Combination Therapy with Inhaled Nitric Oxide and Intravenous Dobutamine During Pulmonary Hypertension in the Rabbit

Abstract

Combination therapy with an intravenous inovasodilator and inhaled nitric oxide (NO) may be appropriate in patients with pulmonary hypertension and associated right ventricular failure. We examined whether dobutamine and inhaled NO would have additive pulmonary vasodilator effects in experimental pulmonary hypertension. Pulmonary hypertension was produced in anesthetized, mechanically ventilated rabbits by infusion of U46619, a thromboxane analogue. Dobutamine was administered in increasing doses (2.5-20 microg/kg/min) with and without inhaled NO (40 ppm). Dobutamine produced dose-dependent decreases in pulmonary vascular resistance (PVR) and mean arterial pressure (MAP) and increases in cardiac output (CO). Inhaled NO alone decreased pulmonary artery pressure (PAP) and PVR with no effect on MAP or CO. The effects of dobutamine and inhaled NO were additive, so that at each dose of dobutamine, inhaled NO decreased PAP and PVR with no effect on systemic hemodynamics. This study suggests that the combination of dobutamine and inhaled NO should produce additive pulmonary vasodilation in patients with pulmonary hypertension and associated right ventricular dysfunction.

Measuring right ventricular function in the normal and hypertensive mouse hearts using admittance-derived pressure-volume loops

“…It has previously been reported that the effects of dobutamine are highly dose-and flow dependent (5,42). As a consequence, the effects of this dose of dobutamine are likely different in CTL and HPH conditions.…”

“…The dosage regimen of 5 g·kg Ϫ1 ·min Ϫ1 was chosen because it is within the dosage range (2.5-10 g·kg Ϫ1 ·min Ϫ1 ) most commonly used in experimental (5,52) and clinical pulmonary hypertension (34). In CTL mice, dobutamine caused a significant decoupling through an increase in contractility and larger increase in effective arterial elastance.…”

Pulmonary vascular effects of dobutamine in experimental pulmonary hypertension

“…Pulmonary Vascular Pressure/Flow Relationships. Dobutamine has been reported to decrease PVR in experimental (1,5) and clinical (4, 6) pulmonary hypertension. Accordingly, dobutamine is believed to act as a pulmonary vasodilator and has been used as such, for example, to evaluate the reversibility of pulmonary hypertension in patients with advanced left heart failure considered for cardiac transplantation (6).…”

“…All these disease states are complicated by variable degrees of pulmonary hypertension (1)(2)(3)(4). At doses usually given in clinical practice (up to 20 g·kg Ϫ1 ·min Ϫ1 ), dobutamine has been reported to decrease pulmonary vascular resistance (PVR), in experimental (1,5) and clinical (4, 6) pulmonary hypertension. However, whether dobutamine decreases PVR independently of associated changes in flow remains uncertain.…”

Management strategies for patients with pulmonary hypertension in the intensive care unit*

“…Dobutamine is an inotrope that acts primarily through ␤ 1 -adrenergic receptors to augment myocardial contractility and reduce left ventricular afterload (54). In animal models of acute pulmonary hypertension, dobutamine in doses up to 5 g/kg per min significantly decreased PVR while slightly increasing cardiac output (55,56). However, at doses of 5-10 g/kg per min, dobutamine caused significant tachycardia without improving pulmonary vascular resistance.…”