Ischemic post-conditioning and vasodilator therapy during standard cardiopulmonary resuscitation to reduce cardiac and brain injury after prolonged untreated ventricular fibrillation

Abstract

Aim of the study We investigated the effects of ischemic postconditioning (IPC) with and without cardioprotective vasodilatory therapy (CVT) at the initiation of cardiopulmonary resuscitation (CPR) on cardio-cerebral function and 48-hour survival. Methods Prospective randomized animal study. Following 15 minutes of ventricular fibrillation, 42 Yorkshire farm pigs weighing an average of 34±2 kg were randomized to receive standard CPR (SCPR, n=12), SCPR+IPC (n=10), SCPR+IPC+CVT (n=10), or SCPR+CVT (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. CVT consisted of intravenous sodium nitroprusside (2 mg) and adenosine (24 mg) during the first minute of CPR. Epinephrine was given in all groups per standard protocol. A transthoracic echocardiogram was obtained on all survivors 1 and 4 hours post-ROSC. The brains were extracted after euthanasia at least 24 hours later to assess ischemic injury in 7 regions. Ischemic injury was graded on a 0–4 scale with (0=no injury to 4= >50% neural injury). The sum of the regional scores was reported as cerebral histological score (CHS). 48 hours survival was reported. Results Post-resuscitation left ventricular ejection (LVEF) fraction improved in SCPR+CVT, SCPR+IPC+CVT and SCPR+IPC groups compared to SCPR (59%±9%, 52%±14%, 52%±14% vs. 35%±11%, respectively, p<0.05). Only SCPR+IPC and SCPR+IPC+CVT, but not SCPR+CVT, had lower mean CHS compared to SCPR (5.8±2.6, 2.8±1.8 vs. 10±2.1, respectively, p<0.01). The 48-hour survival among SCPR+IPC, SCPR+CVT, SCPR+IPC+CVT and SCPR was 6/10, 3/10, 5/10 and 1/12, respectively (Cox regression p<0.01). Conclusions IPC and CVT during standard CPR improved post-resuscitation LVEF but only IPC was independently neuroprotective and improved 48-hour survival after 15min of untreated cardiac arrest in pigs.

Early Effects of Prolonged Cardiac Arrest and Ischemic Postconditioning during Cardiopulmonary Resuscitation on Cardiac and Brain Mitochondrial Function in Pigs

“…Animal preparation has been described previously(6). See Supplement for full description of methods.…”

Anaesthetic Postconditioning at the Initiation of CPR Improves Myocardial and Mitochondrial Function in a Pig Model of Prolonged Untreated Ventricular Fibrillation

“…20,21,26 Consequently, our recent results on the introduction of an ischaemic post conditioning protocol by limited interruptions of chest compressions during the first 3 min of CPR 5,6 were of a similar magnitude, with one important exception: neurologically intact survival after CPR, a decisive marker of resuscitation success, was significantly improved after prolonged untreated cardiac arrest, 5 indicating a considerable potential to improve cardiac and neurologic outcome and survival after a prolonged global ischaemic insult such as cardiac arrest by VF.…”

“…We have recently shown that ischaemic post conditioning at the initiation of standard 5 or sodium nitroprusside-enhanced cardiopulmonary resuscitation (CPR) 6 significantly improved neurologically intact survival following 15 min of untreated ventricular fibrillation (VF) and concomitant global ischaemia in a porcine model of cardiac arrest. CPR was augmented by the use of an active compression/decompression (ACD) device 7 and an impedance threshold device (ITD).…”

Novelties in pharmacological management of cardiopulmonary resuscitation

“…In an effort to restore myocardial and cerebral energy balance with improved perfusion, a series of studies [31,32 ■ ,33–35] using a porcine model of ventricular fibrillation postulated that infusion of SNP during CPR would improve blood flow and perfusion of vital organs thereby improving resuscitation and recovery. Carotid blood flow, end-tidal CO 2 , and arterial pH were all increased with SNP treatment.…”