IMPAIRMENT OF MYOCARDIAL VASCULAR RESPONSIVENESS AFTER TRANSIENT MYOCARDIAL-ISCHEMIA AND REPERFUSION

Coronary vascular responses after brief periods of myocardial ischemia are impaired. Whereas some studies suggest that the ischemic insult s electively depresses endothelium-dependent vasodilator mechanisms, oth er studies indicate that even responses to direct vascular smooth-musc le relaxants such as adenosine may be decreased. This study was undert aken to measure regional myocardial blood flow (RMBF) responses to ade nosine (a direct coronary vasodilator) and serotonin (an indirect, end othelium-dependent vasodilator) in myocardium subjected to regional is chemia followed by reperfusion. Temporary regional ischemia was achiev ed by 20 minutes of occlusion of the left anterior descending coronary artery (LAD) followed by 20 minutes of reflow in 10 open-chest anesth etized dogs. In the left circumflex coronary artery (LCX) territory, w hich served as a nonischemic control, RMBF (measured with radioactive microspheres) increased significantly in response to left atrial infus ions of adenosine (1.29 +/- 0.27 to 3.89 +/- 2.15 ml/min/gm; p < 0.001 ) and serotonin (1.29 +/- 0.27 to 3.29 +/- 1.49 ml/min/gm; p < 0.001) and the percent reduction in coronary vascular resistance (%Delta CVR) was comparable for these two pharmacologic probes (65% +/- 26% vs 62% +/- 19%; difference not significant [NS]). In contrast, in the myocar dium supplied by the LAD, which was subjected to ischemia followed by reperfusion, the augmentation of RMBF by adenosine (1.07 +/- 0.29 to 1 .82 +/- 1.35 ml/min/gm; p < 0.001) and serotonin (1.07 +/- 0.29 to 2.3 7 +/- 1.21 ml/min/gm; p < 0.001) was blunted. The absolute increase in RMBF after adenosine infusion was significantly less than that for se rotonin infusion (p < 0.001), and the %Delta CVR also was significantl y less (43% +/- 24% vs 56% +/- 22%; p < 0.001). Thus despite comparabl e values for heart rate (147 +/- 21 vs 146 +/- 19 beats/min; NS), mean arterial pressure (90 +/- 20 vs 101 +/- 26 mm Hg; NS), cardiac output (3.2 +/- 1.0 vs 3.5 +/- 1.41/min; NS), and %Delta CVR in the control LCX territory during left atrial infusions of adenosine and serotonin, in the previously ischemic LAD bed the vasodilator response to adenos ine was significantly more depressed than the vasodilator response to serotonin. In conclusion, a brief period of regional myocardial ischem ia followed by reperfusion, insufficient to cause structural alteratio ns in the microvasculature, causes a profound depression of vasodilato r responses to adenosine and serotonin. Contrary to the notion that is chemia selectively depresses endothelium-dependent vasodilation, RMBF responses to serotonin, a putative indirect vasodilator, were better p reserved than were RMBF responses to adenosine, a direct smooth-muscle relaxant. The complex interrelation between ischemia followed by repe rfusion and the functional vasodilator responses of the microvasculatu re (at least with respect to these two pharmacologic probes) is more c omplex than previously recognized.