Effects of adenosine in combination with calcium channel blockers in patients with primary pulmonary hypertension

Objectives. The purpose of this study was to evaluate the effects of vasodilator combination therapy in patients with primary pulmonary hypertension. Background. Calcium channel blockers and adenosine have each been shown to be effective in reducing pulmonary artery pressure and pulmonary vascular resistance in patients with primary pulmonary hypertension. However, the effects of combining these vasodilators have not been studied. Methods. To test the combination, 12 patients were placed on oral nifedipine and 3 on diltiazem therapy, using a dose titrated to maximal effect (mean nifedipine dose 103 ± 24 mg, mean diltiazem dose 300 ± 49 mg). Patients were then given maintenance doses of the calcium channel blocker at half the cumulative loading dose at 6-h intervals. One hour after the maintenance dose of calcium blocker, all patients received an infusion of adenosine, starting with 50 μg/kg per min and increasing by 50 μg/kg per min at 2-min intervals to a miximally tolerated dose (180 ± 63 μg/kg per min). Results. Ten patients responded to calcium channel blockers (defined as a ≥20% decrease in pulmonary vascular resistance), with a 16% decrease in mean pulmonary artery pressure (p = 0.057), a 39% decrease in pulmonary vascular resistance (p = 0.002) and a 24% increase in stroke volume (p = 0.007). Five patients were nonresponders, with no significant changes in pulmonary artery pressure, pulmonary vascular resistance, cardiac index or stroke volume. In the calcium channel blocker responders, the combination of adenosine and calcium blocker reduced pulmonary vascular resistance by 49%, increased stroke volume by 33% and decreased mean pulmonary artery pressure by 14% compared with drug-free baseline values. In nonresponders, combination therapy resulted in nonsignificant changes in pulmonary artery pressure and pulmonary vascular resistance. Conclusions. Adenosine has the ability to further decrease pulmonary artery pressure and pulmonary vascular resistance in patients with primary pulmonary hypertension who respond to calcium channel blockers. Those who fail to respond to these agents have little added effect from adenosine.