Histamine H₃ activation depresses cardiac function in experimental sepsis

Abstract

In the heart, histamine (H3) receptors may function as inhibitory presynaptic receptors that decrease adrenergic norepinephrine release in conditions of enhanced sympathetic neural activity. We hypothesized that H3-receptor blockade might improve cardiovascular function in sepsis. In a canine model of Escherichia coli sepsis, we found that H3-receptor blockade increased cardiac output (3.6 to 5.3 l/min, P< 0.05), systemic blood pressure (mean 76 to 96 mmHg, P < 0.05), and left ventricular contractility compared with pretreatment values. Plasma histamine concentrations increased modestly in the H3-blocker–sepsis group compared with values obtained in a nonsepsis–time-control group. In an in vitro preparation, histamine H3 activation could be identified under conditions of septic plasma. We conclude that activation of H3 receptors may contribute to cardiovascular collapse in sepsis.

N,N′,N′-triacetylglucosamine, an inhibitor of lysozyme, prevents myocardial depression in Escherichia coli sepsis in dogs*

“…In the analysis, stroke work (SW) was our primary index of cardiac performance and the primary hemodynamic end point chosen in the in vivo studies (17,18) (see Discussion). At constant preload, SW reflects both the decreases in afterload and the changes in contractile function that accompany sepsis.…”

“…In the pretreatment study, TAC was given before the bacteria were infused. Based on previous studies, it takes approximately 3-4 hrs of constant bacteremia for myocardial depression to develop in this model (12,18). A 3-to 5-hr course of bacteremia was therefore considered necessary to determine whether TAC could block the decline in SW observed at this interval.…”

Presynaptic cannabinoid CB1 receptors are involved in the inhibition of the neurogenic vasopressor response during septic shock in pithed rats

“…Furthermore, in rat mesenteric arteries the overproduction of both nitric oxide and prostanoids by endothelium was shown to reduce the electrically evoked contraction after administration of LPS (Fatehi-Hassanabad et al, 1995). Moreover, Li et al (1998) and Cheng et al (2002) demonstrated that the activation of presynaptic histamine H 3 receptors during sepsis resulted in the depression of left ventricular contractility in canine heart, hence contributing to the cardiovascular collapse.…”

“…Such an effect might have been expected on the basis of our previous report showing the occurrence of H 3 receptors on the sympathetic innervation of rat resistance vessels, which were tonically activated by endogenous histamine . Moreover, the activation of presynaptic histamine H 3 receptors during sepsis resulted in the depression of left ventricular contractility in canine heart (Li et al, 1998) and contributed to the cardiovascular collapse in dogs (Cheng et al, 2002). As the dose of 100 nmol kg À1 of clobenpropit antagonized the effects of the selective H 3 receptor agonists R-a-methylhistamine and imetit in pithed rats , the lack of its activity in the present study may mean that histamine H 3 receptors are not active in the initial phase of septic shock, at least not of rats.…”

Effect of combined histamine H1 and H3 receptor blockade on cutaneous microvascular permeability elicited by compound 48/80

“…Histamine H 3 receptors are located presynaptically on postganglionic sympathetic noradrenergic nerves, including sympathetics innervating the heart and blood vessels (Imamura et al, 1995;Li et al, 1998;Malinowska et al, 1998). The presence of functional H 3 receptors in the cardiovascular system has been demonstrated in vitro in human, guinea pig, rabbit and rat effector systems, and in vivo in the rat, guinea pig and dog (Malinowska et al, 1998).…”