Min Of Untreated Ventricular Fibrillation Research Articles

High Serum Tumor Necrosis Factor Levels in the Early Post-Cardiac Arrest Period Are Associated with Poor Short-Term Survival in a Swine Model of Ventricular Fibrillation.

Most resuscitated victims of out-of-hospital cardiac arrest who survive to hospital expire due to the postresuscitation syndrome. This syndrome is characterized by a sepsis-like proinflammatory state. The objective of this investigation was to determine whether a relationship exists between the rise of tumor necrosis factor (TNF), a proinflammatory cytokine, following return of spontaneous circulation (ROSC), and early postarrest survival in a clinically relevant animal model of spontaneous ventricular fibrillation (VF). Mixed-breed Yorkshire swine (n = 20), weighing 39 ± 5 kg, were anesthetized and catheters placed in the right atrium and left ventricle/ascending aorta for continuous pressure monitoring. VF was induced by occluding the left anterior descending coronary artery with an angioplasty balloon. After 7 min of untreated VF, advanced life support resuscitation attempts were made for up to 20 min. Animals achieving ROSC were monitored for 3 h and fluid and pressor support was administered as needed. TNF levels were measured before VF and at 0, 15, and 30 min after ROSC using quantitative sandwich enzyme-linked immunosorbent assay. Twelve (60%) animals experienced early death, expiring during the 3 hour postarrest period (9 pulseless electrical activity, 2 VF, and 1 asystole). The TNF level at 15 min post-ROSC was significantly associated with death within the first 3 h post-ROSC with a univariate odds ratio of 1.4 [95% confidence interval (CI) 1.05-2.2, P = 0.01]. Using a cutoff TNF level of 525 pg/mL at 15 min post-ROSC had 100% negative predictive value (95% CI 0%-37%) and 67% positive predictive value (95% CI 35%-90%) for early death with a hazard ratio of 6.6 (95% CI 1.9-23.5). TNF increases shortly after ROSC and is predictive of early death. Early identification of resuscitated victims at greatest risk for hemodynamic collapse and recurrent arrest might facilitate the use of early hospital-based interventions to decrease the likelihood of a poor outcome.

IMPACTS OF SYSTEMIC HYPERTENSION AND LEFT VENTRICULAR HYPERTROPHY ON OUTCOME OF CARDIOPULMONARY RESUSCITATION AND THERAPEUTIC HYPOTHERMIA IN A CARDIAC ARREST MODEL OF RAT.

Systemic hypertension and left ventricular hypertrophy (LVH) are major risk factors of cardiac arrest. However, the impacts of hypertension and LVH on the outcome of cardiopulmonary resuscitation (CPR) and post-resuscitation hypothermia are still undetermined. After 4 min of untreated ventricular fibrillation (VF) and 4 min of CPR, defibrillation was attempted in 16 male spontaneously hypertensive rats (SHR) with LVH and 16 male normotensive Wistar Kyoto (WKY) rats. When restoration of spontaneous circulation (ROSC) was achieved, animals were randomized into either hypothermia or normothermia. For animals subjected to hypothermia, rapid cooling was started immediately after ROSC and a temperature of 33.0 ± 0.4°C was maintained for 2 h. Normothermic animals were maintained at 37.0 ± 0.4°C. Baseline mean arterial pressure, heart rate, and left ventricle mass were significantly higher but ejection fraction was lower for hypertensive animals. Coronary perfusion pressure was higher for SHR, but no differences in duration of CPR and number of defibrillations required for resuscitation compared with WKY. All of the animals were successfully resuscitated but post-resuscitation cardiac function was severely impaired in hypertensive animals. Serum levels of cardiac troponin T, amino-terminal pro-brain natriuretic peptide, and S100B measured after ROSC were also markedly higher in SHR groups. Fourteen WKY rats (87.5%) survived, whereas only 1 SHR (6.3%, P < 0.001) survived to 96 h. In this rat model, systemic hypertension and LVH did not affect ROSC. However, survival was dismal due to elevated severity of cardiac and cerebral injury in hypertensive animals regardless of short-duration hypothermia.

Postconditioning Reduces Early Reactive Oxygen Species Production in the Brain in a Porcine Model of Cardiac Arrest and Resuscitation

IntroductionPostconditioning during cardiopulmonary resuscitation (CPR) is an effective intervention to improve neurological function and survival in a porcine model of prolonged cardiac arrest (CA). We tested if ischemic (IPoC) and anesthetic postconditioning (APoC) decrease reactive oxygen species (ROS) production in the brain upon reperfusion with CPR.MethodsAfter 15 min of untreated ventricular fibrillation, 10 pigs were randomized to receive active compression/decompression CPR with IPoC (three 20‐sec pauses in CPR), APoC with 4 Vol% sevoflurane for 3 min, or without postconditioning (control) before organ harvest at 4 min. Cortical brain tissue was immediately frozen in liquid nitrogen and stored at −80°C until ROS measurements were performed by Electroparamagnetic Resonance (EPR). Data are mean±SD. Statistics: ANOVA with SNK‐post hoc testing, alpha = 0.05.ResultsEPR spectral changes showed that APoC (7.0±0.3 arbitrary units) more so than IPoC (7.9±0.3) reduced ROS compared to controls (9.1±0.2).ConclusionsBoth IPoC and APoC result in decreased ROS production in the brain during early CPR. Either strategy has been shown to improve mitochondrial coupling of oxidative phosphorylation and ATP synthesis and delay mPTP opening post CA. Together, our findings provide further evidence that preservation of mitochondrial function is a key element of improving neurological outcome after CA and CPR.Support or Funding InformationR01HL123227

Volume infusion cooling increases end-tidal carbon dioxide and results in faster and deeper cooling during intra-cardiopulmonary resuscitation hypothermia induction.

BackgroundIntra-arrest hypothermia induction may provide more benefit than inducing hypothermia after return of spontaneous circulation. However, little is understood about the interaction between patient physiology and hypothermia induction technology choice during ongoing chest compressions.MethodsAfter 10 min of untreated ventricular fibrillation, mechanical chest compressions were provided for 60 min (100 CPM, 1.25" deep) in 26 domestic swine (30.5 ± 1.7 kg) with concurrent hypothermia induction using one of eight cooling methods. Four cooling methods included volume infusion with cold saline or an ice particulate slurry through the femoral vein or carotid artery (volume infusion cooling group, VC); three included cooling via an intra-vascular heat exchange catheter, nasal cooling, or surface ice bags (no volume cooling group, NVC); and the other was a control group with no cooling (no cooling group, NC). Physiological monitoring included end-tidal carbon dioxide, aortic pressure, right atrial pressure, brain temperature, esophageal temperature, and rectal temperature.ResultsDuring cardiopulmonary resuscitation (CPR), the volume infusion cooling group cooled faster and to lower temperatures than the other groups (VC vs. NVC or NC; ∆T = −5.6 vs. −2.1 °C or −0.6 °C; p < 0.01). The aortic pressure and right atrial pressure were higher in the volume cooling group than the other groups (VC vs. NVC or NC; AOP = 23.6 vs. 16.7 mmHg or 14.7 mmHg; p < 0.02). End-tidal carbon dioxide measurements during CPR were also higher in the volume cooling group (VC vs. NVC; EtCO2 = 23.4 vs. 13.1 mmHg; p < 0.05). Intra-corporeal temperature gradients larger than 3 °C were created by volume cooling during ongoing chest compressions.ConclusionsVolume infusion cooling significantly altered physiology relative to other cooling methods during ongoing chest compressions. Volume cooling led to faster cooling rates, lower temperatures, higher end-tidal carbon dioxide levels, and higher central vascular pressures.IACUC protocol numbers: UPenn (803178), CHOP (997)

Abstract 16154: Head and Shoulder Elevation Improves Cerebral Perfusion Pressure During Active Compression-decompression CPR and Conventional CPR in a Porcine Cardiac Arrest Model

Background: Chest compressions during conventional cardiopulmonary resuscitation (C-CPR) increase arterial and venous pressures simultaneously, delivering bidirectional high pressure compression waves to the brain. It is possible that this may be detrimental neurologically and could be partially overcome by elevating the head during CPR. Previous animal study work using a tilt table has shown that a 30° head up position for the entire body during CPR significantly increases cerebral blood flow and cerebral perfusion pressure (CerPP) over a period of 5 minutes. We hypothesize that elevating the head and shoulders only will increase CerPP over a prolonged period of time with two different CPR techniques. Methods: Female farm pigs were sedated, intubated, anesthetized, and placed on a table designed to elevate the head and shoulders to 30°. After 8 min of untreated ventricular fibrillation and 2 min of automated C-CPR in the supine position, pigs were randomized to head up (HUP) or supine (SUP) CPR for 20 more min. In Group A, pigs were treated after 2 min of C-CPR with automated active compression decompression (ACD) CPR at 100 cycles/min plus an impedance threshold device (ITD), randomized to HUP (n=8) or SUP (n=8). In Group B, pigs were randomized after 2 min of C-CPR to treatment with HUP (n=7) or SUP (n=7) automated C-CPR. After 22 total min of CPR, defibrillation was performed. The primary outcome of the study was the comparison of CerPP at 22 min between HUP and SUP positions within each group. Results: After 22 min of CPR, CerPP (mmHg) was 39±7 with HUP versus 14±4 with SUP CPR (p=0.013) in Group A and 3.4±2.2 with HUP versus -6.3±2.6 with SUP CPR (p = 0.014) in Group B. There was no significant difference within groups for coronary perfusion pressure (CPP) after 22 min, but CPP trended higher with HUP in Group A (32.0 ± 4.9) versus SUP (18.8 ± 4.7)(p=0.072). The CPPs in Group B were 5.8 ± 1.1 with HUP versus 3.3±1.8 with SUP CPR, p=0.26). In Group A, 6/8 pigs were resuscitated in both positions where no pigs could be resuscitated in Group B. Conclusions: The HUP position using two different CPR techniques significantly improved CerPP over a prolonged period of time. This simple maneuver has the potential to improve neurological outcomes after cardiac arrest.

Abstract 10402: Early Reduction of Myocardial Reactive Oxygen Species Production by Postconditioning in a Porcine Model of Cardiac Arrest and Resuscitation

Introduction: Ischemic (IPoC) and anesthetic postconditioning (APoC) during cardiopulmonary resuscitation (CPR) are effective interventions to improve hemodynamic outcome and survival in a porcine model of prolonged cardiac arrest. We hypothesized that both strategies decrease the myocardial production of reactive oxygen species (ROS) early during reperfusion. Methods: After 15 min of untreated ventricular fibrillation (VF), 22 pigs were randomized to receive mechanical CPR for 4 min without (control) or with IPoC (three 20-sec CPR interruptions) or APoC with low- (2 Vol%) or high-dose (4 Vol%) sevoflurane for 3 min before euthanasia and organ harvest. Left ventricular myocardial tissue was immediately frozen in liquid nitrogen and stored at -80°C until electroparamagnetic resonance (EPR) measurements were performed to quantify ROS. Data are mean±SEM. Statistics: ANOVA with SNK-post hoc testing, alpha = 0.05. Results: EPR spectral changes showed that high-dose APoC (10±1 arbitrary units) and IPoC (15±4) reduced reactive oxygen species normalized to dry tissue weight compared to untreated control animals (33±2); low-dose APoC (34±4) did not. Conclusions: Our data show that the cardio- and neuroprotective strategies of IPoC and APoC result in decreased myocardial ROS production that can be detected as early as 4 min after reintroduction of blood flow by mechanical CPR; the effective concentration of sevoflurane, however, has to be high enough to achieve APoC. Our findings underline the importance of early organ-protective strategies and contribute to our understanding of the mechanisms of these important clinical interventions to improve outcome and survival after cardiac arrest.

Abstract 10458: Improved Outcomes of Cardiopulmonary Resuscitation in Rats Treated With Vagus Nerve Stimulation Through Cholinergic Anti-Inflammatory Pathway

Introduction: Studies have demonstrated that vagus nerve stimulation (VNS) reduces ischemia reperfusion (I/R) injury. In this study, we investigated the protective effects of VNS in a rat model of cardiopulmonary resuscitation (CPR). We further investigated whether the beneficial effects of VNS were dependent on the alpha 7 nicotinic acetylcholine receptor (α7nAChR). Methods: The animals were randomized into 4 groups (n=10 each): (1) CPR group (n=10): the rats underwent 8 mins of untreated ventricular fibrillation (VF) followed by 8 mins of CPR and defibrillation. The right vagus nerve was exteriorized but not stimulated.; (2) VNS group (n=10): the treatment was identical to the CPR group except that VNS was initiated at the beginning of precordial compression and continued for 4 hours after the return of spontaneous circulation(ROSC); (3) MLA group(n=10): the treatment was identical to the VNS group except that α7nAChR antagonist MLA (5mg/kg) was administered intraperitoneally (IP) 15 mins prior to VF; (4) GTS group(n=10): the treatment was identical to the CPR group except that α7nAChR agonist GTS-21 (5mg/kg) was IP injected 30 mins before VF. Blood gases, post resuscitation myocardial and cerebral function and the duration of survival were monitored in all animals. Results: There were no differences in mean arterial pressure among 4 groups. Significantly better post-resuscitation myocardial and cerebral functions and longer durations of survival were observed in VNS-treated animals, and these protective effects of VNS could be abolished by MLA and imitated by GTS-21 indicating that these beneficial effects might be dependent on a7nAChR (Figure *P&lt;0.05 vs CPR, **P&lt;0.01 vs CPR, ##P&lt;0.01 vs MLA). In addition, VNS decreased the number of electric shocks and the length of CPR duration. Conclusion: VNS improves the outcomes after CPR and cholinergic anti-inflammatory pathway via α7nAChR plays an important role during CPR.

Abstract 15923: Dose-dependent Effect of Sevoflurane Postconditioning on Coronary Perfusion Pressure During Early Cardiopulmonary Resuscitation in a Pig Model of Prolonged Cardiac Arrest

Introduction: Pharmacologic postconditioning with the inhaled anesthetic sevoflurane (SEVO) during cardiopulmonary resuscitation (CPR) has been shown to improve outcomes in a porcine model of prolonged cardiac arrest. Hypothesis: We hypothesized that SEVO works in part by improving coronary perfusion pressure (CPP) during CPR. Methods: Following 15 min of untreated ventricular fibrillation (VF), 16 pigs received mechanical CPR for 4 min without (CON) or with low- (2 Vol%) or high-dose (4 Vol%) inhaled SEVO for 3 min. CPP was measured as the difference between mean aortic pressure and right atrial pressure during chest decompression. Results: CPP (mean±SEM in mmHg) at min 3 and 4 of CPR was higher in high-dose SEVO (46±4) than in low-dose SEVO (23±3) or CON (34±4); there was no significant difference between the latter two. Conclusions: Our data show that pharmacologic postconditioning with SEVO resulted in improved CPP during mechanical CPR if a sufficiently high dose is given. Combined with negligible metabolism and fast uptake and washout by ventilation due to its low solubility coefficient, SEVO may be a suitable drug to improve outcomes after cardiac arrest when given short-term during early CPR. If SEVO is associated with enhanced blood flow generation due to its known vasodilatory effect needs to be determined in future studies.

Developing a kinematic understanding of chest compressions: the impact of depth and release time on blood flow during cardiopulmonary resuscitation.

Background Effective cardiopulmonary resuscitation is a critical component of the pre-hospital treatment of cardiac arrest victims. Mechanical chest compression (MCC) devices enable the delivery of MCC waveforms that could not be delivered effectively by hand. While chest compression generated blood flow has been studied for more than 50 years, the relation between sternum kinematics (depth over time) and the resulting blood flow have not been well described. Using a five parameter MCC model, we studied the effect of MCC depth, MCC release time, and their interaction on MCC generated blood flow in a highly instrumented swine model of cardiac arrest.MethodsMCC hemodynamics were studied in 17 domestic swine (~30 kg) using multiple extra-vascular flow probes and standard physiological monitoring. After 10 min of untreated ventricular fibrillation, mechanical MCC were started. MCC varied such that sternal release occurred over 100, 200, or 300 ms. MCC were delivered at a rate of 100 per min and at a depth of 1.25″ (n = 9) or at a depth of 1.9″ (n = 8) for a total of 18 min. Transitions between release times occurred every 2 min and were randomized. Linear Mixed Models were used to estimate the effect of MCC depth, MCC release time, and the interaction between MCC depth and release time on physiological outcomes.ResultsBlood pressures were optimized by a 200 ms release. End tidal carbon dioxide (EtCO2) was optimized by a 100 ms release. Blood flows were significantly lower at a 300 ms release than at either a 100 or 200 ms release (p < 0.05). 1.9″ deep MCC improved EtCO2, right atrial pressure, coronary perfusion pressure, inferior vena cava blood flow, carotid blood flow, and renal vein blood flow relative to 1.25″ MCC.ConclusionsDeeper MCC improved several hemodynamic parameters. Chest compressions with a 300 ms release time generated less blood flow than chest compressions with faster release times. MCC release time is an important quantitative metric of MCC quality and, if optimized, could improve MCC generated blood flows and pressures.Electronic supplementary materialThe online version of this article (doi:10.1186/s12938-015-0095-4) contains supplementary material, which is available to authorized users.

Effect of regulating airway pressure on intrathoracic pressure and vital organ perfusion pressure during cardiopulmonary resuscitation: a non-randomized interventional cross-over study.

BackgroundThe objective of this investigation was to evaluate changes in intrathoracic pressure (Ppl), airway pressure (Paw) and vital organ perfusion pressures during standard and intrathoracic pressure regulation (IPR)-assisted cardiopulmonary resuscitation (CPR).MethodsMultiple CPR interventions were assessed, including newer ones based upon IPR, a therapy that enhances negative intrathoracic pressure after each positive pressure breath. Eight anesthetized pigs underwent 4 min of untreated ventricular fibrillation followed by 2 min each of sequential interventions: (1) conventional standard CPR (STD), (2) automated active compression decompression (ACD) CPR, (3) ACD+ an impedance threshold device (ITD) CPR or (4) ACD+ an intrathoracic pressure regulator (ITPR) CPR, the latter two representing IPR-based CPR therapies. Intrapleural (Ppl), airway (Paw), right atrial, intracranial, and aortic pressures, along with carotid blood flow and end tidal CO2, were measured and compared during each CPR intervention.ResultsThe lowest mean and decompression phase Ppl were observed with IPR-based therapies [Ppl mean (mean ± SE): STD (0.8 ± 1.1 mmHg); ACD (−1.6 ± 1.6); ACD-ITD (−3.7 ± 1.5, p < 0.05 vs. both STD and ACD); ACD-ITPR (−7.0 ± 1.9, p < 0.05 vs. both STD and ACD)] [Ppl decompression (mean ± SE): STD (−6.3 ± 2.2); ACD (−13.0 ± 3.8); ACD-ITD −16.9 ± 3.6, p < 0.05 vs. both STD and ACD); ACD-ITPR −18.7 ± 3.5, p < 0.05 vs. both STD and ACD)]. Interventions with the lower mean or decompression phase Ppl also demonstrated lower Paw and were associated with higher vital organ perfusion pressures.ConclusionsIPR-based CPR methods, specifically ACD-ITPR, yielded the most pronounced reduction in both Ppl and Paw and resulted in the most favorable augmentation of hemodynamics during CPR.Electronic supplementary materialThe online version of this article (doi:10.1186/s13049-015-0164-5) contains supplementary material, which is available to authorized users.

Shen-Fu Injection (参附注射液) alleviates post-resuscitation myocardial dysfunction by up-regulating expression of sarcoplasmic reticulum Ca2+-ATPase

To compare the effect of Shen-Fu Injection (SFI) and epinephrine on the expression of sarcoplasmic reticulum Ca(2+) ATPase 2a (SERCA2a) in a pig model with post-resuscitation myocardial dysfunction. Ventricular fibrillation (VF) was electrically induced in Wu-zhi-shan miniature pigs. After 8 min of untreated VF and 2 min of cardiopulmonary resuscitation (CPR), all animals were randomly administered a bolus injection of saline placebo (SA group, n=10), SFI (0.8 mg/kg, SFI group, n=10) or epinephrine (20 μg/kg, EPI group, n=10). After 4 min of CPR, a 100-J shock was delivered. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly resumed for a further 2 min followed by a second defibrillation attempt. Hemodynamic variables were recorded, and plasma concentrations of catecholamines were measured. Adenylate cyclase (AC), cyclic adenosine monophosphate (cAMP) and the expressions of β1-adrenoceptor (AR) and SERCA 2a were determined. Cardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the SA and EPI groups at 4 and 6 h after ROSC. The expression of β1-AR and SERCA2a at 24 h after ROSC were significantly higher in the SFI group than in the SA and EPI groups (P<0.05 or P<0.01). The administration of epinephrine during CPR decreased the expression of SERCA2a and aggravated postresuscitation myocardial function (P<0.01). SFI attenuated post-resuscitation myocardial dysfunction, and the mechanism might be related to the up-regulation of SERCA2a expression.

Tilting for perfusion: Head-up position during cardiopulmonary resuscitation improves brain flow in a porcine model of cardiac arrest

IntroductionCerebral perfusion is compromised during cardiopulmonary resuscitation (CPR). We hypothesized that beneficial effects of gravity on the venous circulation during CPR performed in the head-up tilt (HUT) position would improve cerebral perfusion compared with supine or head-down tilt (HDT). MethodsTwenty-two pigs were sedated, intubated, anesthetized, paralyzed and placed on a tilt table. After 6min of untreated ventricular fibrillation (VF) CPR was performed on 14 pigs for 3min with an automated CPR device called LUCAS (L) plus an impedance threshold device (ITD), followed by 5min of L-CPR+ITD at 0° supine, 5min at 30° HUT, and then 5min at 30° HDT. Microspheres were used to measure organ blood flow in 8 pigs. L-CPR+ITD was performed on 8 additional pigs at 0°, 20°, 30°, 40°, and 50° HUT. ResultsCoronary perfusion pressure was 19±2mmHg at 0° vs. 30±3 at 30° HUT (p<0.001) and 10±3 at 30° HDT (p<0.001). Cerebral perfusion pressure was 19±3 at 0° vs. 35±3 at 30° HUT (p<0.001) and 4±4 at 30° HDT (p<0.001). Brain–blood flow was 0.19±0.04mlmin−1g−1 at 0° vs. 0.27±0.04 at 30° HUT (p=0.01) and 0.14±0.06 at 30° HDT (p=0.16). Heart blood flow was not significantly different between interventions. With 0, 10, 20, 30, 40 and 50° HUT, ICP values were 21±2, 16±2, 10±2, 5±2, 0±2, −5±2 respectively, (p<0.001), CerPP increased linearly (p=0.001), and CPP remained constant. ConclusionDuring CPR, HDT decreased brain flow whereas HUT significantly lowered ICP and improved cerebral perfusion. Further studies are warranted to explore this new resuscitation concept.

Abstract 279: Effects of 2,3-Butanedione Monoxime Administration During Conventional Cardiopulmonary Resuscitation on Ischemic Contracture and Resuscitability in a Pig Model of Out-of-Hospital Cardiac Arrest

Background: Ischemic contracture compromises hemodynamic effectiveness of cardiopulmonary resuscitaton (CPR) and resuscitability. 2,3-Butanedione monoxime (BDM) reduced ischemic contracture by inhibiting actin-myosin cross-bridge formation in an isolated heart model. We investigated the effects of BDM on ischemic contracture and resuscitation outcomes in a pig model of out-of-hospital cardiac arrest (OHCA). Methods: After 15 min of untreated ventricular fibrillation followed by 8 min of basic life support, sixteen pigs were randomized to receive either 2 ml·kg -1 of BDM solution (25 g·l -1 ) (BDM group) or 2 ml·kg -1 of saline (control group) during advanced cardiac life support (ACLS). ACLS was continued until restoration of spontaneous circulation (ROSC) or until 12 min had lapsed since the start of ACLS. To obtain a long axis view of left ventricle (LV) using a transesophageal echocardiography (TEE) probe during CPR, a skin incision was made to the right of the xiphoid process and a pocket extending 4-5 cm under the sternum was made to ensure a free passage of the TEE probe. The primary outcome was ROSC and the secondary outcomes were LV wall thickness and chamber area. Results: There was a trend toward a higher rate of ROSC in the BDM group (8 of 8 versus 4 of 8, p = 0.077). During the ACLS, the control group showed an increase in LV wall thickness from 10.0 cm (10.0-10.8) to 13.0 cm (13.0-13.0) and a decrease in LV chamber area from 8.13 cm 2 (7.59-9.29) to 7.47 cm 2 (5.84-8.43). In contrast, the BDM group showed a decrease in the LV wall thickness from 10 cm (9.0-10.8) to 8.5 cm (7.0-9.8) and an increase in the LV chamber area from 9.86 cm 2 (7.22-12.39) to 12.15 cm 2 (8.02-14.40). Mixed model analyses on LV wall thickness and LV chamber area revealed significant effects for group and significant group-time interactions. Conclusions: BDM administered during cardiopulmonary resuscitation reversed ischemic contracture and tended to improve the resuscitability in a pig model of OHCA.

Abstract 20421: Polarizing State Induced by Adenosine, Lidocaine and Magnesium Administration After Prolonged Circulatory Arrest Improves Cardioprotection and Neuroprotection in a Rat Model of Cardiac Arrest With Extracorporeal Life Support

BACKGROUND: Polarized arrest, a new concept of myocardial protection, has been recently demonstrated to improve cardiac function after cardioplegic arrest during cardiac surgery. The present study investigated whether polarizing state after prolonged cardiac arrest would provide cardioprotective and neuroprotective effects after extracorporeal life support (ECLS). METHODS AND RESULTS: Ventricular fibrillation (VF) was induced in male Wistar rats. After 8 min of untreated VF, veno-arterial ECLS was instituted for 60 min inducing mild therapeutic hypothermia (32°C). At the beginning of ECLS animals were randomized to receive a single iv bolus of 4.5 mL/kg of polarizing solution with adenosine (47 μM), lidocaine (92 μM) and MgSO4 (1 mM) or same volume of saline as control. Restoration of spontaneous circulation was higher in rats that received polarizing solution (p = 0.03). After 24 h survival and neurologic deficit scores were improved and histological damage scores and brain TNF-α were attenuated compared to control (all p&lt;0.05). Polarizing solution administration led to better recovery of left ventricle end-systolic pressure-volume relationship (Ees), preload recruitable stroke work (PRSW), end-diastolic pressure-volume relationship (EDPVR) and Tau (p&lt;0.01). Polarized state enhanced phosphorilation of myocardial ERK1 and 2 and Akt, resulting in a lower apoptotic index (TUNEL, p&lt;0.01). CONCLUSIONS: Polarized state induced by adenosine, lidocaine and magnesium increased survival, neurologic outcome and cardiac function after prolonged cardiac arrest treated with ECLS. Moreover it improved cardioprotection through activation of the pro-survival kinases Akt and ERK1/2.

Effects of the administration of 2,3-butanedione monoxime during conventional cardiopulmonary resuscitation on ischaemic contracture and resuscitability in a pig model of out-of-hospital cardiac arrest

Aim of the studyIschaemic contracture compromises the haemodynamic effectiveness of cardiopulmonary resuscitation and resuscitability. 2,3-Butanedione monoxime (BDM) reduced ischaemic contracture by inhibiting actin-myosin crossbridge formation in an isolated heart model. We investigated the effects of BDM on ischaemic contracture and resuscitation outcomes in a pig model of out-of-hospital cardiac arrest (OHCA). MethodsAfter 15min of untreated ventricular fibrillation, followed by 8min of basic life support, 16 pigs were randomised to receive either 2mlkg−1 of BDM solution (25gl−1) or 2mlkg−1 of saline during advanced cardiac life support (ACLS). ResultsDuring the ACLS, the control group showed an increase in left ventricular (LV) wall thickness from 10.0mm (10.0–10.8) to 13.0mm (13.0–13.0) and a decrease in LV chamber area from 8.13cm2 (7.59–9.29) to 7.47cm2 (5.84–8.43). In contrast, the BDM group showed a decrease in the LV wall thickness from 10mm (9.0–10.8) to 8.5mm (7.0–9.8) and an increase in the LV chamber area from 9.86cm2 (7.22–12.39) to 12.15 cm2 (8.02–14.40). Mixed model analyses of the LV wall thickness and LV chamber area revealed significant group effects and group-time interactions. Spontaneous circulation was restored in four (50%) animals in the control group and in eight (100%) animals in the BDM group (p=0.077). All the resuscitated animals survived during an intensive care period of 4h. ConclusionBDM administered during cardiopulmonary resuscitation reversed ischaemic contracture in a pig model of OHCA.

Hemodynamic improvement of a LUCAS 2 automated device by addition of an impedance threshold device in a pig model of cardiac arrest

IntroductionThe combination of the LUCAS 2 (L-CPR) automated CPR device and an impedance threshold device (ITD) has been widely implemented in the clinical field. This animal study tested the hypothesis that the addition of an ITD on L-CPR would enhance cerebral and coronary perfusion pressures. MethodsTen female pigs (39.0±2.0kg) were sedated, intubated, anesthetized with isofluorane, and paralyzed with succinylcholine (93.3μg/kg/min) to inhibit the potential confounding effect of gasping. After 4min of untreated ventricular fibrillation, 4min of L-CPR+an active ITD or L-CPR+a sham ITD was initiated and followed by another 4min of the alternative method of CPR. Systolic blood pressure (SBP), diastolic blood pressure (DBP), diastolic right atrial pressure (RAP), intracranial pressure (ICP), airway pressure, and end tidal CO2 (ETCO2) were recorded continuously. Data expressed as mean mmHg±SD. ResultsDecompression phase airway pressure was significantly lower with L-CPR+active ITD versus L-CPR+sham ITD (−5.3±2.2 vs. −0.5±0.6; p<0.001). L-CPR+active ITD treatment resulted in significantly improved hemodynamics versus L-CPR+sham ITD: ETCO2, 35±6 vs. 29±7 (p=0.015); SBP, 99±9 vs. 93±15 (p=0.050); DBP, 24±12 vs. 19±15 (p=0.006); coronary perfusion pressure, 29±8 vs. 26±7 (p=0.004) and cerebral perfusion pressure, 24±13 vs. 21±12 (p=0.028). ConclusionsIn pigs undergoing L-CPR the addition of the active ITD significantly reduced intrathoracic pressure and increased vital organ perfusion pressures.

Resuscitation after cardiac arrest in a septic porcine model: adding vasopressin vs epinephrine alone administration.

BackgroundVasopressin administration has been tested in cardiac arrest. However it has not been tested when cardiac arrest occurs in certain circumstances, as in sepsis, where it may have a major role. The aim of the study was to investigate survival after cardiac arrest in a septic porcine model compared with healthy animals and to explore the effectiveness of adding vasopressin vs epinephrine alone administration.MethodsThirty five healthy piglets of both genders were studied. The piglets were randomly assigned into three groups: group A (n = 8), group B (n = 14), group C (n = 13). Animals of groups B and C were given endotoxin to mimic a septic state before arrest. We applied the same resuscitation protocol to all pigs but we replaced the first dose of epinephrine with vasopressin in pigs of group C. Following surgical preparation and 30 min resting period, baseline measurements were recorded. In order to assess tissue oxygenation, we implemented Near Infrared Spectroscopy (NIRS) with the vascular occlusion technique (VOT) in thirteen lipopolysaccharide (LPS)-treated animals, occluding abdominal aorta and inferior vena cava. Afterwards, LPS (100 μg/kg) was infused in a 30 min period to animals of groups B and C and normal saline to group A. New NIRS measurements were obtained again. Subsequently, we provoked ventricular fibrillation (VF). After 3 min of untreated VF, open chest cardiopulmonary resuscitation (CPR) was performed manually. Primary end point was the restoration of spontaneous circulation (ROSC).ResultsThe chance of ROSC for the groups A, B and C was 75%, 35.7%, and 30.7% respectively. A significant difference in ROSC was established between septic (group B + C) and non septic piglets (group A) (P = 0.046). Vasopressin administration had no effect in outcome. LPS administration decreased oxygen consumption rate, as assessed by NIRS, in peripheral tissues (22.6 ± 7.2. vs 18.5 ± 7.2, P = 0.07).ConclusionSeptic piglets have fewer chances to survive after cardiac arrest. No difference in outcome was observed when the first dose of epinephrine was replaced with vasopressin to treat cardiac arrest in the LPS-treated animals.

Kidney Protection by Hypothermic Total Liquid Ventilation after Cardiac Arrest in Rabbits

Total liquid ventilation (TLV) with perfluorocarbons has been shown to induce rapid protective cooling in animal models of myocardial ischemia and cardiac arrest, with improved neurological and cardiovascular outcomes after resuscitation. In this study, the authors hypothesized that hypothermic TLV can also limit kidney injury after cardiac arrest. Anesthetized rabbits were submitted to 15 min of untreated ventricular fibrillation. After resuscitation, three groups of eight rabbits each were studied such as (1) life support plus hypothermia (32°-33 °C) induced by cold TLV (TLV group), (2) life support without hypothermia (control group), and (3) Sham group (no cardiac arrest). Life support was continued for 6 h before euthanasia and kidney removal. Time to target esophageal temperature was less than 5 min in the TLV group. Hypothermia was accompanied by preserved renal function in the TLV group as compared with control group regarding numerous markers including creatinine blood levels (12 ± 1 vs. 16 ± 2 mg/l, respectively; mean ± SEM), urinary N-acetyl-β-(D)-glucosaminidase (1.70 ± 0.11 vs. 3.07 ± 0.10 U/mol of creatinine), γ-glutamyltransferase (8.36 ± 0.29 vs. 12.96 ± 0.44 U/mol of creatinine), or β2-microglobulin (0.44 ± 0.01 vs. 1.12 ± 0.04 U/mol of creatinine). Kidney lesions evaluated by electron microscopy and conventional histology were also attenuated in TLV versus control groups. The renal-protective effect of TLV was not related to differences in delayed inflammatory or immune renal responses because transcriptions of, for example, interferon-γ, tumor necrosis factor-α, interleukin-1β, monocyte chemoattractant protein-1, toll-like receptor-2, toll-like receptor-4, and vascular endothelial growth factor were similarly altered in TLV and control versus Sham. Ultrafast cooling with TLV is renal protective after cardiac arrest and resuscitation, which could increase kidney availability for organ donation.

Adrenaline increases blood-brain-barrier permeability after haemorrhagic cardiac arrest in immature pigs

Adrenaline (ADR) and vasopressin (VAS) are used as vasopressors during cardiopulmonary resuscitation. Data regarding their effects on blood-brain barrier (BBB) integrity and neuronal damage are lacking. We hypothesised that VAS given during cardiopulmonary resuscitation (CPR) after haemorrhagic circulatory arrest will preserve BBB integrity better than ADR. Twenty-one anaesthetised sexually immature male piglets (with a weight of 24.3 ± 1.3 kg) were bled 35% via femoral artery to a mean arterial blood pressure of 25 mmHg in the period of 15 min. Afterwards, the piglets were subjected to 8 min of untreated ventricular fibrillation followed by 15 min of open-chest CPR. At 9 min of circulatory arrest, piglets received amiodarone 1.0 mg/kg and hypertonic-hyperoncotic solution 4 ml/kg infusions for 20 min. At the same time, VAS 0.4 U/kg was given intravenously to the VAS group (n = 9) while the ADR group received ADR 20 μg/kg (n = 12). Internal defibrillation was attempted from 11 min of cardiac arrest to achieve restoration of spontaneous circulation. The experiment was terminated 3 h after resuscitation. The intracranial pressure (ICP) in the post-resuscitation phase was significantly greater in ADR group than in VAS group. VAS group piglets exhibited a significantly smaller BBB disruption compared with ADR group. Cerebral pressure reactivity index showed that cerebral blood flow autoregulation was also better preserved in VAS group. Resuscitation with ADR as compared with VAS after haemorrhagic circulatory arrest increased the ICP and impaired cerebrovascular autoregulation more profoundly, as well as exerted an increased BBB disruption though no significant difference in neuronal injury was observed.

Combination of Epinephrine with Esmolol Attenuates Post-Resuscitation Myocardial Dysfunction in a Porcine Model of Cardiac Arrest

BackgroundRecent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of post resuscitation myocardial dysfunction. The aim of the study was to investigate whether the short-acting β1-selective adrenergic blocking agent, esmolol, would attenuate post resuscitation myocardial dysfunction in a porcine model of cardiac arrest.Methods and ResultsAfter 8 min of untreated ventricular fibrillation and 2 min of basic life support, 24 pigs were randomized to three groups (n = 8 per group), which received central venous injection of either epinephrine combined with esmolol (EE group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 30, 60, 120, 240 and 360 min after return of spontaneous circulation (ROSC). Surviving pigs were euthanatized at 24 h after ROSC, and the hearts were removed for analysis by electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) assay. Compared with the EP and SA groups, EE group had a better outcome in hemodynamic function, (improved dp/dt maxima and minima and cardiac output) (P<0.05), and improved oxygen metabolism (oxygen delivery and oxygen consumption) (P<0.05), which suggesting that EE can protect myocardial tissue from injury and improve post-resuscitation myocardial dysfunction. The protective effect of EE also correlated with reducing cardiomyocyte apoptosis, evidenced by reducing TUNEL-positive cells, increasing anti-apoptotic Bcl-2/Bax ratio and suppression of caspase-3 activity in myocardium.ConclusionsEsmolol, a short-acting β1-selective adrenergic blocking agent, given during CPR has significant effects on attenuating post resuscitation myocardial dysfunction. The current study provides a potential pharmacologic target for post resuscitation myocardial dysfunction.