Cardiopulmonary effects of phosphine poisoning: A preliminary evaluation of milrinone.

Exposure to phosphine (PH) presents with a host of diverse, non-specific symptoms that span multiple organ systems and is characterized by a high mortality rate. While a comprehensive mechanism for PH poisoning remains inconclusive, prior studies have implicated cardiac failure and circulatory compromise as potential pathways central to PH-induced mortality. In this study, milrinone (MLR), a phosphodiesterase-3 inhibitor used to treat cardiac failure, was investigated as a potential countermeasure for PH poisoning. Lethality, physiological responses, and behavioral changes were evaluated in telemetrized female rats pretreated with water (sham) or one of three doses of MLR (40, 200, or 600 μg/kg) and exposed to PH (660 ppm for 25-40 min; 16,500-26,400 ppm × min). Animals receiving prophylactic administration of 600 μg/kg of MLR had nominally improved survivability compared to sham animals, although median lethal concentration-time and time of death did not differ substantially between treatment groups. Changes in respiration and behavior induced by PH appeared largely unaffected by MLR pretreatment, regardless of dose. Conversely, MLR pretreatment alleviated some aspects of PH-induced cardiac function impairment, with slight dose-dependent effects observed for cardiac contractility, mean arterial pressure, and QRS duration. Together, these results illustrate the importance of circulatory compromise in PH poisoning and highlight the potential viability of MLR as a potential countermeasure option or part of a countermeasure regimen when administered prophylactically at 600 μg/kg.