Complement C5a-mediated myocardial ischemia and neutrophil sequestration: two independent phenomena.
The intracoronary infusion of complement C5a causes a decrease in coronary blood flow and contractile dysfunction mediated by thromboxane (TxA2) and leukotrienes. Although these effects are accompanied by polymorphonuclear leukocyte (PMN) sequestration, the role of PMNs and the source of these eicosanoids remain unknown. To assess the contribution of PMNs to the C5a-induced myocardial ischemic response, the left anterior descending (LAD) coronary artery of pigs (n = 13) was cannulated and pump perfused at constant pressure with either normal arterial blood or neutropenic arterial blood (PMN count 0.02 x 10(3) cells/microliters) obtained from animals treated with cyclophosphamide (50 mg/kg iv, given 4 days before). The coronary vein draining the LAD region was cannulated for measurement of leukocyte count and TxB2 levels. Two groups of animals were studied: group 1 (n = 7) neutropenic animals were instrumented and normal animals served as blood donors and group 2 (n = 6) normal animals were instrumented and neutropenic animals served as blood donors. The myocardial response to intracoronary C5a (500 ng) was determined in each animal during coronary perfusion with normal arterial blood and also with neutropenic arterial blood. During perfusion with normal arterial blood, C5a decreased coronary flow to 52.3% and contractile function to 58.8% of preinfusion values. This was accompanied by a transient myocardial accumulation of PMNs (arterial-coronary venous gradient of 5.4 x 10(3) cells/microliters) and increased TxB2 levels in coronary venous blood (from 0.31 to 17.5 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)
Del Balzo
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Department of Veterans Affairs Medical Center, Research Service, San Diego, La Jolla, California.
Engler
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RL
Ito
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BR
D000818:Animals; D001772:Blood Cell Count; D015936:Complement C5a / Q000502:physiology*; D003326:Coronary Circulation; D005260:Female; D006321:Heart / Q000503:physiopathology; D006439:Hemodynamics; D007958:Leukocyte Count; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D009504:Neutrophils / Q000502:physiology*; D013552:Swine; D013929:Thromboxane B2 / Q000096:biosynthesis
D013929:Thromboxane B2; D015936:Complement C5a