The Effect of Reperfusion after Brief, Reversible Myocardial Ischemia on Coronary Vascular Function and Ultrastructure

Kim, Young Hoon

Abstract

BACKGROUND
Reperfusion after brief periods within 20 minutes of myocardial ischemia can result in prolonged depression of contractile function without causing myocardial necrosis-myocardial stunning. It has been also demonstrated that low reflow phenomenon and the impairment of coronary flow reserve(CFR) can occur as the consequences of brief ischemia-reperfusion on the coronary vasculature. Although these vascular functional derangements may occur after various periods of ischemia, a 15-min episode of ischemia is known to be long enough to induce microvascular dysfunction and a briefer 10-min occlusion is not. Whether reperfusion after ischemia for 15-min or 20-min results in structural damage to the large and microvessels, as well as vascular function, and their relationship with contractile dysfunction, remains uncertain. PURPOSE: This study was performed to determine whether 1) c5-min and 20-min coronary occlusion followed by 60 minutes of reperfusion in vivo would result in injury of coronary vasculature, evident as functional and ultrastructural derangements, 2) there are any differences in the severity of vascular alterations by the duration of ischemic period, and 3) these vascular alterations relate to the regional myocardial dysfunction.
METHODS
Open chest dogs underwent a 15-min(n=8) and 20-min(n=10) left circumflex coronary artery occlusion followed by reperfusion for 60 minutes. Coronary blood flow(CBF) was measured with electromagnetic flow probes. At 30 minutes and 60 minutes of reperfusion, CFR was determined after intracoronary acetylcholine(ACH, 0.01microg/kg), adenosine(ADE, 1.5microg/kg) and reactive hyperemia(RH) after 20 seconds coronary occlusion. Segmental LV function was assessed with % myocardial thickening and % endocardial wall motion by 2D echocardiography. The ultrastructure of epicardial artery and the microvessels in the endocardium was examined.
RESULTS
Following reperfusion, increase in CBF and decrease in coronary vascular resistance in reponse to ACH, endothelium dependent vasodilator, was significantly impaired in both 15-min and 20-min occlusion groups. The CBF response to ADE, endothelium independent vasodilator, was intract in 15-min occlusion group, whereas significantly impaired in 20-min occlusion group. The CBF response to RH was significantly depressed in both groups. On ultrastructural examination, there was no evidence of injury in the microvessels of the subendocardium in all subjects. In the large epicardial arteries, the endothelium was damaged in all subjects and its severity was milder in 15-min occlusion group than those with 20-min occlusion. Furthermore, in 50% cases of 20-min occlusion group, the injury of superficial layer of medial smooth muscle was accompanied. There was no difference in the severity of segmental LV dysfunction between two groups, and there was no appreciable correlation between myocardial dysfunction and the depressed CBF responses to ACH, ADE and RH.
CONCLUSION
1) Reperfusion after occulsion for 15 minutes produced selective dysfunction and damage to the endothelium of epicardial artery, whereas those after 20 minutes significantly decreased coronary flow reserve and induced more pronounced damage to the epicardial artery, indicated that the severity of vascular alterations is determined by the duration of ischemic period even within 20 minutes. 2) These vascular derangements are not related to the severity of contractile dysfunction, suggesting that brief ischemia-reperfusion precipitates vascular stunning as an independent phenomenon of myocardial stunning.