Abstract
Hemorrhage is the primary cause of preventable death in both military and civilian trauma cases, and the effective therapeutic options are limited. Activation of Protein Kinase C epsilon (PKC-ε) was shown to have a protective role in ischemia-reperfusion injury models. Thus, we evaluated the effects of a PKC-ε activator peptide in a swine model of controlled hemorrhagic shock. Controlled hemorrhage was induced in 25 Sus Domesticus female pigs by blood withdrawal. Fifteen animals were treated with PKC-ε activator peptide (3 mg/kg IM) five minutes following the initiation of hemorrhage, and 8 animals were bled without receiving the peptide. Two additional animals were treated with the peptide without having been bled for safety validation. Hemodynamic and biochemical parameters were monitored for 7 h, and mitochondrial function markers were analyzed and compared between groups. 73.3% of the pigs that received the peptide survived the hemorrhage until the end of the follow-up compared to only 25% of non-treated control animals. Kaplan-Meier survival analysis showed a significant difference between the groups (p = 0.044). This benefit was associated with a more favorable hemodynamic profile, including more stable blood pressure, heart rate and cardiac output, and a better acid-base balance. Mitochondrial analysis identified a significant increase in electron transport chain complex-I activity in the myocardium of treated animals compared with the controls (p = 0.033). In conclusion, Administration of PKC-ε activator is associated with improved survival, hemodynamic stability, and mitochondrial function in a porcine model of controlled hemorrhage.