Constriction of canine coronary arteries by platelet activating factor after brief ischemia.
Platelet activating factor (PAF) has been suggested as a mediator of coronary spasm and acute myocardial ischemia. However, PAF can have either vasodilator or vasoconstrictor activities according to various reports. Because of the importance of endothelium in regulating vascular tone, we hypothesized that changes in endothelial function could modulate some of the observed differences in the activities of PAF. To test this hypothesis, PAF was infused directly into the left anterior descending coronary artery (LAD) of dogs at a rate of 0.3 microgram/min before and after 20 min of LAD ligation followed by reperfusion. Coronary blood flow (CBF) was measured continuously via a Doppler flow probe. Likewise, responses to the endothelium dependent vasodilator, acetylcholine (ACh) were measured before and after the LAD ligation. Before ligation, PAF produced a vasodilatory response in the LAD, resulting in 28.4 +/- 11.0% increase in CBF and a 21.5 +/- 5.8% decrease in coronary vascular resistance (CVR). However, after ligation and subsequent reperfusion, 0.3 microgram/min PAF produced vasoconstriction, resulting in a 10.2 +/- 8.7% decrease in CBF (p < 0.01 compared to pre-infusion change in (CBF), and a 27.8 +/- 23.2% increase in CVR (p = 0.05) compared to pre-infusion change in CVR). The vasodilator response to ACh was markedly blunted by ischemia. These results suggest that the coronary vascular response to PAF may depend upon the functional integrity of the endothelium, with endothelial damage resulting in constrictor responses to PAF.(ABSTRACT TRUNCATED AT 250 WORDS)
Kim
Y D
YD
Department of Anesthesia, Georgetown University Medical Center, Washington, D.C. 20007.
Danchak
R M
RM
Heim
K F
KF
Lees
D E
DE
Myers
A K
AK
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D004285:Dogs; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology / Q000503:physiopathology; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010972:Platelet Activating Factor / Q000494:pharmacology*; D012039:Regional Blood Flow / Q000187:drug effects; D015424:Reperfusion; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects
D010972:Platelet Activating Factor; D000109:Acetylcholine