ARTERIAL HYPOTENSION (AH) AND THE DYNAMICS OF IRON NITROSYL HEMOGLOBIN (HBNO) IN A RAT MODEL OF BLAST-INDUCED INJURY

Abstract

Cardio-pulmonary contusion and hemorrhage followed by AH are the common features of polytruma produced by blast shock waves (SW). Presumably vascular resistance and AH are associated with effects of neuro-humoral factors such as nitric oxide (NO). To address these NO effects in blast polytrauma we compared two models (1) pulmonary injury produced by experimental SW combined with isobaric hemorrhage (H), and (2) AH produced by exogenous NO. To this goal, Sprague-Dawley rats were exposed to SW at peak overpressure ~120 kPa. At ~50 min after SW impact, exposed animals were subjected to H (40 mmHg MAP for 100 min). Vascular consumption of the released NO was induced by iv administration of (MGD)2Fe2+, a NO-trapping agent. SIN-1 and DEA NONOate (NO release with half-time 40 min and 2 min respectively) were administered through trachea with dose 6 mg/kg and 4.5 mg/kg respectively. Electron paramagnetic resonance was used to measure levels of NO-adducts with hemoglobin (HbNO) in blood collected from femoral artery. Exposure to SW led to a decrease in the both of the mean arterial blood pressure (MAP) (~30%) and heart rate (HR) (~25%). These alteration were accompanied by 2-fold increase in the blood HbNO levels. H led to further decrease in MAP and HR (respectively ~65% and ~45%) and 8-fold increase in blood HbNO adducts. MAP and HR were restored by administration of (MGD)2Fe2+ and, in part, by administration of lactated Ringer's saline. These effects induced by SW and H were simulated by SIN-1 and DEA NONOate. The dynamic of alterations induced by these NO-donors was in accordance with their rates of NO release. We speculate that the AH of blast is caused in part by the vasodilatory action of NO and in part by effects of NO in the autonomic regulation of HR. Supported by DoD PRMRG 033201.