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 beta 2-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.(ABSTRACT TRUNCATED AT 250 WORDS)
Remme
W J
WJ
Sticares Cardiovascular Research Foundation and Zuiderziekenhuis, Rotterdam, The Netherlands.
von Schelven
D
D
Bartels
G L
GL
Kruijssen
H A
HA
de Leeuw
P W
PW
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D000368:Aged; D000804:Angiotensin II / Q000097:blood; D006328:Cardiac Catheterization; D004298:Dopamine / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005260:Female; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D007741:Labetalol / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D012083:Renin / Q000097:blood
D000319:Adrenergic beta-Antagonists; D018377:Neurotransmitter Agents; D000804:Angiotensin II; D012083:Renin; D007741:Labetalol; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine