Hemodynamic and neurohumoral effects of ketanserin, a 5-HT2 receptor antagonist in patients with congestive heart failure.
Ketanserin, a recently developed 5-HT2 receptor antagonist, competitively and selectively blocks the vasoconstrictor activity of 5-hydroxytryptamine (serotonin). We explored a possible contribution of serotonin to augmented vascular tone in patients with severe heart failure, using intravenous and oral formulations of ketanserin. When administered intravenously (10 mg bolus, 4 mg/hr infusion for +/- 40 min) to 10 patients with congestive heart failure (NYHA III or IV) secondary to congestive cardiomyopathy (n = 8) or ischemic heart disease (n = 2), the drug produced a significant increase in cardiac output (rest 24%, p less than 0.001; exercise 19%, p less than 0.01) which was accompanied by a fall in systemic arterial pressure (rest 7%, p less than 0.001; exercise 10%, p less than 0.05) and pulmonary wedge (rest 17%, p less than 0.05; exercise 23%, p less than 0.001) pressure. Calculated systemic vascular resistance (SVR, rest 27%, p less than 0.001; exercise 23%, p less than 0.05) decreased significantly. No significant hemodynamic changes were observed when 40 mg of ketanserin was administered orally to the same group of patients. Plasma catecholamines (norepinephrine, NEP:epinephrine, EP:dopamine) were measured before and after ketanserin at rest and during exercise. Baseline NEP levels were markedly elevated at rest and during exercise in all patients (rest: 878 +/- 381 ng/mL, exercise: 1453 +/- 697 ng/mL). Baseline EP levels were within normal limits. Ketanserin did not produce any change in catecholamine concentration.(ABSTRACT TRUNCATED AT 250 WORDS)
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002395:Catecholamines / Q000097:blood*; D004298:Dopamine / Q000097:blood; D004837:Epinephrine / Q000097:blood; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D007650:Ketanserin / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood
D002395:Catecholamines; D007650:Ketanserin; D004298:Dopamine; D009638:Norepinephrine; D004837:Epinephrine