Effects of a novel acetaminophen analog on cardiorespiratory compensatory responses and survival in a male rat model of traumatic hemorrhage.

When pain is associated with traumatic hemorrhage, medics must be concerned about secondary effects of analgesics on cardiorespiratory systems. A novel analog of acetaminophen, D-112, was developed to circumvent liver toxicity and improve analgesic efficacy. D-112 causes dose-related inhibition of formalin-induced licking. The objective of this study was to test the effects of D-112 on survival and cardiorespiratory variables following hemorrhage and extremity trauma (ET). We hypothesized that D-112 would significantly change cardiorespiratory responses to HEM and thereby decrease survival. Male rats received either vehicle (lactated Ringer's) or D-112 (50 mg/kg) after conscious hemorrhage of either 37% (n = 10, vehicle and D-112) or 50% (n = 8, vehicle; n = 11, D-112) of blood volume following ET, which consisted of soft tissue injury and fibula fracture. Rats were observed for 4 h after the start of hemorrhage. Neither survival times (37% hemorrhage: p = 0.474; 50% hemorrhage: p = 0.306) nor survival curves (37% hemorrhage: p = 0.146; 50% hemorrhage: p = 0.280) differed between treatments. Mean arterial pressure did not differ between treatments (37% hemorrhage: p = 0.742; 50% hemorrhage: p = 0.521). D-112 transiently elevated minute ventilation (p < 0.001) after both hemorrhages. D-112 does not alter cardiorespiratory responses to the point of depressing survival, suggesting that D-112 could be an appropriate analgesic following traumatic hemorrhage.