Platelet-activating-factor-induced changes in cardiovascular function and oxyradical status of myocardium in presence of the PAF antagonist CV-6209.
The effects of platelet-activating factor (PAF) on cardiac function and contractility and its mechanism of action are not fully understood. The authors investigated the effects of PAF in the absence or presence of a potent PAF antagonist CV-6209 on the cardiac function and contractility; lipid peroxidation product malondialdehyde (MDA), an indirect measure of oxygen free radicals; serum creatine kinase (CK); blood lactate; and pH in anesthetized dogs. CV-6209 (1 mg/kg, IV) did not produce significant changes in the various parameters studied. PAF (1 microgram/kg, IV) produced decreases in the cardiac function (cardiac index, left ventricular work index) and indices of cardiac contractility [(+) and (-) dp/dt, dp/dt at CPIP, (dp/dt)/IP, dp/dt at CPIP/IP, Vmax] and increases in the systemic and pulmonary vascular resistance. It also produced increases in cardiac MDA, serum CK, blood lactate, and H+ and decreases in blood pH and HCO3-. CV-6209 completely prevented the PAF-induced changes in the hemodynamic and biochemical parameters. These results suggest that PAF-induced cardiac depression may be due to PAF-induced release of oxyradicals from neutrophils and that PAF antagonist may be useful in counteracting the deleterious effects of PAF on the cardiovascular system.
Gupta
J B
JB
Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
Prasad
M
M
Kalra
J
J
Prasad
K
K
D000818:Animals; D003402:Creatine Kinase / Q000097:blood; D004285:Dogs; D005260:Female; D005609:Free Radicals; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D007773:Lactates / Q000097:blood; D015227:Lipid Peroxidation; D008297:Male; D008315:Malondialdehyde / Q000032:analysis; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000378:metabolism*; D010100:Oxygen / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors* / Q000502:physiology*; D011726:Pyridinium Compounds / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000502:physiology
D005609:Free Radicals; D007773:Lactates; D010972:Platelet Activating Factor; D011726:Pyridinium Compounds; C053321:CV 6209; D008315:Malondialdehyde; D003402:Creatine Kinase; D010100:Oxygen