Effect of a critical coronary stenosis on myocardial neutrophil accumulation during ischemia and early reperfusion in dogs.

Abstract

In many experimental models of ischemia and reperfusion, reperfusion is performed abruptly, allowing full reactive hyperemia to occur. In the clinical setting, however, reperfusion after thrombolysis is often limited by residual stenosis. Some experimental models attempt to mimic this situation with a "critical stenosis" (defined as a coronary constriction sufficient to abolish reactive hyperemia without altering baseline flow). The purpose of this study was to determine whether preventing reactive hyperemia during the initial phase of reperfusion would modify the transmural distribution of myocardial blood flow or the myocardial accumulation of polymorphonuclear leukocytes (PMNs). The left circumflex artery was occluded for 90 minutes and then reperfused for 60 minutes in anesthetized, open-chest dogs. Autologous PMNs were isolated, labeled with`lIn, and reinjected 1 hour before coronary occlusion.`251-labeled albumin was injected simultaneously to correct for "'in associated with plasma proteins and to permit calculation of the number of PMNs in the inner, middle, and outer thirds of nonischemic and ischemic-reperfused tissue. The presence of a critical stenosis abolished reactive hyperemia during the first 5 minutes of reperfusion, but did not substantially affect blood flow measured after 55 minutes of reperfusion. In both groups, there was a significant accumulation of PMNs in all layers of the ischemic-reperfused bed compared with the nonischemic bed, and the magnitude of this PMN accumulation was not altered by the presence of a critical stenosis. Moreover, infarct size, estimated by triphenyl tetrazolium chloride (TTC) loss after 60 minutes of reperfusion, was not affected by the presence of a critical stenosis. Thus, the presence of a critical stenosis abolished the hyperemic blood flow after reperfusion but did not influence the early PMN response to ischemia and reperfusion or the early loss of TTC staining. (Circulation 1989;80:1805-1815 T he severity and duration of an ischemic interval are the major determinants of whether cardiac myocytes will recover or undergo necrosis after reperfusion. It has been postulated in recent years, however, that the fate of some myocytes may be determined, in part, by events One potentially important variable aspect of reperfusion is the distal arterial pressure and consequent rate of flow through the microvasculature during the initial phase of reperfusion. In many experimental models, coronary occlusion is followed by an abrupt, complete reopening of the artery, permitting a marked hyperemic flow through the ischemically dilated microvasculature. In clinical circumstances, however, reperfusion is usually achieved more slowly (e.g., by thrombolytic therapy), and reactive hyperemia may be limited by the residual stenosis caused by underlying atherosclerotic plaque.4 Some investigators mimic this situation in their experimental models of ischemia and reperfusion by imposing a persistent partial constriction on the occluded and reopened artery.3 This "critical steno...

Effect of anti-CD18 antibody on myocardial neutrophil accumulation and infarct size after ischemia and reperfusion in dogs.

“…Myocardial edema and an increase in tissue plasma proteins have been reported previously after either reversible or irreversible ischemic injury of myocytesl, 19,36 and as observed previously, were transmural even though the myocyte necrosis was primarily in the subendocardial half of the ischemic region. These changes presumably indicate functional and/or anatomic changes in the microvasculature, but the precise mechanism of such microvascular injury is unknown.…”

“…The protocol for isolation and labeling of PMNs was that of Richard et al, 19 with several modifications. These modifications have resulted in improved PMN survival upon readministration of the labeled cells to the dogs, as indicated by a higher cell-associated/total bloodindium ratio, and a longer circulating half-life of the labeled cells compared with our earlier studies.…”

Evidence against the "early protection-delayed death" hypothesis of superoxide dismutase therapy in experimental myocardial infarction. Polyethylene glycol-superoxide dismutase plus catalase does not limit myocardial infarct size in dogs.

“…However, we have recently observed that the number of neutrophils that progressively accumulate in the reperfused myocardium and are a major proposed source of superoxide radicals, and also of infarct size, was not affected by the presence or absence of a critical stenosis at the onset of reperfusion. 34 Finally, it must be considered that a small therapeutic effect might not be detected in the relatively small number of dogs used per group in the present study. To evaluate this possibility, we have analyzed our results after enlarging the control group by including the control dogs from our preceding study.…”