Mild therapeutic hypothermia is superior to controlled normothermia for the maintenance of blood pressure and cerebral oxygenation, prevention of organ damage and suppression of oxidative stress after cardiac arrest in a porcine model

Abstract

BackgroundMild therapeutic hypothermia (HT) has been implemented in the management of post cardiac arrest (CA) syndrome after the publication of clinical trials comparing HT with common practice (ie, usually hyperthermia). Current evidence on the comparison between therapeutic HT and controlled normothermia (NT) in CA survivors, however, remains insufficient.MethodsEight female swine (sus scrofa domestica; body weight 45 kg) were randomly assigned to receive either mild therapeutic HT or controlled NT, with four animals per group. Veno-arterial extracorporeal membrane oxygenation (ECMO) was established and at minimal ECMO flow (0.5 L/min) ventricular fibrillation was induced by rapid ventricular pacing. After 20 min of CA, circulation was restored by increasing the ECMO flow to 4.5 L/min; 90 min of reperfusion followed. Target core temperatures (HT: 33°C; NT: 36.8°C) were maintained using the heat exchanger on the oxygenator. Invasive blood pressure was measured in the aortic arch, and cerebral oxygenation was assessed using near-infrared spectroscopy. After 60 min of reperfusion, up to three defibrillation attempts were performed. After 90 min of reperfusion, blood samples were drawn for the measurement of troponin I (TnI), myoglobin (MGB), creatine-phosphokinase (CPK), alanin-aminotransferase (ALT), neuron-specific enolase (NSE) and cystatin C (CysC) levels. Reactive oxygen metabolite (ROM) levels and biological antioxidant potential (BAP) were also measured.ResultsSignificantly higher blood pressure and cerebral oxygenation values were observed in the HT group (P<0.05). Sinus rhythm was restored in all of the HT animals and in one from the NT group. The levels of TnI, MGB, CPK, ALT, and ROM were significantly lower in the HT group (P<0.05); levels of NSE, CysC, and BAP were comparable in both groups.ConclusionsOur results from animal model of cardiac arrest indicate that HT may be superior to NT for the maintenance of blood pressure, cerebral oxygenation, organ protection and oxidative stress suppression following CA.

Remote Postconditioning Alone and Combined with Hypothermia Improved Postresuscitation Cardiac and Neurological Outcomes in Swine

“…However, animal studies have confirmed that TH protected postresuscitation heart and brain by decreasing oxidant stress, inflammation, and apoptosis. Earlier, Ostadal et al [33] demonstrated that HT produced cardiac protection through the suppression of oxidative stress following CA. Recently, another two studies demonstrated that TH protected post-CPR heart and brain by reducing the expression of inflammatory cytokines and cell apoptosis [28, 29].…”

Inducibility of ventricular fibrillation during mild therapeutic hypothermia: electrophysiological study in a swine model

“…According to animal studies [9-13], early induction of MTH is supposed to be beneficial, but clinical trials did not prove it consistently yet [14-17]. Consequently, earliest possible induction of MTH is emphasized in some recent protocols using nasopharyngeal evaporative cooling and peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) hoping to improve the neurological outcome [18-22].…”

Therapeutic Hypothermia Reduces Oxidative Damage and Alters Antioxidant Defenses after Cardiac Arrest

“…BAP was also evaluated in the serum of animals receiving MTH in a porcine model of CA, but no significant difference was found [12]. The BAP provides a global measurement of many enzymatic and nonenzymatic antioxidants together, indistinctly.…”

“…MTH also prevents damage to other tissues, including the myocardium, liver, and kidney [12]. Damage protection by MTH is reinforced by studies demonstrating reduced oxidative damage after treatment [11–13].…”