Histamine and the heart.
ABSTRACT Histamine has been known as a cardiac stimulant for over 70 years. Work in our laboratory over the past decade has established that histamine receptors exist in the hearts of various species. The type of histamine receptor varies not only between species but also in the various regions of the heart. In the guinea pig heart H1 receptors are found in left atria and ventricles while H2 receptors are found in right atria and are the predominant histamine receptor in the ventricles. Rabbit atria contain both H1 and H2 receptors while the ventricles appear to possess only H1. Rat and cat heart do not seem to have histamine receptors and the positive inotropic and chronotropic effects elicited by histamine in cardiac preparations of these species are due to the release of noradrenaline. Dog heart contains H1 receptors while human heart has H2 receptors. In all cases H2 receptors are associated with adenylate cyclase and stimulation of such receptors results in an increase in cyclic AMP levels. H1 receptors are not associated with cyclic nucleotides in the heart. There are certain similarities between beta-adrenergic and H2-histaminergic receptors as well as between alpha-adrenergic and H1-histaminergic receptors. Stimulation of either histamine receptor must result in an increase in the free calcium ion concentration in the cardiac cell but the mechanisms involved are obviously different.
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ABSTRACT: Objective – To review the human and veterinary literature on histamine physiology and pathophysiology and potential applications for clinical use in veterinary critical care.Data Sources – Human and veterinary clinical studies, reviews, texts, and recent research in histamine receptor and antagonist therapy.Human Data Synthesis – Recent progress in molecular biology has led to a more complete understanding of the enzymes involved in histamine metabolism and histamine receptor physiology. The past decade of research has confirmed the role of histamine in the classical functions (contraction of smooth muscle, increase in vascular permeability, and stimulation of gastric acid secretion) and has also elucidated newer ones that are now under investigation. Data on the roles of histamine in angiogenesis, circadian rhythm, bone marrow regeneration, bacterial eradication, and cancer are emerging in the literature. Newer histamine antagonists are currently in drug trials and are expected to advance the clinical field in treatment of allergic, gastrointestinal, and cognitive disorders.Veterinary Data Synthesis – Veterinary histamine research is directed at identifying the effects of certain pharmacological agents on blood histamine concentrations and establishing the relevance in clinical disease states. Research demonstrates important species differences in regards to histamine receptor physiology and tissue response. Studies in the area of trauma, sepsis, anaphylaxis, allergy, and gastrointestinal disorders have direct applications to clinical veterinary medicine.Conclusions – Histamine plays a key role in the morbidity and mortality associated with allergy, asthma, gastric ulcers, anaphylaxis, sepsis, hemorrhagic shock, anesthesia, surgery, cardiovascular disease, cancer, CNS disorders, and immune-mediated disease. Histamine antagonism has been in common use to block its adverse effects. With recent advances in the understanding of histamine receptor physiology, pharmaceutical agents targeting these receptors have increased the therapeutic options.Journal of Veterinary Emergency and Critical Care. 07/2009; 19(4):311 - 328.
Article: Anaphylaxis in dogs and cats.[Show abstract] [Hide abstract]
ABSTRACT: To review and summarize current information regarding the pathophysiology and clinical manifestations associated with anaphylaxis in dogs and cats. The etiology, diagnosis, treatment, and prognosis is discussed. Anaphylaxis is a systemic, type I hypersensitivity reaction that often has fatal consequences. Many of the principal clinical manifestations involve organs where mast cell concentrations are highest: the skin, the lungs, and the gastrointestinal tract. Histamine and other deleterious inflammatory mediators promote vascular permeability and smooth muscle contraction; they are readily released from sensitized mast cells and basophils challenged with antigen. Anaphylaxis may be triggered by a variety of antigens including insect and reptile venom, a variety of drugs, vaccines, and food. Anaphylaxis is a clinical diagnosis made from a collection of signs and symptoms. It is most commonly based on pattern recognition. Differential diagnoses include severe asthma, pheocromocytoma, and mastocytosis. Epinephrine is considered the drug of choice for the treatment of anaphylaxis. It acts primarily as a vasopressor in improving hemodynamic recovery. Adjunctive treatments include fluid therapy, H1 and H2 antihistamines, corticosteroids, and bronchodilators; however, these do not substitute for epinephrine. Prognosis depends on the severity of the clinical signs. The clinical signs will vary among species and route of exposure. The most severe clinical reactions are associated when the antigen is administered parenterally.Journal of veterinary emergency and critical care (San Antonio, Tex. : 2001). 07/2013;
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ABSTRACT: Histamine is a normal constituent of mammalian heart. It affects cardiac function mainly through stimulating histamine H1- and H2-receptor subtypes. The simultaneous activation of H1- and H2-receptors in the heart results in: a positive inotropic and chronotropic effect, a negative dromotropic effect, increased automaticity and increased coronary blood flow. H1- and H2-receptors have already been cloned from different, but not yet from cardiac, tissue. They are two independent molecular entities differing in the length of their amino acid sequence, pathways of transmembrane and intracellular signalling, characteristics of their binding sites and selectivity for the specific agonists and/or antagonists. Our results of radioligand binding studies show the presence in the heart of a high-affinity (K D 0.4 nmol/L andB max 100 fmol/mg of protein) and a low-affinity (K D 4.5 nmol/L,B max 466 fmol/mg of protein) H1-receptor-binding site and only a single population of less-abundant high-affinity H2-receptor binding sites (K D 1.0 nmol/L andB max 27 fmol/mg of protein). The role of the histamine in cardiac pathophysiology is well established but the physiological role is unclear. The only proposed physiological role of histamine in the heart is the modulation of noradrenaline release from sympathetic nerve terminals, where H3-receptor subtypes might be involved.Inflammopharmacology 09/1996; 4(3):241-257.