Inflammation Research · 6 authors, 4 centres
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In a preclinical guinea pig model, continuous intravenous histamine infusion at 8 µg/kg/min raised plasma histamine and induced tachycardia and hemodynamic instability. Pretreatment with 4 mg/kg rhDAO_mHBM significantly reduced plasma histamine, heart rate, and urinary histamine metabolites while preventing rebound mean arterial pressure changes.
In the main experiment, guinea pigs were pretreated with either rhDAO_mHBM (2 or 4 mg/kg) or buffer, then challenged with continuous histamine infusion. Continuous histamine infusion raised mean peak plasma histamine from 5 to 28 ng/mL after 30 min. Pretreatment with 4 mg/kg rhDAO_mHBM significantly reduced heart rate, plasma histamine concentrations, and urinary histamine and 1-Methylhistamine compared to controls, while maintaining higher body core temperature. Cessation of histamine infusion caused a rebound increase in mean arterial pressure in controls, which was prevented by rhDAO_mHBM pretreatment. The 2 mg/kg dose was abandoned after two animals due to insufficient efficacy. Limitations include the small, all-female guinea pig cohort, species differences in histamine cardiovascular effects, and the exploratory preclinical nature of the study. Findings support further translational evaluation of rhDAO_mHBM in human histamine challenge studies.
