Adverse hemodynamic and clinical effects of calcium channel blockade in pulmonary hypertension secondary to obliterative pulmonary vascular disease.
The hemodynamic and clinical responses to calcium channel blockade with verapamil and nifedipine were compared with those of hydralazine in 12 patients with pulmonary hypertension secondary to obliterative pulmonary vascular disease. All three drugs produced a marked and similar decrease in pulmonary vascular resistance; however, this was accompanied by a significant increase in cardiac index with hydralazine (+0.71 liter/min per m2, p less than 0.01), no change in cardiac index with nifedipine and a significant decrease in cardiac index with verapamil (-0.25 liter/min per m2, p less than 0.05). Mean pulmonary artery pressure decreased markedly with both calcium channel blocking drugs (-16.0 mm Hg with verapamil and -14.5 mm Hg with nifedipine, both p less than 0.01), but this was associated with a concomitant increase in mean right atrial pressure (+6.2 mm Hg with verapamil and +4.4 mm Hg with nifedipine, both p less than 0.01); neither variable changed after hydralazine. Hence, right ventricular performance (as reflected by right ventricular stroke work index) deteriorated during treatment with both calcium channel blocking drugs, despite the decrease in resistance to right ventricular ejection; in contrast, right ventricular stroke work index increased after hydralazine. The unfavorable hemodynamic effects of calcium channel blockade were accompanied by severe adverse clinical events, including profound hypotension and cardiogenic shock during acute drug administration and the exacerbation of right heart failure during long-term treatment. These deleterious responses to verapamil and nifedipine are likely the result of a direct depressant effect exerted by these drugs on right ventricular function independent of their pulmonary vasodilatory actions.
D000328:Adult; D002121:Calcium Channel Blockers / Q000009:adverse effects / Q000627:therapeutic use*; D002302:Cardiac Output / Q000187:drug effects; D005080:Exercise Test; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006830:Hydralazine / Q000009:adverse effects / Q000627:therapeutic use; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009543:Nifedipine / Q000009:adverse effects / Q000627:therapeutic use; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation / Q000187:drug effects; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014700:Verapamil / Q000009:adverse effects / Q000627:therapeutic use
D002121:Calcium Channel Blockers; D006830:Hydralazine; D014700:Verapamil; D009543:Nifedipine