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Background Systematic reviews have disclosed a lack of clinically relevant cardiac arrest animal models. The aim of this study was to develop a cardiac arrest model in pigs encompassing relevant cardiac arrest characteristics and clinically relevant post‐resuscitation care. Methods and Results We used 2 methods of myocardial infarction in conjunction with cardiac arrest. One group (n=7) had a continuous coronary occlusion, while another group (n=11) underwent balloon‐deflation during arrest and resuscitation with re‐inflation after return of spontaneous circulation. A sham group was included (n=6). All groups underwent 48 hours of intensive care including 24 hours of targeted temperature management. Pigs underwent invasive hemodynamic monitoring. Left ventricular function was assessed by pressure‐volume measurements. The proportion of pigs with return of spontaneous circulation was 43% in the continuous infarction group and 64% in the deflation‐reinflation group. In the continuous infarction group 29% survived the entire protocol while 55% survived in the deflation‐reinflation group. Both cardiac arrest groups needed vasopressor and inotropic support and pressure‐volume measurements showed cardiac dysfunction. During rewarming, systemic vascular resistance decreased in both cardiac arrest groups. Median [25%;75%] troponin‐I 48 hours after return of spontaneous circulation, was 88 973 ng/L [53 124;99 740] in the continuous infarction group, 19 661 ng/L [10 871;23 209] in the deflation‐reinflation group, and 1973 ng/L [1117;1995] in the sham group. Conclusions This article describes a cardiac arrest pig model with myocardial infarction, targeted temperature management, and clinically relevant post‐cardiac arrest care. We demonstrate 2 methods of inducing myocardial ischemia with cardiac arrest resulting in post‐cardiac arrest organ injury including cardiac dysfunction and cerebral injury.

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Background Neurological injury is the primary cause of death after out-of-hospital cardiac arrest. There is a lack of studies investigating cerebral injury beyond the immediate post-resuscitation phase in a controlled cardiac arrest experimental setting. Methods The aim of this study was to investigate temporal changes in measures of cerebral injury and metabolism in a cardiac arrest pig model with clinically relevant post-cardiac arrest intensive care. A cardiac arrest group (n = 11) underwent 7 min of no-flow and was compared with a sham group (n = 6). Pigs underwent intensive care with 24 h of hypothermia at 33 °C. Blood markers of cerebral injury, cerebral microdialysis, and intracranial pressure (ICP) were measured. After 48 h, pigs underwent a cerebral MRI scan. Data are presented as median [25th; 75th percentiles]. Results Return of spontaneous circulation was achieved in 7/11 pigs. Time to ROSC was 4.4 min [4.2; 10.9]. Both NSE and NfL increased over time (p < 0.001), and were higher in the cardiac arrest group at 48 h (NSE 4.2 µg/L [2.4; 6.1] vs 0.9 [0.7; 0.9], p < 0.001; NfL 63 ng/L [35; 232] vs 29 [21; 34], p = 0.02). There was no difference in ICP at 48 h (17 mmHg [14; 24] vs 18 [13; 20], p = 0.44). The cerebral lactate/pyruvate ratio had secondary surges in 3/7 cardiac arrest pigs after successful resuscitation. Apparent diffusion coefficient was lower in the cardiac arrest group in white matter cortex (689 × 10–6 mm2/s [524; 765] vs 800 [799; 815], p = 0.04) and hippocampus (854 [834; 910] vs 1049 [964; 1180], p = 0.03). N-Acetylaspartate was lower on MR spectroscopy in the cardiac arrest group (− 17.2 log [− 17.4; − 17.0] vs − 16.9 [− 16.9; − 16.9], p = 0.03). Conclusions We have developed a clinically relevant cardiac arrest pig model that displays cerebral injury as marked by NSE and NfL elevations, signs of cerebral oedema, and reduced neuron viability. Overall, the burden of elevated ICP was low in the cardiac arrest group. A subset of pigs undergoing cardiac arrest had persisting metabolic disturbances after successful resuscitation.

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BackgroundCardiac arrest carries a poor prognosis. The typical cardiac arrest patient is comorbid, and studies have shown that diabetes mellitus is an independent risk factor for increased mortality after cardiac arrest. Despite this, animal studies lack to investigate cardiac arrest in the setting of diabetes mellitus.We hypothesize that type 2 diabetes mellitus in a rat model of cardiac arrest is associated with increased organ dysfunction when compared with non-diabetic rats.MethodsZucker diabetic fatty (ZDF) rats (n = 13), non-diabetic Zucker lean control (ZLC) rats (n = 15), and non-diabetic Sprague Dawley (SprD) rats (n = 8), underwent asphyxia-induced cardiac arrest. Animals were resuscitated and monitored for 180 min after return of spontaneous circulation (ROSC).Blood levels of neuron-specific enolase were measured to assess neurological injury. Cardiac function was evaluated by echocardiography.ResultsNo differences in cardiac output or neuron-specific enolase existed between the groups at baseline. Median levels of neuron-specific enolase 180 min after ROSC was 10.8 μg/L (Q25;Q75—7.6;11.3) in the ZDF group, which was significantly higher compared to the ZLC group at 2.0 μg/L (Q25;Q75—1.7;2.3, p < 0.05) and the SprD group at 2.8 μg/L (Q25;Q75—2.3;3.4, p < 0.05). At 180 min after ROSC, cardiac output was 129 mL/min/kg (SD 45) in the ZDF group, which was not different from 106 mL/min/kg (SD 31) in the ZLC group or 123 mL/min/kg (SD 26, p = 0.72) in the SprD group.ConclusionsIn a cardiac arrest model, neuronal injury is increased in type 2 diabetes mellitus animals compared with non-diabetic controls. Although this study lacks to uncover the specific mechanisms causing increased neuronal injury, the establishment of a cardiac arrest model of type 2 diabetes mellitus lays the important foundation for further experimental investigations within this field.

Background Thiamine supplementation has demonstrated protective effects in a mouse model of cardiac arrest. The aim of this study was to investigate the neuroprotective effects of thiamine in a clinically relevant large animal cardiac arrest model. The hypothesis was that thiamine reduces neurological injury evaluated by neuron‐specific enolase levels. Methods and Results Pigs underwent myocardial infarction and subsequently 9 minutes of untreated cardiac arrest. Twenty minutes after successful resuscitation, the pigs were randomized to treatment with either thiamine or placebo. All pigs underwent 40 hours of intensive care and were awakened for assessment of functional neurological outcome up until 9 days after cardiac arrest. Nine pigs were included in both groups, with 8 in each group surviving the entire intensive care phase. Mean area under the curve for neuron‐specific enolase was similar between groups, with 81.5 μg/L per hour (SD, 20.4) in the thiamine group and 80.5 μg/L per hour (SD, 18.3) in the placebo group, with an absolute difference of 1.0 (95% CI, −57.8 to 59.8; P =0.97). Likewise, there were no absolute difference in neurological deficit score at the end of the protocol (2 [95% CI, −38 to 42]; P =0.93). There was no absolute mean group difference in lactate during the intensive care period (1.1 mmol/L [95% CI, −0.5 to 2.7]; P =0.16). Conclusions In this randomized, blinded, placebo‐controlled trial using a pig cardiac arrest model with myocardial infarction and long intensive care and observation for 9 days, thiamine showed no effect in changes to functional neurological outcome or serum levels of neuron‐specific enolase. Thiamine treatment had no effect on lactate levels after successful resuscitation.