Assessment of the delta opioid agonist DADLE in a rat model of lethal hemorrhage treated by emergency preservation and resuscitation

Resuscitation
Tomas DrabekPatrick M Kochanek

Abstract

Emergency preservation and resuscitation (EPR) is a new approach for resuscitation of exsanguination cardiac arrest (CA) victims. EPR uses a cold aortic flush to induce deep hypothermic preservation during no-flow to buy time for transport and damage control surgery, followed by resuscitation with cardiopulmonary bypass (CPB). We reported previously that 20-60 min EPR in rats was associated with intact outcome, while 75 min EPR resulted in high mortality and neurological impairment in survivors. The delta opioid agonist DADLE ([D-Ala(2),D-Leu(5)]-enkephalin) was shown previously to be protective against ischemia-reperfusion injury in multiple organs, including brain. We hypothesized that DADLE could augment neurological outcome after EPR in rats. After rapid lethal hemorrhage, EPR was initiated by perfusion with ice-cold crystalloid to induce hypothermia (15 degrees C). After 75 min EPR, resuscitation was attempted with CPB. After randomization, three groups were studied (n=10 per group): DADLE 0mg/kg (D0), 4 mg/kg (D4) or 10mg/kg (D10) added to the flush and during reperfusion. Survival, overall performance category (OPC; 1=normal, 5=death), neurological deficit score (NDS; 0-10% normal, 100%=max deficit), and histological dam...Continue Reading

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Citations

Jun 26, 2009·Critical Care Medicine·Eugene Y Fukudome, Hasan B Alam
Oct 2, 2009·Peptides·Richard J Bodnar
Sep 11, 2009·Resuscitation·Marco CarmignaniGuido Valle
Jun 21, 2016·Neurological Research·Kaiyin LiuYuchuan Ding
May 26, 2017·The Journal of Trauma and Acute Care Surgery·Samuel A TishermanPatrick M Kochanek
Dec 29, 2017·Shock·Andrea WolfGregory J Beilman

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