In this study, the consequences of large increases of P50 (O2 partial pressure at 50% oxyhemoglobin saturation) on coronary blood flow (CBF) were investigated in isolated Wistar rat heart. Rightward shifts of the O2 dissociation curve (ODC), obtained by lysing and resealing erythrocytes to encapsulate inositol hexaphosphate (IHP), led to a very large increase in P50 without side effects. Each heart was perfused alternatively with control stored human blood [P50 = 18.8 +/- 0.3 (SE) mmHg] and IHP-treated human blood (P50 = 47.1 +/- 1.7 mmHg), according to the technique of Langendorff (mean perfusion pressure 80 mmHg; hematocrit 25%). Arterial PO2 of 180 mmHg was maintained to keep arterial O2 content identical for both types of blood. When hemoglobin affinity was lowered, CBF decreased from 5.32 +/- 0.20 to 3.40 +/- 0.14 ml X min-1 X g-1, coronary sinus PO2 (PcsO2) rose from 39.9 +/- 0.9 to 69.9 +/- 4.2 mmHg, and myocardial O2 consumption (MVO2) rose slightly from 0.125 +/- 0.005 to 0.149 +/- 0.010 ml O2 X min-1 X g-1 (P less than 0.05). A significant negative correlation was found between CBF and P50 (r = -0.90; n = 32) and a significant positive correlation between PcsO2 and P50 (r = +0.84; n = 28). The coronary blood flow response to high P50 values was not abolished when maximal dilation was induced by adenosine, so this response seems independent of metabolic needs. These experiments have demonstrated that if O2 uptake by erythrocytes remains constant, in the presence of a high P50, sufficient O2 supply may be achieved with substantially less blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)