title: Reperfusion enhances the local release of endothelin after regional myocardial ischemia.
abstract: The role of endothelin, a potent long-acting vasoconstrictor peptide, in the pathogenesis of the "no-reflow" phenomenon was investigated in nine closed-chest mongrel dogs undergoing 90 minutes of proximal left anterior descending artery occlusion and 3.5 hours of reperfusion. Endothelin levels were measured serially from the coronary sinus (CS) and aorta (Ao) by radioimmunoassay and correlated with regional myocardial blood perfusion. Prolonged anesthesia, surgery, and vascular instrumentation did not change endothelin levels in four sham animals. A progressive and parallel increase in CS and Ao endothelin levels occurred during coronary occlusion. A further increase in CS levels was observed during the reperfusion period, resulting in significantly higher values of the peptide at 30 and 60 minutes (30 minutes: CS 22.1 +/- 3.5 vs Ao 15.1 +/- 5.1 pg/ml; 60 minutes: CS 21.1 +/- 4.5 vs Ao 15.0 +/- 3.6 pg/ml; p < 0.05 by analysis of variance). Microvascular perfusion determined semiquantitatively with fluorescent beads was significantly reduced in the central ischemic zone (CIZ) compared with that in the nonischemic zone (NIZ) (CIZ endocardium 1.14 +/- 0.4 beads/m2, CIZ midmyocardium 1.19 +/- 0.3 beads/m2, NIZ 3.8 +/- 0.6 beads/m2; p < 0.05). A significant correlation was noted between mean reperfusion levels of endothelin in the CS and endocardial flow in the CIZ (r = -0.88; p = 0.009). This study demonstrates that reperfusion per se enhanced the spillover of endothelin from the cardiac interstitium. Local release of endothelin may contribute to the progressive decrease in microvascular flow in the reperfused bed.
authors.affiliation: Department of Medicine, Vanderbilt University School of Medicine.
authors.forename: C E
authors.initials: CE
authors.lastname: Velasco
authors.forename: M
authors.initials: M
authors.lastname: Turner
authors.forename: T
authors.initials: T
authors.lastname: Inagami
authors.forename: J B
authors.initials: JB
authors.lastname: Atkinson
authors.forename: R
authors.initials: R
authors.lastname: Virmani
authors.forename: E K
authors.initials: EK
authors.lastname: Jackson
authors.forename: J J
authors.initials: JJ
authors.lastname: Murray
authors.forename: M B
authors.initials: MB
authors.lastname: Forman
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism; D003326:Coronary Circulation; D004285:Dogs; D016232:Endothelins / Q000378:metabolism* / Q000502:physiology; D005260:Female; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism*; D015425:Myocardial Reperfusion; D011863:Radioimmunoassay; D012039:Regional Blood Flow
chemical_list: D016232:Endothelins