C5a decreases regional coronary blood flow and myocardial function in pigs: implications for a granulocyte mechanism.
Granulocytes cause some of the pathophysiological effects associated with the capillary no-reflow phenomenon during ischemia and in ischemia-reperfusion injury. However, no study has examined the consequences of in vivo granulocyte activation during normal perfusion pressures. In this study, we examined the effects of intracoronary administration of the complement component C5a, which is known to be a potent granulocyte activating factor. Nine open-chest, anesthetized pigs were instrumented to monitor regional coronary blood flow and segment shortening, left ventricular dP/dt, heart rate, and pulmonary artery and aortic blood pressures and to sample arterial and regional coronary venous blood for oxygen content and complete blood counts. Intracoronary infusion of human or porcine C5a in doses ranging from 10 to 500 ng produced a significant reduction in regional coronary blood flow and myocardial function. Although perfusion pressure and heart rate remained constant, venous oxygen content fell, indicating an imbalance between myocardial oxygen supply and demand. In addition, the arteriovenous difference of white blood cells was increased significantly after anaphylatoxin infusion, indicating intravascular trapping in the myocardium. Granulocytes accounted entirely for the differences in leukocyte counts because no significant changes in platelet, lymphocyte, or hematocrit levels were observed. Injection of vehicle alone did not alter any of the monitored variables.(ABSTRACT TRUNCATED AT 250 WORDS)
Martin
S E
SE
Department of Medicine, University of California, San Diego, La Jolla.
Chenoweth
D E
DE
Engler
R L
RL
Roth
D M
DM
Longhurst
J C
JC
D000818:Animals; D001696:Biomechanical Phenomena; D003182:Complement C5 / Q000494:pharmacology*; D015936:Complement C5a; D003326:Coronary Circulation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006098:Granulocytes / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006439:Hemodynamics / Q000187:drug effects; D007267:Injections; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine; D014661:Vasoconstriction
D003182:Complement C5; D011189:Potassium Chloride; D015936:Complement C5a