| dc.description.abstract | Pulmonary hypertension increases perioperative morbidity and mortality after cardiac surgery or heart transplantation. Intravenous vasodilator therapy lacks selectivity for the pulmonary vasculature and may induce arterial hypotension. Inhaled nitric oxide (NO) selectively dilates pulmonary vessels but, due to toxicity, it requires specialized systems for its administration. Prostacyclin (PGI2) is a non-toxic biomediator with potent vasodilatory and platelet stabilizing properties and milrinone is an inodilator drug. Inhalation of these agents may induce selective pulmonary vasodilation without systemic effects. The aims of the study were to investigate and compare the central hemodynamic effects of inhaled vasodilatory agents (PGI2, milrinone, NO and PGI2+milrinone) and the potential platelet stabilizing effect of inhaled PGI2.Methods: A pulmonary arterial thermodilution catheter was used for the evaluation of central hemodynamics. Thirty cardiac surgical patients with postoperative pulmonary hypertension inhaled incremental concentrations of aerosolized PGI2 (2.5, 5 and 10 µg x ml-1, n=9) or aerosolized milrinone (0.25, 0.5 and 1 mg x ml-1, n=9) and PGI2 (10µg x ml-1) + milrinone (1 mg x ml-1) (n=12). Spontaneously breathing heart transplant candidates with pulmonary hypertension (n=9) were evaluated during inhaltion of NO (40 ppm) or inhalation of PGI2 (10µg x ml-1). Platelet function was evaluated during a six hour inhalation of 0.9% sodium chloride (n=8) or PGI2 (5 µg x ml-1, n=10 or 10 µg x ml-1, n=10) in patients undergoing uncomplicated cardiac surgery. Platelet aggregation, in vivo bleeding time, thrombelastography-variables (TEG) and chest-tube drainage were measured and plasma was analyzed for the stable metabolite of PGI2, 6-keto-PGF1a.Results: Inhalation of the different vasodilatory agents caused no changes in mean arterial blood pressure or systemic vascular resistance. Inhalation of PGI2 or milrinone, decreased pulmonary vascular resistance (PVR) with maximal effects at the highest concentrations (-29% vs 20%). Inhaled PGI2+inhaled milrinone decreased PVR by an additional 9%, and increased cardiac output (5%) when compared to PGI2 alone. Inhalation of NO or PGI2 reduced PVR (-43% vs 49%). The platelet aggregation response was impaired after six hours of PGI2-inhalation, regardless of inhaled dose. The TEG reaction time was prolonged after 6 hours of inhalation in the PGI2-group receiving 10 µg x ml-1. There were no differences between groups with respect to bleeding time and chest tube drainage or any of the other measured variables examined. Conclusions: Inhaled aerosolized PGI2 or inhaled aerosolized milrinone induces selective pulmonary vasodilation without systemic effects in postcardiac surgical patients with pulmonary hypertension. The pulmonary vasodilatory effect of inhaled PGI2 is comparable to that of inhaled NO in heart transplant candidates with elevated PVR. Furthermore, inhaled milrinone may have an additive pulmonary vasodilatory effect when combined with inhaled PGI2. Finally, a six hour inhalation of PGI2 after cardiac surgery is associated with impaired platelet aggregation in vitro without any in vivo signs of platelet dysfunction. In summary, inhaled vasodilatory agents or combination of agents, may be clinically important therapeutic options for treatment of patients with pulmonary hypertension and severe right ventricular dysfunction after cardiac surgery or heart transplantation. | en |
