ACUTE HEMODYNAMIC AND NEUROHUMORAL PROFILE OF DILEVALOL IN HYPERTENSIVE PATIENTS WITH ISCHEMIC-HEART-DISEASE

Acute systemic and, possibly. coronary vasoconstriction may limit the usefulness of i.v. beta-blockade for the management of hypertension in ischemic patients. The acute hemodynamic and neurohumoral profile of i.v. dilevalol (50 mg/5 min), a nonselective beta-antagonist and selective partial beta2-agonist, was evaluated for 1 h in nine patients with stable angina, significant (>50%) coronary artery disease, and mild hypertension. Immediately after administration, arterial pressures fell significantly by 13% and remained lowered for the entire study period. Concomitantly, heart rate slowed from 76 +/- 2 (mean +/- SEM; control) to 67 +/- 2 beats/min (60 min postadministration, p < 0.05), and cardiac index and stroke work decreased significantly by 15 and 21%, respectively. Isovolumetric contractility indices (measured at fixed heart rates) fell progressively by 9-12%, whereas relaxation (Tau1 and Tau2) slowed by 10% (all p < 0.05 vs. control). Consequently, left ventricular end-diastolic and right atrial pressures increased significantly from 17 +/- 3 and 9 +/- 1.2 mm Hg at baseline to 21 +/- 2.5 and 12 +/- 2.1 mm Hg, respectively. Dilevalol did not affect systemic or coronary resistance. However, coronary flow decreased by 24% (p < 0.05 vs. control), accompanied by significant reductions in myocardial oxygen demand and consumption of 23 and 14%, respectively. Levels of circulating norepinephrine and dopamine increased by 35 and 71%, whereas those of renin and angiotensin II decreased by 26 and 33%, respectively (all p < 0.05 vs. control). Adverse side effects did not occur. None of the patients became ischemic. Thus, at the dose level used, dilevalol has predominant beta-blocking effects. However, both the absence of systemic and coronary vasoconstrictor effects, despite the fall in arterial pressures, and the beneficial myocardial energetic effects of dilevalol discriminate it from commonly used selective or nonselective beta-antagonists, and may provide the background for further evaluation of its usefulness in the acute management of hypertension in patients with concomitant ischemic heart disease.