Captopril in primary pulmonary hypertension.

Seven women with primary pulmonary hypertension underwent hemodynamic evaluation, at rest and during exercise, before and after the oral administration of captopril. Dose-response curves were generated for the 25-, 50- and 100-mg doses. Captopril significantly reduced systemic blood pressure and systemic vascular resistance; these effects persisted at submaximal levels of exercise. Captopril did not alter pulmonary artery pressure or resistance, cardiac output or stroke volume at rest or during exercise. Exercise tolerance did not improve. Four of the patients also received captopril chronically for 12 weeks at doses of 75 and 100 mg every 8 hours. Resting and exercise hemodynamic evaluation was repeated at the end of the 12-week period. Except for a persistent reduction in mean systemic blood pressure at rest, chronic captopril administration did not elicit hemodynamic changes. Measured exercise duration did not change during continuous captopril treatment, although one patient reported mild subjective improvement in activity tolerance. In primary pulmonary hypertension, captopril exerts its major effect on systemic vasculature, with little or no effect on the pulmonary circuit. While an occasional patient may experience some clinical improvement with captopril therapy, the majority of adult patients with severe primary pulmonary hypertension will not benefit from its chronic administration.

Vasodilators and prostaglandin inhibitors in primary pulmonary hypertension.

Ten women with primary pulmonary hypertension had resting hemodynamic measurements taken before and after the nonparenteral administration of various vasodilators and prostaglandin inhibitors. Only sublingual isoproterenol, alone or combined with sublingual isosorbide dinitrate, effected a substantial (greater than 20%) drop in pulmonary vascular resistance; this decrease was accompanied by little change in pulmonary artery pressure. Isosorbide dinitrate was the only drug that elicited any reduction in pulmonary artery pressure; pulmonary vascular resistance decreased modestly. The oral administration of diazoxide, hydralazine, phentolamine, and tolazoline elicited little change in pulmonary artery pressure or resistance. Except for tolazoline, all these agents significantly decreased systemic blood pressure and resistance. Prostaglandin inhibition by indomethacin (acute and chronic dosing) increased pulmonary and systemic vascular resistances and reduced cardiac output. Aspirin combined with dipyridamole elicited no changes. The vasodilators and prostaglandin inhibitors studied evoked little improvement in resting pulmonary hemodynamic abnormalities in primary pulmonary hypertension.

The effect of vasodilator therapy on systolic and diastolic time intervals in congestive heart failure.

To determine the effects of vasodilator drugs on systolic and diastolic time intervals in patients with congestive heart failure, these noninvasive measurements were made in 50 patients with moderately severe disease before and after vasodilator therapy. These data were compared with direct hemodynamic measurements obtained simultaneously from a flow-directed triple-lumen pulmonary artery catheter placed in each patient. Oral vasodilators included isosorbide dinitrate 20 mg (n-8), hydralazine 75 mg (n-8), and 100 mg (n-8), and first-dose prazosin 2 mg (n-8) and 5 mg (n-8). Ten additional patients received intravenous dose-response infusions of isosorbide dinitrate, nitroglycerin, and nitroprusside. Increases in cardiac output and stroke volume effected a decrease (improvement) in the systolic time interval parameter of ventricular performance, PEP/LVET. The correlation coefficient for vasodilator-induced changes in cardiac output vs changes in PEP/LVET was -0.82 (P less than 0.05) and for changes in stroke volume and PEP/LVET was -0.75 (P less than 0.05). In general, the diastolic time period was not significantly affected by these drugs. The systolic time intervals are a simple and useful method for evaluation of vasodilator therapy in patients with congestive heart failure.

Effects of hydralazine on coronary blood flow and myocardial energetics in congestive heart failure.

The acute effects of oral hydralazine, 1 mg/kg, on coronary vascular resistance, coronary blood flow (estimated using the coronary sinus thermodilution technique), and myocardial oxygen consumption were evaluated in 10 patients with chronic (New York Heart Association class III and IV) nonischemic congestive heart failure. Central hemodynamic responses demonstrated a modest decrease in mean arterial pressure, pulmonary capillary wedge pressure and systemic vascular resistance (12%, 15% and 29%, respectively), while the cardiac index increased from 2.3 +/- 0.1 to 3.1 +/- 0.3 and left ventricular stroke work index from 24 +/- 3.7 to 28 +/- 3.4 (p less than 0.01). Heart rate and diastolic filling time did not change. Coronary blood flow increased approximately 50%, from 144 +/- 17 to 218 +/- 30 ml/min, and coronary vascular resistance decreased from 0.55 +/- 0.09 to 0.36 +/- 0.08 mm Hg/ml/min (both p less than 0.01). Oral hydralazine increased myocardial oxygen consumption by 33%, from 15 +/- 1.6 to 20 +/- 2.7 ml/min. Despite this moderate augmentation in myocardial oxygen consumption, the arterial-coronary sinus oxygen difference decreased from 104 +/- 6.2 to 94 +/- 7.5 and the myocardial oxygen extraction ratio decreased from 71% to 64% (both p less than 0.05). The ratio of coronary vascular resistance to systemic vascular resistance decreased with hydralazine therapy, while coronary blood flow increased from 3.5% to 4.3 % of total cardiac output. In this group of patients with nonischemic cardiomyopathy, hydralazine had a favorable effect on the coronary circulation and improved the critical myocardial oxygen supply-demand ratio.