Abstract

Delt-E was investigated as a pharmaceutical intervention in the ischemic hemorrhagic model. In order to monitor the hemodynamic biomarkers MAP and HR, and to facilitate intravenous injections, rats were surgically fitted with femoral artery and vein catheters under anesthesia. After removal of 48% of total blood volume (12-15 ml), post hemorrhage intravenous injections of 5.5 mg/kg Delt-E were found to significantly (P < 0.05) increase maximum mean arterial pressure (MAP), pulse pressure and survival post hemorrhage while lactic acid was decreased when compared to saline injections. The results for the 5.5 mg/kg Delt-E treated animals versus saline controls showed: maximum MAP, 54 ± 5 vs. 35 ± 5 mmHg; lactic acid, 6.5 ± 1.25 vs. 8.9 ± 0.12 mmol/L; pulse pressure, 47.9 ± 1.10 vs. 38.3 ± 1.49 mmHg; and at least a four fold increase in survival, 331 ± 18 vs. 50 ± 8 minutes, respectively. Heart Rate (HR) in Delt-E treated groups was not significantly different than saline; 396 ± 79 vs. 425 ± 93 bpm. Using logistic analysis, Delt-E did not significantly alter the baroreflex sensitivity. However, a significant Delt-E dose dependent correlation was found between survival time and lactic acid production. Increased pulse pressure was also correlated with survival. Glibenclamide, a K _ATP sensitive channel blocker did not interfere with the positive effects of Delt-E. Only the antagonists tested, known to affect δ₂ opioid receptors, interfered with the Delt-E survival benefit post hemorrhage. Conclusion: Delt-E is an effective pharmaceutical intervention in severe hemorrhagic shock and perhaps in other ischemic shock scenarios when administered after the onset of stress and therefore may have clinical potential.