Recombinant human diamine oxidase prevents hemodynamic effects of continuous histamine infusion in guinea pigs

Objective: To test whether recombinant human diamine oxidase (rhDAO) with a mutated heparin-binding motif (mHBM), which shows an increased alpha-distribution half-life, prevents histamine-induced hemodynamic effects.Material: Thirty-eight female guinea pigs were either pretreated with rhDOA_mHBM or buffer.Treatment and methods: Guinea pigs received a continuous infusion of histamine. Heart rate (HR), body core temperature and mean arterial pressure (MAP) were measured and blood was collected.Results: Continuous intravenous infusion of 8 mu g/kg/min histamine increased mean peak plasma histamine levels from 5 (+/- 0.3 SEM) to 28 ng/mL (+/- 4.9 SEM) after 30 min but had no effect on oxygen saturation. Guinea pigs pretreated with 4 mg/kg rhDAO_mHBM showed lower mean HR (p = 0.008), histamine plasma concentrations (p = 0.002), and higher body core temperatures at the end of the histamine challenge (p = 0.02) compared to controls. Cessation of histamine infusion led to a rebound increase in MAP, but this hemodynamic instability was prevented by rhDAO_mHBM. Pretreatment with 4 mg/kg rhDAO_mHBM reduced urinary histamine (p = 0.004) and 1-Methylhistamine (p < 0.0001) concentrations compared to controls.Conclusions: Prophylactic infusion of rhDAO_mHBM prevents hemodynamic effects in a guinea pig model of continuous histamine infusion. These findings might help in the translation from animals to humans and in the selection of the optimal dosing of rhDAO_mHBM during human histamine challenge studies.

Automated summary

This study aimed to investigate the preventive effects of recombinant human diamine oxidase with a mutated heparin-binding motif (rhDAO_mHBM) on histamine-induced hemodynamic effects. The results demonstrated that pretreatment with rhDAO_mHBM in guinea pigs led to lower heart rate, histamine plasma concentrations, and higher body core temperatures at the end of the histamine challenge. Furthermore, rhDAO_mHBM prevented the hemodynamic instability caused by histamine infusion. These findings suggest that rhDAO_mHBM has potential clinical applications in preventing histamine-induced hemodynamic effects.