Positive inotropic effects of histamine in anaesthetized dogs

Abstract

1 The cardiovascular effects of histamine were examined in dogs anaesthetized with pentobarbitone 2 The effect of histamine on heart rate, blood pressure, left ventricular pressure, dP/dt,,,nv, and dP/dt: IIT (integrated isometric tension) was compared in the presence and absence ofautonomic reflexes and blood pressure control. 3 In innervated animals with no attempt to control blood pressure, histamine produced dosedependent decreases in blood pressure and heart rate and either positive or negative inotropic actions. 4 When autonomic reflexes were abolished, this variability in inotropic response was reduced and histamine produced a slight positive inotropic response. There was a decrease in blood pressure and a positive chronotropic response to histamine. 5 When blood pressure was controlled and the cardiac nerves were intact, histamine produced a decrease in heart rate. However, in the denervated animals, there was a slight increase in heart rate. 6 Inotropic responses to histamine in the blood pressure controlled groups were less variable than when blood pressure was uncontrolled. In all of these animals there was an increase in contractility, the increase being more marked in the denervated group. 7 The H2-receptor agonist impromidine produced a positive inotropic action in intact animals with uncontrolled blood pressure.

The effects of neuropeptide Y on myocardial contractility and coronary blood flow

“…Since histamine H2-receptors mediate a positive inotropic response in the canine heart (Einstein et al, 1987), the effect of NPY on these receptors was studied. NPY had no significant effect on the responses to impromidine injection, showing that NPY has no modulatory role on H2-receptors.…”

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

“…In view of the known dependence of changes in contractility on changes in rate [20], interpretation of the above results is not unequivocal. The use of intact anesthetized dogs to determine the inotropic effects of histamine by measuring changes in left ventricular dP/dt has yielded conflicting results ranging from negative [12,13] to positive [11,13] responses, including a lack of effect [14]. In addition to the confounding influence of chronotropic changes already alluded to, the results obtained in this type of preparation were undoubtedly affected by extracardiac actions of histamine, notably hypotension.…”

“…The importance of these factors in determining the nature of histamine-induced changes in dP/dt were well-documented by Reinhardt et al [13], who observed that the apparent negative inotropic effect of histamine was reversed to a positive response by preventing the histamine-induced hypotension. Einstein et al [11] have also illustrated this point by determining that the variable inotropic effects of histamine in intact dogs became increasingly positive after cardiac denervation, blood pressure stabilization, and a combination of both maneuvers. It is interesting that the only study in intact dogs in which histamine was administered into the coronaries, thus obviating systemic effects, was also the only one in which a lack of inotropic responses was reported [14].…”

“…A delay of 60-100 ms between atrial and ventricular stimuli was introduced to maintain the AV delay constant. The vagi were cut and the stellate ganglia were decentralized to prevent any reflexly-mediated actions of histamine [11]. For intracoronary drug administration, a cannula was inserted into the left common carotid artery and advanced so that its tip lay just distal to the aortic valve.…”

“…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. Such conflicting results are apparently due to the varying degrees of reliability of the methods used to measure changes in cardiac contractility, as well as to the confounding influence of the reflex and general hemodynamic actions of histamine in intact preparations.…”