The most effective way to limit myocardial ischemic necrosis is reperf
usion, but reperfusion itself may result in tissue injury, which has b
een difficult to separate from ischemic injury. This report identifies
elements of apoptosis (programmed cell death) in myocytes as a respon
se to reperfusion but not ischemia. The hallmark of apoptosis, nucleos
omal ladders of DNA fragments (approximate to 200 base pairs), was det
ected in ischemic/reperfused rabbit myocardial tissue but not in norma
l or ischemic-only rabbit hearts. Granulocytopenia did not prevent nuc
leosomal DNA cleavage. In situ nick end labeling demonstrated DNA frag
mentation predominantly in myocytes. The pattern of nuclear chromatin
condensation was distinctly different in reperfused than in persistent
ly ischemic tissue by transmission electron microscopy. Apoptosis may
be a specific feature of reperfusion injury in cardiac myocytes, leadi
ng to late cell death.