平没有下降。同样，心肌去甲肾上腺素释放仅在长时间持续性缺血期间大幅增加。因此，短暂的间歇性缺血可减轻心脏腺苷酸降解和糖原动员；这种缺血性损伤还能在再灌注后立即更好地清除乳酸和H+。间歇性缺血的另一个有益作用是几乎完全没有游离的间质去甲肾上腺素，而去甲肾上腺素会加重心肌缺血性损伤。此外，缺血前心率-压力乘积与缺血后嘌呤释放之间的指数相关表明，缺血前的能量需求可能决定缺血兔心肌中的ATP分解。
