The wavefront phenomenon of ischemic cell death. 1. Myocardial infarct size vs duration of coronary occlusion in dogs.

Abstract

Irreversible ischemic myocardial cell injury developes in an increasing number of cells as the duration of coronary occlusion is prolonged. The present study quantitates myocardial necrosis produced by 40 minutes, 3 hours, or 6 hours of temporary circumflex coronary occlusion (CO) followed by 2 to 4 days of reperfusion, or by 24 or 96 hours of permanent circumflex ligation in pentobarbital anesthetized open chest dogs. After 40 minutes of ischemia, myocyte necrosis was subendocardial but with increasing duration of coronary occlusion, irreversible injury progressed as a wavefront toward the subepicardium. Transmural necrosis was 38 +/- 4% after 40 min, 57 +/- 7% after 3 hours, 71 +/- 7% after 6 hours and 85 +/- 2% after 24 hours of ischemic injury. These results document the presence of a subepicardial zone of ischemic but viable myocardium which is available for pharmacologic or surgical salvage for at least three and perhaps six hours following circumflex occlusion in the dog.

Relationship between infarct size and severity measured by gated SPECT and long-term left ventricular remodelling after acute myocardial infarction

“…Conversely, our study demonstrates that the reduction of infarct size beyond the subacute phase may occur in all patients, in agreement with prior scintigraphic reports [6,24,25]. This means that infarct resorption could be a spontaneous event occurring after AMI independently of its size and of the patients' outcome [26,27]. Analysing separately patients with and without LV remodelling, however, a significant correlation between infarct resorption and LV functional changes was observed only in the latter group.…”

“…The presence of vascular stunning in the region of the infarction may persist for weeks after restoration of blood flow [26] and the gradual recovery of microvascular function may then result in a delayed reduction of the perfusion defect size. Furthermore, the myocardial infarction area may decrease in the weeks after AMI due to oedema reabsorption and phagocytation of dead myocardial cells and collagen production and contraction [27]. We found a significant relationship between late reduction in infarct size and improvement in LV function.…”

Myocardial reperfusion: a double-edged sword?

“…It has been observed repeatedly in experimental animals that infarcts produced by transient periods of ischemia followed by reperfusion contain areas of hemorrhage (5,30). Hemorrhagic myocardium has also been found at necropsy in patients with acute myocardial infarction who underwent thrombolytic reperfusion or surgical revascularization (31).…”

“…However, the angiographic finding by DeWood et al (3) in 1980 of obstructive coronary thrombi in a large majority of patients studied during the first hours of acute transmural myocardial infarction, coupled with the experimental observation that myocardium can be salvaged by early reperfusion (4,5), led to efforts to dissolve, mechanically compress, or surgically remove or bypass the offending thrombi. The demonstration that coronary thrombi can be lysed successfully in the majority ofpatients by the intracoronary injection of streptokinase (6) as well as by the technically much simpler technique of the intravenous administration of tissue plasminogen activator (7,8) has raised the hope that large quantities of ischemic myocardium in the distribution of the occluded coronary artery, which are otherwise destined to become necrotic, might be salvaged by timely application of thrombolytic reperfusion.…”

Limitation of infarct size and ventricular remodeling in patients with completely reperfused anterior acute myocardial infarction—the potential role of ischemia time

“…In the dog, myocardial necrosis is believed to begin 20 min after coronary artery occlusion and to spread from endocardium to epicardium with increasing duration of ischemia. 12 In the rat and pig, with less developed intercoronary collaterals, necrosis begins sooner and spreads more rapidly. Thus, there are species differences in the rate of development of myocardial infarction.…”