Abstract 129: Ischemic Postconditioning with or Without Vasodilator Therapy at the Beginning of CPR Prevents Neural Damage by Histopathology After 15 Minutes of Untreated Ventricular Fibrillation
Background: Ischemic postconditioning (IPC) at the initiation of reperfusion reduces the size of myocardial infarction and ischemic stroke. Vasodilatory therapy (VDT) with sodium nitroprusside and adenosine protects heart and brain from ischemic injury. We hypothesize that IPC and VDT at the initiation of CPR would improve cerebral function and reduce ischemic brain injury compared to standard CPR (SCPR).
Methods: Following 15 minutes of untreated V-fib, 39 pigs were randomized to receive SCPR (n=9), SCPR+IPC (n=10), SCPR+IPC+VDT (n=10), or SCPR+VDT (n=10). IPC was delivered during the first 3 minutes of CPR with 4 cycles of 20 seconds of chest compressions followed by 20-second pauses. The VDT consisted of intravenous SNP (2 mg) and adenosine (24 mg) during the first minute of CPR. Epinephrine was given in all groups as a 0.5 mg at minute 3 and repeated every 3 minutes until return of spontaneous circulation (ROSC). The brains were extracted after euthanasia at least 24 hours later. Animals that were found dead were excluded from histological analysis. A total of 24 brains (6, 9, 5 and 4 for SCR, IPC, IPC+VDT and VDT, respectively) underwent fixation with formalin and were stained with hematoxilin and eosin. Eight cerebral regions were analyzed and graded on a 0-4 scale (0: no injury, 1 to 4, mild to severe). Scores from each region were added to provide the total cerebral histological score (CHS) of each animal. ANOVA and Cox regression analysis were used for statistical analysis.
Results: All but one animal in VDT group had ROSC. The 48hr survival among IPC, VDT, IPC+VDT and SCPR was 6/10, 3/10, 5/10 and 1/9, respectively (p<0.01). IPC was independently associated with a decrease in the risk of death [HR 0.13, 95% CI (0.035,0.53), p=0.004] and there was no synergy observed with IPC and VDT. IPC and IPC+VDT resulted in significantly lower CHS compared to SCPR group (5.8±2.6, 2.8±1.8 versus 10±2.1, respectively, p<0.01). VDT alone did not improve CHS compared to SCPR (p=0.1). CPC score improved with IPC, IPC+VDT and VDT alone, compared to SCPR group (2.2±0.9; 1.8±0.8, 2.3±1.6 and 3.8±0.4, respectively, p<0.05).
Conclusions: IPC at the initiation of SCPR prevents post resuscitation histological brain injury and improves neurological intact survival at 48 hours.
- Ventricular fibrillation
- Cardiopulmonary resuscitation
- Vasodilator agents
- Post cardiac resuscitation
- © 2012 by American Heart Association, Inc.