A comparison of four potential agents for reducing necrosis after prolonged coronary occlusion

In anesthetized closed-chest dogs, four vasodilators were compared after prolonged coronary occlusion induced by catheter wedging in a coronary branch. With treatment given between 1 hour and 2 hours of occlusion, five groups were studied: no treatment, isosorbide dinitrate, nitroprusside, dipyridamole, and methylprednisolone. Measured were heart rate, cardiac pressures and blood flow (with 85Kr); and cardiac index, left ventricular ejection fraction with vascular resistance, left ventricular minute work index, and an oxygen consumption index were calculated. At sacrifice, ischemic inner/outer wall isotope distribution and myocardial K+, Na+, and H2O were determined. With no treatment, left ventricular end-diastolic pressure and vascular resistances rose while cardiac index, ejection fraction, minute work index, and index of myocardial oxygen consumption fell, with no further change between 1 and 2 hours. Vasodilators did not affect coronary hemodynamics or isotope distribution. Hemodynamic effects of isosorbide dinitrate and nitroprusside differed qualitatively from dipyridamole and methylprednisolone. The latter drugs caused increases in ejection fraction, and dipyridamole also significantly increased cardiac index and minute work index. Only nitroprusside decreased minute work index and O2 consumption index. Only nitroprusside and dipyridamole, despite differing hemodynamics, tended to reduce K+ loss and Na+ and H2O gain in ischemic tissue. Further extended studies with these agents are warranted.