title: Activated neutrophils aggravate endothelial dysfunction after reperfusion of the ischemic feline myocardium.
abstract: Endothelial dysfunction, as evidenced by decreased stimulated release of endothelium-derived relaxing factor (EDRF), occurs after reperfusion of the ischemic myocardium. To better understand this endothelial dysfunction, isolated cat hearts were perfused under constant flow by the Langendorff procedure with Krebs-Henseleit solution devoid of blood cells. Following global ischemia (90 minutes) and reperfusion (20 minutes), coronary vasorelaxation to the endothelium-dependent vasodilator acetylcholine (ACh) was 70 +/- 3% of initial values (p less than 0.01) compared with 90 +/- 4% in nonischemic control perfused hearts. No decrement occurred in response to the endothelium-independent vasodilator nitroglycerin (NTG). Coronary artery rings isolated from the ischemic left circumflex coronary artery showed a similar degree of endothelial dysfunction to ACh, with normal relaxation in response to NaNO2. Autologous cat neutrophils (100 million cells), activated with 100 nmol/L f-met-leu-phe infused into the heart directly before and throughout reperfusion, resulted in a further decrement in ACh-induced vasodilation, to 55 +/- 5% of initial response, with no effect on NTG-induced vasodilation. Similar results were obtained with coronary artery rings isolated from perfused cat hearts and exposed to neutrophils. This neutrophil-enhanced endothelial dysfunction was inhibited by human superoxide dismutase as well as by an antibody to the adherence glycoprotein complex CD-18 (i.e., MAbR 15.7). Therefore endothelial dysfunction occurs initially upon reperfusion of the previously ischemic heart and is aggravated by superoxide radicals produced by activated neutrophils.
authors.affiliation: Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
authors.forename: P S
authors.initials: PS
authors.lastname: Tsao
authors.forename: X L
authors.initials: XL
authors.lastname: Ma
authors.forename: A M
authors.initials: AM
authors.lastname: Lefer
mesh_terms: D000818:Animals; D002415:Cats; D003327:Coronary Disease / Q000503:physiopathology*; D003331:Coronary Vessels / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D015425:Myocardial Reperfusion; D009504:Neutrophils / Q000502:physiology*