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

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 damage score (HDS) were assessed in survivors on day 3. In D0 group, 2/10 rats survived, while in D4 and D10 groups, 4/10 and 5/10 rats survived, respectively (p=NS). Survival time (h) was 26.7+/-28.2 in D0, 36.3+/-31.9 in D4 and 47.1+/-30.3 in D10 groups, respectively (p=0.3). OPC, NDS and HDS were not significantly different between groups. In conclusion, DADLE failed to confer benefit on functional or histological outcome in our model of prolonged rat EPR.

• Authors: Tomas Drabek, Fei Han, Robert H Garman, Jason Stezoski, Samuel A Tisherman, S William Stezoski, Ryan C Morhard, Patrick M Kochanek
• Journal: Resuscitation (Resuscitation) Vol. 77 Issue 2 Pg. 220-8 (May 2008) ISSN: 0300-9572 [Print] Ireland
• PMID: 18207625 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Enkephalin, Leucine-2-Alanine

Topics

• Animals
• Cardiopulmonary Bypass
• Disease Models, Animal
• Enkephalin, Leucine-2-Alanine (pharmacology)
• Hypothermia, Induced
• Male
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Resuscitation (methods)
• Shock, Hemorrhagic (therapy)
• Statistics, Nonparametric
• Survival Rate