Cardiopulmonary Resuscitation In Pigs Research Articles

The Protective Effect and Mechanism of Mild Hypothermia on Lung Injury after Cardiopulmonary Resuscitation in Pigs.

To explore the protective effect and mechanism of mild hypothermia on lung tissue damage after cardiopulmonary resuscitation in pigs. In this experiment, we electrically stimulated 16 pigs (30 ± 2 kg) for 10 min to cause ventricular fibrillation. The successfully resuscitated animals were randomly divided into two groups, a mild hypothermia group and a control group. We took arterial blood 0.5, 1, 3, and 6 h after ROSC recovery in the two groups of animals for blood gas analysis. We observed the structural changes of lung tissue under an electron microscope and calculate the wet weight/dry weight (W/D) ratio. We quantitatively analyzed the expression differences of representative inflammatory factors [interleukin-6 (IL-6) and tumor necrosis factor-alpha TNF-α)] through the ELISA test. We detected the expression levels of Bax, Bcl-2, and Caspase-3 proteins in lung tissues by Western blot. After 3 h and 6 h of spontaneous circulation was restored, compared with the control group, PaO2/FiO2 decreased significantly (P < 0.05). In addition, the pathological changes, lung W/D and lung MDA of the mild hypothermia group were better than those of the control group. The levels of IL-6 and TNF-α in the lung tissue of the mild hypothermia group were significantly lower than those of the control group (P < 0.05). The content of Caspase-3 and Bax in the mild hypothermia group was significantly lower than that of the control group. Our experiments have shown that mild hypothermia can reduce lung tissue damage after cardiopulmonary resuscitation.

Effects of Prolonged Serum Calcium Suppression during Extracorporeal Cardiopulmonary Resuscitation in Pigs.

Controlled reperfusion by monitoring the blood pressure, blood flow, and specific blood parameters during extracorporeal reperfusion after cardiac arrest has the potential to limit ischemia-reperfusion injury. The intracellular calcium overload as part of the ischemia-reperfusion injury provides the possibility for the injury to be counteracted by the early suppression of serum calcium with the aim of improving survival and the neurological outcome. We investigated the effects of prolonged serum calcium suppression via sodium citrate during extracorporeal resuscitation using the CARL protocol (CARL-controlled automated reperfusion of the whole body) compared to a single-dose approach in a porcine model after prolonged cardiac arrest. A control group (N = 10) was resuscitated after a 20 min cardiac arrest, initially lowering the intravascular calcium with the help of a single dose of sodium citrate as part of the priming solution. Animals in the intervention group (N = 13) received additional sodium citrate for the first 15 min of reperfusion. In the control group, 9/10 (90.0%) animals survived until day 7 and 7/13 (53.8%) survived in the intervention group (p = 0.09). A favorable neurological outcome on day 7 after the cardiac arrest was observed in all the surviving animals using a species-specific neurological deficit score. The coronary perfusion pressure was significantly lower with a tendency towards more cardiac arrhythmias in the intervention group. In conclusion, a prolonged reduction in serum calcium levels over the first 15 min of reperfusion after prolonged cardiac arrest tended to be unfavorable regarding survival and hemodynamic variables compared to a single-dose approach in this animal model.

Abstract 11244: Active Decompression During Device Assisted Elevation of the Head and Thorax, an Impedance Threshold Device, and Active Compression Decompression Cardiopulmonary Resuscitation is Needed for Sustained Hemodynamic Benefit in a Porcine Model of Prolonged Cardiac Arrest

Introduction: Active compression decompression cardiopulmonary resuscitation (CPR), an impedance threshold device (ITD), and automated device-assisted controlled head up positioning, collectively termed AHUP CPR, work synergistically to lower intracranial pressure, augment venous return to the heart and significantly improve neurological survival versus conventional (C)-CPR in animals and patients in cardiac arrest. The current study focused on the role of active decompression (AD) during prolonged AHUP CPR, since AD can be difficult to perform manually for an extended period. Hypothesis: Full AD is needed to optimize hemodynamics during prolonged AHUP CPR Methods: Six female and male farm pigs (~40 kg) were sedated, intubated, anesthetized, and monitored. After 8 min of untreated ventricular fibrillation followed by ≥ 30 min of AHUP CPR with an automated device, AHUP CPR was continued except that AD was intentionally reduced from an average of 3.33 ± 0.37 cm of lift to 0 cm lift above the resting neutral position as this is the amount of decompression that occurs with C-CPR and passive chest wall recoil. After 1 min of AHUP CPR with 0 cm lift, AD was progressively increased back to 3 cm of lift over 3 min. Hemodynamics (mean ± SD) were compared using Student’s t test, where p&lt;0.05 was considered statistically significant. Results Coronary perfusion pressure (CorPP) (p&lt;0.005), cerebral perfusion pressure (CerPP) (p&lt;0.001), and ETCO2 (p&lt;0.0001) significantly decreased after AD was discontinued (Fig.1). With restoration of AD to 3 cm, CorPP (p&lt;0.009) and ETCO2 (p&lt;0.001) significantly improved and CerPP trended higher (p=0.084). Conclusion During prolonged (≥ 30 min) AHUP CPR in pigs, active lift of the chest wall is essential to maintain stable hemodynamics. Hemodynamics deteriorated rapidly with intentional loss of AD, but could be partially restored with resumption of AD.

The Effects of Alda-1 Treatment on Renal and Intestinal Injuries After Cardiopulmonary Resuscitation in Pigs.

AimAfter successful cardiopulmonary resuscitation (CPR), most survivors will develop acute kidney injury and intestinal barrier dysfunction, both of which contribute to the poor outcomes of cardiac arrest (CA) victims. Recently, the aldehyde dehydrogenase 2 (ALDH2) agonist, Alda-1 was shown to effectively alleviate regional ischemia/reperfusion injury of various organs. In the present study, we investigated the effects of Alda-1 treatment on renal and intestinal injuries after CA and resuscitation in pigs.MethodsTwenty-four male domestic pigs were randomly divided into one of the three groups: sham (n = 6), CPR (n = 10), or CPR+Alda-1 (n = 8). CA was induced and untreated for 8 min, and then CPR was performed for 8 min in the CPR and CPR+Alda-1 groups. At 5 min after resuscitation, a dose of 0.88 mg/kg of Alda-1 was intravenously administered in the CPR+Alda-1 group. The biomarkers of renal and intestinal injuries after resuscitation were regularly measured for a total of 24 h. Subsequently, the animals were euthanized, and then renal and intestinal tissues were obtained for the measurements of ALDH2 activity and expression, and cell apoptosis and ferroptosis.ResultsFive of the 10 animals in the CPR group and six of the eight animals in the CPR+Alda-1 group were successfully resuscitated. After resuscitation, the levels of biomarkers of renal and intestinal injuries were significantly increased in all animals experiencing CA and resuscitation compared with the sham group; however, Alda-1 treatment significantly alleviated renal and intestinal injuries compared to the CPR group. Post-resuscitation ALDH2 activity was significantly decreased and its expression was markedly reduced in the kidney and intestine in those resuscitated animals compared with the sham group; nevertheless, both of them were significantly greater in those animals receiving Alda-1 treatment compared to the CPR group. In addition, renal, intestinal apoptosis and ferroptosis after resuscitation were observed in the CPR and CPR+Alda-1 groups, in which both of them were significantly milder in the CPR+Alda1 group than in the CPR group.ConclusionsThe activation of ALDH2 by Alda-1 treatment significantly alleviated post-resuscitation renal and intestinal injuries through the inhibition of cell apoptosis and ferroptosis in a pig model of CA and resuscitation.

Protective effect and mechanism of mild hypothermia on liver injury after cardiopulmonary resuscitation in pigs

Objective: To investigate the effect of mild hypothermia therapy on liver after cardiopulmonary resuscitation. Methods: Thirty-three inbred Chinese Wuzhishan (WZS) minipigs, weighted (28±2) kg, were used to establish a ventricular fibrillation model. And 30 animals survived after cardiopulmonary resuscitation reached basic life support. The surviving animals were randomly divided into two groups: mild hypothermia group (group M, n=15) and conventional treatment group (group C, n=15). All the animals were observed for 24 hours. Blood samples were extracted at baseline, 0.5, 1, 2, 4, 6, 12 and 24 h after successful resuscitation. The concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected at the time points. The enzyme-linked immunosorbent assay (ELISA) was used to detect the concentrations of interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α). The data were compared between the two groups, LSD test was used when the variance was homogeneous, and Tamhane T2 test was used when the variance was uneven. Results: Eleven pigs (73.3%) in the group M and 8(53.3%) in the group C survived at 24 h after successful resuscitation, with no statistically significant difference between the two groups (χ(2)=1.229, P=0.225). After successful resuscitation, the AST, ALT increased in both group but less in M group (all P<0.05). After successful resuscitation, the concentrations of TFN-α and IL-6 in the blood increased in both groups, reached the peak at 4h, and then decreased gradually. The concentrations of TFN-α in group M were lower than those in group C at 0.5, 2, 4 and 6 h after successful resuscitation (t=0.01, 0.01, 0.87, 0.86, all P<0.05). The concentrations of IL-6 in the group M were lower than those in group C at 0.5, 1, 2 and 4 h after successful resuscitation (t=0.23, 0.78, 0.11, 0.80, all P<0.05). Conclusions: After successful resuscitation, the release of inflammatory mediators, such as TNF-α and IL-6, and cell apoptosis may involve in liver ischemia reperfusion injury. After successful resuscitation, the liver undergoes ischemia-reperfusion injury, which may be related to the release of inflammatory mediators such as TNF-α and IL-6. Mild hypothermia therapy can prevent the release of TNF-α, IL-6 to reduce the degree of liver damage after resuscitation.

Effects of different adrenaline doses on cerebral oxygenation and cerebral metabolism during cardiopulmonary resuscitation in pigs

BackgroundThe influence of adrenaline during cardiopulmonary resuscitation (CPR) on the neurological outcome of cardiac arrest survivors is unclear. As little is known about the pathophysiological effects of adrenaline on cerebral oxygen delivery and cerebral metabolism we investigated its effects on parameters of cerebral oxygenation and cerebral metabolism in a pig model of CPR. MethodsFourteen pigs were anesthetized, intubated and instrumented. After 5 min of cardiac arrest CPR was started and continued for 15 min. Animals were randomized to receive bolus injections of either 15 or 30 μg/kg adrenaline every 5 min after commencement of CPR. ResultsMeasurements included mean arterial pressure (MAP), intracranial pressure (ICP), cerebral perfusion pressure (CPP), cerebral regional oxygen saturation (rSO2), brain tissue oxygen tension (PbtO2), arterial and cerebral venous blood gases and cerebral microdialysis parameters, e.g. lactate/pyruvate ratio. Adrenaline induced a significant increase in MAP and CPP in all pigs. However, increases in MAP and CPP were short-lasting and tended to decrease with repetitive bolus administration. There was no statistical difference in any parameter of cerebral oxygenation or metabolism between study groups. ConclusionsBoth adrenaline doses resulted in short-lasting CPP peaks which did not translate into improved cerebral tissue oxygen tension and metabolism. Further studies are needed to determine whether other dosing regimens targeting a sustained increase in CPP, may lead to improved brain oxygenation and metabolism, thereby improving neurological outcome of cardiac arrest patients.

Protective effect of ulinastatin on myocardial injury after cardiopulmonary resuscitation in pigs

Objective To evaluate the protective effect of ulinastatin (UTI) on myocardial injury after post-cardiac arrest syndrome (PCAS) of cardiopulmonary resuscitation in pigs. Methods Twelve male 3-4 months pigs were randomly divided into two groups, UTI group and control group. The ventricular fibrillation (VF) animal model was replicated by programmed stimulation method. Among the 12 pigs, 11 pigs were successfully resuscitated by CPR after 5 min VF, of which, 6 pigs were in the UTI group and 5 pigs in the control group. Immediately after resuscitation, pigs in the UTI group was given 100 kU dissolved in 5 mL normal saline with slowly injection every 3 h until 24 h after recovery (no drug was given at 24 h). In the control group, 5 mL normal saline was given with same delivery time and frequency as that in the UTI group. The venous blood of the pigs was collected at VF, 2, 4, 6, 12, and 24 h after ROCS, and tumor necrosis factor -α (TNF-α), interleukin-6 (IL-6), superoxide dismutase (SOD), malondialdehyde (MDA), and ischemia modified albumin (IMA) were measured by enzyme-linked immunosorbent assay (ELISA) method. Because IMA was sensitive and increased rapidly, venous blood was detected at 1 h after ROSC, and the rest test time were same with the rest of the blood factors. Statistical analysis was performed using LSD-t test and variance analysis. The pigs were sacrificed 24 h after ROSC, and specimens from heart tissue were taken for HE staining. Results Before ventricular fibrillation in three groups, there was no significant difference in serum levels of inflammatory cytokines, oxidative stress indexes, and myocardial ischemia markers between the two groups (P>0.05). At 2 h after ventricular fibrillation, the levels of TNF-α and IL-6 level in the UTI group was significantly lower than those in the control group. At 4 h, MDA level in the UTI group was significantly lower than that in the control group (P 0.05). HE staining results showed that the damage degree of myocardial tissue in the UTI group was significantly lower than that in the control group at 24 h after ROSC. Conclusions UTI can significantly antagonize inflammatory response, reduce oxidative stress, and improve the myocardial tissue injury after resuscitation. It can protect myocardial injury after cardiopulmonary resuscitation. Key words: Ulinastatin; Cardiopulmonary resuscitation; Post-cardiac arrest syndrome; Tumor necrosis factor -αInterleukin-6; Superoxide dismutase; Ischemia modified albumin

Protective effect of extracorporeal membrane oxygenation on intestinal mucosal injury after cardiopulmonary resuscitation in pigs.

The present study aimed to explore the protective effects of extracorporeal membrane oxygenation (ECMO) on intestinal mucosal injury following cardiopulmonary resuscitation (CPR), and to assess the potential mechanisms involved. A total of 24 healthy adult domestic pigs were selected as the study subjects. A ventricular fibrillation model was induced through programmed electric stimulation. Subsequently, the animals were randomly divided into conventional CPR and CPR+ECMO groups (n=12 per group). The mortality and hemodynamic parameters of the two groups were compared. The expression levels of inflammatory cytokines in the serum and intestinal mucosa were detected by ELISAs. The intestinal mucosa was subjected to hematoxylin and eosin, and immunohistochemical staining, followed by electron microscopy, to assess the degree of apoptosis and necrosis. The animals in both groups recovered from the programmed ventricular fibrillation. In the CPR group, two animals died at 2 h and two more animals died a further 2 h later, resulting in a 33.3% mortality rate, whereas no cases of mortality were observed in the CPR+ECMO group. Compared with the animals in the CPR group, the hemodynamic parameters of the animals in the CPR+ECMO group revealed significantly improved outcomes. Multiple inflammatory factors (tumor necrosis factor α, interleukin-1 and interleukin-6), myeloperoxidase and malondialdehyde levels were decreased, whereas Na/Ca-ATPase and superoxide dismutase levels were elevated in the intestinal mucosa of animals in the CPR+ECMO group compared with those in the CPR group. Additionally, pathological staining demonstrated that the intestinal mucosa tissue in the CPR+ECMO group exhibited less apoptosis, necrosis and inflammatory cell infiltration, which was further supported by a decrease in Bax expression and an increase in Bcl-2 expression. Overall, ECMO after CPR reduced the intestinal mucosal barrier injury after spontaneous circulation recovery, and the mechanism involved decreased inflammation and apoptosis.

Effects of Shenfu injection on the expression of transcription factors T-bet / GATA-3 in pigs with post-resuscitation myocardial dysfunction

To examine whether Shenfu injection (SFI) reduces post-resuscitation myocardial dysfunction in a pig model by modulating expression imbalance of transcription factors of regulatory T cell, namely GATA-3 and T-bet. Thirty pigs were randomly divided into sham group (n = 6) and cardiopulmonary resuscitation (CPR) group (n = 24) according to the random number table method, and the pigs in the CPR group were randomly subdivided into normal saline (NS) group, epinephrine (EP) group, and SFI group (n = 8 per group). After 8 minutes of untreated ventricular fibrillation (VF) followed by 2 minutes of CPR, animals in three groups respectively received central venous injection of either 20 mL SFI (1.0 mL/kg, SFI group), EP (0.02 mg/kg, EP group) or NS (NS group). Blood samples were obtained before VF and 0.5, 2, 6 hours after restoration of spontaneous circulation (ROSC), and the parameters of hemodynamics and oxygen metabolism were determined. Surviving pigs were sacrificed at 24 hours after ROSC, the pathological changes in myocardium were observed, the levels of interleukin-4 (IL-4), tumor necrosis factor-α (TNF-α) and γ-interferon (IFN-γ) were measured by enzyme linked immunosorbent assay (ELISA), and expressions of protein and mRNA of GATA-3 and T-bet were determined by Western Blot and quantitative real-time polymerase chain reaction (RT-qPCR), respectively. Six pigs of three resuscitation groups were successfully resuscitated. The CPR time, number of defibrillation, defibrillation energy, and ROSC time were significantly decreased in the EP and SFI groups compared with those in the NS group. Compared with the sham group, the parameters of left ventricular systolic function and oxygen metabolism were significantly decreased, myofibril organelles were extensively damaged, and progressive and severe deterioration of the myocardium was found, and mitochondrial structure was not recognizable in the NS group; the level of IL-4 in myocardium were markedly decreased, while that of TNF-α, IFN-γ and IFN-γ/ IL-4 [reflecting helper T cell 1/2 (Th1/Th2)] were significantly increased. Protein and mRNA expressions of GATA-3 were markedly reduced in the myocardium of pigs in the NS group compared with that of the sham group at 24 hours after ROSC, while T-bet was significantly increased. Compared with the NS group, animals treated with SFI had minimal myocardial intracellular damage, with decreased heart rate (HR, bpm: 90.33 ± 3.79 vs. 106.83 ± 5.36) and increased mean arterial pressure (MAP), cardiac output (CO), oxygen delivery (DO₂), and oxygen consumption (VO₂) at 6 hours after ROSC [MAP (mmHg, 1 mmHg = 0.133 kPa): 107.67 ± 1.96 vs. 86.83 ± 1.85, CO (L/min): 2.47 ± 0.08 vs. 2.09 ± 0.04, DO₂ (mL/min): 364.31 ± 4.21 vs. 272.33 ± 3.29, VO₂(mL/min): 95.00±2.22 vs. 82.50 ±2 .28, all P < 0.05]. Compared with the NS groups at 24 hours after ROSC, level of IL-4 was markedly increased in myocardial cells (ng/L: 33.80 ± 3.06 vs. 16.15 ± 1.34, P < 0.05), while the levels of TNF-α, IFN-γ and IFN-γ/IL-4 were lowered significantly [TNF-α (ng/L): 18.16 ± 0.71 vs. 29.64 ± 1.89, IFN-γ (ng/L): 373.75 ± 18.36 vs. 512.86 ± 27.86, IFN-γ/IL-4: 16.15 ± 1.34 vs. 33.80 ± 3.06, all P < 0.05], and myocardial T-bet protein and mRNA expressions were reduced [T-bet protein (gray value): 0.41 ± 0.07 vs. 0.59 ± 0.11, T-bet mRNA (2(-ΔΔCt)): 4.37 ± 0.21 vs. 7.57 ± 0.55, both P < 0.05], furthermore, myocardial GATA-3 protein and mRNA expressions were significantly up-regulated in SFI group [GATA-3 protein (gray value): 0.25 ± 0.07 vs. 0.16 ± 0.07, GATA-3 mRNA (2(-ΔΔCt)): 0.63 ± 0.07 vs. 0.34 ± 0.05, both P < 0.05]. The parameters in SFI group were significantly improved compared with those of the EP group. Myocardial immune dysfunction is induced by Th1/Th2 imbalance following myocardial injury subsequent to CPR in pigs. SFI can attenuate myocardial injury and regulate myocardial immune disorders, protect post-resuscitation myocardial injury by modulating expression imbalance of transcription factors GATA-3 and T-bet.

Argon: a novel therapeutic option to treat neuronal ischemia and reperfusion injuries?

Neuronal injury and neuroprotection: Ischemia and reperfusion injuries in neuronal cells such as acute ischemic stroke - represent the third leading cause of death in the world. Current therapeutic concepts mainly aim to re-establish cerebral blood flow within a time window of less than 3 hours with the goal of limiting secondary brain injury. Secondary brain injury of the “penumbra” develops exponentially, causing severe mental and physical disabilities. The resulting morbidity and mortality in patients of all ages leads to an enormous economic burden. Neurons are well-known to possess a limited potential to recover and regenerate their basic function once damaged. Therefore the protection and especially the therapy of neuronal injuries in cells and organ systems has emerged as a major focus of research in recent years. The aim is to maximize neuronal function not only by restoring sufficient blood flow to the areas at risk, but also by protecting neuronal cells with various novel interventions. Many of these interventions, such as intravascular cooling, focus on the reduction of neuronal metabolism in an effort to induce protection.

Effect of ulinastatin on improving inflammatory response and myocardial and lung tissue injury after cardiopulmonary resuscitation in pigs

To evaluate the effects of ulinastatin (UTI) on improving inflammatory response and myocardial and lung tissue injury after cardiopulmonary resuscitation (CPR) in porcine model. Ventricular fibrillation (VF) was induced in 20 female pigs by programmed stimulation method. CPR was begun 8 minutes after VF. Pigs with recovery of spontaneous circulation (ROSC) were randomly divided into two groups: group UTI, UTI was given immediately after resuscitation, with 100 kU dissolved in 5 ml of normal saline by slow intravenous injection every 3 hours, up to 24 hours after resuscitation. In control group, 5 ml of normal saline was given with same delivery time and frequency as that in the UTI group. Before VF, immediately after ROSC, 3 hours, 12 hours and 24 hours after ROSC, samples of venous blood were collected for examination of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), using the enzyme-linked immunospecific assay (ELISA) method. The pigs were sacrificed at 24 hours after ROSC for myocardium and lung pathological and ultrastructural examinations. Among a total of 20 domestic pigs, 15 pigs were successfully resuscitated after 8-minute VF. Eight pigs in UTI group and 7 pigs in control group survived for 24 hours. Pro-inflammatory factors of the both groups were increased gradually after ROSC. Levels of TNF-α, IL-1β, ICAM-1 and VCAM-1 were not significant different between UTI and control groups before VF and immediately after ROSC. But TNF-α and IL-1β levels were significantly lower in the UTI group than those of the control group beginning from 3 hours after ROSC (TNF-α: 28.79±9.49 ng/L vs. 44.01±17.01 ng/L, IL-1β: 153.50±67.47 ng/L vs. 252.09±80.41 ng/L, both P<0.05); ICAM-1 and VCAM-1 levels were significantly lower in the UTI group than those of the control group from 12 hours after ROSC (ICAM-1: 11.05±5.11 μg/L vs. 17.09±5.69 μg/L, VCAM-1: 11.17±4.75 μg/L vs. 16.62±4.63 μg/L, both P<0.05). The myocardium and lung injuries at 24 hours after ROSC were significantly milder in UTI group than that of the control group. UTI can significantly reduce the pro-inflammatory reaction and the extent of myocardial and lung tissue injury after resuscitation.

Shen-Fu Injection Reduces Postresuscitation Myocardial Dysfunction in a Porcine Model of Cardiac Arrest by Modulating Apoptosis

Shen-Fu injection (SFI) following cardiac arrest exhibits cardioprotective effects, but its effect on myocardial dysfunction, a critical issue following resuscitation, is unclear. This study sought to examine whether SFI reduces postresuscitation myocardial dysfunction in a porcine model of cardiac arrest by modulating apoptosis. After 8 min of untreated ventricular fibrillation and 2 min of basic life support, 24 pigs were randomized divided into three groups, which received central venous injection of either Shen-Fu (SFI group; 1.0 mL/kg), epinephrine (EP group; 0.02 mg/kg), or saline (SA group). After successful return of spontaneous circulation (ROSC), hemodynamic status and blood samples were obtained at 0, 30, 120, and 360 min after ROSC. Surviving pigs were killed at 24 h after ROSC, and the hearts were removed for analysis by electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay. Compared with the EP and SA groups, animals treated with SFI had improved left ventricular function (P < 0.05), lower troponin T levels (P < 0.01), and increased tissue perfusion and oxygen metabolism (P < 0.05). Shen-Fu injection was associated with a reduction in (i) Bcl-2, Bax, and caspase 3 protein expression (P < 0.05); (ii) caspase 3 mRNA upregulation; and (iii) apoptosis, compared with the EP and SA groups. Caspase 3-mediated apoptosis occurs following myocardial injury after cardiopulmonary resuscitation in pigs. Shen-Fu injection decreased myocardial injury; improved myocardial ultrastructure; inhibited Bcl-2, Bax, and caspase 3 expression; and reduced myocardial apoptosis. Therefore, SFI could significantly attenuate postresuscitation myocardial dysfunction by modulating apoptosis.

Impairment of carotid artery blood flow by supraglottic airway use in a swine model of cardiac arrest

ObjectiveSupraglottic airway devices (SGDs) are often used as an alternative to endotracheal tube (ETT) during cardiopulmonary resuscitation (CPR). SGDs can be inserted ‘blindly’ and rapidly, without stopping compressions. These devices utilize pressurized balloons to direct air to the trachea and prevent esophagus insufflation. We hypothesize that the use of a SGD will compress the carotid artery and decrease carotid blood flow (CBF) during CPR in pigs. MethodsVentricular fibrillation (VF) was induced in 9 female pigs (32±1kg) followed by 4min without compressions. CPR was then performed continuously for 3–6-min intervals. During each interval, an ETT was used for the first 3min, followed by 3min of each SGD (King LTS-D™, LMA Flexible™, Combitube™) in a random order. The primary endpoint was mean CBF (ml/min). Statistical comparisons among the 4 airway devices were performed by Wilcoxon Rank test. Post mortem carotid arteriographies were performed with SGDs in place. ResultsCBF (median ml/min; 25/75 percentile) was significantly lower with each SGD [King (10; 6/41), LMA (10; 4/39), and Combitube (5; −0.4/15)] versus ETT (21; 14/46) (p<0.05 for each SGD compared with ETT). Arteriograms showed that with each SGD there was compression of the internal and external carotid vessels. ConclusionThe use of 3 different SGDs during CPR significantly decreased CBF in a porcine model of cardiac arrest. While the current study is limited to pigs, the findings suggest that further research on the effects of SGD use in humans and the effects on carotid artery blood flow is warranted.

Investigation of Myocardial Stunning after Cardiopulmonary Resuscitation in Pigs

Objective To investigate cardiac function and myocardial perfusion during 48 h after cardiopulmonary resuscitation (CPR), further to test myocardial stunning and seek indicators for long-term survival after CPR. Methods After 4 min of untreated ventricular fibrillation, fifteen anesthetized pigs were studied at baseline and 2 h, 4 h, 24 h, and 48 h after restoration of spontaneous circulation (ROSC). Hemodynamic data, echocardiography and gated-single photon emission computed tomography myocardial perfusion images were carried out. Results Mean arterial pressure (MAP), coronary perfusion pressure (CPP) and cardiac troponin I (CTNI) showed significant differences between eventual survival animals and non-survival animals at 4 h after ROSC (109.2±10.7 mmHg vs. 94.8±12.3 mmHg, P=0.048; 100.8±6.9 mmHg vs. 84.4±12.6 mmHg, P=0.011; 1.60±0.13 ug/L vs. 1.75±0.10 ug/L, P=0.046). Mitral valve early-to-late diastolic peak velocity ratio, mitral valve deceleration time recovered 24 h; ejection faction and the summed rest score recovered 48 h after ROSC. Conclusion Cardiac systolic and early active relaxation dysfunctions were reversible within survival animals; cardiac stunning might be potentially adaptive and protective after CPR. The recovery of MAP, CPP, and CTNI could be the indicators for long-term survival after CPR.

Adrenal glands blood flow and noradrenaline plasma concentration during cardiopulmonary resuscitation in pigs

In comparison to adrenaline, administration of vasopressin during cardiopulmonary resuscitation (CPR) increases adrenal glands perfusion (1), but decreases catecholamine secretion when compared to saline placebo (2). In experimental CPR, animals that were subsequently resuscitated had increased noradrenaline concentrations after administration of adrenaline, while in contrast, animals that could not be resuscitated had either no change or decreased plasma noradrenaline levels after exogenous adrenaline (3).

The effects on brain function and ultrastructure changes by elevating mean arterial pressure after cardio-pulmonary resuscitation in pigs

To investigate the effects on brain function and ultrastructure changes by elevating mean arterial pressure (MAP) with norepinephrine after cardiopulmonary resuscitation (CPR) in pigs. After 4 minutes of untreated ventricular fibrillation, CPR was begun in 10 piglets, followed by defibrillation. Following the restoration of spontaneous circulation (ROSC), the animals were randomly assigned to two treatment groups: the hypertension group (HT, n=5), in which animals were given an infusion of norepinephrine to maintain the MAP to 130% above that before ventricular fibrillation, and the normal perfusion group (NP, n=5) who received an infusion of norepinephrine to maintain the MAP to that obtained right after ROSC. Sham-operation group of 2 animals were treated identically, with the exception that neither cardiac arrest was induced nor CPR was performed, to serve as control group. Variables of hemodynamics were measured at baseline and also 4 hours after ROSC. The overall performance categories (OPC) was evaluated 24 hours after ROSC. Then, animals were sacrificed and the brains were removed for histopathological examination of cerebral cortex, CA1 region of hippocampus, cerebellar cortex, and corpus striatum for the assay of histological damage score (HDS), and apoptosis of cerebral neurons were evaluated [terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)] 24 hours after ROSC. The ultrastructure of neurons was characterized, using transmission electron microscopy. Five animals in the HT group showed good OPC (OPC 1-2), while 3 animals in the NP group showed good OPC (OPC 1-3). Brain tissue from different regions was normal in sham-operation group. The HDS in the cerebral cortex and CA1 region of hippocampus in the HT group was lower than that in the NP group (cerebral cortex: 1.6±0.5 vs. 2.2±0.8, hippocampus: 1.8±0.8 vs. 2.8±0.5, both P<0.05). The TUNEL- positive cells in the cerebella and the CA1 region of hippocampus were significantly reduced in the HT group compared with the NP group (cerebella:21.2±3.2 vs. 38.6±3.8, hippocampus: 22.7±7.6 vs. 35.0±6.8, both P<0.05). With transmission electron microscopy, necrotic neurons were found in the cerebral cortex, striatum and the CA1 region of hippocampus, while in cerebella only granular cells and glial cells in the CA1 region of hippocampus showed apoptosis. The damages to neurons were significantly reduced in HT group. Hypertension induced by norepinephrine is a safe and effective method to reduce brain damages and prevent apoptosis of neurons.

No assisted ventilation cardiopulmonary resuscitation and 24-hour neurological outcomes in a porcine model of cardiac arrest

To evaluate the effect of no assisted ventilation cardiopulmonary resuscitation on neurologically intact survival compared with ten positive pressure ventilations/minute cardiopulmonary resuscitation in a pig model of cardiac arrest. Prospective randomized animal study. Animal laboratory. Sixteen female intubated pigs (25.2 +/- 2.1 kg) anesthetized with propofol. : fter 8 mins of untreated ventricular fibrillation, the intubated animals were randomized to 8 mins of continuous chest compressions (100/min) and either no assisted ventilation (n = 9) or 10 positive pressure ventilations/min (Smart Resuscitator Bag with 100% O2 flow at 10 L/min) (n = 7). The primary end point, neurologically intact 24-hr survival, was evaluated using a pig cerebral performance category score by a veterinarian blinded to the cardiopulmonary resuscitation method. MEASUREMENTS, AND MAIN RESULTS: During cardiopulmonary resuscitation, aortic and coronary perfusion pressure were similar between groups but cerebral perfusion pressure was significantly higher in the positive pressure ventilation group (33 +/- 15 vs. 14 +/- 14, p = .04). After 7.5 mins of cardiopulmonary resuscitation, arterial pO2 (mm Hg) and mixed venous O2 saturation (%) were significantly higher in the positive pressure ventilation compared with the no assisted ventilation group (117 +/- 29 and 41 +/- 21 vs. 40 +/- 24 and 10.8 +/- 7; p = .01 for both). Paco2 was significantly lower in the positive pressure ventilation group (48 +/- 10 vs. 77 +/- 26, p = .01). After 24 hrs, four of nine no assisted ventilation pigs were alive with a mean cerebral performance category score of 3 +/- 0 vs. five of seven alive and neurologically intact positive pressure ventilation pigs with a cerebral performance category score of 1 +/- 0.3 (p < .001 for cerebral performance category score). No assisted ventilation cardiopulmonary resuscitation results in profound hypoxemia, respiratory acidosis, and significantly worse 24-hr neurologic outcomes compared with positive pressure ventilation cardiopulmonary resuscitation in pigs.

Effects of stomach inflation on haemodynamic and pulmonary function during cardiopulmonary resuscitation in pigs

Aim Stomach inflation during cardiopulmonary resuscitation (CPR) is frequent, but the effect on haemodynamic and pulmonary function is unclear. The purpose of this study was to evaluate the effect of clinically realistic stomach inflation on haemodynamic and pulmonary function during CPR in a porcine model. Methods After baseline measurements ventricular fibrillation was induced in 21 pigs, and the stomach was inflated with 0 L ( n = 7), 5 L ( n = 7) or 10 L air ( n = 7) before initiating CPR. Results During CPR, 0, 5, and 10 L stomach inflation resulted in higher mean pulmonary artery pressure [median (min–max)] [35 (28–40), 47 (25–50), and 51 (49–75) mmHg; P < 0.05], but comparable coronary perfusion pressure [10 (2–20), 8 (4–35) and 5 (2–13) mmHg; P = 0.54]. Increasing (0, 5, and 10 L) stomach inflation decreased static pulmonary compliance [52 (38–98), 19 (8–32), and 12 (7–15) mL/cmH 2O; P < 0.05], and increased peak airway pressure [33 (27–36), 53 (45–104), and 103 (96–110) cmH 2O; P < 0.05). Arterial oxygen partial pressure was higher with 0 L when compared with 5 and 10 L stomach inflation [378 (88–440), 58 (47–113), and 54 (43–126) mmHg; P < 0.05). Arterial carbon dioxide partial pressure was lower with 0 L when compared with 5 and 10 L stomach inflation [30 (24–36), 41(34–51), and 56 (45–68) mmHg; P < 0.05]. Return of spontaneous circulation was comparable between groups (5/7 in 0 L, 4/7 in 5 L, and 3/7 in 10 L stomach inflation; P = 0.56). Conclusions Increasing levels of stomach inflation had adverse effects on haemodynamic and pulmonary function, indicating an acute abdominal compartment syndrome in this CPR model.

Hands-Only (Compression-Only) Cardiopulmonary Resuscitation: A Call to Action for Bystander Response to Adults Who Experience Out-of-Hospital Sudden Cardiac Arrest

Hands-Only (Compression-Only) Cardiopulmonary Resuscitation: A Call to Action for Bystander Response to Adults Who Experience Out-of-Hospital Sudden Cardiac Arrest

Neurocognitive performance after cardiopulmonary resuscitation in pigs

To test the feasibility of a neurocognitive test based on operant conditioning in a porcine model of cardiac arrest and cardiopulmonary resuscitation. Furthermore, to characterize the influence of different durations of cardiac arrest on cognitive performance and the accompanying neurohistopathological changes. Randomized controlled laboratory animal study. Animal research facility of a university hospital. Seventeen male domestic pigs. Animals were anesthetized and mechanically ventilated before arterial and pulmonary artery catheters were inserted. Cardiac arrest was induced electrically after randomization of the animals into two groups (n = 7/group) left untreated for either 5 or 8 mins. Cardiopulmonary resuscitation was performed with 100% oxygen and cardiac compressions at 100/min for 5 mins before defibrillation was attempted. Three animals treated identically, with the exception that neither cardiac arrest was induced nor cardiopulmonary resuscitation was performed, served as controls. Hemodynamic variables as well as variables of gas exchange were measured at baseline and 10, 60, 120, 240, and 360 mins after cardiopulmonary resuscitation. Neurocognitive performance was evaluated using a test based on operant conditioning 5 days before and 4 days after cardiopulmonary resuscitation. On the fifth postoperative day, animals were killed and the brains removed for histopathological evaluation of vulnerable brain regions. No noteworthy differences in hemodynamics or gas exchange were observed at baseline or after cardiopulmonary resuscitation. Animals exposed to 8 mins of untreated cardiac arrest showed severe neurocognitive dysfunction, which was statistically significant on postoperative days 2 and 3 in comparison to animals exposed to 5 mins of cardiac arrest or controls. Neurohistopathological evaluation revealed a significantly greater proportion of ischemically damaged neurons in the caudate nucleus and putamen in pigs subjected to 8 mins of cardiac arrest. Neurocognitive testing is feasible in this setting. Performance worsens with increasing ischemia time and is structurally associated with alterations in the caudate nucleus and the putamen.