title: Reduction in coronary vasodilator reserve following coronary occlusion and reperfusion in anesthetized dog: role of endothelium-derived relaxing factor, myocardial neutrophil infiltration and prostaglandins.
abstract: To examine the effects of acute myocardial ischemia and reperfusion on regional coronary vasodilator (or flow) reserve, peak reactive hyperemic blood flow following a 10 s occlusion was obtained in dogs subjected to circumflex (Cx) coronary artery occlusion for 1 h followed by reperfusion for 1 h. Acute myocardial ischemia resulting from Cx artery occlusion-reperfusion caused an attenuation in peak reactive hyperemic Cx flow (mean +/- S.E., from 215 +/- 29% to 87 +/- 17%, P less than or equal to 0.001). Acetylcholine-induced increase in Cx flow was also significantly (P less than or equal to 0.01) attenuated following Cx occlusion-reperfusion. These alterations were not observed in the left anterior descending (LAD) coronary artery, which was not subjected to occlusion. Pre-treatment of four dogs with indomethacin inhibited prostaglandin release (P less than or equal to 0.01), but did not affect peak reactive hyperemic coronary flow or acetylcholine-induced increase in coronary flow before or after occlusion-reperfusion. Histopathology revealed extensive myocardial neutrophil infiltration in the Cx-supplied region compared to the LAD-supplied region. Myocardial myeloperoxidase activity, an index of neutrophil infiltration, was also increased in the Cx compared to the LAD region (P less than or equal to 0.02). Myocardial neutrophil accumulation and myeloperoxidase activity were similar in the control and indomethacin-treated animals. These observations suggest that acute myocardial ischemia resulting from coronary artery occlusion-reperfusion impairs coronary vasodilator reserve in anesthetized dogs. This impairment, which was not modified by prostaglandin inhibition, may be related to the loss of endothelium-derived relaxing factor and/or decreased microvascular cross-sectional area resulting from capillary plugging by neutrophils.
authors.affiliation: Department of Medicine, University of Florida, College of Medicine, Gainesville.
authors.forename: W W
authors.initials: WW
authors.lastname: Nichols
authors.forename: J L
authors.initials: JL
authors.lastname: Mehta
authors.forename: W H
authors.initials: WH
authors.lastname: Donnelly
authors.forename: D
authors.initials: D
authors.lastname: Lawson
authors.forename: L
authors.initials: L
authors.lastname: Thompson
authors.forename: M
authors.initials: M
authors.lastname: ter Riet
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001685:Biological Factors / Q000502:physiology*; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism*; D003331:Coronary Vessels / Q000502:physiology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000166:cytology; D009504:Neutrophils / Q000201:enzymology / Q000502:physiology*; D009569:Nitric Oxide; D009195:Peroxidase / Q000032:analysis; D011453:Prostaglandins / Q000097:blood / Q000502:physiology*; D015424:Reperfusion; D014664:Vasodilation
chemical_list: D001685:Biological Factors; D011453:Prostaglandins; D009569:Nitric Oxide; D009195:Peroxidase; D000109:Acetylcholine; D007213:Indomethacin