Reduction in infarct size by ischemic preconditioning persists in a chronic rat model of myocardial ischemia-reperfusion injury.
Ischemic preconditioning (PC) has been consistently observed to reduce infarct size in models of regional myocardial ischemia. However, it is also known to render the heart resistant to injury for only a finite period of time (< 2 h). Myocardial adenosine is widely believed to be one of the mediators of PC and may produce myoprotection in part through an anti-neutrophil effect during the early reperfusion period. When infarct size is assessed following a relatively short period of reperfusion (< 3 h) PC hearts may appear protected although reperfusion injury in the myocardium may be ongoing. Thus, infarct expansion may occur as the effects of PC fade. To substantiate that PC produces a sustained reduction in myocardial necrosis, 27 male Sprague-Dawley rats were anesthetized with pentobarbital and instrumented for regional coronary occlusion (30 min) and reperfusion (7 days). Animals were randomized to a control group (n = 16) or PC (n = 11), which consisted of 2 cycles of 5 min of ischemia and 5 min of reperfusion immediately prior to coronary occlusion. Successful reperfusion was confirmed visually and the occluding suture was left in the chest during recovery. Seven days later, staining for risk area was made by the injection of Evans blue dye while the occluder was in place and necrosis was detected with triphenyltetrazolium chloride staining. Planimetry was performed by a blinded investigator who found the risk area to be 27.2 +/- 1.6 and 33.6 +/- 1.7% of the left ventricle (p = NS) in PC and controls, respectively. All hemodynamic measurements were comparable between groups at all times during ischemia and reperfusion. PC reduced infarct size from 43.3 +/- 2.0% of area at risk to 20.6 +/- -2.1%, a 48% reduction (p < 0.01), and eliminated transmural necrosis which was common in the control group. From these studies we conclude that ischemic PC results in a permanent reduction in infarct size rather than a transient reduction in infarct size in the context of a gradually evolving infarction due to reperfusion injury.
Lott
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Department of Pharmacology, Amgen Inc., Thousand Oaks, CA 91320, USA.
Guo
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Toombs
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CF
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D002908:Chronic Disease; D006339:Heart Rate / Q000502:physiology; D006439:Hemodynamics / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D009336:Necrosis; D009929:Organ Size / Q000502:physiology; D010101:Oxygen Consumption / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley