Ischemic Postconditioning and Nitric Oxide Administration Failed to Confer Protective Effects in a Porcine Model of Extracorporeal Cardiopulmonary Resuscitation

Abstract

The protective effects of ischemic postconditioning (IPC) and nitric oxide (NO) administration have been demonstrated in several ischemic scenarios. However, current evidence regarding the effect of IPC and NO in extracorporeal cardiopulmonary resuscitation remains lacking. Fifteen female swine (body weight 45 kg) underwent veno-arterial extracorporeal membrane oxygenation (ECMO) implantation; cardiac arrest-ventricular fibrillation was induced by rapid ventricular pacing. After 20 min of cardiac arrest, blood flow was restored by increasing the ECMO flow rate to 4.5 L/min. The animals (five per group) were then randomly assigned to receive IPC (three cycles of 3 min ischemia and reperfusion), NO (80 ppm via oxygenator), or mild hypothermia (HT; 33.0°C). Cerebral oximetry and aortic blood pressure were monitored continuously. After 90 min of reperfusion, blood samples were drawn for the measurement of troponin I, myoglobin, creatine-phosphokinase, alanine aminotransferase, neuron-specific enolase, cystatin C, and reactive oxygen metabolite (ROM) levels. Significantly higher blood pressure and cerebral oxygen saturation values were observed in the HT group compared with the IPC and NO groups (P < 0.05). The levels of troponin I, myoglobin, creatine phosphokinase, and alanine aminotransferase were significantly lower in the HT group (P < 0.05); levels of neuron-specific enolase, cystatin C, and ROM were not significantly different. IPC and NO were comparable in all monitored parameters. The results of the present study indicate that IPC and NO administration are not superior interventions to HT for the maintenance of blood pressure, cerebral oxygenation, organ protection, and suppression of oxidative stress following extracorporeal cardiopulmonary resuscitation.

Adenosine 2A Receptor Activation Attenuates Ischemia Reperfusion Injury During Extracorporeal Cardiopulmonary Resuscitation

“…We standardized our approach with pre-arrest central cannulation, which is more durable then strategies used in other porcine models 30,31 . Different from 30 or 60 minutes of circulatory arrest as used by Rojas and colleagues, we chose a 20-min period due to its clinical relevance and high success rate of electric defibrillation back to sinus rhythm after induction of ECPR 5,31 . The duration of ECMO support in the present study is longer than that reported by other groups in an effort to capture a more complete assessment of IRI after cardiac arrest and ECPR 5 .…”

“…Different from 30 or 60 minutes of circulatory arrest as used by Rojas and colleagues, we chose a 20-min period due to its clinical relevance and high success rate of electric defibrillation back to sinus rhythm after induction of ECPR 5,31 . The duration of ECMO support in the present study is longer than that reported by other groups in an effort to capture a more complete assessment of IRI after cardiac arrest and ECPR 5 . The median duration of support for patients undergoing ECPR in clinical practice ranges from 54-130 hours 32 .…”

“…Even if the restoration of circulation occurs, survivors have a poor prognosis with less than one-third surviving to discharge 3,4 . Global ischemia during cardiac arrest triggers several pathologic pathways that worsen after reperfusion 5 . Ischemia-reperfusion injury (IRI) after cardiac arrest leads to the development of post-arrest reperfusion syndrome, which is responsible for enhanced tissue damage, often with fatal outcomes 6 .…”

“…Extensive efforts have been made to prevent the development and progression of post-cardiac arrest syndrome. To date, the only protective intervention proven to reduce this deadly syndrome and improve clinical outcomes is targeted temperature management, which includes induction of mild hypothermia or controlled normothemia 5 .…”

“…3,4 Global ischemia during cardiac arrest triggers several pathologic pathways that worsen after reperfusion. 5 Ischemia-reperfusion injury (IRI) after cardiac arrest leads to the development of postarrest reperfusion syndrome, which is responsible for enhanced tissue damage, often with fatal outcomes. 6 Extensive efforts have been made to prevent the development and progression of postcardiac arrest syndrome.…”