Adenosine triphosphate: A potential therapy for hypoxic pulmonary hypertension

In this study we investigated whether a low-dose infusion of ATP-MgCl₂ could ameliorate the pulmonary hypertension resulting from hypoxic pulmonary vasoconstriction. Three-week-old piglets were anesthetized, intubated, ventilated with room air, and cannulated for the measurement of pulmonary and systemic arterial pressure and pulmonary artery flow (cardiac output). The ventilator inflow was then changed to a mixture containing 10% oxygen, 4% CO₂, and balance nitrogen. Serial infusions of ATP-MgCl₂ at 0.1, 0.5 and 1.0 mg/kg/min were compared to preinfusion hypoxia baselines. Hypoxia alone produced a significant elevation in pulmonary artery pressure. Although all dose rates of ATP-MgCl₂ produced a significant decrease (30%) in mean pulmonary artery pressure, we observed a maximum decrease in MPAP at the lowest rate of ATP infusion. Pulmonary artery flow rose slightly during ATP infusion; therefore, it was the change in pulmonary vascular resistance that accounted for the decrease in pulmonary artery pressure. In contrast, the systemic pressure was significantly decreased only during the 1.0 mg/kg/min infusion. The predominant pulmonary effects are a result of the virtual clearance of ATP-MgCl₂ in a single pass through the circulation. Adenosine in the presence or absence of MgCl₂ produced only a 10% reduction in mean pulmonary artery pressure, and MgCl₂ had no effect when infused alone. From these results, we conclude that a low-dose infusion of ATP-MgCl₂ could ameliorate the vasoconstriction associated with hypoxic pulmonary hypertension without significant deleterious systemic side effects.