Randomized Comparative Study of Intravenous ATP-MgCl₂ and Inhaled Nitric Oxide as Selective Pulmonary Vasodilators in Hypoxia Induced Pulmonary Hypertension

Abstract 1320 Poster Session I, Saturday, 5/1 (poster 108)

Background: Use of inhaled Nitric Oxide (NO) as a selective pulmonary vasodilator for treatment of pulmonary hypertension has increased. Its potential toxic effects and complex delivery system has stimulated the search for a safer agent. Continuous infusion of ATP-MgCl₂ effectively dilates pulmonary vasculature without systemic effects. We report the first comparison trial between intravenous ATP-MgCl₂ and inhaled Nitric oxide in a open chest piglet model of hypoxic pulmonary hypertension.

Methods and Results: Thirteen two-week old piglets were anesthetized, intubated, ventilated and surgically cannulated for direct measurements of systemic (MAP) and pulmonary (PAP) arterial pressures, along with right and left atrial pressures. Ultrasonic flow probes were placed around aorta and main pulmonary artery for measuring systemic (Qs) and pulmonary (Qp) flows. Pulmonary hypertension was induced by changing the inflow gas to 12% oxygen and balanced nitrogen. NO at 10ppm and ATP-MgCl₂ at 0.1mg/kg/min and 0.2mg/kg/min were given to all subjects in random order with return to normoxia between treatments. Hypoxia induced a 67% increase in PAP from baseline. NO decreased the PAP by 30% (p<0.001) while ATP-MgCl₂ decreased PAP by 19% (p<0.05) and 32% (p<0.002) at 0.1mg/kg/min and 0.2 mg/kg/min respectively. Also a significant decrease in PVR with both, NO by 41% (p<0.05) and ATP-MgCl₂ by 37% (p<0.05) was found. There was a trend in increase of pulmonary flows (Qp) but it did not reach statistical significance. MAP, Qs and SVR remained unchanged during treatment with both drugs.

Conclusion: Our data indicate that ATP-MgCl₂ is a selective pulmonary vasodilator which can ameliorate vasoconstriction associated with hypoxic pulmonary hypertension. Intravenous ATP-MgCl₂ was found to be equally effective as inhaled NO. Human studies with ATP-MgCl₂ are warranted to define its more extensive clinical use.

This study was funded by the Grant-In-Aid Program for Faculty of Virginia Commonwealth University.