Microvascular dysfunction after myocardial ischemia

Abstract

Endothelium-mediated relaxation and smooth muscle function in large coronary arteries are resistant to prolonged global ischemia. We used a small-vessel myograph to test the hypothesis that small intramyocardial artery endothelium and smooth muscle function have greater sensitivity to ischemic injury than large artery endothelium and smooth muscle. Normothermic global ischemia was induced in 15 porcine hearts. Intramyocardial arterial ring segments were assessed at 0, 30, 60, 90, and 120 minutes of ischemia in vitro with a small-vessel myograph. Potassium determined smooth muscle contraction, bradykinin endothelium-mediated relaxation, and sodium nitroprusside direct smooth muscle relaxation. Endothelium-mediated relaxation after 30 minutes of ischemia was similar to control (56% versus 66%) but was impaired at 60, 90, and 120 minutes of ischemia (32%, 11%, and 6%). Smooth muscle contraction was unchanged at 30 and 60 minutes compared with control (56 and 53 versus 63 mm Hg) but was significantly decreased at 90 and 120 minutes (33 and 13 mm Hg). Direct smooth muscle relaxation was significantly decreased at 120 minutes of ischemia compared with control (58% versus 95%). In a previous study, epicardial coronary artery endothelium-mediated smooth muscle vasodilation and direct smooth muscle vasodilation were preserved until 160 minutes of ischemia. After 160 minutes of ischemia, endothelium-mediated relaxation was lost and only direct smooth muscle vasodilation was preserved. In contrast to vasodilation, vasoconstriction was significantly reduced at 140 minutes of ischemia. These data indicate a greater and earlier adverse effect of ischemia on intramyocardial arterial endothelium-mediated relaxation than smooth muscle contraction or relaxation. These data support the hypothesis that there is an early functional endothelial cell injury associated with global ischemia. Relaxation that is endothelium-dependent in intramyocardial arteries is more sensitive to ischemic injury than in epicardial arteries. Unique to this study was the evaluation of small intramyocardial arteries (281 +/- 29 microns) that are the primary sites of coronary vascular resistance. Microvascular endothelial dysfunction after ischemia, therefore, may contribute to the "no-reflow phenomenon" seen during reperfusion injury.

Coronary no‐reflow phenomenon: From the experimental laboratory to the cardiac catheterization laboratory

“…Cellular and interstitial edema were also noted. Dignan et al [6] confirmed these observations in studies of ischemia in the porcine heart. Ischemia for less than 30 min did not have a significant effect on the small vessels.…”

Role of Large-conductance Calcium-activated Potassium Channels of Coronary Arteries in Heart Preservation

“…In the present study, we focused our investigation on ischemia, although some kind of reperfusion injury is inevitable in the experiments. As reported by Dignan and colleagues, 4 in vascular studies, separating the effect of ischemia and reperfusion is a necessary step for understanding the pathologic process of the complex I-R injury. The effect of reperfusion on BK Ca , however, awaits further study.…”

“…To strictly mimic clinical ischemic conditions, the hearts were maintained in a small amount of Krebs solution to prevent desiccation and sealed with an air-tight plastic bag for 1 hour at room temperature. 4 In both groups, after exposure either to normoxia or ischemia for 1 hour, segments of the left anterior descending coronary artery (for electrophysiologic studies) or the major branches of the artery (diameter 800 to 1,000 m, for isometric force studies) were dissected out.…”

S-nitroso Human Serum Albumin Attenuates Ischemia/Reperfusion Injury After Cardioplegic Arrest in Isolated Rabbit Hearts

“…The 2 fundamental mechanisms for the loss of NO bioactivity are reduced synthesis and increased oxidative inactivation by reactive oxygen intermediates, leading to the "no-reflow phenomenon" seen during I/R and, as a consequence, to post-ischemic myocardial dysfunction. 6 Providing supplemental L-arginine to individuals with inadequate NO has been suggested as a rational approach to increase NO production by the endothelium.…”