Retroperfusion of arterial blood through the coronary sinus reduces infarct size if therapy starts immediately after coronary artery occlusion. To determine if a new system of non-electrocardiogram-synchronized retroperfusion is able to reduce infarct size after delays consistent with clinical use, anesthetized pigs were subjected to 4 hours of left anterior descending coronary artery occlusion followed by 1 hour of reperfusion. Retroperfusion of arterial blood commenced immediately after occlusion of the left anterior descending coronary artery in the no-delay group (n = 10) and after a 1-hour (n = 10) and a 2-hour (n = 8) delay in two other groups. In the control group (n = 10), no therapy was used. In all groups, retroperfusion of arterial blood was terminated after 4 hours of occlusion of the left anterior descending coronary artery. Infarct size, expressed as a percentage of the in vivo area at risk (+/- the standard deviation), was smaller in the no-delay group (44.1 +/- 12.9) and marginally smaller in the 1-hour delay group (71.0 +/- 9.8) compared with controls (86.3 +/- 7.5) (p < 0.05). Infarct size in the 2-hour delay group (75.0 +/- 10.7) was not significantly different from controls. Mean coronary sinus pressure (+/- the standard deviation) was 56 +/- 25 mm Hg, 39 +/- 9 mm Hg, and 47 +/- 9 mm Hg in the no-delay, 1-hour delay and 2-hour delay groups, respectively. Thus, this new retroperfusion system limits infarct size by 50% if it is started immediately after coronary occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)