Influence of histamine receptors on basal left ventricular contractile tone in humans: assessment using the H2 receptor antagonist famotidine and the beta-adrenoceptor antagonist esmolol as pharmacologic probes.
Histamine has a positive inotropic action in humans. Recent controversial data have suggested that histamine2 (H2) receptor blockade depresses overall left ventricular systolic performance in healthy volunteers. To explore the possibility that H2 receptors positively influence basal left ventricular contractile tone, 10 normal subjects were studied by using imaging and Doppler echocardiography and calibrated subclavian pulse data in a blinded, randomized, two-period crossover trial with measurements obtained at the end of each 7-day period. Oral drug administration consisted of either the potent H2 antagonist famotidine (40 mg/day) or placebo. Left ventricular circumferential end-systolic wall stress-rate-corrected velocity of fiber shortening (Vcfc) relations were generated over a range of loads with methoxamine. Contractility was assessed by using Vcfc at a common end-systolic wall stress. During each study, data were obtained before and during high dose intravenous esmolol administration to determine the contributions, if any, of sympathetic reflex responses. Famotidine did not alter blood pressure, left ventricular percent fractional shortening, circumferential end-systolic wall stress, stroke volume index, cardiac index, total vascular resistance or ventricular contractile state in comparison with placebo but did decrease heart rate by 3 beats/min (p less than 0.05). With beta-adrenergic blockade, no differences in contractility were evident between esmolol alone and famotidine plus esmolol. Thus, H2 receptor blockade with famotidine does not alter myocardial mechanics or cardiac sympathetic tone, suggesting that in humans basal left ventricular contractile state is not physiologically dependent on the H2-mediated effects of histamine.
Department of Medicine, University of Chicago Medical Center, Illinois 60637.
K M
KM
Borow
D
D
Ehler
R
R
Berlin
A
A
Neumann
D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D000328:Adult; D004311:Double-Blind Method; D015150:Echocardiography, Doppler; D015738:Famotidine / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006632:Histamine / Q000097:blood; D006801:Humans; D008875:Middle Aged; D009129:Muscle Tonus / Q000187:drug effects* / Q000502:physiology; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology; D011412:Propanolamines / Q000008:administration & dosage / Q000494:pharmacology*; D011970:Receptors, Histamine H2 / Q000187:drug effects* / Q000502:physiology; D012016:Reference Values; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D011412:Propanolamines; D011970:Receptors, Histamine H2; D015738:Famotidine; D006632:Histamine; C036604:esmolol