Abstract 41: Early Post-Resuscitation Levels of Cytochrome- c and Interleukin-6 after Prolonged Porcine Cardiac Arrest

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
David D Salcido ◽  
Eric S Logue ◽  
Brian P Suffoletto ◽  
Jon C Rittenberger ◽  
James J Menegazzi

Background: The identification of serum biomarkers of ischemic injury could provide a means of assessing interventions designed to limit reperfusion injury after return of spontaneous circulation (ROSC). We sought to characterize the early post-ROSC timecourse of two candidate biomarkers of ischemic injury (cytochrome- c and IL-6) in a swine model of ventricular fibrillation (VF). We hypothesized that these two biomarkers would be elevated immediately after ROSC. Methods: Twenty-five mixed breed domestic swine were anesthetized and instrumented with ECG, temperature probe, and aortic and right atrial pressure transducers. VF was induced with a transthoracic shock and untreated for 8 minutes. Then mechanical CPR was done for 2 minutes, before drugs were given (epinephrine, vasopressin, and propranolol) with 3 additional minutes of CPR (first defibrillation attempt at 13 minutes of VF). Blood samples were drawn at the end of instrumentation (i.e. just prior to VF), and at 20, 40, and 60 minutes after ROSC. Samples were centrifuged and serum extracted. Cytochrome- c was analyzed via Western immunoblotting. IL-6 was analyzed with ELISA. Results: No cytochrome- c was detected in any animal, at any timepoint through 60 min. IL-6 was similar to baseline levels through 40 min, but was 121% of baseline at 60. Conclusions: Neither biomarker was elevated immediately after ROSC. Mitochondrial damage (as indicated by the absence of cytochrome- c ) may be delayed by as much as an hour after ROSC, hinting at a possible therapeutic window for interventions like hypothermia. Likewise, inflammatory cascades (as indicated by IL-6) may not begin immediately post-ROSC, but might by one hour.

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Mohamad H Tiba ◽  
Brendan M McCracken ◽  
Brandon C Cummings ◽  
Carmen I Colmenero ◽  
Chandler J Rygalski ◽  
...  

Introduction: Despite advancements in CPR, survival to hospital discharge remains low for in- and out-of-hospital cardiac arrest (CA). Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) is an evolving tool for temporary control of non-compressible truncal hemorrhage. In this investigation, we examined whether REBOA use during non-traumatic CA would produce favorable hemodynamic changes associated with return of spontaneous circulation (ROSC). Hypothesis: We hypothesized that REBOA use during CPR would result in higher coronary perfusion pressure (CPP) and common carotid artery blood flow (C-Flow) in a prolonged model of CA. Methods: Six male swine were anesthetized and instrumented to measure and monitor CPP, and C-Flow. A REBOA catheter (Prytime Medical Devices) was advanced into zone 1 of the aorta through the femoral artery. Ventricular fibrillation was electrically induced and untreated for 8 minutes. CPR was started manually at minute-8, then changed to mechanical CPR at minute-12 for the duration of the experiment. Continuous infusion of epinephrine (0.0024mg/kg/min) was simultaneously started with mechanical CPR. The REBOA balloon was inflated beginning at minute-16 for 3 minutes then deflated for 3 minutes for a total of 6 cycles. At the end of the final cycle (REBOA inflation), CPR was stopped (after 33 minutes of total arrest time) and animals were defibrillated using 200 J biphasic shocks, repeated up to 6 times. Animals achieving ROSC were monitored for an additional 25 minutes. Results: Analysis using repeated measure ANOVA showed significant differences between balloon deflation and inflation periods for CPP (p<0.0001) with mean difference(SD) of 14(2.6) (Range: 17 to 42) mmHg and for C-Flow (p<0.0001) with mean difference(SD) 16(23) (Range: 115 to 269) mL/min across all animals. Three animals achieved ROSC and had significantly higher CPP (48 vs. 24mmHg, p<0.0001) and C-Flow (249 vs. 168mL/min) by t-test (p<0.0001). Post-mortem aortic histology did not reveal any changes produced by balloon inflation. Conclusion: REBOA significantly increased CPP and C-Flow in this swine model of prolonged CA. These increases may have contributed to the ability to achieve ROSC after greater than 30 min of CA.


Author(s):  
Yi-Rong Chen ◽  
Chi-Jiang Liao ◽  
Han-Chun Huang ◽  
Cheng-Han Tsai ◽  
Yao-Sing Su ◽  
...  

High-quality cardiopulmonary resuscitation (CPR) is a key element in out-of-hospital cardiac arrest (OHCA) resuscitation. Mechanical CPR devices have been developed to provide uninterrupted and high-quality CPR. Although human studies have shown controversial results in favor of mechanical CPR devices, their application in pre-hospital settings continues to increase. There remains scant data on the pre-hospital use of mechanical CPR devices in Asia. Therefore, we conducted a retrospective cohort study between September 2018 and August 2020 in an urban city of Taiwan to analyze the effects of mechanical CPR devices on the outcomes of OHCA; the primary outcome was attainment of return of spontaneous circulation (ROSC). Of 552 patients with OHCA, 279 received mechanical CPR and 273 received manual CPR, before being transferred to the hospital. After multivariate adjustment for the influencing factors, mechanical CPR was independently associated with achievement of any ROSC (OR = 1.871; 95%CI:1.195–2.930) and sustained (≥24 h) ROSC (OR = 2.353; 95%CI:1.427–3.879). Subgroup analyses demonstrated that mechanical CPR is beneficial in shorter emergency medical service response time (≤4 min), witnessed cardiac arrest, and non-shockable cardiac rhythm. These findings support the importance of early EMS activation and high-quality CPR in OHCA resuscitation.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tiffany S. Ko ◽  
Constantine D. Mavroudis ◽  
Ryan W. Morgan ◽  
Wesley B. Baker ◽  
Alexandra M. Marquez ◽  
...  

AbstractNeurologic injury is a leading cause of morbidity and mortality following pediatric cardiac arrest. In this study, we assess the feasibility of quantitative, non-invasive, frequency-domain diffuse optical spectroscopy (FD-DOS) neuromonitoring during cardiopulmonary resuscitation (CPR), and its predictive utility for return of spontaneous circulation (ROSC) in an established pediatric swine model of cardiac arrest. Cerebral tissue optical properties, oxy- and deoxy-hemoglobin concentration ([HbO2], [Hb]), oxygen saturation (StO2) and total hemoglobin concentration (THC) were measured by a FD-DOS probe placed on the forehead in 1-month-old swine (8–11 kg; n = 52) during seven minutes of asphyxiation followed by twenty minutes of CPR. ROSC prediction and time-dependent performance of prediction throughout early CPR (< 10 min), were assessed by the weighted Youden index (Jw, w = 0.1) with tenfold cross-validation. FD-DOS CPR data was successfully acquired in 48/52 animals; 37/48 achieved ROSC. Changes in scattering coefficient (785 nm), [HbO2], StO2 and THC from baseline were significantly different in ROSC versus No-ROSC subjects (p < 0.01) after 10 min of CPR. Change in [HbO2] of + 1.3 µmol/L from 1-min of CPR achieved the highest weighted Youden index (0.96) for ROSC prediction. We demonstrate feasibility of quantitative, non-invasive FD-DOS neuromonitoring, and stable, specific, early ROSC prediction from the third minute of CPR.


Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Joseph M Wider ◽  
Erin Gruley ◽  
Jennifer Mathieu ◽  
Emma Murphy ◽  
Rachel Mount ◽  
...  

Background: Mitochondrial dysfunction contributes to cardiac arrest induced brain injury and has been a target for neuroprotective therapies. An emerging concept suggests that hyperactivation of neuronal mitochondria following resuscitation results in hyperpolarization of the mitochondrial membrane during reperfusion, which drives generation of excess reactive oxygen species. Previous studies from our group demonstrated that limiting mitochondrial hyperactivity by non-invasively modulating mitochondrial function with specific near infrared light (NIR) wavelengths can reduce brain injury in small animal models of global and focal ischemia. Hypothesis: Inhibitory wavelengths of NIR will reduce neuronal injury and improve neurocognitive outcome in a clinically relevant swine model of cardiac arrest. Methods: Twenty-eight male and female adult swine were enrolled (3 groups: Sham, CA/CPR, and CA/CPR + NIR). Cardiac arrest (8 minutes) was induced with a ventricular pacing wire and followed by manual CPR with defibrillation and epinephrine every 30 seconds until return of spontaneous circulation (ROSC), 2 of the 20 swine that underwent CA did not achieve ROSC and were not enrolled. Treatment groups were randomized prior to arrest and blinded to the CPR team. Treatment was applied at onset of ROSC by irradiating the scalp with 750 nm and 950 nm LEDs (5W) for 2 hours. Results: Sham-operated animals all survived (8/8), whereas 22% of untreated animals subjected to cardiac arrest died within 45 min of ROSC (CA/CPR, n= 7/9). All swine treated with NIR survived the duration of the study (CA/CPR + NIR, n=9/9). Four days following cardiac arrest, neurological deficit score was improved in the NIR treatment group (50 ± 21 CA/CPR vs. 0.8 ± 0.8 CA/CPR + NIR, p < 0.05). Additionally, neuronal death in the CA1/CA3 regions of the hippocampus, assessed by counting surviving neurons with stereology, was attenuated by treatment with NIR (17917 ± 5534 neurons/mm 3 CA/CPR vs. 44655 ± 5637 neurons/mm 3 CA/CPR + NIR, p < 0.05). All data is reported as mean ± SEM. Conclusions: These data provide evidence that noninvasive modulation of mitochondria, achieved by transcranial irradiation of the brain with NIR, mitigates post-cardiac arrest brain injury.


Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Lawrence D Sherman ◽  
James T Niemann ◽  
Thomas D Rea ◽  
John P Rosborough ◽  
James D Waters ◽  
...  

Background: The Logarithm of the Absolute Correlations (LAC) is a measure which estimates VF duration based on the fractal dimension of the waveform. We hypothesized that the LAC measures the underlying physiology of the myocardium and would enable identification of those who would have return of spontaneous circulation (ROSC) in response to the initial shock. We tested this hypothesis in a swine model and among humans treated for out-of-hospital cardiac arrest Methods: 20 swine were placed in VF either by electrical stimulation (n=10) or through ischemia produced by percutaneous balloon occlusion of the left anterior descending artery (n=10). After 7 minutes of VF, CPR was performed for 1 min followed by defibrillation. Response to shock was recorded as ROSC if a BP of 60 mm Hg was present. The LAC was calculated for five second intervals during VF. In the human cohort, the AED ECG recordings of 165 subjects were analyzed. The average interval from 9 –1–1 call to EMS scene arrival was 5 minutes. Response to shock was recorded as ROSC if an organized rhythm corresponded with a palpable BP as determined by review of audio and written EMS report. The LAC was calculated on the 6 seconds of VF preceding the initial shock. In both the swine and human experience, we compared the mean LAC between those with and without ROSC. We calculated receiver operating characteristic (ROC) curves and measured the area under the curve to assess the diagnostic ability of the LAC. Results: In the swine model, the mean LAC differed significantly between swine with and without ROSC following the initial shock (with ROSC: 5.17±0.19 [n=6] versus without ROSC: 4.88±0.27 [n=14]: p = 0.033). The AUC for the LAC measure was 0.80. In the human cohort, the LAC also differed significantly between those with and without ROSC following the initial shock (5.21±0.34 [n=36] versus 4.81±0.47 [n=129], p < 0.0001). The AUC for the LAC measure was 0.76. Conclusions: The LAC measure predicts ROSC in both swine and human VF and can be used to guide resuscitation care. Swine ischemic VF is similar to that seen in humans.


Circulation ◽  
2019 ◽  
Vol 140 (Suppl_2) ◽  
Author(s):  
Felipe Teran ◽  
Claire Centeno ◽  
Alex L Lindqwister ◽  
William J Hunckler ◽  
William Landis ◽  
...  

Background: Lifeless shock (LS) (previously called EMD and pseudo-PEA) is a global hypotensive ischemic state with retained coordinated myocardial contractile activity and an organized ECG. We have previously described our hypoxic LS model. The role of standard external chest compressions remains unclear in the setting of LS and its associated intrinsic hemodynamics. Although it is known the patients with LS have better prognosis compared to PEA, it is unclear what is the best treatment strategy. Prior work has shown that chest compressions (CC) when synchronized with native systole results in significant hemodynamic improvement, most notably coronary perfusion pressure (CPP), and hence it is plausible that standard dyssynchronous CC may be detrimental to hemodynamics. Furthermore, retrospective clinical data has shown that LS patients treated with vasopressors and no CC, may have better outcomes. We compared epinephrine only versus epinephrine and chest compression, in a porcine model of LS. Methods: Our porcine model of hypoxic LS has previously been described. We randomized pigs to episodes of LS treated with epinephrine only (control) (0.0015 mg/kg) versus epinephrine plus standard external chest compressions (intervention). Animals were endotracheally intubated and mechanically ventilated, and the fraction of inspired oxygen (FiO 2 ) was gradually lowered from room air (20-30% O 2 ) to a target FiO 2 of 3-7% O 2 . This target FiO 2 was maintained until the systolic blood pressure (SBP) dropped to 30 mmHg for 30 seconds, or the animal became bradycardic (HR less than 40), which was defined as the start of LS. FiO 2 was then raised to 100%, and then animal would receive control or intervention. Return of spontaneous circulation (ROSC) was defined as SBP 60 mmHg, stable after 2 minutes. Results: Twenty-six episodes of LS in 11 animals received epinephrine only control and 21 episodes the epinephrine plus chest compression intervention. The rates of ROSC in two minutes or less were 5/26 (19%) in the control arm vs 14/21 (67%) in the intervention arm (P=0.001;95% CI 19.7 %-67.2%). Conclusions: In a swine model of hypoxia induced LS, epinephrine plus CPR may be superior to epinephrine alone.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Michael K Levy ◽  
Karl B Kern ◽  
Dana Yost ◽  
Bjarne Madsen Hardig ◽  
Fred W Chapman

Recent observational studies have found associations between poorer outcomes and treatment that included mechanical CPR devices, contradicting findings from randomized trials. Resuscitation time bias is a systematic error occurring in observational studies of interventions applied to pulseless patients later in resuscitation attempts. Previous observational studies lack data on duration of resuscitation, a factor strongly related to outcome. We retrospectively analyzed cardiac arrest data to learn how resuscitation time and device use relate to clinical outcomes, and determine whether resuscitation time bias was present. Methods and Results: We analyzed data from all 49 patients with ventricular fibrillation, out-of-hospital cardiac arrest treated by our emergency medical service in one year. We compared 19 patients who received only standard manual CPR (the sCPR group) to 30 patients who received manual followed by mechanical CPR (the mCPR group). Response to CPR differed between groups even before device application. All sCPR patients achieved return of spontaneous circulation (ROSC), and did so after a median (IQR) of 3.3 (2.2-5.1) minutes of manual CPR. Patients in the mCPR group failed to get ROSC through 6.9 (5.3-11.0) min of manual CPR; mCPR patients that did get ROSC did so after 11.2 (5.7-23.8) additional minutes of CPR, delivered by a mechanical device. mCPR patients also received significantly more defibrillations and ALS drugs. ROSC and survival to hospital discharge were higher in the sCPR than the mCPR group (100% vs. 70%, P = 0.008; 74% vs. 43%, P = 0.045). Conclusion: Only patients remaining pulseless after early resuscitation efforts received mechanical CPR. Consequently, mechanical CPR devices assisted by facilitating prolonged treatment of patients who already had lower chances of survival before device application. Resuscitation time bias was present, and must be considered when interpreting registry reports comparing sCPR and mCPR.


Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Matthias Kohlhauer ◽  
Alexandra Demelos ◽  
Emilie Boissady ◽  
Bijan Ghaleh ◽  
Renaud Tissier

Introduction: Ultra-fast hypothermia through total liquid ventilation (TLV) has been shown to be neuroprotective after cardiac arrest. Hypothesis: The mechanism could involve a modification in brain metabolic substrat. Method: Anesthetized rabbits were instrumented with a carotid flow probe as well as arterial and jugular venous catheters. A microdialysis catether was implanted in the right brain cortex. Animals were then submitted to 10 min of ventricular fibrillation and cardiopulmonary resuscitation. After resumption of spontaneous circulation (ROSC), they were randomly submitted to ultra-fast cooling to 32°C by TLV (TLV group) or normothermic follow-up (Control) during 4h. Cerebral consumption of lactate, glucose and O 2 was calculated using arteriovenous differences in their content times mean carotid blood flow. Results: In Control, cerebral blood flow was significantly and sustainly decreased after ROSC (61±6 vs 101±6 ml/min after 240 min vs baseline), with a further decrease with hypothermia in TLV group (23±2 ml/min after 240 min, p<0.05). As compared to Control, TLV reduced the cerebral consumption of glucose (-69% at 240 min) and O 2 (-73% at 240 min). Importantly, Control animals showed a dramatic but transient cerebral consumption of lactate during the first 120 min after cardiac arrest (e.g. 124±31 mmol/min at 60 min). Concomitantly, this was associated with an increase in pyruvate extracellular stocks in brain (e.g. 57±10 μmol/L at 30 min). In TLV group, hypothermia blunted this initial burst of lactate consumption (e.g. 41±12 mmol/min at 60 min, p<0,05) and led to an accumulation in extracellular lactate ( e.g. 2053±68 vs 1246±278 μmol/L at 60 min, in TLV and Control respectively). This early build-up of lactate was then progressively consumed after 120 min in TLV group, allowing a delayed accumulation in pyruvate extracellular stocks from 120 min until the end of follow-up (103±19 and 17±4 μmol/L of pyruvate at 240 min in TLV vs Control respectively). Conclusion: Ultra-fast hypothermia reduces the cerebral consumption of lactate during the first 120 min after ROSC, allowing a delayed renewal in pyruvate stocks. This could explain the potent benefit of hypothermia during this early therapeutic window of 120 min.


Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
David D Salcido ◽  
Allison C Koller ◽  
Ericka L Fink ◽  
Robert A Berg ◽  
James J Menegazzi

Background: Current AHA guidelines for the delivery of chest compressions (CC) for infants and children are largely consensus based, and recommended depths of 1.5 inches or 1/3 anterior-posterior chest diameter (APD). It is unclear whether these have equal potential for injury. Objectives: We sought to examine and compare injury characteristics of CC delivered at 1.5 inches or 1/3 APD in an infant-sized model of asphyxial OHCA. Methods: Thirty-six juvenile swine weighing 10.6kg +/- 0.84 (approximating the 50 th percentile for a 12-month-old) were anesthetized, paralyzed, intubated, and mechanically ventilated (FiO2 21%). APD was measured and by two investigators via a sliding T-square. After instrumentation, the endotracheal tube was manually occluded to induce asphyxia, and occlusion was maintained for 9 minutes. Animals with an organized rhythm after 8 minutes 45 seconds of asphyxia received a single, 3-second transthoracic shock to induce ventricular fibrillation. At 9 minutes, each was then randomized to receive CC with a depth of 1.5 inches (Group 1) or 1/3 APD (Group 2), both with a rate of 100 per minute. ALS drugs were administered after 13 minutes, followed by initial defibrillation attempt at 14 minutes. Resuscitation continued until return of spontaneous circulation (ROSC) or 20 minutes of failed resuscitation. Survivors were sacrificed with KCl after 20 minutes of observation. Veterinary staff blinded to group assignment conducted necropsies to assess lung injury, rib fracture, hemothorax, airway bleeding, great vessel dissection, and heart/liver/spleen contusion. Characteristics were compared via Chi-Squared test or Mann-Whitney U-test using an alpha = 0.05. Results: Group 1 had n=18 and Group 2 had n=18 animals. Mean (SD) APD overall was 5.58 (0.22) inches, yielding a mean 1/3 APD depth of 1.86 inches. APD did not differ between groups. ROSC rates did not differ between groups (Group 1: 66.7% vs Group 2: 83.33%; p = 0.248. No injury characteristics differed significantly between groups. Airway bleeding rates were noteworthy though not different between groups (Group 1: 18.8% vs Group 2: 42.1%; p = 0.219). Conclusions: In a swine model of infant OHCA and resuscitation, both CC depth strategies had similar injury characteristics.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Matt Oberdier ◽  
Jing Li ◽  
Dan Ambinder ◽  
Xiangdong Zhu ◽  
Sarah Fink ◽  
...  

Background: Out-of-hospital sudden cardiac arrest is a leading cause of death in the United States, affecting over 350,000 people per year with an overall survival rate around 10%. CPR, defibrillation, and therapeutic hypothermia are common resuscitation strategies, but hypothermia is difficult to implement timely to achieve survival benefit. A cell-permeable peptide TAT-PHLPP9c has been shown to alter metabolic pathways similar to hypothermia, and decreases the release of two biomarkers, taurine and glutamate, during the high osmotic stress of heart stunning and brain injury in a mouse arrest model. Hypothesis: TAT-PHLPP9c, given during CPR, enhances 24-hour survival in a swine ventricular fibrillation (VF) model. Methods: In 14 (8 controls and 6 treated) sedated, intubated, and mechanically ventilated swine, after 5 min of VF, ACLS with vest CPR and periodic defibrillations was performed. Venous blood samples were collected at baseline, after 2 min of CPR, and at 2 and 30 min after return of spontaneous circulation (ROSC). The animals were survived up to 24 hrs and plasma samples were analyzed for glutamate and taurine in 2 controls and 1 animal given peptide. Results: Three of the control animals had ROSC, but none survived for 24 hrs, while 4 of 6 treated animals achieved neurologically intact survival at 24 hrs (p < 0.02). Compared to baseline, both taurine and glutamate plasma concentrations increased in the control group, but the increase was reduced substantially by the peptide treatment at 30 min after ROSC (Figure). Conclusion: The use of the cooling mimicking peptide TAT-PHLPP9c administered during CPR significantly improved 24-hour survival in this swine model of cardiac arrest. It reduced the increase of cerebral and myocardial metabolic biomarkers, which encourages utilizing a strategy of cell-permeable peptides for intravenous administration for more rapid onset of hypothermia-like salutary effects than are possible with current CPR cooling devices.


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