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 selec tive partial beta2-agonist, was evaluated for 1 h in nine patients wit h stable angina, significant (>50%) coronary artery disease, and mild hypertension. Immediately after administration, arterial pressures fel l significantly by 13% and remained lowered for the entire study perio d. Concomitantly, heart rate slowed from 76 +/- 2 (mean +/- SEM; contr ol) to 67 +/- 2 beats/min (60 min postadministration, p < 0.05), and c ardiac index and stroke work decreased significantly by 15 and 21%, re spectively. Isovolumetric contractility indices (measured at fixed hea rt rates) fell progressively by 9-12%, whereas relaxation (Tau1 and Ta u2) slowed by 10% (all p < 0.05 vs. control). Consequently, left ventr icular end-diastolic and right atrial pressures increased significantl y 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 coron ary resistance. However, coronary flow decreased by 24% (p < 0.05 vs. control), accompanied by significant reductions in myocardial oxygen d emand and consumption of 23 and 14%, respectively. Levels of circulati ng 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 th e patients became ischemic. Thus, at the dose level used, dilevalol ha s predominant beta-blocking effects. However, both the absence of syst emic and coronary vasoconstrictor effects, despite the fall in arteria l pressures, and the beneficial myocardial energetic effects of dileva lol 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 wit h concomitant ischemic heart disease.