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<p>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 (<i>p</i> = 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 (<i>p</i> = 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.</p>

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Protein kinase C epsilon activation improves early survival in an acute porcine model of controlled hemorrhage

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月17日

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  • Maya Simchoni,
  • Linn Wagnert-Avraham,
  • Estela Derazne,
  • Dean Nachman,
  • Yuval Gershon,
  • Eliraz Cohen Levi,
  • Adi Horesh,
  • Yaron Cohen,
  • Maya Nitecki,
  • Yuval Glick,
  • Arik Eisenkraft,
  • Nir Suissa,
  • Gilad Twig,
  • S. David Gertz,
  • Ann Saada,
  • Ariel Furer

摘要

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.