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

Abstract

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.

Glucocorticoid Treatment Prevents Progressive Myocardial Dysfunction Resulting From Experimental Coronary Microembolization

“…[1][2][3] Using an experimental model of coronary microembolization, 4 we have demonstrated that progressive myocardial contractile dysfunction develops within hours after an initial rapid recovery from the immediate microembolization-induced ischemic dysfunction. The present experiments confirmed this progressive myocardial dysfunction, and eventual full recovery was observed after 5 to 6 days.…”

“…[1][2][3] Using an experimental model of coronary microembolization, 4 we have demonstrated that after a rapid (ie, minutes) recovery from the immediate microembolizationinduced ischemic dysfunction, a progressive (ie, hours) contractile dysfunction develops in the presence of unchanged regional myocardial blood flow. 5 Such perfusion-contraction mismatch was associated with a local inflammatory response characterized by leukocyte infiltration.…”

Coronary Flow Velocity Reserve After Percutaneous Interventions Is Predictive of Periprocedural Outcome

“…10,11 This phenomenon seems to be due to adenosine-induced hyperemia of the myocardium surrounding the embolized microregions. 12 This interpretation is further supported by a study reporting that patients who experienced a prolonged hyperemic response after a percutaneous intervention had higher creatine phosphokinase values than patients without hyperemia.…”

Detection of Coronary Microembolization by Doppler Ultrasound in Patients With Stable Angina Pectoris Undergoing Elective Percutaneous Coronary Interventions

“…The high incidence of an impaired CFVR was due to an elevated baseline APV after PCI. Hori et al 30,31 showed that coronary microembolization increased baseline APV by release of adenosine in anesthetized dogs. Herrmann et al 2 reported an association of a periprocedural enzyme elevation with increased baseline APV and a reduced CFVR after stenting in patients with stable angina pectoris.…”

“…Whereas we have focused on patients with chronic stable angina undergoing elective PCI, patients in the PROTECT-TIMI 30 trial had acute coronary syndromes with prior microembolization and subsequent release of adenosine, as well as thrombogenic and vasoconstrictor substances that may have confounded the assessment of coronary reserve. 30,31,40 …”