In situ apoptosis assay for the detection of early acute myocardial infarction

Abstract

Detection and age determination of myocardial infarction (MI) is often necessary in both clinical and pathological settings. Conventional histopathological techniques are of limited utility in the demonstration of myocardial ischemic cell death (MICD) within the first 6 hours of MI. In this study, an in situ apoptosis assay was evaluated for the determination of early MICD or early MI. Sections of formalin-fixed, paraffin-embedded archival tissue blocks from 80 hearts were stained for the presence of apoptotic cells by specific labeling of nuclear DNA fragmentation. Conventional hematoxylin and eosin stain showed acute MI (group A, n = 32), equivocal evidence for MICD or early infarction (group B, n = 35), or no abnormal findings (group C, n = 13). The sensitivity and specificity of the in situ apoptosis assay for MICD were confirmed in groups A and C patients. We showed that apoptosis of myocardial cells can occur after ischemic myocardial cell injury. Virtually all documented cases of acute MI (group A) revealed a sizeable distribution of apoptotic cells visible on gross examination of glass slides. Special attention was given to patients in group B, who were at high risk for MI and for suspected but not proved cardiac death. In this group, 34/35 cases (97%) showed focal or diffuse nuclear positivity of varying degrees for apoptosis, confirming the presence of MICD. A sizeable distribution of apoptotic cells, similar to that observed in group A, was noted in 13/35 cases (37%) of group B, suggesting acute MI in these cases. The in situ assay of DNA fragmentation can detect MICD while the histological diagnosis is still inconclusive. It is estimated that with this assay one can detect MICD as early as 2 to 4 hours.