Role of adenosine in hyperemic response of coronary blood flow in microembolization

To investigate the pathophysiology of acute embolization of small coronary vessels and the role of adenosine in this abnormality, regional coronary blood flow (CBF), coronary vascular resistance, arteriovenous O2 difference, lactate extraction ratio, and adenosine release were studied in 39 anesthetized open-chest dogs after acute coronary embolization with microspheres of three different diameters (15 +/- 1, 94 +/- 8, and 293 +/- 23 microns). In 16 dogs, the left anterior descending coronary artery was embolized by repetitive injections of 15-microns microspheres, up to 4.4 +/- 0.4 X 10(5)/g myocardium; at this point CBF, determined by the electromagnetic flowmeter at the proximal site of the artery, was reduced toward zero. Up to 37% of total embolization, resting CBF increased to 175 +/- 36% of control; thereafter it decreased almost linearly as the extent of embolization was increased. After embolization, coronary arteriovenous O2 difference was significantly (P less than 0.01) decreased with a marked release of adenosine in the coronary vein. Despite a hyperemic flow response of CBF in the embolized area, myocardial ischemia was not prevented; maximal increase in CBF after 100-microns microsphere embolization (141 +/- 11% of control CBF, n = 6) was significantly (P less than 0.05) less than that in 15-micron microsphere embolization, whereas 300-microns microsphere embolization minimally increased CBF (123 +/- 13%, P greater than 0.1; n = 5). Hyperemic flow remained unchanged for at least 3 h when adenosine was persistently released. Theophylline significantly attenuated this response. These results indicate that in embolization with microspheres less than 300 microns in diameter, hyperemic response of coronary blood flow occurs, probably due to the hyperemia of nonoccluded vessels in the adjacent area of ischemic foci to adenosine released from the ischemic myocardium.