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Contractile studies were performed in an organ bath on isolated, electrically driven (1\u00a0Hz) left atrial preparations and spontaneously beating right atrial preparations from H<jats:sub>2<\/jats:sub>-TG mice and wild-type (WT) littermate control mice. The basal beating rate in the right atrial preparations from H<jats:sub>2<\/jats:sub>-TG mice was lowered by hypothermia (23\u00a0\u00b0C) and elevated by hyperthermia (42\u00a0\u00b0C). Furthermore, the efficacy of histamine (0.01\u2013100\u00a0\u00b5M) at exerting positive inotropic effects was more severely attenuated in the left and right H<jats:sub>2<\/jats:sub>-TG mouse atria under hypothermia and hyperthermia than under normothermia (37\u00a0\u00b0C). Similarly, the inotropic response to histamine was attenuated under hypothermia and hyperthermia in isolated electrically stimulated (1\u00a0Hz) right atrial preparations obtained from humans undergoing cardiac surgery. The phosphorylation state of phospholamban at serine 16 at 23\u00a0\u00b0C was inferior to that at 37\u00a0\u00b0C in left atrial preparations from H<jats:sub>2<\/jats:sub>-TG mice in the presence of 10\u00a0\u00b5M histamine. In contrast, in human atrial preparations, the phosphorylation state of phospholamban at serine 16 in the presence of 100\u00a0\u00b5M histamine was lower at 42\u00a0\u00b0C than at 37\u00a0\u00b0C. Finally, under hyperthermia, we recorded more and longer lasting arrhythmias in right atrial preparations from H<jats:sub>2<\/jats:sub>-TG mice than in those from WT mice. We conclude that the inotropic effects of histamine in H<jats:sub>2<\/jats:sub>-TG mice and in human atrial preparations, as well as the chronotropic effects of histamine in H<jats:sub>2<\/jats:sub>-TG mice, are temperature dependent. Furthermore, we observed that, even without stimulation of the H<jats:sub>2<\/jats:sub> receptors by exogenous agonists, temperature elevation can increase arrhythmias in isolated right atrial preparations from H<jats:sub>2<\/jats:sub>-TG mice. We propose that H<jats:sub>2<\/jats:sub> receptors play a role in hyperthermia-induced supraventricular arrhythmias in human patients.<\/jats:p>","DOI":"10.1007\/s00210-023-02457-x","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T11:04:46Z","timestamp":1679569486000},"page":"2137-2150","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Temperature alters the inotropic, chronotropic and proarrhythmic effects of histamine in atrial muscle preparations from humans and H2-receptor overexpressing mice"],"prefix":"10.1007","volume":"396","author":[{"given":"Robert J. 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The animals were handled and maintained according to the approved protocols of the Animal Welfare Committee of the University of Halle-Wittenberg, Halle, Germany. Humans: This study complies with the Declaration of Helsinki and has been approved by the local ethics committee (hm-b\u00fc 04.08.2005).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Informed written\u00a0consent was obtained from all patients included in the study.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"All authors declare that they have seen and approved the submitted version of this manuscript.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}