Animal Model Of Cardiac Arrest Research Articles

Shorter defibrillation interval promotes successful defibrillation and resuscitation outcomes

AimCurrent cardiopulmonary resuscitation guidelines recommend performing defibrillation every 2 min during resuscitation. This study aimed to compare the rate of successful defibrillation using 1- and 2-min defibrillation intervals. MethodsTwenty-six pigs were randomly assigned to 1- or 2-min interval groups. After inducing ventricular fibrillation (VF), we observed pigs for 2 min. Thereafter, basic life support was initiated with a 30:2 compression-to-ventilation ratio for 8 min. Defibrillation was performed with an energy of 2 J/kg at 10 min after VF and was repeated every 1 or 2 min according to randomization. Advanced cardiac life support, including continuous chest compression with ventilation every 6 s and intravenous injection of 1 mg epinephrine every 3 min, was performed until the return of spontaneous circulation (ROSC) or until 20 min after VF induction. Haemodynamic parameters and baseline arterial blood gas profiles were compared between groups. ROSC, 24 -h survival, and the neurologic deficit score (NDS) were evaluated at 24 h. ResultsHaemodynamic parameters during resuscitation and baseline arterial blood gas profiles did not differ between groups. ROSC was more frequently observed in the 1-min interval group (p = 0.047). Time to ROSC was not different between groups (p = 0.054). The 24 -h survival was higher (p = 0.047) and NDS at 24 h was lower (92 ± 175) in the 1-min interval group than in the 2-min interval group (272 ± 190) (p = 0.028). ConclusionsDefibrillation success and resuscitation outcomes were superior when using a 1-min defibrillation interval in animal models of cardiac arrest.

Abstract P-018: ANALYSIS OF CHEST COMPRESSIONS QUALITY DURING RESUSCITATION IN A PEDIATRIC ANIMAL MODEL AFTER ASPHYXIAL CARDIAC ARREST

Aims & Objectives: To analyze quality of chest compressions (CC) during resuscitation and its impact on the return of spontaneous circulation (ROSC) in a pediatric animal model of cardiac arrest (CA) using a real-time feedback-device. Methods Depth and rate of CC were measured with an accelerometer (ZOLL®) during resuscitation in an experimental model of asphyxial CA in piglets. Compression depth between 3.8 and 5 cm and a rate between 100 and 120 compressions per minute were considered optimal. Results CC quality was recorded in 19 piglets. Twelve of them (63.2%) achieved ROSC. Only 41.3% of CC were optimal regarding rate and depth. Compression depth was optimal in 48.9%, too deep in 43.2% and too shallow in 7.9%. CC rate was optimal in 80.3%, too fast in 4.6% and slow in 15.1%. Compressions were more shallow and faster in piglets who recovered spontaneous circulation than in those who didn´t (table 1). Optimal compressions (rate and depth) (52.7 ± 25% vs 21.7 ± 16.2% p=0.010) and optimal depth (61.9 ± 28.2% vs 26.5 ± 17% p=0.008) were associated with higher ROSC. Animals who suffered airway bleeding or thoracic injuries had received deeper CC after 3 minutes of CPR, p=0.006. There was a correlation between mean arterial pressure and quality of CC (table 2).Conclusions In this pediatric CA model, only 41.3% of chest compressions were optimal. Optimal quality of CPR was associated with higher survival. Excessive CC depth was associated with airway bleeding or thoracic injuries and increased mortality.

Enhancing preclinical research by a software supporting randomised, blinded and adaptive study designs

Purpose of the study: Prospective randomised controlled trials are accepted as gold standard of clinical research. For the comparison of two defibrillation techniques in an animal model of cardiac arrest we aimed to transfer this standard to preclinical research.

Alterations in Cerebral Blood Flow after Resuscitation from Cardiac Arrest.

Greater than 50% of patients successfully resuscitated from cardiac arrest have evidence of neurological disability. Numerous studies in children and adults, as well as in animal models have demonstrated that cerebral blood flow (CBF) is impaired after cardiac arrest. Stages of cerebral perfusion post-resuscitation include early hyperemia, followed by hypoperfusion, and finally either resolution of normal blood flow or protracted hyperemia. At the level of the microcirculation the blood flow is heterogeneous, with areas of no flow, low flow, and increased flow. CBF directed therapies in animal models of cardiac arrest improved neurological outcome, and therefore, the alterations in CBF after cardiac arrest likely contribute to the development of hypoxic ischemic encephalopathy. Current intensive care after cardiac arrest is centered upon maintaining systemic oxygenation, normal blood pressure values for age, maintaining general homeostasis, and avoiding hyperthermia. Assessment of CBF and oxygenation is not routinely performed after cardiac arrest. Currently available and underutilized techniques to assess cerebral perfusion include transcranial doppler, near-infrared spectroscopy, and arterial spin labeling magnetic resonance imaging. Limited clinical studies established the role of CBF and oxygenation monitoring in prognostication after cardiac arrest and few studies suggest that guiding critical care post-resuscitation to mean arterial pressures above the minimal autoregulatory range might improve outcome. Important knowledge gaps thus remain in cerebral monitoring and CBF and oxygen goal-directed therapies post-resuscitation from cardiac arrest.

The future is now: neuroprotection during cardiopulmonary resuscitation.

Survival with favorable neurological function after cardiac arrest remains low. The purpose of this review is to identify recent advances that focus on neuroprotection during cardiopulmonary resuscitation (CPR). Multiple strategies have been shown to enhance neuroprotection during CPR. Brain perfusion during CPR is increased with therapies such as active compression decompression CPR and intrathoracic pressure regulation that improve cardiac preload and decrease intracranial pressure. Head Up CPR has been shown to decrease intracranial pressure thereby increasing cerebral perfusion pressure and cerebral blood flow. Sodium nitroprusside enhanced CPR increases cerebral perfusion, facilitates heat exchange, and improves neurologic survival in swine after cardiac arrest. Postconditioning has been administered during CPR in laboratory settings. Poloxamer 188, a membrane stabilizer, and ischemic postconditioning have been shown to improve cardiac and neural function after cardiac arrest in animal models. Postconditioning with inhaled gases protects the myocardium, with more evidence mounting for the potential for neural protection. Multiple promising neuroprotective therapies are being developed in animal models of cardiac arrest, and are in early stages of human trials. These therapies have the potential to be bundled together to improve rates of favorable neurological survival after cardiac arrest.

WITHDRAWN: Cardiac arrest animal model: a simple device for small animals’ chest compression

WITHDRAWN: Cardiac arrest animal model: a simple device for small animals’ chest compression

Effect of intrathoracic pressure on diastolic function of the heart during cardiopulmonary resuscitation in an animal model of cardiac arrest

Effect of intrathoracic pressure on diastolic function of the heart during cardiopulmonary resuscitation in an animal model of cardiac arrest

Comparison between pressure-recording analytical method (PRAM) and femoral arterial thermodilution method (FATD) cardiac output monitoring in an infant animal model of cardiac arrest.

BackgroundThe pressure-recording analytical method is a new semi-invasive method for cardiac output measurement (PRAM). There are no studies comparing this technique with femoral artery thermodilution (FATD) in an infant animal model.MethodsA prospective study was performed using 25 immature Maryland pigs weighing 9.5 kg. Fifty-eight simultaneous measurements of cardiac index (CI) were made by FATD and PRAM at baseline and after return of spontaneous circulation. Differences, correlation, and concordance between both methods were analyzed. The ability of PRAM to track changes in CI was explored with a polar plot.ResultsMean CI measurements were 4.5 L/min/m2 (95 % CI, 4.2–4.8 L/min/m2; coefficient of variation, 27 %) by FATD and 4.0 L/min/m2 (95 % CI, 3.6–4.3 L/min/m2; coefficient for variation, 37 %) by PRAM (difference, 0.5 L/min/m2; 95 % CI for the difference, 0.1–1.0 L/min/m2; p = 0.003; n = 58). No correlation between both methods was observed (r = 0.170, p = 0.20). Limits of agreement were −2.9 to 4.0 L/min/m2 (−69.9 to 84.9 %). Percentage error was 80.6 %. Only 26.1 % of data points lied within an absolute deviation of ±30° from the polar axis.ConclusionsNo correlation nor concordance between both methods was observed. Limits of agreement and percentage of error were high and clinically not acceptable. No concurrence between both methods in CI changes was observed. PRAM is not a useful method for measurement of the CI in this pediatric model of cardiac arrest.

Protocol for meta-analysis of temperature reduction in animal models of cardiac arrest.

Targeted temperature management (TTM) of 32–34 °C has been the standard treatment for out‐of‐hospital cardiac arrest since clinical trials in 2002 showed benefits to survival and neurological outcome. Recently, this treatment has been challenged by another clinical trial showing no difference in outcome between TTM of 33 °C and 36 °C. This protocol describes the methodology for a meta‐analysis detailing temperature‐reducing interventions to treat global ischaemia in animal models. By combining relevant data sets in the literature, we will explore the experimental evidence for TTM. Our aims are to explain possible translational gaps and provide methodological considerations for future experimental research and clinical trials.

Abstract 19510: Cytochrome C Levels in Post-cardiac Arrest Patients

Introduction: Cytochrome C is an essential component of the electron transport chain loosely bound to the inner mitochondrial membrane. Plasma Cytochrome C levels have shown to be elevated and associated with mortality in an animal model of cardiac arrest. Hypothesis: We hypothesized that cytochrome C levels would be elevated in post-cardiac arrest patients and higher in non-survivors as compared to survivors. Methods: We enrolled adult, out-of-hospital cardiac arrest patients with return of spontaneous circulation as part of the four-center COMICA study. Blood draws were performed after return of spontaneous circulation. We also performed blood draws in controls without acute illness. We measured plasma cytochrome C levels by applying the human cytochrome C Platinum ELISA (eBioceience, CA) kit to a MSD platform (Meso Scale Discovery, MD) to achieve greater dynamic range and sensitivity. We compared groups using the Wilcoxon Rank-Sum test. We used Spearman’s correlation coefficient (rs) to assess the correlation between Cytochrome C levels and initial lactate levels. Results: A total of 103 post-cardiac arrest patients and 40 controls had Cytochrome C levels measured. Cytochrome C levels were higher in post-cardiac arrest patients as compared to control subjects (2.18 nmol/L [quartiles: 0.74, 7.74] vs 0.20 nmol/L [0.03, 1.12], p < 0.001, Figure 1). Fifty-five (53%) patients in the cardiac arrest group died. Patients who died had higher Cytochrome C levels as compared to survivors (3.66 nmol/L [1.40, 14.8] vs. 1.27 nmol/L [0.16, 2.37], p = 0.001, Figure 2). There was also a significant difference in Cytochrome C levels between patients with a good vs. a poor neurological outcome (1.3 nmol/L [0.3, 3.5] vs. 2.8 nmol/L [0.9, 9.9], p = 0.04). Cytochrome C levels were correlated with initial lactate levels (rs = 0.36, p = 0.001). Conclusion: Cytochrome C levels are elevated in post-cardiac arrest patients and non-survivors has higher levels.

Increased return of spontaneous circulation at the expense of neurologic outcomes: Is prehospital epinephrine for out-of-hospital cardiac arrest really worth it?

IntroductionCurrent guidelines for the management of out-of-hospital cardiac arrest (OHCA) recommend the use of prehospital epinephrine by initial responders. This recommendation was initially based on data from animal models of cardiac arrest and minimal human data, but since its inception, more human data regarding prehospital epinephrine in this setting are now available. Although out-of-hospital return of spontaneous circulation (ROSC) may be higher with the use of epinephrine, worse neurologic outcomes may be associated with its use. MethodsA systematic review of the literature was conducted by search of databases including PubMed, Embase, and OVID to identify studies comparing patients with OHCA who had received epinephrine before arrival to the hospital with those who had not. Studies were assessed for quality and bias, and data were abstracted from studies deemed appropriate for inclusion. A meta-analysis was conducted using a Mantel-Haenszel model for dichotomous outcomes. Outcomes studied were prehospital ROSC, survival at 1 month, survival to discharge, and positive neurologic outcome. ResultsA total of 14 studies with 655853 patients were included for the meta-analysis. The use of epinephrine for OHCA before arrival to the hospital was associated with a significant increase in ROSC (odds ratio, 2.86; P < .001) and a significant increase in the risk of poor neurologic outcome at the time of discharge (odds ratio 0.51, P = .008). There was no significant difference in survival at 1 month or survival to discharge. ConclusionUse of epinephrine before arrival to the hospital for OHCA does not increase survival to discharge but does make it more likely for those who are discharged to have poor neurologic outcome. There is a need for additional randomized controlled trials.

A Rat Model of Ventricular Fibrillation and Resuscitation by Conventional Closed-chest Technique.

A rat model of electrically-induced ventricular fibrillation followed by cardiac resuscitation using a closed chest technique that incorporates the basic components of cardiopulmonary resuscitation in humans is herein described. The model was developed in 1988 and has been used in approximately 70 peer-reviewed publications examining a myriad of resuscitation aspects including its physiology and pathophysiology, determinants of resuscitability, pharmacologic interventions, and even the effects of cell therapies. The model featured in this presentation includes: (1) vascular catheterization to measure aortic and right atrial pressures, to measure cardiac output by thermodilution, and to electrically induce ventricular fibrillation; and (2) tracheal intubation for positive pressure ventilation with oxygen enriched gas and assessment of the end-tidal CO2. A typical sequence of intervention entails: (1) electrical induction of ventricular fibrillation, (2) chest compression using a mechanical piston device concomitantly with positive pressure ventilation delivering oxygen-enriched gas, (3) electrical shocks to terminate ventricular fibrillation and reestablish cardiac activity, (4) assessment of post-resuscitation hemodynamic and metabolic function, and (5) assessment of survival and recovery of organ function. A robust inventory of measurements is available that includes - but is not limited to - hemodynamic, metabolic, and tissue measurements. The model has been highly effective in developing new resuscitation concepts and examining novel therapeutic interventions before their testing in larger and translationally more relevant animal models of cardiac arrest and resuscitation.

The efficacy of hypertonic saline treatment in cardiopulmonary resuscitation in animal model with cardiac arrest: a Meta-analysis

To evaluate the efficacy of hypertonic saline (HS) treatment in cardiopulmonary resuscitation (CPR) in animal models of cardiac arrest (CA). PubMed and EMBASE data were retrieved from January 1st, 1966 to September 30th, 2014, and Wanfang data and CNKI were searched from January 1st, 1990 to September 30th, 2014 for randomized controlled trials (RCTs) regarding CPR intervention of CA animal models with HS. HS was intravenously infused at the initiation of CPR in HS group, without limiting its dosage or concentration. The same volume of normal saline (NS) was given in NS group. Meta-analysis concerning the rate of restoration of spontaneous circulation (ROSC), the serum sodium concentration before CA and during CPR, and related hemodynamic parameters, including mean arterial pressure (MAP) and coronary perfusion pressure (CPP) at the immediate beginning of CPR and 90 minutes after ROSC was conducted by RevMan 5.3 software. A total of 8 RCTs were included. Meta-analysis showed that compared with NS group, the rate of ROSC [relative risk (RR) = 1.23, 95% confidence interval (95%CI) = 1.05-1.43, P = 0.010], serum sodium concentration during CPR [weight mean difference (WMD) = 17.44, 95%CI = 12.57-22.31, P < 0.01], and the level of MAP at 90 minutes after ROSC (WMD = 4.81, 95%CI = 1.58-8.03, P = 0.003) were significantly improved in HS group. There was no significant statistic difference in other hemodynamic parameters, including serum sodium concentration before CA (WMD = 0.78, 95%CI = -0.26-1.82, P = 0.14), MAP (WMD = 5.43, 95%CI = -0.74-11.59, P = 0.08) and CPP at the immediate beginning of CPR (WMD = 6.82, 95%CI = -5.54-19.19, P = 0.28), and CPP at 90 minutes after ROSC (WMD = -0.77, 95%CI = -10.33-8.80, P = 0.88) between two groups. It was showed by funnel chart that bias was not significant in the published articles. This systematic review indicates that HS infusion is followed by an improved ROSC rate, serum sodium concentration during CPR, and MAP at 90 minutes after ROSC in animal models of CA.

Modeling cardiac arrest and resuscitation in the domestic pig.

Cardiac arrest remains a leading cause of death and permanent disability worldwide. Although many victims are initially resuscitated, they often succumb to the extensive ischemia-reperfusion injury inflicted on the internal organs, especially the brain. Cardiac arrest initiates a complex cellular injury cascade encompassing reactive oxygen and nitrogen species, Ca(2+) overload, ATP depletion, pro- and anti-apoptotic proteins, mitochondrial dysfunction, and neuronal glutamate excitotoxity, which injures and kills cells, compromises function of internal organs and ignites a destructive systemic inflammatory response. The sheer complexity and scope of this cascade challenges the development of experimental models of and effective treatments for cardiac arrest. Many experimental animal preparations have been developed to decipher the mechanisms of damage to vital internal organs following cardiac arrest and cardiopulmonary resuscitation (CPR), and to develop treatments to interrupt the lethal injury cascades. Porcine models of cardiac arrest and resuscitation offer several important advantages over other species, and outcomes in this large animal are readily translated to the clinical setting. This review summarizes porcine cardiac arrest-CPR models reported in the literature, describes clinically relevant phenomena observed during cardiac arrest and resuscitation in pigs, and discusses numerous methodological considerations in modeling cardiac arrest/CPR. Collectively, published reports show the domestic pig to be a suitable large animal model of cardiac arrest which is responsive to CPR, defibrillatory countershocks and medications, and yields extensive information to foster advances in clinical treatment of cardiac arrest.

Abstract 149: Zoniporide Combined with α-Methylnorepinephrine Promotes Greater Hemodynamic Stability than Either Agent Alone During Chest Compression in Rats

Background: We have reported in animal models of cardiac arrest that sodium hydrogen exchanger-1 (NHE-1) inhibition - by attenuating reperfusion injury - helps preserve left ventricular distensibility yielding higher forward blood flows during chest compression. Others have reported that α-methylnorepinephrine (α-MNE) - a selective peripheral α2-adrenoreceptor agonist - is superior to epinephrine given its lack of β-agonist effect that intensifies myocardial ischemia. We examined in a rat model of VF the effects of combining the NHE-1 inhibitor zoniporide (ZNP) with α-MNE during CPR, expecting to elicit a vasopressor effect (α-MNE) that is better maintained over time because of ZNP. Methods: VF was electrically induced in 32 male retired breeder Sprague-Dawley rats and left untreated for 8 minutes. Chest compression was then initiated, gradually increasing the depth of compression (maximum 17 mm) to attain an aortic diastolic pressure of 28 mmHg by the end of minute 2, maintaining such level for the remaining 6 minutes of chest compression, time at which defibrillation was attempted. The rats were randomized 1:1:1:1 to receive a 3 mg/kg bolus of ZNP or 0.9% NaCl before starting chest compression and a 100 μg/kg bolus of α-MNE or its vehicle at minute 2 of chest compression with the investigators blind to the assignment. Results: The ratio between the aortic diastolic pressure and depth of compression (Figure) was higher - as expected - in rats that received α-MNE(+) given its vasopressor effect. The effect, however, was not maintained and declined over time; but to a significantly lesser degree in rats that also received ZNP; i.e., α-MNE(+)/ZNP(+) group. Conclusions: The findings support a favorable interaction between α-MNE and ZNP; the first prompting needed peripheral vasoconstriction - likely with less concomitant myocardial injury - and the latter preserving left ventricular distensibility, which combined enhance the hemodynamic efficacy of chest compression.

Abstract 211: Delayed Cell Death in CA1 Region in a Cardiac Arrest Rat Model: Continuing After 2 Weeks of Survival?

Background: Evolution of histological lesions in selectively vulnerable brain regions in animal models of cardiac arrest (CA)give evidence of potential therapeutic windows. Delayed cell death is of special interest in this regard. Methods: In male Sprague-Dawley rats (350g) ventricular fibrillation (VF) CA was induced for 6 min followed by chest compressions, ventilation and drugs for 2 min. To achieve return of spontaneous circulation animals were defibrillated every 2 min. Animals were sacrificed after one week (n=5) or two weeks (n=7) of survival and compared to four sham animals. Brains were fixed in formalin, embedded in paraffin wax and cut into 3 μm thick coronary sections for histological examination. Viable neurons with nucleolus were counted in Hematoxylin-Eosin (HE)-stained sections in a 250 μm sector of the medial CA1 region. FluoroJade B staining was applied to count dying neurons in the same sector. Results: In HE-staining sham animals had 31±4 viable neurons. In one week survivors 11±9 viable neurons (p=0.003) and in two week survivors 7±7 viable neurons (p=0.001 vs sham, p=0.49 vs one week survivors) were counted. Furthermore, a lot of degenerated hypereosinophilic neurons were present in HE-staining in both CA-groups. FluoroJade B-staining was negative in sham animals. In one week survivors 29±8 dying neurons (p=0.006) and in two week survivors 33±13 dying neurons (p= 0.016 vs sham, p=0.343 vs one week survivors) were detectable. Conclusions: Consistent damage in the medial CA1 region was present after 6 min VFCA in both survival time groups. Lesions seemed to be constant, with no significant differences between time points. Contrary to expectations, FluoroJade B-staining was still positive after two weeks of survival, suggesting that delayed cell death might go on for a longer time period than assumed so far.

Post-conditioning to improve cardiopulmonary resuscitation.

Despite decades of advances in prehospital and in-hospital medical care, patients with out-of-hospital cardiac arrest continue to have poor neurologic and cardiac function following otherwise successful resuscitation. This review examines the mechanisms and therapeutic strategies currently under development to activate the post-conditioning pathways and thereby improve survival and function. Post-conditioning utilizes the reperfusion injury salvage kinase (RISK) and survivor activating factor enhancement (SAFE) pathways as common avenues to promote cell survival and function. Ischemic post-conditioning and multiple medications activate these pathways resulting in improved cardiac and neurological function in animal models of cardiac arrest. Detailed knowledge of the RISK and SAFE pathways can be used for further drug development. Human studies are now underway to test some of these strategies, but further clinical trials are necessary to translate these therapies to clinical practice.

Epinephrine for Cardiac Arrest

Epinephrine for Cardiac Arrest: Are We Doing More Harm Than Good? Vijay Krishnamoorthy;Monica Vavilala;Michael Fettiplace;Guy Weinberg; Anesthesiology

An Evidence-Based Review of Epinephrine Administered via the Intraosseous Route in Animal Models of Cardiac Arrest

Intraosseous (IO) access, enabling the rapid administration of epinephrine during cardiac arrest (CA), is crucial in promoting optimal postresuscitation outcomes in patients with poor vascular access. There is a question whether IO-administered epinephrine is equivalent to intravenously administered epinephrine during CA. The question guiding this evidence-based review was as follows: in adults suffering CA given epinephrine via the IO route, what is the resulting serum concentration of the drug compared to when administered intravenously? A search was conducted and the evidence appraised and leveled. Four animal studies met the inclusion criteria. The sources showed no definitive evidence supporting equivalence between intravenous and IO epinephrine administered during CA. Intravenously administered epinephrine provides increased and faster appearing serum concentrations than IO-administered epinephrine. Evidence indicated epinephrine given via the sternal IO route more closely approaches equivalence with intravenously administered epinephrine than when administered by the tibial IO route. The clinician should consider using proximal IO infusion sites such as the sternum or humerus when administering advanced cardiac life support drugs to rapidly achieve maximal therapeutic concentrations. Further studies are needed to determine the differences seen when epinephrine is administered by these routes during CA.

Normal saline versus colloid solutions for induction of hypothermia: the effect of specific heat capacity on cooling.

The prevention of ischemic injury to preserve both end-organ function and improve neurological recovery by the implementation of therapeutic hypothermia has been well established in the literature. However, not only the means by which body temperature is cooled but also the rate by which target temperature is attained remains an area of continued interest and research. The induction of therapeutic hypothermia to begin the process of body temperature lowering through the infusion of a cold solution intravenously into the body may be one variable that influences not only rapidity of cooling but also subsequent clinical outcome. In a recent issue of Critical Care, Skulec and colleagues compared the induction of therapeutic hypothermia by cold normal saline versus cold colloid solution containing hydroxyethyl starch in a porcine animal model of cardiac arrest, assessing both the rate of temperature change and target temperature achieved, in addition to changes in intracranial pressure.