Histamine: metabolism, physiology, and pathophysiology with applications in veterinary medicine

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.