Effects of PGE₁ in Experimental Vasoconstrictive Pulmonary Hypertension

Abstract

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)/Cl). Following PGF_2α infusion (5–10 µg/kg/min) significant pulmonary hypertension was observed (2- to 3-fold increase in PAP). PGF_2α infusion also resulted in a significant rise in heart rate and systemic vascular resistance (SVR) while CI was reduced. PGF_2α 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.

Role of potassium channels and nitric oxide in the effects of iloprost and prostaglandin E1 on hypoxic vasoconstriction in the isolated perfused lung of the rat

“…The decrease of the hypoxic vasoconstriction by iloprost and PGE 1 observed in our study confirms the pharmacological properties of these prostanoids in the pulmonary circulation (Kadowitz et al , 1975; Lock et al , 1980; Dagher et al , 1993). In our experimental conditions, the relaxant potency of iloprost was 10 fold greater than that described in the human isolated pulmonary artery (Haye‐Legrand et al , 1987) and the relaxant potency of PGE 1 was 100 fold greater than that obtained in the rat isolated pulmonary arterial ring precontracted with phenylephrine (Fullerton et al , 1994).…”

“…Pulmonary hypertension may be secondary to hypoxic vasoconstriction enhancing complex changes in the pulmonary vascular bed. Since endogenous prostaglandins play a role in the regulation of pulmonary blood flow, the use of exogenous prostaglandins that are known to dilate pulmonary vessels such as prostaglandin E 1 (PGE 1 ) and stable analogues of prostacyclin (PGI 2 ) have been advocated for the treatment of pulmonary hypertension (Dagher et al , 1993; Welte et al , 1993). PGI 2 and PGE 1 are usually regarded as agents mediating their effects through prostacyclin (IP)‐and (or) EP‐re‐ceptors coupled to adenylate cyclase, inducing smooth muscle relaxation by increasing the intracellular concentration of adenosine 3′,5′‐cyclic monophosphate (cyclic AMP) (Coleman et al , 1994).…”

Benefit of prostaglandin infusion in severe heart failure

“…An AMP-dependent effect has been demonstrated on isolated atrial preparations by Scandinavian researchers [23], while in ischemic patients, a positive effect on plasma cytokine levels as interleukin-8, TNF-alpha [24] was described. The PGE1 have less hypotensive effects on the systemic system than the prostacyclin (PGI2) [25][26][27][28][29] and this could explain the negative effect on survival found using the latter in the FIRST study.…”

Dose-Effect Relationships of Prostaglandin E1 in Severe Endstage Chronic Heart Failure.

“…However, a significant increase in cardiac output by The potent vasodilatory action of prostaglandin E1 has been frequently used with success in conditions which are associated with pulmonary hypertension and to test pulmonary vasoreactivity in heart transplant candidates. 3,,18-20) However, a systemic effect of prostaglandin E1 is usually present in experimental and clinical studies, 21,22) and there is little evidence that the drug produces selective pulmonary vasodilatation in spite of a high lung metabolism.23,24) Obviously, PGE1 or one of its metabolites passes through the lungs in concentrations high enough to interact with the systemic vasculature, particularly if extraction efficiency of the lung is impaired. 17,25) In an experimental study in intact dogs PGE1 reduced pulmonary artery pressure in a dose dependent manner without modifying the ratio of the pulmonary over the systemic vascular resistance.…”