Pharmacological postconditioning with sevoflurane after cardiopulmonary resuscitation reduces myocardial dysfunction

Abstract

IntroductionIn this study, we sought to examine whether pharmacological postconditioning with sevoflurane (SEVO) is neuro- and cardioprotective in a pig model of cardiopulmonary resuscitation.MethodsTwenty-two pigs were subjected to cardiac arrest. After 8 minutes of ventricular fibrillation and 2 minutes of basic life support, advanced cardiac life support was started. After successful return of spontaneous circulation (N = 16), animals were randomized to either (1) propofol (CONTROL) anesthesia or (2) SEVO anesthesia for 4 hours. Neurological function was assessed 24 hours after return of spontaneous circulation. The effects on myocardial and cerebral damage, especially on inflammation, apoptosis and tissue remodeling, were studied using cellular and molecular approaches.ResultsAnimals treated with SEVO had lower peak troponin T levels (median [IQR]) (CONTROL vs SEVO = 0.31 pg/mL [0.2 to 0.65] vs 0.14 pg/mL [0.09 to 0.25]; P < 0.05) and improved left ventricular systolic and diastolic function compared to the CONTROL group (P < 0.05). SEVO was associated with a reduction in myocardial IL-1β protein concentrations (0.16 pg/μg total protein [0.14 to 0.17] vs 0.12 pg/μg total protein [0.11 to 0.14]; P < 0.01), a reduction in apoptosis (increased procaspase-3 protein levels (0.94 arbitrary units [0.86 to 1.04] vs 1.18 arbitrary units [1.03 to 1.28]; P < 0.05), increased hypoxia-inducible factor (HIF)-1α protein expression (P < 0.05) and increased activity of matrix metalloproteinase 9 (P < 0.05). SEVO did not, however, affect neurological deficit score or cerebral cellular and molecular pathways.ConclusionsSEVO reduced myocardial damage and dysfunction after cardiopulmonary resuscitation in the early postresuscitation period. The reduction was associated with a reduced rate of myocardial proinflammatory cytokine expression, apoptosis, increased HIF-1α expression and increased activity of matrix metalloproteinase 9. Early administration of SEVO may not, however, improve neurological recovery.

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

“…45 This may also be the reason why some previously conducted studies were unable to find an improvement in neurological deficit score or cerebral cellular and molecular pathways when the anaesthetic was given after achievement of ROSC in a pig model of cardiac arrest for only 8 min. 37,46 Whether noble gases differ in this context and provide neurologic and myocardial protection when given later is the subject of ongoing research. 37,39 Certainly, due to their anaesthetic effects volatile anaesthetics require a tight seal and greater caution and need to be scavenged to avoid environmental contamination and potential danger to the emergency personnel when compared to noble gases.…”

Bundled postconditioning therapies improve hemodynamics and neurologic recovery after 17min of untreated cardiac arrest

“…Though the specific mechanisms remain unclear, sevoflurane has previously been shown to improve myocardial function, prevent apoptosis, and reduce cytokine production post-cardiac arrest [14]. …”

“…Ischemic postconditioning, which utilizes structured pauses in CPR, was shown to improve left ventricular ejection fraction (LVEF) and neurologically intact survival in a porcine model of cardiac arrest including 15 minutes of untreated VF [12]. Sevoflurane has been shown to reduce release of cardiac biomarkers, reduce apoptosis, and improve LVEF; however, no difference in neurologic function was reported [13, 14]. Poloxamer 188 (P188) is a nonionic copolymer thought to adhere to gaps in the cell membrane, thereby blocking pores caused by severe cellular stress [15].…”

New Developments in Cardiac Arrest Management

“…Although its exact signaling mechanisms are still unclear, postconditioning likely includes activation of the reperfusion injury salvage kinase and survival activating factor enhancement pathways, and result in reduced apoptosis and improved cardiac and neurologic function and eventually increased survival in different animal models of cardiac arrest [67]. For example, the introduction of several short well-defined pauses limited to only the very beginning of CPR [68], or the very early administration of pharmacologic agents [69–71] to trigger postconditioning pathways show highly promising results in the experimental setting. Before their translation into clinical practice, however, conclusive clinical trials are needed to understand and validate their benefit in humans.…”