Effects of PGE1 in experimental vasoconstrictive pulmonary hypertension.
The pulmonary vascular and systemic effects of PGE1 were studied in a canine model of pulmonary hypertension. Systemic arterial, central venous and pulmonary arterial pressures were monitored and an electromagnetic flow probe was placed around the ascending aorta for continuous cardiac index (CI) measurements. Through a laparotomy, an arteriovenous fistula was created between the abdominal aorta and inferior vena cava. Gradual opening of this fistula significantly affected CI and these values were used to generate pressure-flow curves (pulmonary arterial pressure (PAP)/CI). Following PGF2 alpha infusion (5-10 micrograms/kg/min) significant pulmonary hypertension was observed (2- to 3-fold increase in PAP). PGF2 alpha infusion also resulted in a significant rise in heart rate and systemic vascular resistance (SVR) while CI was reduced. PGF2 alpha significantly increased both the line slope (vascular resistance) and intercept (outflow pressure) of the pressure-flow curves. Intravenous PGE1 infusion in doses ranging from 40 to 320 ng/ml/min elicited a dose-dependent reduction of both pulmonary and systemic vascular resistances, the former being slightly more affected. With PGE1 infusions only the intercept of the pressure-flow curve was affected suggesting that specific components of the pulmonary vascular bed modulating the outflow pressure were involved. High doses of PGE1 significantly decreased arterial PO2, indicating that this prostaglandin derivative deteriorates pulmonary gas exchanges.
Dagher
E
E
Département de Pharmacologie, Faculté de Médecine, Université de Montréal, Qué., Canada.
Dumont
L
L
Chartrand
C
C
Blaise
G
G
D000527:Alprostadil / Q000494:pharmacology*; D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D006439:Hemodynamics / Q000187:drug effects*; D006976:Hypertension, Pulmonary / Q000503:physiopathology*; D011659:Pulmonary Gas Exchange / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction
D015237:Dinoprost; D000527:Alprostadil