Alterations in the circulatory system of anaesthesized dogs following administration of histamine and histamine H1- and H2-receptor antagonists in relation to plasma histamine levels

Abstract

The effects of histamine on the circulatory system have been the subject of a great number of investigations [1]. There was a wide range in doses of histamine applied, in methods used for determining circulatory parameters and in laboratory animals involved, and the results obtained were often contradictory. In order to contribute to the main problem whether endogenous histamine is involved in pathophysiological or clinical stituations it was the aim of the present study to answer the following questions:(1) Do the effects of histamine in the circulatory system depend on the actual histamine levels?(2) How do H1-and H2-receptor antagonists influence the histamine actions? (3) Do H1-and Ha-receptor antagonists alter the actual plasma histamine levels? MethodsThe experiments were carried out in 23 mongrel dogs (both sexes, 14-28 kg body weight) which were anaesthesized with pentobarbitone and breathed room air spontaneously. The acid-base balance and the body temperature were controlled.Aortal plasma histamine concentration was measured by a specific ftuorometric test [2,3]. Blood pressure was recorded in aorta, pulmonal artery, portal vein and inferior caval vein by Statham strain gauges and was determined at end exspiration. Blood flow in the superior mesenteric artery and hepatic artery was estimated using electromagnetic flow meters (Statham). Cardiac output was calculated with the thermodilution method [4,5]. Resistance in several regions of the vascular bed was calculated from the equation R = Ap/Q 9 kg body weight [6]. Pulse rate and breath rate were counted from the blood pressure curves recorded.The experiments were started 30 minutes after completing the operation (laparotomy, insertion of catheters, flow probes and the thermistors, calibrations).Only one dose of histamine (10 ~g/kg histamine dihydrochloride corresponding to 6 ~g/kg histamine base) was injected into the inferior caval vein. 30 minutes later 5 mg/kg dimethpyrindene (Zyma-Blaes, Munich) or 10 mg/kg burimamide (SK & F, Welwyn Garden, UK) were administered into the same vein. 10 minutes later on again 6 ~-g/kg histamine base were applied. Blood samples for plasma histamine assay were taken immediately before and 30 seconds after the injection of histamine. Results(a) Effects of a single dose of histamine (6 sg/kg on plasma histamine levels and circulatory parameters (Table 1) The plasma histamine concentration increased by about 6000% though the dose of histamine applied (about 120 ~g/animal) by no means was life-threatening or even fatal to the dogs.Cardiac output and pulse rate were not altered, but arterial and central venous pressures as well as total systemic resistance decreased considerably. Since arterial pressure and total systemic resistance decreased to the same extent the effect of this dose of histamine on the mean aortal pressure was mainly caused by peripheral vasodilatation and not by negative inotropic action of histamine on the heart.At the time of maximum aortal hypotension there was no increase in pulmonal arterial pressur...

Chronotropic cardiac effects of histamine in the conscious dog with chronic atrioventricular block: interactions with the autonomic nervous system

“…In addition, Black et al [26] have reported that greater catecholamine release occurs in the cat than in the dog. Indeed, their results show that this release in the dog cannot be other than very slight, and this is supported by the lack of histamine-induced tachycardia in the anesthetized dog [6,29]. The fact that activation of the histamine receptors does not seem to be responsible for the atrial chronotropic effects of histamine at doses between 0.2 and 25 ~tg/kg is at variance with the results of Powell and Brody [7], Tucker et al [8] and Hirschowitz etal.…”

“…In the anesthetized dog, histamine at i.v. dose of 6 ~tg/kg has been reported to produce no chronotropic effect [6]. Under the same experimental conditions (anesthesia), histamine at i.v.…”

Effects of histamine on atrial and ventricular contractility in the canine isovolumic heart

“…The dog appears to be much more sensitive to the vascular effects of histamine than to its actions on the heart. Thus, a dose of the amine eliciting marked peripheral dilator and constrictor responses had minimal influence on cardiac function [6,7]. In this species, either positive [8][9][10][11], negative [12,13], or lack of [14] inotropic effects have been reported.…”

Effect of Intravenous Histamine, Allergen <i>(Ascaris suum</i> Extract) and Compound 48/80 and Inhaled Allergen-Aerosol on Bronchoconstriction and Histamine Release

“…Histamine release was defined as an increase in peak plasma histamine level greater than 1 ng/ml [Lo renz, 1976;Lorenz et al, 1972bLorenz et al, , 1976a. Furthermore, the effects of histamine on the respiratory and circulatory system have been the subject of a great number of inves tigations [Lorenz et al, 1973[Lorenz et al, , 1974cThermann et al, 1975;Tauber et al, 1974]. These authors showed that injection of a single histamine dose, causing short-acting but remarkable effects on the circulatory system, induced plasma histamine levels as high as those found after administration of histamine releaser.…”