The purpose of this study was to evaluate the efficacy of time-controlled intermittent coronary sinus occlusion (ICSO) in preserving regional and global mechanical function during acute ischemia in an animal preparation without significant arterial collateral vessels. Seventeen (eight control, nine ICSO) swine heart preparations undergoing extracorporeal coronary perfusion in situ were subjected to ligation of the left anterior descending coronary artery (LAD) distal to the first major diagonal branch. Data were obtained before and immediately after coronary artery ligation in both animal groups. ICSO, 15 sec of occlusion alternating with 5 sec of release, was then begun in the treatment group. Additional data were obtained in both control and treatment groups at 15 min intervals for 1 hr starting immediately after coronary artery ligation. Global left ventricular function was assessed by shifts in left ventricular end-diastolic pressure and left ventricular dP/dt with left ventricular systolic pressure maintained at about 100 mm Hg. Regional mechanical function was evaluated with transmurally placed ultrasonic crystals. Pressure was also measured directly in the coronary sinus and LAD distal to the ligature. Regional myocardial blood flow was measured in the ischemic bed using 9 micron diameter radiolabeled microspheres injected before, immediately after, and 60 min after coronary artery ligation in both treated and control animals. LAD mean pressure measured distal to the ligation (less than 16 mm Hg) and ischemic bed myocardial blood flow (less than 0.01 ml/g/min) confirmed the absence of significant arterial-arterial collaterals in this preparation. Mean coronary sinus pressure increased significantly (p less than .001) in treated animals during ICSO (e.g., 11.2 +/- 1.6 to 66.2 +/- 10.0 mm Hg at 15 min after coronary ligation). Mean LAD pressure distal to the coronary ligature also increased during ICSO (14.2 +/- 1.2 to 26.8 +/- 1.6 mm Hg), with a similar but delayed rate of pressure rise. No significant differences in left ventricular end-diastolic pressure or left ventricular dP/dt were noted between control or treated animals after coronary ligation. Ischemic bed systolic wall thickening, present before coronary ligation, was not present after occlusion and was not improved during intermittent coronary sinus occlusion in the treatment group. We conclude that in an animal preparation without significant collateral circulation, intermittent coronary sinus occlusion is incapable of restoring regional or global left ventricular mechanical function during conditions of acute ischemia.