The effect of coronary sinus (CS) occlusion produced with a specially designed balloon catheter on coronary hemodynamics and ischemia-induced ventricular fibrillation was studied in anesthetized open-chest dogs. Heart rate (HR), aortic blood pressure (BP), left ventricular max dp/dt, coronary blood flow (CBF) and cardiac output decreased slightly with coronary sinus occlusion, while left ventricular end-diastolic pressure was not affected. These changes were attenuated but did not disappear, by pre-treatment with atropine. This result suggests that, at least partly, these changes were direct effects of venous congestion in the ventricular wall. CBF decreased in the diastolic, but increased in the systolic phase. Coronary sinus pressure (CSP) markedly increased especially in systole after CS occlusion, resulting in a pressure pattern resembling the left ventricular pressure pattern. The CSP exceeded the left ventricular pressure in the diastolic phase. Peak flow, reactive hyperemia flow, and repayment after a brief coronary artery occlusion were all decreased. Myocardial O(2) extraction increased by about 9%, and the increase correlated well with the elevation of mean CSP. When the left anterior descending coronary artery was occluded, CS-occlusion increased retrograde pressure from 22±4mmHg to 33±7mmHg, and the incidence of ventricular fibrillation was decreased. Washout of the metabolites by retrograde flow from the ischemic myocardium would seem to be responsible for this reduction of ventricular fibrillation.