PGI₂ Aerosol versus Nitric Oxide for Selective Pulmonary Vasodilation in Hypoxic Pulmonary Vasoconstriction

Abstract

Intravenous prostacyclin (PGI2) is a potent pulmonary vasodilator in pulmonary hypertension. However, dose-dependent systemic vasodilation, an increase in intrapulmonary shunt and hypoxemia limit its clinical application. Recently, inhaled nitric oxide (NO) has been reported to elicit selective pulmonary vasodilation, but its clinical use is restricted by its potential toxicity; furthermore, the feasibility of NO application in clinical practice seems difficult. Therefore, we investigated the effects of PGI2 aerosol on pulmonary and systemic circulation and compared the hemodynamic effects to those of inhaled NO. In 6 dogs, ventilation with a hypoxic gas mixture (F102 0.09–0.11) increased pulmonary vascular resistance (PVR) by 196% (HPV). Aerosolization of a PGI₂ solution at a concentration of 430 ng/ml reduced hypoxia-induced increase of pulmonary artery pressure by 48% and PVR by 52% within 6-10 min without systemic vasodilation. The administered dose of PGI2 was 0.87 ± 0.26 ng/kg/min. In 2 dogs, doubling the PGI2 concentration (860 ng/ml) did not enhance the vasodilatory effect. After termination of PGI₂ inhalation, HPV was restored within 10–15 min. Inhaled NO (50 ppm) decreased the HPV-induced increase in PAP by 76% and in PVR by 73% within 5-10 min. Clinically relevant systemic vasodilation was not observed. It is concluded that inhalation of aerosolized PGI₂ leads to selective pulmonary vasodilation in hypoxia-induced pulmonary hypertension. Aerosolized PGI₂ at a concentration of 430 ng/ml was less potent than NO (50 ppm). However, due to the lack of known toxicity and its uncomplicated mode of application, inhaled PGI₂ may be one alternative to inhaled NO in the treatment of acute pulmonary hypertension.

Inhaled Nitric Oxide versus Inhaled Prostacyclin and Intravenous versus Inhaled Prostacyclin in Acute Respiratory Failure with Pulmonary Hypertension in Piglets

“…PGI, indicating the local vasodilating effect of inhaled PGI,. In our study the inhaled PGI, dose of 30-60 nglkglmin was significantly higher than the dose applied by Welte et al (27) in dogs and slightly higher than the dose applied to humans with ARDS (26). The real aerosol deposit in the lungs is rather small (<5%) (31,32) and cannot be easily determined.…”

“…In addition, they speculated that an increase in the dose of aerosolized PGI, might cause "spillover" of the prostanoid into the systemic circulation. In 1993 Welte et al (27) reported their investigation on the effects of PGI, aerosol on pulmonary and systemic circulation compared with NO inhalation in 6 dogs with hypoxic pulmo- …”

“…In addition, as PGI, vasodilates pulmonary vessels in ventilated and nonventilated areas of the lung, increased intrapulmonary shunt with increased venous admixture might occur. Recently, aerosolized PGI, has been reported both in clinical and experimental settings to be a selective pulmonary vasodilator without side effects on the systemic vasculature (26,27).…”

Inhaled Nitric Oxide Versus Aerosolized Iloprost in Secondary Pulmonary Hypertension in Children With Congenital Heart Disease

“…However, this is unlikely on the basis of other reports. 10,29,30 In children with PHT and CHD, both iNO and aerosolized iloprost are equally effective in selectively lowering pulmonary vascular resistance through a selective increase in cGMP or cAMP, respectively. However, the combination of both vasodilators failed to prove more potent than either substance alone.…”

Toxicity of prolonged high dose inhaled PGE1 in ventilated neonatal pigs

“…Intravenous PGE 1 (ivPGE 1 ) and PGI 2 , potent vasodilators used empirically in the treatment of NHRF, are associated with systemic hypotension and worsening of oxygenation due to increased venous admixture (2)(3)(4)(5)(6). This has led investigators to explore the delivery of PGE 1 and PGI 2 directly to the lungs as an inhalation, thus minimizing systemic effects and achieving selective pulmonary vasodilation (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21). Compared to PGI 2 , PGE 1 has a shorter half-life, lower pH (6.3 versus 10.5), bronchodilator action, anti-proliferative and anti-inflammatory effects on the alveolar, interstitial and vascular spaces of the lung (8,(22)(23)(24)(25).…”