Porcine Model Of Prolonged Cardiac Arrest Research Articles

Abstract 122: Effects of Early Administration of Argatroban on CPR Quality in Porcine Model of Prolonged Out-of-Hospital Cardiac Arrest

Background: The effectiveness of CPR declines over time during prolonged cardiac arrest (CA). Intravascular thrombosis may be a contributing factor. As part of a larger study examining antithrombotic therapy in a porcine model of prolonged CA, the impact of early administration of argatroban on CPR hemodynamics is reported. Hypothesis: Early administration of argatroban during CPR improves the quality of goal-directed CPR (gdCPR). Methods: In a blinded and randomized study, 48 swine (40±5kg) underwent an 8min untreated period of ventricular fibrillation CA followed by a gdCPR protocol for 30min (total arrest time 38min). Manual and mechanical chest compressions with the use of an impedance threshold device (ITD) were introduced to maintain end-tidal CO 2 (Et-CO 2 ) >20mmHg. Argatroban (350mg/kg) or placebo (20mL NSS) were administered to respective groups (n=24 per group) 12mins after initiation of CA. Et-CO 2 , coronary perfusion pressure (CPP), end-diastolic pressure (EDP), and intracranial pressure (ICP) were monitored continuously. Averages were taken over the course of gdCPR for hemodynamic parameters. Arterial blood gases (ABGs) were obtained at the end of gdCPR. Analysis between groups was performed using an unpaired t-test (significance = p <0.05). Results: Average hemodynamic parameters were not statistically different between argatroban vs. placebo groups (Et-CO 2 22.6±6.7 vs. 21.5±5.9 mmHg; EDP 25.6±10.7 vs. 23.7±9.6 mmHg; ICP 25.7±2.0 vs.20.9±2.7 cmH 2 O; CPP 8.7±11.2 vs. 7.0±11.2 mmHg). Final ABG values were also not statistically different between argatroban vs. placebo groups (pH 7.23±0.1 vs. 7.23±0.2; PaO 2 187.4±146.3 vs. 132.2±187.4 mmHg; PaCO 2 38.8±16.6 vs. 43.0±26.1 mmHg; lactate 8.5±1.7 vs. 8.8±1.4 mmol/L). Conclusion: These results demonstrate that early administration of argatroban during CPR did not have a significant effect on gdCPR quality in a porcine model of prolonged CA.

Abstract 12024: Changes in Respiratory System Static Compliance After Resuscitation in a Porcine Model of Prolonged Cardiac Arrest

Introduction: Acute lung injury happens commonly after resuscitation due to ischemia reperfusion injury and complications of cardiopulmonary resuscitation (CPR). The static compliance of the respiratory system (Csrs) is a reliable indicator of lung injury, together with chest-wall compliance (Cscw) and lung compliance (Csl). In the present study, we investigated the changes in Csrs, Cscw and Csl after resuscitationin a porcine mode of prolonged cardiac arrest (CA). Hypothesis: Both Csrs and Csl are decreased after prolonged CA and CPR without significant changes in Cscw. Methods: Ventricular fibrillation was electrically induced and left untreated for 10 mins in six male domestic pigs weighing 39±3 kg. Defibrillation was then attempted by a single 150 J shock after 4 min of CPR. All the animals were resuscitated successfully. Succinylcholine chloride (1.0mg/kg) was given intravenously to relax the respiratory muscles and static pressure-volume (P-V) curves were obtained by constant low-flow method at baseline, 1, 2 and 8h after resuscitation. Airway opening pressure, esophageal pressure, transpulmonary pressure and tidal volume were assessed. Csrs, Cscw and Csl were calculated as the slope rates of the liner portion of the corresponding P-V curves. Results: Significant decreases in both Csrs and Csl were observed after resuscitation when compared with baseline (Figure). However, Cscw increased slightly at 1 h after resuscitation and returned to baseline 2 h post-resuscitation. Conclusion: Both Csrs and Csl were reduced significantly following resuscitation without significant changes of Cscw in a porcine model of prolonged CA and CPR.

Comparison of epinephrine and Shen-Fu injection on resuscitation outcomes in a porcine model of prolonged cardiac arrest

Background Epinephrine has been used as a first-choice vasopressor drug for cardiac arrest (CA) since 1974. However, the administration of epinephrine is controversial. This study aims to compare the effects of Shen-Fu injection (SFI) and epinephrine on resuscitation outcomes in a porcine model of prolonged CA. Methods Ventricular fibrillation (VF) was electrically induced. After 8 minutes of untreated VF and 2 minutes of chest compressions, 24 pigs were randomly divided into 3 groups (n=8 per group): central venous injection of SFI (SFI group), epinephrine (EPI group), or saline solution (SA group). The haemodynamic status and oxygen metabolism parameters, including cardiac output, mean arterial pressure, left ventricular dp/dtmax and negative dp/dtmax, oxygen delivery (DO2), and oxygen consumption (VO2), were calculated. Results SFI shortened the time to restoration of spontaneous circulation (ROSC) and decreased the number of shocks, similar to epinephrine. However, the mean arterial pressure, cardiac output, left ventricular dp/dtmax and negative dp/dtmax were significantly higher in the SFI group than in the EPI group at 4 and 6 hours after ROSC. VO2 and ERO2 decreased after ROSC and then increased. VO2 and ERO2 were significantly higher in the SFI group than in the EPI and SA groups after ROSC, while those were lowest in the EPI group among all groups. Conclusions SFI shortened the time to ROSC and decreased the number of shocks, similar to epinephrine. However, SFI improved oxygen metabolism, and produced a better hemodynamic status compared with epinephrine. SFI might be a potentially vasopressor drug for the treatment of CA.

Comparison of shock-first strategy and cardiopulmonary resuscitation-first strategy in a porcine model of prolonged cardiac arrest

ObjectiveThe choice of a shock-first or a cardiopulmonary resuscitation (CPR)-first strategy in the treatment of prolonged cardiac arrest (CA) is still controversial. The purpose of this study was to compare the effects of these strategies on oxygen metabolism and resuscitation outcomes in a porcine model of 8min CA. MethodsVentricular fibrillation (VF) was electrically induced. After 8min of untreated VF, 24 male inbred Wu-Zhi-Shan miniature pigs were randomized to receive either defibrillation first (ID group) or chest compression first (IC group). In the ID group, a shock was delivered immediately. If the defibrillation attempt failed to attain restoration of spontaneous circulation (ROSC), manual chest compressions were rapidly initiated at a rate of 100compressionsmin−1, and the compression-to-ventilation ratio was 30:2. If VF persisted after five cycles of CPR, a second defibrillation attempt was made. In the IC group, chest compressions were delivered first, followed by a shock. ResultsHemodynamic variables, the VF waveform and blood gas analysis outcomes were recorded. Oxygen metabolism parameters and the amplitude spectrum area (AMSA) of the VF waveform were computed. There were no significant differences in the rate of ROSC and 24h survival between two groups. The ID group had lower lactic acid levels, higher cardiac output, better oxygen consumption and better oxygen extraction ratio at 4 and 6h after ROSC than the IC group. ConclusionsIn a porcine model of prolonged CA, the choice of a shock-first or CPR-first strategy did not affect the rate of ROSC and 24h survival, but the shock-first strategy might result in better hemodynamic status and better oxygen metabolism than the CPR-first strategy at the first 6h after ROSC.

HYDROGEN SULFIDE DOES NOT INCREASE RESUSCITABILITY IN A PORCINE MODEL OF PROLONGED CARDIAC ARREST

Treatment options to improve resuscitability and neurological prognosis after cardiac arrest (CA) are limited. Hydrogen sulfide has demonstrated remarkable improvements in outcomes in small animal models of severe hypoxia or hemorrhage. We investigated the influence of sodium sulfide (Na2S), a liquid hydrogen sulfide donor, on resuscitability, postresuscitation hemodynamics, and neurological performance in a porcine model of prolonged CA and cardiopulmonary resuscitation. Twenty-four male pigs were instrumented with arterial and pulmonary artery catheters before 10 min of CA was induced. During resuscitation, animals were randomized to receive either high-dose (1 mg/kg; n = 8) or low-dose (0.3 mg/kg; n = 8) Na2S (IK-1001; Ikaria, Clinton, NJ) or control (saline placebo; n = 8) i.v. injection and consecutive infusion. Cardiopulmonary resuscitation was performed for 6 min before defibrillation was attempted. Hemodynamic variables were taken at baseline and 10, 30, 60, 120, and 240 min after successful resuscitation. Neurological outcome was evaluated on 4 postoperative days before brains and hearts were harvested for histopathologic analysis. No differences in hemodynamic parameters were observed at baseline. Initial resuscitability was not improved by Na2S. Animals exposed to high- and low-dose Na2S showed significantly reduced cardiac output, heart rate, and pulmonary arterial pressure compared with control animals during the early postresuscitation period. Strikingly, two of the high-dose Na2S animals died during the postresuscitation period, whereas all other animals survived. High-dose Na2S significantly decreased microglial activation in striatal areas, although this did not translate into improved neurological outcome. Although animals receiving Na2S developed higher troponin T serum levels, these differences remained insignificant. In this investigation, Na2S did not improve resuscitability but significantly compromised postresuscitation hemodynamics.