Effect of platelet depletion and inhibition of platelet cyclooxygenase on C5a-mediated myocardial ischemia.
Activation of the complement cascade is involved in the myocardial injury resulting from transient ischemia and reperfusion. We previously showed that the complement anaphylatoxin C5a causes myocardial ischemia in vivo, mediated in part via thromboxane (Tx) A2. In the present study, we assess the role of platelets in the C5a-induced myocardial ischemia and Tx release. The left anterior descending coronary artery of anesthetized pigs was perfused with arterial blood at constant pressure and measured flow (coronary blood flow). Segment function (percent segment shortening) was measured with sonomicrometry, and regional coronary venous blood was sampled and assayed for TxB2 (by radioimmunoassay). We found that the C5a-induced decrease in coronary blood flow and percent segment shortening and the release of Tx were indistinguishable whether the left anterior descending coronary artery bed was perfused with normal arterial blood, with arterial blood obtained from animals depleted of platelets (cyclophosphamide, n = 6), or with arterial blood from aspirin-treated animals (n = 9) in which the platelets were unable to produce Tx. These data demonstrate that platelet-derived Tx does not contribute to the C5a-induced myocardial ischemia and Tx release in this model and that these cells do not play an integral role in this phenomenon.
Ito
B R
BR
Department of Medicine, University of California, San Diego.
Del Balzo
U
U
D000818:Animals; D001792:Blood Platelets / Q000201:enzymology / Q000502:physiology*; D001794:Blood Pressure; D003094:Collagen / Q000494:pharmacology; D015936:Complement C5a / Q000633:toxicity*; D003326:Coronary Circulation / Q000187:drug effects; D066298:In Vitro Techniques; D017202:Myocardial Ischemia / Q000097:blood* / Q000139:chemically induced / Q000503:physiopathology; D010974:Platelet Aggregation / Q000187:drug effects; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*; D012016:Reference Values; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood; D013997:Time Factors
D013929:Thromboxane B2; D015936:Complement C5a; D003094:Collagen; D011451:Prostaglandin-Endoperoxide Synthases