Influence of methylprednisolone on ultrastructural and cytochemical changes during myocardial ischemia. Selective effects on various cell inclusions and organelles including lysosomes

Occlusion of the circumflex branch of the coronary artery of rabbit hearts for 45 minutes elicits structural and cytochemical changes in myocytes similar to those observed in ischemic dog myocardium, which are indicative of irreversible cell injury. When methylprednisolone is administered prior to occluding the artery, myocytes are transiently protected and many of the electron microscopic signs of irreversible damage are delayed for 15 minutes or more. During this period, the steroid preferentially protects mitochondria, lysosomes, and sarcolemma from the ischemic changes that normally develop. However, some other events, including depletion of glycogen and margination of nuclear chromatin, are only minimally influenced by the therapy, if at all. In all hearts, treated and untreated, the development of severe cell damage, whenever it occurs, is closely associated with cell swelling, mitochondrial dilation with concomitant appearance of amorphous osmiophilic densities, and abnormalities in and, ultimately, disappearance of lysosomes, suggesting that damage to cell membranes is a central event in the progression of reversible injury to irreversible infarction and that protection of membrane integrity should be a reasonable aim in efforts to ameliorate or delay ischemic injury.