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

Abstract

Background Anaesthetic postconditioning (APoC) attenuates myocardial injury following coronary ischaemia/reperfusion. We hypothesised that APoC at the initiation of cardiopulmonary resuscitation (CPR) will improve post resuscitation myocardial function along with improved mitochondrial function in a pig model of prolonged untreated ventricular fibrillation. Methods In 32 pigs isoflurane anaesthesia was discontinued prior to induction of ventricular fibrillation that was left untreated for 15 min. At the initiation of CPR, 15 animals were randomised to controls (CON), and 17 to APoC with 2 Vol% sevoflurane during the first 3 min CPR. Pigs were defibrillated after 4 min of CPR. After return of spontaneous circulation (ROSC), isoflurane was restarted at 0.8-1.5 Vol% in both groups. Systolic and diastolic blood pressures were measured continuously. Of the animals that achieved ROSC, 8 CON and 8 APoC animals were randomised to have their left ventricular ejection fraction (LVEF%) assessed by echocardiography at 4 hrs. Seven CON and 9 APoC were randomised to euthanasia 15 min after ROSC to isolate mitochondria from the left ventricle for bioenergetic studies. Results ROSC was achieved in 10/15 CON and 15/17 APoC animals. APoC improved haemodynamics during CPR and post-CPR LVEF%. Mitochondrial ATP synthesis, coupling of oxidative phosphorylation and calcium retention capacity were improved in cardiac mitochondria isolated after APoC. Conclusions In a porcine model of prolonged untreated cardiac arrest, APoC with inhaled sevoflurane at the initiation of CPR, is associated with preserved mitochondrial function and improved post resuscitation myocardial dysfunction.

Deferoxamine-activated hypoxia-inducible factor-1 restores cardioprotective effects of sevoflurane postconditioning in diabetic rats

“…Sevoflurane, a commonly used inhalation anaesthetic agent in clinical practice, is considered the cornerstone of this drug class because of its favourable characteristics, including smooth induction of anaesthesia, rapid post-operative recovery and minimal impact on hemodynamics. Several studies have demonstrated that SpostC can protect healthy myocardium from I/R injury, [6][7][8][9]28 but the underlying mechanism remains unclear. Interestingly, our previous studies found that the protective effects of SpostC on isolated myocardial mitochondria can be attributed to the upregulation of HIF-1a.…”

“…5 Sevoflurane is an ideal inhaled anaesthetic agent that is widely used in peri-operative anaesthesia. [6][7][8][9] Unfortunately, diabetes abolishes the cardioprotective effects of SpostC, [10][11][12] and the underlying mechanism remains unclear. [6][7][8][9] Unfortunately, diabetes abolishes the cardioprotective effects of SpostC, [10][11][12] and the underlying mechanism remains unclear.…”

“…On normal myocardium, sevoflurane postconditioning (SpostC) has cardioprotective effects that are similar to ischaemic preconditioning, and SpostC is a potentially important approach for the prevention of perioperative cardiac ischaemia/reperfusion (I/R) injury. [6][7][8][9] Unfortunately, diabetes abolishes the cardioprotective effects of SpostC, [10][11][12] and the underlying mechanism remains unclear. Therefore, it is of great significance to improve or restore SpostC cardioprotection under diabetic conditions and thereby reduce the incidence of adverse peri-operative cardiac events.…”

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

“…At the conclusion of the experimental protocol, mitochondria were isolated at 4°C via differential centrifugation from the left ventricle of the heart and brain as described previously(12,13). State 3 (S3) and State 4 (S4) respiration, the rate of ATP synthesis, and calcium retention capacity (CRC) were quantified as previously described(12).…”

“…State 3 (S3) and State 4 (S4) respiration, the rate of ATP synthesis, and calcium retention capacity (CRC) were quantified as previously described(12). The respiratory control index (RCI) was calculated as the ratio of S3 to S4 respiration.…”