Mechanism of the beneficial effect of dexamethasone on myocardial cell integrity in acure myocardial ischemia.

Abstract

Dexamethasone (6 mg/kg) given intravenously to anesthetized cats exerted no significant hemodynamic effect on control open-chest cats or in cats subjected to acute myocardial ischemia by coronary artery ligature. However, dexamethasone normalized elevated S-T segments toward preischemic values, and prevented much of the increase in plasma CPK activity following coronary artery ligation. Moreover, dexamethasone prevented loss of CK activity within ischemic myocardial tissue five hours after the onset of ischemia. Dexamethasone also reduced the extent of ischemic damage as assessed by a nitro-blue tetrazolium staining technique, providing anatomic verification of the reduced ischemic damage. Moreover, dexamethasone prvented the swelling and vacuolization of myocardial lysosomes in the ischemic region, indicating a stabilization of lysosomal membranes within the heart. These data indicate that lysosomal disruption is an important consequence of myocardial ischemia and that early treatment with dexamethasone prevents the loss of myocardial lysosomal and cellular enzymes as reflected in normalization of the ECG and plasma CK activity of ischemic cats. In this way, dexamethasone may act to retard the spread of the developing infarct within the ischemic myocardium.