Chronic hypoxemia was produced in 16 dogs by surgical transposition of the caudal vena cava to the left atrium to determine if chronic hypoxemia would alter the response of the myocardium to acute ischemia. An electromagnetic aortic flow probe, left atrial tube, and occlusive cuff on the left circumflex coronary artery were permanently implanted in 11 hypoxemic and 26 normal control dogs. The animals were studied in the conscious state after recovery from the surgery. Dogs with hypoxemia had a blood hematocrit value of 54.3 +/- 1.0% (SE), arterial PO(2) of 43.2 +/- 1.4 mm Hg, and 80.2 +/- 1.6% oxygen saturation. There was no difference from control animals in the ratio of left ventricular weight to body weight, but the right ventricular weight was significantly decreased in the hypoxemic dogs. Cardiac output from the left ventricle was twice that of the right ventricle. Aortic blood flow was 3.68 +/- 0.22 liters/min in hypoxemic animals and 2.64 +/- 0.19 liters/min in normal dogs. Myocardial blood flow measured with 15-mu diameter tracer microspheres was increased from 79 +/- 10 and 59 +/- 8 ml/100 g/min in left ventricular endocardial and epicardial halves, respectively, in normal dogs to 212 +/- 48 and 172 +/- 39 in dogs with chronic hypoxemia. There were no deaths in 10 hypoxemic dogs within 24 hours after complete circumflex coronary artery occlusion; 7 of 26 (27%) normal dogs died after circumflex coronary artery occlusion during the conscious state. Gross infarct size was extremely variable in both groups. Median infarct size was smaller in dogs with hypoxemia and was directly correlated with arterial PO(2) in hypoxemic dogs. There was a mild, but statistically not significant, increase in the anastomotic index of hypoxemic dogs compared with that of normal animals, suggesting that a metabolic adaptive change rather than increased collateral circulation may have been responsible for the decreased mortality and smaller infarct size in hypoxemic dogs.