Complement C5a-mediated myocardial ischemia and neutrophil sequestration: two independent phenomena
Del Balzo, U.; Engler, R.L.; Ito, B.R.
American Journal of Physiology 264(2 Pt 2): H336-H344
1993
ISSN/ISBN: 0002-9513 PMID: 8447449 Document Number: 409592
The intracoronary infusion of complement C5a causes a decrease in coronary blood flow and contractile dysfunction mediated by thromboxane (TxA-2) 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 times 10-3 cells/mu-l) 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 TxB-2 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 times 10-3 cells/mu-l) and increased TxB-2 levels in coronary venous blood (from 0.31 to 17.5 ng/ml). The infusion of C5a during coronary perfusion with neutropenic blood resulted in a similar myocardial response with coronary flow and contractile function decreasing to 49.7 and 52.4%, respectively, accompanied by an increase in TxB-2 levels in coronary effluent from 0.17 to 19.4 ng/ml. Severe neutropenia did not attenuate the C5a-induced myocardial dysfunction and thromboxane production. Although C5a-mediated intramyocardial neutrophil trapping occurs, this phenomenon is not causally related to the myocardial ischemic response, and this circulating cell type is not the source for thromboxane production in response to C5a.