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Treatment with phosphodiesterase inhibitors type III and V: milrinone and sildenafil is an effective combination during thromboxane-induced acute pulmonary hypertension.

Abstract：

OBJECTIVES:To evaluate the effects of phosphodiesterase type III and V (PDEIII and PDEV) inhibition on pulmonary and systemic haemodynamics in a porcine model of acute pulmonary hypertension. METHODS:Twenty-four adult swine were anaesthetized with 1 MAC isoflurane and mechanically ventilated with an FI(O(2)) of 100%. Micromanometer-tipped catheters were placed in the ascending aorta, pulmonary artery and right ventricle. Pulmonary flow was measured with a perivascular probe using transit time ultrasound. Pulmonary hypertension was induced with a continuous infusion of the thromboxane analogue, U46619. The animals were then randomized to four groups: Group 1 (n=6) received 50 mg of sildenafil (PDEV inhibitor) diluted in water via an orogastric tube; Group 2 (n=6) received 50 microg kg(-1) of i.v. milrinone (PDEIII inhibitor); Group 3 (n=6) received sildenafil followed by milrinone; and Group 4 (n=6) received placebo via an orogastric tube. RESULTS:Pulmonary hypertension was achieved in all animals. Calculated pulmonary vascular resistance decreased by an average of 36% after sildenafil (P<0.05), 41% after milrinone (P<0.05), and 61% with both drugs combined (P<0.05). Systemic vascular resistance decreased by 37% (P<0.05) with milrinone alone, and 36% (P<0.05) with milrinone and sildenafil combined but it was preserved in the sildenafil group. Cardiac output and right ventricular dP/dT were significantly improved after milrinone or both drugs combined, but not with sildenafil. CONCLUSION:Milrinone and sildenafil are effective pulmonary vasodilators, with independent action and additive effect. Both drugs combined achieved a better haemodynamic profile, with greater pulmonary vasodilatation and increased contractility but without additional systemic vasodilatation. The systemic haemodynamic profile (systemic vasodilation, cardiac output, right ventricular dP/dT) is improved with milrinone but not with sildenafil.

journal_name

Br J Anaesth

journal_title

British journal of anaesthesia

authors

Lobato EB,Beaver T,Muehlschlegel J,Kirby DS,Klodell C,Sidi A

doi

10.1093/bja/ael009

subject

Has Abstract

pub_date

2006-03-01 00:00:00

pages

317-22

issue

eissn

0007-0912

issn

1471-6771

pii

S0007-0912(17)35202-9

journal_volume

pub_type

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Treatment with phosphodiesterase inhibitors type III and V: milrinone and sildenafil is an effective combination during thromboxane-induced acute pulmonary hypertension.