BACKGROUND: The effects of isoflurane on distribution of transmural blood flow and transmural intramyocardial tissue pressure (IMP) were studied in chronically instrumented dogs, to address following aims: (1) to evaluate the direct effects of isoflurane on transmural blood flow distribution in the absence of compounding effects of baseline anesthetics, acute surgery, and indirect effects caused by changes in systemic blood pressures and heart rate--factors that were not well controlled in the past studies; (2) to examine the relation between transmural myocardial perfusion pressure and concurrent changes in transmural blood flow distribution during isoflurane anesthesia; and (3) to evaluate the effects of isoflurane on transmural myocardial oxygen supply-demand relation. METHODS: Dogs were allowed to recover at least 1 week after surgery for instrumentation. Blood flow of the left anterior descending coronary artery and subendocardial and subepicardial blood flows, regional IMPs, regional segmental dimension, heart rate, aortic pressure and left ventricular pressure were measured while dogs were awake and during 1.3% isoflurane anesthesia, with and without correction of heart rate and aortic pressure. Concurrently regional myocardial perfusion pressure, regional myocardial stroke work, and systolic pressure time index were calculated, based on direct measurements of IMP in subendocardium and subepicardium. RESULTS: Without correction of aortic pressure, neither left anterior descending coronary artery flow nor transmural blood flow distribution was altered with isoflurane. When aortic pressure and heart rate were corrected to the awake values, left anterior descending coronary artery flow increased (37 +/- 2%) and the increase was preferentially distributed to subendocardium, resulting in a shift in transmural blood flow. The subendocardial/subepicardial blood flow ratio increased from 1.2 +/- 0.3 to 1.4 +/- 0.4 (p, 0.05). The transmural blood flow changes were closely related to changes in regional myocardial perfusion pressure ratio between subendocardium and subepicardium (r = 0.76, P < 0.001). Concurrent with marked increases in blood flow (55 +/- 4% increase), regional myocardial stroke work and systolic pressure time index of subendocardium were decreased more than 50% with isoflurane, resulting in a favorable subendocardial oxygen supply-demand balance. CONCLUSIONS: Isoflurane is a coronary vasodilator and redistributes blood flow in favor of subendocardium and depresses subendocardial work when heart rate and aortic pressure are controlled. These changes in regional myocardial blood flow, regional myocardial stroke work, and systolic pressure time index appear to be a result of changes in regional IMP.