Untreated Ventricular Fibrillation Research Articles

Abstract 231: Volume And Direction Of Carotid Blood Flow During Cardiopulmonary Resuscitation In A Porcine Model Of Ventricular Fibrillation

Introduction: Hemodynamics during cardiopulmonary resuscitation (CPR) is not well understood. We aimed to quantitatively evaluate the volume and direction of carotid blood flow (CBF) during CPR in a porcine model of ventricular fibrillation (VF) cardiac arrest. Methods: Nineteen male domestic pigs were intubated and ventilated mechanically. Following baseline measurements, VF was electrically induced. CBF was measured continuously using a flow probe positioned around the common carotid arteries. After 0 or 5 min no-flow time of untreated VF, CPR was initiated, involving chest compressions and ventilation with oxygen. CPR was continued for 25 min, with mechanical (L1, L2, and L3) and manual (M1 and M2) CPR alternated at 5 min intervals. A Friedman test was used to compare the groups in each phase. Post hoc analysis was performed using a Wilcoxon signed-rank test (Bonferroni corrected). Results: CBF was calculated as the average of each phase. The net flow was calculated through subtracting the retrograde flow from the anterograde flow. Average net flow (median, interquartile range [IQR], mL/min) during CPR was 58.1 (24.0-111.3), 19.8 (8.4-24.9), 21.2 (9.5-37.9), 15.4 (8.4-24.9), and 16.4 (10.3-30.1) in phases L1, M1, L2, M2, and L3, respectively ( p < 0.001, L1 vs. M1). The ratio (median, IQR, %) of retrograde to anterograde flow was 41.3 (16.7-58.7), 48.6 (33.1-60.4), 42.2 (36.5-76.4), 49.1 (39.4-68.5), and 50.0 (38.0-79.0) in phases L1, M1, L2, M2, and L3, respectively ( p = 0.299). Conclusions: In this VF cardiac arrest model, the net flow of the carotid artery during CPR decreased with time. Both mechanical and manual CPR produced substantial retrograde flow, although the ratio of retrograde to anterograde flow did not change.

Abstract 196: Association Between Continuous Carotid Blow Flow And Continuous Cerebral Perfusion Indexes Assessment By NIRS In A Porcine Model Of Ventricular Fibrillation During CPR

[Background]: Maintenance of cerebral blood flow during cardiopulmonary resuscitation (CPR) is a critical factor affecting the neurological outcome of patients after cardiac arrest. However, dynamic indicator of cerebral blood flow during CPR is not established. Near infrared spectroscopy (NIRS) is a non-invasive technique capable of detecting changes in cerebral blood volume continuously. The aim of this study is to compare cerebral perfusion during CPR obtained by continuous measure of carotid blow flow (CBF) using flow sensor with continuous cerebral perfusion indices (CPI) assessment by NIRS in a porcine model of ventricular fibrillation (VF) cardiac arrest. [Methods]: CBF during CPR were measured in 21 swine (25± 3 kg) using extra-vascular flow probes positioned around the common carotid arteries. The optodes of the NIRS were attached to the skull bone. Following baseline measurements, VF was electrically induced. After the interval of untreated VF, CPR was continued for 25 min, during which mechanical and manual CPR was alternated at every 5 min intervals. CBF and CPI were measured continuously during CPR. The mean volume of CBF and CPI was calculated average 10 beats in each phase. Correlations between CBF volume and CPI were analyzed by Spearman's rank correlation. [Results]: The followability of CBF and CPI during CPR was good. The Spearman's rank correlation coefficient between CBF volume and CPI was different by sections and it was suggested that the CBF volume was too small to assess the correlation in many sections. If the sections with CBF volume>0.4 ml were extracted and reanalyzed, the rate of sections correlated between CBF volume and CPI were increased (Spearman’s correlation coefficient≧0.4 was 41.3%, Spearman’s correlation coefficient≧0.7 was 17.5%).(Table) [Conclusions]: It was suggested that CPI by NIRS can reflect the CBF during CPR in the sections where enough CBF is.

Influence of oxygen concentration on the neuroprotective effect of hydrogen inhalation in a rat model of cardiac arrest.

BackgroundPost-cardiac arrest (CA) brain injury is the main cause of death in patients resuscitated from CA. Previous studies demonstrated that hydrogen inhalation mitigates post-CA brain injury. However, factors affecting the efficacy of hydrogen remain unknown. In the present study, we investigated the influence of oxygen concentration and targeted temperature on neuroprotective effect in a CA rat model of ventricular fibrillation (VF).MethodsCardiopulmonary resuscitation (CPR) was initiated after 7 min of untreated VF in adult male Sprague–Dawley rats. Immediately following successful resuscitation, animals were randomized to be ventilated with 21% oxygen and 79% nitrogen (21%O2); 2% hydrogen, 21% oxygen, and 77% nitrogen (2%H2 + 21%O2); 2% hydrogen, 50% oxygen, and 48% nitrogen (2%H2 + 50%O2); or 2% hydrogen and 98% oxygen (2%H2 + 98%O2) for 3 h. For each group, the target temperature was 37.5°C for half of the animals and 35.0°C for the other half.ResultsNo statistical differences in baseline measurements and CPR characteristics were observed among groups. For animals with normothermia, 2%H2 + 50%O2 (123 [369] vs. 500 [393], p = 0.041) and 2%H2 + 98%O2 (73 [66] vs. 500 [393], p = 0.002) groups had significantly lower neurological deficit scores (NDSs) at 96 h and significantly higher survival (75.0 vs. 37.5%, p = 0.033 and 81.3 vs. 37.5%, p = 0.012) than 21%O2 group. For animals with hypothermia, no statistical difference in NDS among groups but 2%H2 + 98%O2 has significantly higher survival than the 21%O2 group (93.8 vs. 56.3%, p = 0.014).ConclusionIn this CA rat model, inhaling 2% hydrogen combined with a high concentration of oxygen improved 96-h survival, either under normothermia or under hypothermia.

HEAD AND THORAX ELEVATION PREVENTS THE RISE OF INTRACRANIAL PRESSURE DURING EXTRACORPOREAL RESUSCITATION IN SWINE.

Aim: Head and thorax elevation during cardiopulmonary resuscitation improves cerebral hemodynamics and ultimate neurological outcome after cardiac arrest. Its effect during extracorporeal cardiopulmonary resuscitation (E-CPR) is unknown. We tested whether this procedure could improve hemodynamics in swine treated by E-CPR. Methods and Results: Pigs were anesthetized and submitted to 15 minutes of untreated ventricular fibrillation followed by E-CPR. Animals randomly remained in flat position (flat group) or underwent head and thorax elevation since E-CPR institution (head-up group). Electric shocks were delivered after 30 minutes until the return of spontaneous circulation (ROSC). They were followed during 120 minutes after ROSC. After 30 minutes of E-CPR, ROSC was achieved in all animals, with no difference regarding blood pressure, heart rate, and extracorporeal membrane of oxygenation flow among groups. The head-up group had an attenuated increase in ICP as compared with the flat group after cardiac arrest (13 ± 1 vs. 26 ± 2 mm Hg at the end of the follow-up, respectively). Cerebral perfusion pressure tended to be higher in the head-up versus flat group despite not achieving statistical difference (66 ± 1 vs 46 ± 1 mm Hg at the end of the follow-up). Carotid blood flow and cerebral oxygen saturation were not significantly different among groups. Conclusion: During E-CPR, head and thorax elevation prevents ICP increase. Whether it could improve the ultimate neurological outcome in this situation deserves further investigation.

Effects of Sodium Nitroprusside Administered Via a Subdural Intracranial Catheter on the Microcirculation, Oxygenation, and Electrocortical Activity of the Cerebral Cortex in a Pig Cardiac Arrest Model.

BackgroundPostischemic cerebral hypoperfusion has been indicated as an important contributing factor to secondary cerebral injury after cardiac arrest. We evaluated the effects of sodium nitroprusside administered via a subdural intracranial catheter on the microcirculation, oxygenation, and electrocortical activity of the cerebral cortex in the early postresuscitation period using a pig model of cardiac arrest.Methods and ResultsTwenty‐nine pigs were resuscitated with closed cardiopulmonary resuscitation after 14 minutes of untreated ventricular fibrillation. Thirty minutes after restoration of spontaneous circulation, 24 pigs randomly received either 4 mg of sodium nitroprusside (IT‐SNP group) or saline placebo (IT‐saline group) via subdural intracranial catheters and were observed for 5 hours. The same dose of sodium nitroprusside was administered intravenously in another 5 pigs. Compared with the IT‐saline group, the IT‐SNP group had larger areas under the curve for tissue oxygen tension and percent changes of arteriole diameter and number of perfused microvessels from baseline (all P<0.05) monitored on the cerebral cortex during the 5‐hour period, without severe hemodynamic instability. This group also showed faster recovery of electrocortical activity measured using amplitude‐integrated electroencephalography. Repeated‐measures analysis of variance revealed significant group–time interactions for these parameters. Intravenously administered sodium nitroprusside caused profound hypotension but did not appear to increase the cerebral parameters.ConclusionsSodium nitroprusside administered via a subdural intracranial catheter increased post–restoration of spontaneous circulation cerebral cortical microcirculation and oxygenation and hastened electrocortical activity recovery in a pig model of cardiac arrest. Further studies are required to determine its impact on the long‐term neurologic outcomes.

Protection Against Post-resuscitation Acute Kidney Injury by N-Acetylcysteine via Activation of the Nrf2/HO-1 Pathway.

Background and ObjectiveAcute kidney injury (AKI), the common complication after cardiopulmonary resuscitation (CPR), seriously affects the prognosis of cardiac arrest (CA) patients. However, there are limited studies on post-resuscitation AKI. In addition, it has been demonstrated that N-acetylcysteine (N-AC) as an ROS scavenger, has multiorgan-protective effects on systemic and regional ischaemia-reperfusion injuries. However, no studies have reported its protective effects against post-resuscitation AKI and potential mechanisms. This study aimed to clarify the protective effects of N-AC on post-resuscitation AKI and investigate whether its potential mechanism was mediated by activating Nrf-2/HO-1 pathway in the kidney.MethodsWe established cardiac arrest models in rats. All animals were divided into four groups: the sham, control, N-AC, and ZnPP groups. Animals in each group except for the ZnPP group were assigned into two subgroups based on the survival time: 6 and 48 h. The rats in the control, N-AC, and ZnPP groups underwent induction of ventricular fibrillation (VF), 8 min untreated VF and cardiopulmonary resuscitation. Renal function indicators, were detected using commercial kits. Renal pathologic changes were assessed by haematoxylin–eosin (HE) staining. Oxidative stress and inflammatory responses were measured using the corresponding indicators. Apoptosis was evaluated using terminal uridine nick-end labeling (TUNEL) staining, and expression of proteins associated with apoptosis and the Nrf-2/HO-1 pathway was measured by western blotting.ResultsN-AC inhibited post-resuscitation AKI. We observed that N-AC reduced the levels of biomarkers of renal function derangement; improved renal pathological changes; and suppressed apoptosis, oxidative stress, and inflammatory response. Additionally, the production of ROS in the kidneys markedly decreased by N-AC. More importantly, compared with the control group, N-AC further upregulated the expression of nuclear Nrf2 and endogenous HO-1 in N-AC group. However, N-AC-determined protective effects on post-resuscitation AKI were markedly reversed after pretreatment of the HO-1 inhibitor zinc protoporphyrin (ZnPP).ConclusionsN-AC alleviated renal dysfunction and prolonged survival in animal models of CA. N-AC partially exerts beneficial renal protection via activation of the Nrf-2/HO-1 pathway. Altogether, all these findings indicated that N-AC as a common clinical agent, may have the potentially clinical utility to improve patients the outcomes in cardiac arrest.

Hypothermia preconditioning improves cardiac contractility after cardiopulmonary resuscitation through AMPK-activated mitophagy.

Hypothermia preconditioning (HPC) improves cardiac function after cardiac arrest, yet the mechanism is unclear. We hypothesized that HPC-activated adenosine monophosphate-activated protein kinase (AMPK) activity may be involved. Adult male Wistar rats were randomly divided into normothermia Control, HPC (cooling to 32-34°C for 30 min), and HPC + Compound C (Compound C 10 mg/kg was injected intraperitoneally 30 min before HPC group). The rats underwent 7 min of untreated ventricular fibrillation (VF) followed by cardiopulmonary resuscitation (CPR). Cardiac function and hemodynamic parameters were evaluated at 4 h after return of spontaneous circulation (ROSC). Survival status was determined 72 h after ROSC. Mechanistically, we further examined the AMPK-Unc-51 Like Autophagy Activating Kinase 1 (ULK1)-mitophagy pathway and autophagic flux in vivo and in vitro. Six of twelve rats in the Control group, 10 of 12 rats in the HPC group, and 7 of 12 rats in HPC + Compound C group were successfully resuscitated. The 72-h survival rates were 1 of 12 Control, 6 of 12 HPC, and 2 of 12 HPC + Compound C rats, respectively (P = 0.043). Rats in the HPC group demonstrated greater cardiac contractility and hemodynamic stability which were compromised by Compound C. Furthermore, HPC increased the protein levels of p-AMPKα and p-ULK1 and promoted the expression of mitochondrial autophagy-related genes. Compound C decreased the expression of mitochondrial autophagy-related genes and reduced autophagic flux. Consistent with the observations obtained in vivo, in vitro experiments in cultured neonatal rat cardiomyocytes (CMs) demonstrated that HPC attenuated simulated ischemia-reperfusion-induced CM death, accompanied by increased AMPK-ULK1-mitophagy pathway activity. These findings suggest that AMPK-ULK1-mitophagy pathway was activated by HPC and has a crucial role in cardioprotection during cardiac arrest. Manipulation of mitophagy by hypothermia may merit further investigation as a novel strategy to prevent cardiac ischemia-reperfusion injury.

Trimetazidine Alleviates Postresuscitation Myocardial Dysfunction and Improves 96-Hour Survival in a Ventricular Fibrillation Rat Model.

BackgroundMyocardial dysfunction is a critical cause of post‐cardiac arrest hemodynamic instability and circulatory failure that may lead to early mortality after resuscitation. Trimetazidine is a metabolic agent that has been demonstrated to provide protective effects in myocardial ischemia. However, whether trimetazidine protects against postresuscitation myocardial dysfunction is unknown.Methods and ResultsCardiopulmonary resuscitation was initiated after 8 minutes of untreated ventricular fibrillation in Sprague‐Dawley rats. Animals were randomized to 4 groups immediately after resuscitation (n=15/group): (1) normothermia control (NTC); (2) targeted temperature management; (3) trimetazidine‐normothermia; (4) trimetazidine‐targeted temperature management. TMZ was administered at a single dose of 10 mg/kg in rats with trimetazidine. The body temperature was maintained at 34.0°C for 2 hours and then rewarmed to 37.5°C in rats with targeted temperature management. Postresuscitation hemodynamics, 96‐hours survival, and pathological analysis were assessed. Heart tissues and blood samples of additional rats (n=6/group) undergoing the same experimental procedure were collected to measure myocardial injury, inflammation and oxidative stress‐related biomarkers with ELISA‐based quantification assays. Compared with normothermia control, tumor necrosis factor‐α, and cardiac troponin‐I were significantly reduced, whereas the left ventricular ejection fraction and 96‐hours survival rates were significantly improved in the 3 experimental groups. Furthermore, inflammation and oxidative stress‐related biomarkers together with collagen volume fraction were significantly decreased in rats undergoing postresuscitation interventions.ConclusionsTrimetazidine significantly alleviates postresuscitation myocardial dysfunction and improves survival by decreasing oxidative stress and inflammation in a ventricular fibrillation rat model. A single dose of trimetazidine administrated immediately after resuscitation can effectively improve cardiac function, whether used alone or combined with targeted temperature management.

Alda-1, an Activator of ALDH2, Improves Postresuscitation Cardiac and Neurological Outcomes by Inhibiting Pyroptosis in Swine

Aldehyde dehydrogenase 2 (ALDH2) has been proven to protect the heart and brain against regional ischemia/reperfusion injury, in which the protective role is related to the inhibition of pyroptosis. In the present study, we investigated whether an ALDH2 activator N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichloro-benzamide (Alda-1) would improve postresuscitation cardiac and neurological outcomes in a clinically relevant swine model of cardiac arrest (CA) and resuscitation. The animal model was established by 8min of untreated ventricular fibrillation and then 8min of cardiopulmonary resuscitation (CPR). After restoring spontaneous circulation, the animals were randomly divided to receive either Alda-1 (0.88mg/kg, n = 6) or saline (n = 5). Postresuscitation hemodynamic parameters, cardiac function, and cardiac and cerebral injuries were periodically measured for a total of 24h. At 24h postresuscitation, neurological function was evaluated, and then the animals were sacrificed, and cardiac and cerebral tissue samples were obtained for the measurements of oxidative stress, inflammation and pyroptosis. Consequently, postresuscitation cardiac and neurological dysfunction were significantly improved accompanied with significantly milder cardiac and cerebral injuries in the Alda-1 group compared with the CPR group. In addition, the increase in NLR family pyrin domain-containing 3 inflammasome expression and proinflammatory cytokine production, which indicated the occurrence of inflammatory response, were significantly less in the Alda1 group than in the CPR group. The expression level of gasdermin D used as a protein marker of pyroptosis was also significantly reduced in all resuscitated animals receiving Alda1 treatment. Moreover, the severity of oxidative stress indicated by the changes of 4-hydroxy-2-nonenal and malondialdehyde was significantly decreased in the heart and brain in all animals treated with Alda-1 compared to the CPR group. Thus, Alda-1 mitigated postresuscitation cardiac and neurological dysfunction and injuries possibly by inhibiting oxidative stress-mediated NLRP3 inflammasome activation and pyroptosis in a swine model of CA and resuscitation.

Abstract 14195: Impact of Leukocyte Filtration and Leukocyte Modulation on Recovery of Heart Function After Prolonged Cardiac Arrest Treated With ECPR in a Porcine Model

Background: Extracorporeal cardiopulmonary resuscitation (ECPR) improves survival of patients with prolonged cardiac arrest (CA) that is refractory to standard CPR and ACLS. It has been proposed that ECPR accentuates inflammation after CA, potentially limiting its effectiveness. The benefits of leukocyte filters or leukocyte-modulating devices in conjunction with ECPR have not been studied. Hypothesis: When paired with ECPR, inflammation-modulating devices targeting leukocytes may improve recovery of cardiac function after prolonged cardiac arrest. Methods: In a randomized study, 24 swine (40±5kg) underwent 8min of untreated ventricular fibrillation CA followed by CPR with mechanical chest compressions and impedance threshold device for 30 min (total arrest time = 38min), immediately followed by 8h of ECPR with heparin anticoagulation and temperature maintained at 33°C. Group 1 (n=8) had standard ECPR system (control), Group 2 (n=8) had a leukocyte filter device (LF) added to the ECPR circuit, an and Group 3 (n=8) had a leukocyte modulation device (LMOD) added to the ECPR circuit. Recovery of cardiac function was measured using a cardiac resuscitablity score (CRS) and left ventricular ejection fraction (LVEF) via transthoracic echocardiography. Data was collected at baseline (prior CA) and after 8h of ECPR. Data analysis: single-factor ANOVA test (p&lt;0.05 significance). Results: There were no statically significant differences between the groups in CRS (Control = 3.3 ± 2.4, LF = 4.0 ± 2.8, LMOD = 2.1 ± 2.6; p=0.37) or LVEF (Control = 59% ± 27%, LF = 49% ± 29% LMOD = 34% ± 38%: p=0.34) at 8 hours after ECPR initiation (Table 1). Discussion: In this swine model of prolonged cardiac arrest treated with ECPR, addition of a leukocyte filter or leukocyte modulation device to the ECPR circuit did not improve recovery of cardiac function during the first 8 hours after initiating ECPR.

Abstract 9934: High Mean Arterial Pressure Aggravates Cerebral Hemodynamics After Extracorporeal Resuscitation in Swine

Introduction: Extracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest but the optimal target to reach for mean arterial pressure (MAP) remains to be determined. Hypothesis: We hypothesized that MAP levels modify cerebral hemodynamics during E-CPR. Accordingly, we tested two MAP targets (65-75 vs 80-90 mmHg) in a porcine model of E-CPR. Methods: Pigs were anesthetized and instrumented for the evaluation of cerebral and systemic hemodynamics. They were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Electric attempts of defibrillation were then delivered until resumption of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min with a standardized volume expansion in both groups. The dose of epinephrine was set to reach either a standard or a high MAP target level (65-75 vs 80-90 mmHg, respectively). Animals were followed during 120 min after ROSC. Results: Six animals were included in both groups. After cardiac arrest, MAP was maintained at the expected level (Figure). During E-CPR, high MAP transiently improved carotid blood flow as compared to standard MAP. This blood flow progressively decreased after ROSC in high vs standard MAP, while intra-cranial pressure increased. Interestingly, this was associated with a significant decrease in cerebral oxygen consumption (26±8 vs 54±6 L O 2 /min/kg at 120 min after ROSC, respectively; p&lt;0.01) (Figure). The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, became positive in high MAP (0.47±0.02) vs standard MAP group (-0.16±0.10), demonstrating altered cerebral autoregulation with high MAP. Conclusion: Increasing MAP above 80 mmHg with epinephrine aggravates cerebral hemodynamics after E-CPR. Figure: Mean arterial pressure (MAP), cerebral blood flow and oxygen consumption (*, p&lt;0.05)

Targeted high mean arterial pressure aggravates cerebral hemodynamics after extracorporeal resuscitation in swine

BackgroundExtracorporeal cardiopulmonary resuscitation (E-CPR) is used for the treatment of refractory cardiac arrest. However, the optimal target to reach for mean arterial pressure (MAP) remains to be determined. We hypothesized that MAP levels critically modify cerebral hemodynamics during E-CPR and tested two distinct targets (65–75 vs 80–90 mmHg) in a porcine model.MethodsPigs were submitted to 15 min of untreated ventricular fibrillation followed by 30 min of E-CPR. Defibrillations were then delivered until return of spontaneous circulation (ROSC). Extracorporeal circulation was initially set to an average flow of 40 ml/kg/min. The dose of epinephrine was set to reach a standard or a high MAP target level (65–75 vs 80–90 mmHg, respectively). Animals were followed during 120-min after ROSC.ResultsSix animals were included in both groups. During E-CPR, high MAP improved carotid blood flow as compared to standard MAP. After ROSC, this was conversely decreased in high versus standard MAP, while intra-cranial pressure was superior. The pressure reactivity index (PRx), which is the correlation coefficient between arterial blood pressure and intracranial pressure, also demonstrated inverted patterns of alteration according to MAP levels during E-CPR and after ROSC. In standard-MAP, PRx was transiently positive during E-CPR before returning to negative values after ROSC, demonstrating a reversible alteration of cerebral autoregulation during E-CPR. In high-MAP, PRx was negative during E-CPR but became sustainably positive after ROSC, demonstrating a prolonged alteration in cerebral autoregulation after ROSC. It was associated with a significant decrease in cerebral oxygen consumption in high- versus standard-MAP after ROSC.ConclusionsDuring early E-CPR, MAP target above 80 mmHg is associated with higher carotid blood flow and improved cerebral autoregulation. This pattern is inverted after ROSC with a better hemodynamic status with standard versus high-MAP.

Targeted Delivery of Electrical Shocks and Epinephrine, Guided by Ventricular Fibrillation Amplitude Spectral Area, Reduces Electrical and Adrenergic Myocardial Burden, Improving Survival in Swine.

BackgroundWe previously reported that resuscitation delivering electrical shocks guided by real‐time ventricular fibrillation amplitude spectral area (AMSA) enabled return of spontaneous circulation (ROSC) with fewer shocks, resulting in less myocardial dysfunction. We now hypothesized that AMSA could also guide delivery of epinephrine, expecting further outcome improvement consequent to less electrical and adrenergic burdens.Methods and ResultsA swine model of ventricular fibrillation was used to compare after 10 minutes of untreated ventricular fibrillation a guidelines‐driven (n=8) resuscitation protocol, delivering shocks every 2 minutes and epinephrine every 4 minutes, with an AMSA‐driven shocks (n=8) protocol, delivering epinephrine every 4 minutes, and with an AMSA‐driven shocks and epinephrine (ADSE; n=8) protocol. For guidelines‐driven, AMSA‐driven shocks, and ADSE protocols, the time to ROSC (mean±SD) was 569±164, 410±111, and 400±80 seconds (P=0.045); the number of shocks (mean±SD) was 5±2, 3±1, and 3±2 (P=0.024) with ADSE fewer than guidelines‐driven (P=0.03); and the doses of epinephrine (median [interquartile range]) were 2.0 (1.3–3.0), 1.0 (1.0–2.8), and 1.0 (0.3–3.0) (P=0.419). The ROSC rate was similar, yet survival after ROSC favored AMSA‐driven protocols (guidelines‐driven, 3/6; AMSA‐driven shocks, 6/6; and ADSE, 7/7; P=0.019 by log‐rank test). Left ventricular function and survival after ROSC correlated inversely with electrical burden (ie, cumulative unsuccessful shocks, J/kg; P=0.020 and P=0.046) and adrenergic burden (ie, total epinephrine doses, mg/kg; P=0.042 and P=0.002).ConclusionsDespite similar ROSC rates achieved with all 3 protocols, AMSA‐driven shocks and ADSE resulted in less postresuscitation myocardial dysfunction and better survival, attributed to attaining ROSC with less electrical and adrenergic myocardial burdens.

Exogenous Nicotinamide Adenine Dinucleotide Attenuates Postresuscitation Myocardial and Neurologic Dysfunction in a Rat Model of Cardiac Arrest.

To investigate the therapeutic potential and underlying mechanisms of exogenous nicotinamide adenine dinucleotide+ on postresuscitation myocardial and neurologic dysfunction in a rat model of cardiac arrest. Thirty-eight rats were randomized into three groups: 1) Sham, 2) Control, and 3) NAD. Except for the sham group, untreated ventricular fibrillation for 6 minutes followed by cardiopulmonary resuscitation was performed in the control and NAD groups. Nicotinamide adenine dinucleotide+ (20 mg/kg) was IV administered at the onset of return of spontaneous circulation. University-affiliated research laboratory. Sprague-Dawley rats. Nicotinamide adenine dinucleotide+. Hemodynamic and myocardial function were measured at baseline and within 4 hours following return of spontaneous circulation. Survival analysis and Neurologic Deficit Score were performed up to 72 hours after return of spontaneous circulation. Adenosine triphosphate (adenosine triphosphate) level was measured in both brain and heart tissue. Mitochondrial respiratory chain function, acetylation level, and expression of Sirtuin3 and NADH dehydrogenase (ubiquinone) 1 alpha subcomplex, 9 (NDUFA9) in isolated mitochondrial protein from both brain and heart tissue were evaluated at 4 hours following return of spontaneous circulation. The results demonstrated that nicotinamide adenine dinucleotide+ treatment improved mean arterial pressure (at 1 hr following return of spontaneous circulation, 94.69 ± 4.25 mm Hg vs 89.57 ± 7.71 mm Hg; p < 0.05), ejection fraction (at 1 hr following return of spontaneous circulation, 62.67% ± 6.71% vs 52.96% ± 9.37%; p < 0.05), Neurologic Deficit Score (at 24 hr following return of spontaneous circulation, 449.50 ± 82.58 vs 339.50 ± 90.66; p < 0.05), and survival rate compared with that of the control group. The adenosine triphosphate level and complex I respiratory were significantly restored in the NAD group compared with those of the control group. In addition, nicotinamide adenine dinucleotide+ treatment activated the Sirtuin3 pathway, down-regulating acetylated-NDUFA9 in the isolated mitochondria protein. Exogenous nicotinamide adenine dinucleotide+ treatment attenuated postresuscitation myocardial and neurologic dysfunction. The responsible mechanisms may involve the preservation of mitochondrial complex I respiratory capacity and adenosine triphosphate production, which involves the Sirtuin3-NDUFA9 deacetylation.

High-resolution respirometry for evaluation of mitochondrial function on brain and heart homogenates in a rat model of cardiac arrest and cardiopulmonary resuscitation

The physiology and physiopathology process of mitochondrial function following cardiac arrest remains poorly understood. We aimed to assess mitochondrial respiratory function on the heart and brain homogenates from cardiac arrest rats. The expression level of SIRT1/PGC-1α pathway was measured by immunoblotting. 30 rats were assigned to the CA group and the sham group. Rats of CA were subjected to 6 min of untreated ventricular fibrillation (VF) followed by 8 min of cardiopulmonary resuscitation (CPR). Mitochondrial respiratory function was compromised following CA and I/R injury, as indicated by CIL (451.46 ± 71.48 vs. 909.91 ± 5.51 pmol/min*mg for the heart and 464.14 ± 8.22 vs. 570.53 ± 56.33 pmol/min*mg for the brain), CI (564.04 ± 64.34 vs. 2729.52 ± 347.39 pmol/min*mg for the heart and 726.07 ± 85.78 vs. 1762.82 ± 262.04 pmol/min*mg for the brain), RCR (1.88 ± 0.46 vs. 3.57 ± 0.38 for the heart and 2.05 ± 0.19 vs. 3.49 ± 0.19, for the brain) and OXPHOS coupling efficiency (0.45 ± 0.11 vs. 0.72 ± 0.03 for the heart and 0.52 ± 0.05 vs. 0.71 ± 0.01 for the brain). However, routine respiration was lower in the heart and comparable in the brain after CA. CIV did not change in the heart but was enhanced in the brain. Furthermore, both SIRT1 and PGC-1α were downregulated concurrently in the heart and brain. The mitochondrial respiratory function was compromised following CA and I/R injury, and the major affected respiratory state is complex I-linked respiration. Furthermore, the heart and the brain respond differently to the global I/R injury after CA in mitochondrial respiratory function. Inhibition of the SIRT1/PGC-1α pathway may be a major contributor to the impaired mitochondrial respiratory function.

Severe Myocardial Dysfunction after Non-Ischemic Cardiac Arrest: Effectiveness of Percutaneous Assist Devices.

Introduction: Despite the improvements in standardized cardiopulmonary resuscitation, survival remains low, mainly due to initial myocardial dysfunction and hemodynamic instability. Our goal was to compare the efficacy of two left ventricular assist devices on resuscitation and hemodynamic supply in a porcine model of ventricular fibrillation (VF) cardiac arrest. Methods: Seventeen anaesthetized pigs had 12 min of untreated VF followed by 6 min of chest compression and boluses of epinephrine. Next, a first defibrillation was attempted and pigs were randomized to any of the three groups: control (n = 5), implantation of an percutaneous left ventricular assist device (Impella, n = 5) or extracorporeal membrane oxygenation (ECMO, n = 7). Hemodynamic and myocardial functions were evaluated invasively at baseline, at return of spontaneous circulation (ROSC), after 10–30–60–120–240 min post-resuscitation. The primary endpoint was the rate of ROSC. Results: Only one of 5 pigs in the control group, 5 of 5 pigs in the Impella group, and 5 of 7 pigs in the ECMO group had ROSC (p < 0.05). Left ventricular ejection fraction at 240 min post-resuscitation was 37.5 ± 6.2% in the ECMO group vs. 23 ± 3% in the Impella group (p = 0.06). No significant difference in hemodynamic parameters was observed between the two ventricular assist devices. Conclusion: Early mechanical circulatory support appeared to improve resuscitation rates in a shockable rhythm model of cardiac arrest. This approach appears promising and should be further evaluated.

Inhaled nitric oxide preserves ventricular function during resuscitation using a percutaneous mechanical circulatory support device in a porcine cardiac arrest model: an echocardiographic myocardial work analysis

BackgroundResuscitation using a percutaneous mechanical circulatory support device (iCPR) improves survival after cardiac arrest (CA). We hypothesized that the addition of inhaled nitric oxide (iNO) during iCPR might prove synergistic, leading to improved myocardial performance due to lowering of right ventricular (RV) afterload, left ventricular (LV) preload, and myocardial energetics. This study aimed to characterize the changes in LV and RV function and global myocardial work indices (GWI) following iCPR, both with and without iNO, using 2-D transesophageal echocardiography (TEE) and GWI evaluation as a novel non-invasive measurement.MethodsIn 10 pigs, iCPR was initiated following electrically-induced CA and 10 min of untreated ventricular fibrillation (VF). Pigs were randomized to either 20 ppm (20 ppm, n = 5) or 0 ppm (0 ppm, n = 5) of iNO in addition to therapeutic hypothermia for 5 h following ROSC. All animals received TEE at five pre-specified time-points and invasive hemodynamic monitoring.ResultsLV end-diastolic volume (LVEDV) increased significantly in both groups following CA. iCPR alone led to significant LV unloading at 5 h post-ROSC with LVEDV values reaching baseline values in both groups (20 ppm: 68.2 ± 2.7 vs. 70.8 ± 6.1 mL, p = 0.486; 0 ppm: 70.8 ± 1.3 vs. 72.3 ± 4.2 mL, p = 0.813, respectively). LV global longitudinal strain (GLS) increased in both groups following CA. LV-GLS recovered significantly better in the 20 ppm group at 5 h post-ROSC (20 ppm: − 18 ± 3% vs. 0 ppm: − 13 ± 2%, p = 0.025). LV-GWI decreased in both groups after CA with no difference between the groups. Within 0 ppm group, LV-GWI decreased significantly at 5 h post-ROSC compared to baseline (1,125 ± 214 vs. 1,835 ± 305 mmHg%, p = 0.011). RV-GWI was higher in the 20 ppm group at 3 h and 5 h post-ROSC (20 ppm: 189 ± 43 vs. 0 ppm: 108 ± 22 mmHg%, p = 0.049 and 20 ppm: 261 ± 54 vs. 0 ppm: 152 ± 42 mmHg%, p = 0.041). The blood flow calculated by the Impella controller following iCPR initiation correlated well with the pulsed-wave Doppler (PWD) derived pulmonary flow (PWD vs. controller: 1.8 ± 0.2 vs. 1.9 ± 0.2L/min, r = 0.85, p = 0.012).ConclusionsiCPR after CA provided sufficient unloading and preservation of the LV systolic function by improving LV-GWI recovery. The addition of iNO to iCPR enabled better preservation of the RV-function as determined by better RV-GWI. Additionally, Impella-derived flow provided an accurate measure of total flow during iCPR.

Prediction of cerebral perfusion pressure during CPR using electroencephalogram in a swine model of ventricular fibrillation.

Measuring the quality of cardiopulmonary resuscitation (CPR) is important for improving outcomes in cardiac arrest. Cerebral perfusion pressure (CePP) could represent cerebral circulation during CPR, but it is difficult to measure non-invasively. In this study, we developed the electroencephalogram (EEG) based brain index (EBRI) derived from EEG signals by machine learning techniques, which could estimate CePP accurately in a porcine cardiac arrest model. We conducted a randomised crossover study using nine female pigs. After 1min of untreated ventricular fibrillation, we performed CPR with 12 different 2-min tilting angle sessions, including two different head-up tilt (HUT) angles (30°, 15°) twice, horizontal angle (0°) four times and two different head-down tilt (HDT) angles (-15°, -30°) twice with the random order. We collected EEG signals using a single channel EEG electrode in real-time during CPR. We derived the EBRI models to predict the CePP classified by the 5 or 10 groups using three different machine learning algorithms, including the support vector machine (SVM), k-nearest neighbour (KNN) and random forest classification (RFC) method. We assessed the accuracy, sensitivity and specificity of each model. The accuracy of the EBRI model using an SVM algorithm in the 5-group CePP classification was 0.935 with a standard deviation (SD) from 0.923 to 0.946. The accuracy in the 10-group classification was 0.904 (SD: 0.896, 0.913). The accuracy of the EBRI using the KNN method in the 5-group classification was 0.927 (SD: 0.920, 0933) and in the 10-group was 0.894 (SD: 0.880, 0.907). The accuracy of the RFC algorithm was 0.947 (SD: 0.931, 0.963) in the 5-group classification and 0.920 (SD: 0.911, 0.929) in the 10-group classification. We developed the EBRI model using non-invasive acquisition of EEG signals to predict CePP during CPR. The accuracy the EBRI model was 0.935, 0.927 and 0.947 for each machine learning algorithm, and the EBRI could be used as a surrogate indicator for measuring cerebral perfusion during CPR.

Assessment of a new volumetric capnography-derived parameter to reflect compression quality and to predict return of spontaneous circulation during cardiopulmonary resuscitation in a porcine model.

We aimed to evaluate a volumetric capnography (Vcap)-derived parameter, the volume of CO2 eliminated per minute and per kg body weight (VCO2/kg), as an indicator of the quality of chest compression (CC) and to predict the return to spontaneous circulation (ROSC) under stable ventilation status. Twelve male domestic pigs were utilized for the randomized crossover study. After 4min of untreated ventricular fibrillation (VF), mechanical cardiopulmonary resuscitation and ventilation were administered. Following 5-min washout periods, each animal underwent two sessions of experiments: three types of CC quality for 5min stages in the first session, followed by advanced life support, consecutively in two sessions. Different CC quality had a significant effect on the partial pressure of end-tidal carbon dioxide (PetCO2), VCO2/kg, aortic pressure (mean), aortic systolic pressure, aortic diastolic pressure, right atrial pressure (mean), and carotid blood flow (P < 0.05). With the improvement in CC quality, the values of PetCO2 and VCO2/kg also increased, and the difference between the groups was statistically significant (P < 0.05). The Spearman rank test revealed a significant correlation between the Vcap-derived parameters and hemodynamics. PetCO2 and VCO2/kg have similar capabilities for discriminating survivors from non-survivors, and the area under the curve for both was 0.97. VCO2/kg had similar performance as PetCO2 in reflecting the quality of CC and prediction of achieving ROSC under stable ventilation status in a porcine model of VF-related cardiac arrest. However, VCO2/kg requires a longer time to achieve a stable state after adjusting for quality of CC than PetCO2.

Correlation of EEG-based brain resuscitation index and end-tidal carbon dioxide in porcine cardiac arrest model

Evaluation and monitoring perfusion of vital organs is important during resuscitation from cardiac arrest. We developed a non-invasive electroencephalogram (EEG) based brain resuscitation index (EBRI) as a physiologic indicator measuring organ perfusion during cardiopulmonary resuscitation (CPR) and evaluated the correlation of EBRI and end-tidal carbon dioxide (ETCO2). A randomized crossover experimental study using a porcine cardiac arrest model was designed. After 1 minute of untreated ventricular fibrillation, 10 periods of higher-quality CPR (compression depth 5 cm and compression rate 100/min) for 50 seconds and lower-quality CPR (compression depth 3 cm and compression rate 60/min) for 50 seconds were performed in alternation. EBRI was calculated from the single EEG channel with the lowest noise. Mixed-model analysis was conducted to compare the differences of hemodynamic parameters, ETCO2, and EBRI between higher-quality CPR periods and lower-quality CPR periods. Pearson’s correlation coefficient was calculated to assess correlation between EBRI and ETCO2. The experiment was performed on 5 female swine (44.6 ± 2.8 kg). Higher-quality CPR showed significantly higher delta EBRI (median [IQR] 0.1 [0.0–0.2]) than did lower-quality CPR (median [IQR] –0.1 [–0.2–0.0], p &lt; 0.01). EBRI had a statistically moderate positive correlation with ETCO2 (r = 0.51). In this porcine cardiac arrest model, EBRI was successfully obtained during resuscitation and had a statistically moderate correlation with ETCO2.