Role of cardiac mast cells in complement C5a-induced myocardial ischemia.
Activated complement component C5a causes myocardial ischemia mediated by thromboxane (Tx) A2 and leukotrienes C4/D4. Blood cells are not involved in either the mediator release or the myocardial effects of C5a, suggesting that a C5a-sensitive, cardiac resident inflammatory cell is responsible. The goals of this study were to determine whether 1) cardiac mast cell activation accompanies the C5a response, 2) inhibition of mast cell degranulation inhibits the response, and 3) histamine release plays a role in the C5a-induced myocardial ischemia. The left anterior descending coronary artery (LAD) of open-chest pigs (n = 13) was perfused with arterial blood at constant pressure (95 mmHg). Coronary blood flow (CBF) was measured (in-line flowmeter) and regional function [percent segment shortening (%SS)] determined with sonomicrometry. A coronary vein was cannulated for measurement of plasma TxB2 and histamine (a marker of mast cell degranulation). Intracoronary C5a (500 ng) decreased coronary blood flow (45% of preinfusion levels) and LAD %SS (65% of preinfusion) and was accompanied by increases in coronary venous TxB2 (delta 63.3 ng/ml) and histamine (delta 200 nM). Mast cell inhibition with lodoxamide (2 mg/kg iv, n = 8) attenuated the C5a-induced fall in CBF (14 vs. 53% decrease, P < 0.01) and %SS (10 vs. 38% decrease, P < 0.01) and also reduced the C5a-induced increase in both coronary venous histamine (delta 26 vs. 278 nM, P < 0.05) and TxB2 (delta 0.34 vs. 63.3 ng/ml, P < 0.01). However, histamine H1 (pyrilamine) and H2 (ranitidine) receptor blockade had no effect on the C5a-induced fall in CBF or LAD %SS.(ABSTRACT TRUNCATED AT 250 WORDS)
Ito
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Department of Medicine, University of California, San Diego 92103.
Engler
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del Balzo
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D000818:Animals; D015936:Complement C5a; D003326:Coronary Circulation / Q000187:drug effects; D005260:Female; D006632:Histamine / Q000097:blood; D006633:Histamine Antagonists / Q000494:pharmacology; D006636:Histamine Release; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D017202:Myocardial Ischemia / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology*; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D013552:Swine
D006633:Histamine Antagonists; D015936:Complement C5a; D006632:Histamine; D010072:Oxamic Acid; C021702:lodoxamide ethyl