CPR Groups Research Articles

Biomarkers for neuroprognostication after standard versus extracorporeal cardiopulmonary resuscitation – A sub-analysis of Prague-OHCA study

BackgroundLimited evidence exists for prognostic performance of biomarkers in patients resuscitated from out-of-hospital cardiac arrest (OHCA) with extracorporeal CPR (ECPR). We hypothesized that (1) the time course and (2) prognostic performance of biomarkers might differ between CPR and ECPR in a sub-analysis of Prague-OHCA study. MethodsPatients received either CPR (n = 164) or ECPR (n = 92). The primary outcome was favorable neurologic survival at 180 days [cerebral performance category (CPC) 1–2]. Secondary outcomes included biomarkers of neurologic injury, inflammation and hemocoagulation. ResultsFavorable neurologic outcome was not different between groups: CPR 29.3% vs. ECPR 21.7%; p = 0.191. Biomarkers exhibited similar trajectories in both groups, with better values in patients with CPC 1–2. Procalcitonin (PCT) was higher in ECPR group at 24–72 h (all p < 0.01). Neuron-specific enolase (NSE), C-reactive protein and neutrophil-to-lymphocyte ratio did not differ between groups. Platelets, D-dimers and fibrinogen were lower in ECPR vs. CPR groups at 24–72 h (all p < 0.001). ROC analysis (24–48–72 h) showed the best performance of NSE in both CPR and ECPR groups (AUC 0.89 vs. 0.78; 0.9 vs. 0.9; 0.91 vs. 0.9). PCT showed good performance specifically in ECPR (0.72 vs. 0.84; 0.73 vs. 0.87; 0.73 vs. 0.86). Optimal cutoff points of NSE and PCT were higher in ECPR vs. CPR. ConclusionsBiomarkers exhibited similar trajectories although absolute values tended to be higher in ECPR. NSE had superior performance in both groups. PCT showed a good performance specifically in ECPR. Additional biomarkers may have modest incremental value. Prognostication algorithms should reflect the resuscitation method.

Abstract No. : ABS2796: Comparative evaluation of transaortic coeliac plexus rhizolysis with bilateral splanchnic nerve radio frequency ablation in patients of upper gastro-intestinal malignancies with intractable pain : A prospective interventional study.

Background and Aims:This study aimed for a comparative evaluation of transaortic coeliac plexus rhizolysis with bilateral splanchnic nerve radio frequency ablation for decrease in visual analogue scale(VAS) score and oral morphine requirements, in patients having upper gastrointestinal (GI) malignancies with intractable pain.Methods:Patients were randomly allocated in two group of 30 eackGroup 1 received bilateral splanchnic nerve radio-frequency ablation(SRF group) and group 2 had trans-aortic coeliac plexus rhizolysis (CPR group). Study was conducted over a period of 18 months. Following data were collected:VAS score, oral morphine requirement , adverse effects, and improvement in the quality of life.Results:Total of 33 patients (17 in SRF and 16 in CPR group) completed full 6 months follow-up Other patients were followed up until their demise. At the end of 6 months VAS score was reduced to 2.13±1.48 (cm) and 3.28±1.4 (cm) in SRF and CPR groups respectively and mean morphine consumption was 13.4 ± 15.3 mg/day and 26.11 ± 23.5 mg/day in SRF group and CPR group respectively..Conclusion:In upper GI cancer patients with severe intractable abdominal pain, interventional approach along with pharmacological management provides better analgesic efficacy . Both the techniques (bilateral splanchnic nerve RFA and trans-aortic coeliac plexus rhizolysis) were effective for the relief of severe intractable abdominal pain in upper GI malignancies.

Investigation on the Association of Cardiovascular Markers with Severity of Chronic Pyelonephritis.

Chronic kidney disease (CKD) is an established independent risk factor for cardiovascular disease (CVD) and is caused by chronic pyelonephritis (CP). This study aimed to investigate the effect of the association of cardiovascular markers with the course of CP on the comorbidity of CP with ischemic heart disease. The study participants included 125 patients with CP without symptoms of urinary tract obstruction who were divided into three groups. The first group (n=45) consisted of patients with recurrent CP (CPr) three or more times per year. The second group (n=42) included patients with active phase pyelonephritis (CPa), with a frequency of two times or less per year, with concomitant pathology (stable coronary artery disease, functional class I - II), and the third group (n=38) included patients with an inactive phase of the disease (CPi), with a history of pyelonephritis of at least five years. The patients' carotid artery augmentation index (AI %) and the change in the diameter of the brachial artery (D %) in CPi, CPa, and CPr groups were 8.44±1.76, 15.47±4.00, 11.71±1.70, 13.81±3.06, 12.75±2.55 and 6.54±3.27, respectively. The left ventricular ejection fraction (EF) index in the three study groups was estimated to be 68.92±3.76, 64.76±2.75, and 66.28±3.45%, respectively. An analysis of the results showed the most significant changes in the parameters of the cardiovascular system in patients with a comorbid and relapsing course of CP. The results showed a significant increase in pulmonary artery diameter, EF, left ventricular pressure and volume, pulse wave velocity in the aorta, and vascular resistance index.

Time boundaries of the three-phase time-sensitive model for ventricular fibrillation cardiac arrest

AimVentricular fibrillation (VF) cardiac arrest may consist of three time-sensitive phases: electrical, circulatory, and metabolic. However, the time boundaries of these phases are unclear. We aimed to determine the time boundaries of the three-phase model for VF cardiac arrest. MethodsWe reviewed 20,741 out-of-hospital cardiac arrest cases with initial VF and presumed cardiac origin from the All-Japan Utstein-style registry between 2013 and 2017. The study endpoint was 1-month neurologically intact survival. The collapse-to-shock interval was defined as the time from collapse to the first shock delivery by emergency medical service personnel. The patients were divided into the bystander cardiopulmonary resuscitation (CPR, n=11,606) and non-bystander CPR (n=9135) groups. ResultsIn the bystander CPR group, the collapse-to-shock times that were associated with increased adjusted 1-month neurologically intact survival, compared with those in the non-bystander CPR group, ranged from 7min (42.9% [244/4999] vs. 26.0% [119/458], adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.44–2.63; P<0.0001) to 17min (17.1% [70/410] vs. 7.3% [21/288], aOR, 2.82; 95% CI, 1.62–4.91; P=0.0002). However, the neurologically intact survival rate of the bystander CPR group was statistically insignificant compared with that of the non-bystander CPR group when the collapse-to-shock time was outside this range. ConclusionsThe time boundaries of the three-phase time-sensitive model for VF cardiac arrest may be defined as follows: electrical phase, from collapse to <7min; circulatory phase, from 7 to 17min; and metabolic phase, from >17min onward.

An Early Experience of Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) in the Republic of Korea: A Retrospective Multicenter Study

Purpose: This retrospective multicenter study analyzed trauma patients who underwent resuscitative endovascular balloon occlusion of the aorta (REBOA) in the Republic of Korea. Methods: This study was conducted from February 2017 to May 2018 at three regional trauma centers in the Republic of Korea. The patients were divided into two groups (cardiopulmonary resuscitation [CPR] and No-CPR) for comparative analysis based on two criteria (complication and mortality) for logistic regression analysis (LRA). Results: There were significant differences between the CPR and No-CPR groups in mortality (p=0.003) and treatment administered (p=0.016). By LRA for complications, total occlusion has significantly lesser risk than intermittent or partial occlusion in both univariate (odds ratio [OR] 0.06, 95% confidence interval [CI] 0.00-0.36, p=0.01) and multivariate (OR 0.05, 95% CI 0.00-0.38, p=0.01) analyses. The Rescue had a higher risk than the Coda or Reliant in univariate analysis (OR 4.91, 95% CI 1.14-34.25, p=0.05); however, it was not statistically significant in multivariate a nalysis (OR 6.98, 95% CI 1.03-74.52, p=0.07). By LRA for mortality, the CPR group was the only variable that had a significantly higher risk of mortality than the No-CPR group in both univariate (OR 17.59, 95% CI 3.05-335.25, p=0.01), and multivariate (OR 24.92, 95% CI 3.77-520.51, p=0.01) analyses. Conclusions: This study was conducted in the early stages of REBOA implementation in the Republic of Korea and showed conflicting results from studies conducted by multiple institutions. Therefore, additional research with more accumulated data is needed.

Radiological (Magnetic Resonance Image and Ultrasound) and biochemical effects of virtual reality training on balance training in football players with chronic low back pain: A randomized controlled study.

Virtual reality training is commonly used for balance problems in neurological conditions with the use of visual and auditory biofeedback. The knowledge about the effective implementation of this training in chronic low back pain is lacking. The objective of this study is to find the radiological and biochemical effects of virtual reality training in football players with chronic low back pain. A randomized, single-blinded controlled study was conducted on 36 participants. The first group received virtual reality training (VRT; n= 12), the second group received combined physical rehabilitation (CPR; n= 12), and the third group (control group; n= 12) received conventional training exercises for four weeks. Radiological (muscle cross-sectional area and muscle thickness) and biochemical (CRP, TNF-α, IL-2, IL-4, IL-6) values were measured at baseline and after four weeks. Four weeks following training, the VRT group showed more significant changes in the muscle cross-sectional area than the CPR and control groups (p⩽ 0.001). Biochemical measures such as CRP, TNF-α, IL-2, IL-4, and IL-6 also showed significant improvement in the VRT group compared to the other two groups (p⩽ 0.001). The results show that virtual reality training has positive effects on the radiological and biochemical aspects in university football players with chronic low back pain.

Effects of dexmedetomidine postconditioning on brain injury after cardiac arrest and resuscitation in a swine model

Objective To investigate the effects of dexmedetomidine postconditioning on brain injury after cardiac arrest and resuscitation in a swine model. Methods Twenty-eight healthy male domestic pigs, weighing 36±2 kg, were randomized (random number) into 4 groups (n=7 each group): sham operation group (S group), cardiopulmonary resuscitation group (CPR group), low-dose dexmedetomidine postconditioning group (LDP group), and high-dose dexmedetomidine postconditioning group (HDP group). Animals in the S group only underwent the surgical preparation. In the other three groups, the experimental model was established by 8 mins of electrically induced ventricular fibrillation and then 5 mins of cardiopulmonary resuscitation. At 5 min after resuscitation, a loading dose of dexmedetomidine of 0.25 μg/kg was intravenously infused followed by continuous infusion at a rate of 0.25 μg/(kg·h) for 6 h in the LDP group, and a loading dose of dexmedetomidine of 0.5 μg/kg was infused followed by continuous infusion at a rate of 0.5 μg/(kg·h) for 6 h in the HDP group. The same amount of normal saline was administered in the S and CPR groups. At 1 h, 3 h, 6 h and 24 h after resuscitation, the levels of serum neuron specific enolase (NSE) and S100B protein were measured. At 24 h after resuscitation, neurologic deficit score (NSD) was evaluated. After that, the animals were euthanized and cerebral cortex was obtained for the determination of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and malondialdehyde (MDA) contents, superoxide dismutase (SOD) activity, cell apoptosis and caspase-3 expression. Results Compared with the S group, post-resuscitation neurologic dysfunction and brain injury were observed in the other three groups, which were indicated by significantly higher NDS and markedly greater levels of serum NSE and S100B (all P<0.05). Compared with the CPR group, the score of NDS at 24 h post-resuscitation were significantly lower and the levels of serum NSE and S100B at 6 h and 24 h post-resuscitation were significantly less in the LDP and HDP groups [NDS: 194±26, 103±16 vs 278±23 at 24 h; NSE (ng/mL): 32.4±1.8, 28.6±3.7 vs 36.2±2.8 at 6 h, 39.9±4.2, 35.1±1.5 vs 45.1±3.0 at 24 h;S100B (pg/mL): 2 534±207, 2 382±170 vs 2 825±113 at 6 h, 3 719±164, 3 246±176 vs 4 085±161 at 24 h, all P<0.05]. Compared with the LDP group, neurologic dysfunction and brain injury at 24 h post-resuscitation were further significantly alleviated in the HDP group (all P<0.05). Pathological analysis indicated that brain inflammation, oxidative stress and cell apoptosis were observed after resuscitation in the CPR, LDP and HDP groups. However, the contents of TNF-α, IL-6 and MDA were significantly lower while the activity of SOD was significantly higher, and cell apoptosis and caspase-3 expression were significantly reduced in the brain after resuscitation in the LDP and HDP groups compared with the CPR group (all P<0.05). In addition, those pathological injuries mentioned above were further significantly alleviated in the brain after resuscitation in the HDP group compared to the LDP group (all P<0.05). Conclusions Dexmedetomidine postconditioning significantly alleviated the severity of post-resuscitation brain injury in a dose-dependent manner, in which the protection was produced possibly through reducing tissue inflammation, oxidative stress and cell apoptosis. Key words: Cardiac arrest; Cardiopulmonary resuscitation; Dexmedetomidine; Brain injury; Inflammatory response; Oxidative stress; Cell apoptosis; Swine

Abstract 298: Identification of LncRNA-miRNA-mRNA Network in Myocardium After Successful Resuscitation in a Rat Model of Prolonged Cardiac Arrest

Introduction: Previous studies have indicated that lncRNA participates in regional myocardial ischemia-reperfusion injury (IRI). However, the lncRNA-miRNA-mRNA crosstalk in the global myocardial IRI, which is implicated in the pathophysiology of post-resuscitation myocardial dysfunction (PRMD), has still not been explored. Hypothesis: To identify lncRNA-miRNA-mRNA regulatory network in myocardium after successful resuscitation in a rat model of prolonged cardiac arrest. Methods: Six male Sprague Dawley rats were randomized into sham control and ventricular fibrillation (VF)-CPR groups, with three rats in each group. VF was induced and untreated for 8 minutes. Defibrillation was attempted after 8 minutes of CPR. Heart tissue was obtained at 6 hours after resuscitation and lncRNA, miRNA and mRNA expression profiles were examined by using high-throughput sequencing. LncRNA-miRNA-mRNA interaction network was predicted and constructed. Results: Numbers of differentially expressed (DE) lncRNA, miRNA and mRNA were detected (Fig 1A). LncRNAs co-located or co-expressed target mRNAs and DE mRNAs were revealed (Fig 1B). The intersection of DE mRNAs with targeted mRNA of DE miRNAs was made (Fig 1C). A total of 129 feed forward loops were predicted as lncRNA-associated ceRNA networks,with 126 lncRNA (up)-miRNA (down)-mRNA (up) and 3 lncRNA (down)-miRNA (up)-mRNA (down) (Fig 2). Conclusions: LncRNA-miRNA-mRNAs network was predicted and constructed in myocardium after successful resuscitation in a rat model of prolonged cardiac arrest. Further exploration into the specific functional roles of the ceRNA regulatory network will be conducive for the treatment of PRMD.

End-tidal CO2-guided automated robot CPR system in the pig. Preliminary communication

BackgroundOur aim was to compare the efficacy of the end-tidal CO2-guided automated robot CPR (robot CPR) system with manual CPR and mechanical device CPR. MethodsWe developed the algorithm of the robot CPR system which automatically finds the optimal compression position under the guidance of end-tidal CO2 feedback in swine models of cardiac arrest. Then, 18 pigs after 11 min of cardiac arrest were randomly assigned to one of three groups, robot CPR, LUCAS CPR, and manual CPR groups (n = 6 each group). Return of spontaneous circulation (ROSC) and Neurological Deficit Score 48 h after ROSC were compared. ResultsA ROSC was achieved in 5 pigs, 4 pigs, and 3 pigs in the robot CPR, LUCAS CPR, and manual CPR groups, respectively (p = 0.47). Robot CPR showed a significant difference in Neurological Deficit Score 48 h after ROSC compared to manual CPR, whereas LUCAS CPR showed no significant difference over manual CPR. (p = 0.01; Robot versus Manual adjusted p = 0.04, Robot versus LUCAS adjusted p = 0.07, Manual versus LUCAS adjusted p = 1.00). ConclusionsThe end-tidal CO2-guided automated robot CPR system did not significantly improve ROSC rate in a swine model of cardiac arrest. However, robot CPR showed significant improvement of Neurological Deficit Score 48 h after ROSC compared to Manual CPR while LUCAS CPR showed no significant improvement compared to Manual CPR.

Abstract 21301: Effect of Chest Compression Parameter Variation on Waveform Characteristics of the Ventricular Fibrillation Electrocardiogram

Introduction: The ventricular fibrillation (VF) electrocardiogram (ECG) waveform is known to deteriorate over time if untreated, recover with CPR, and to predict defibrillation success. VF ECG measures could inform CPR quality feedback algorithms based on patient physiologic response. Objectives: Investigate the effects of chest compression parameters (rate, depth and duty cycle (DC)) on VF ECG waveform characteristics in a swine cardiac arrest model. Methods: Twelve mixed-breed domestic swine were sedated, anesthetized and paralyzed, followed by endotracheal intubation and mechanical ventilation. Animals were instrumented with a battery of physiological sensors, including multi-lead ECG, recorded continuously with a high-fidelity data acquisition unit at 1000Hz. VF was induced with a 3-second 100mA transthoracic shock. After 7 minutes, animals were randomized to receive continuous CPR with a custom robotic device using 1 of 6 pre-programmed, cross-over 2-phase CPR schemes that varied 1 parameter in 5 x 1-minute intervals per phase while holding the other 2 parameters fixed. Frequency (AMSA) and slope-based (MS) quantitative ECG characteristics of the ECG were calculated at the end of each 1-minute interval and compared between rate, depth and DC schemes, as well as experimental phases. Correlations between CPR parameter settings and ECG characteristics were calculated. Results: Compression rate showed a low-to-moderate correlation (0.454) with change in MS in Phase I, however neither DC nor depth showed a correlation with either AMSA or MS. In ANOVA models, MS differed between CPR groups at the end of Phase I (p = 0.046) but not AMSA, suggesting similar response of quantitative ECG measures after extended time intervals. Conclusions: In this study only chest compression rate in early phase CPR appeared to be related to quantitative characteristics of the VF ECG. Rate may be important clinically in the early phase of CPR.

Can the cerebroplacental ratio (CPR) predict intrapartum fetal compromise? A prospective observational study

Objective: To investigate the potential clinical use of serial fetal CPR measurements during the last month of pregnancy for the prediction of adverse perinatal outcome in unselected low-risk pregnancies. Methods: A multicenter prospective observational cohort study in 315 consecutively recruited low-risk pregnancies. All eligible pregnancies underwent serial sonographic evaluation of fetal weight and Doppler indices at two week intervals, from 36 weeks gestation until delivery. Data were converted into centiles correcting for gestational age. These data were not available for the obstetrical team and hence, could not influence management decisions. Primary outcomes were operative delivery for presumed fetal compromise and a composite neonatal outcome (arterial cord Ph 90th centile). Results: Three hundred fifteen women were recruited in this study. We ecxluded 32 pregnancies because of small for gestational age babies (SGA), leaving 293 women and 583 CPR values for data-analysis. There were 85 (27%) adverse neonatal outcomes and 29 patients (9%) underwent operative delivery for presumed fetal compromise. Both primary and secondary outcomes were not significant different between the different CPR groups. Furthermore, we examined if individual serial CPR measurements could predict adverse outcome and found no linear correlation between repeated measurements of CPR and adverse outcomes. Conclusion: Our study shows that routine serial screening by CPR measurements provides poor prediction for adverse perinatal outcome in uncomplicated pregnancies.

Neuromuscular electrical stimulation as an adjunct to endurance and resistance training during pulmonary rehabilitation in stable chronic obstructive pulmonary disease

Aim: The purpose of this study was to investigate whether adding neuromuscular electrical stimulation (NMES) to a comprehensive pulmonary rehabilitation (cPR) program would have additive effects on clinical-functional outcomes. Methods: Twenty-seven chronic obstructive pulmonary disease patients participating in a 10-week cPR program were randomly allocated to NMES + cPR (n = 13) or Sham + cPR (n = 14) groups. Quadriceps strength, exercise capacity, symptoms, mood, activities of daily living and quality of life were evaluated pre- and post-interventions. Results: There were no significant differences in any of the physiological and subjective improvements induced by NMES + cPR versus Sham + cPR (p > 0.05). In fact, the NMES + cPR group showed lower increases in incremental shuttle walk test (ISWT) distance (38.4 vs 69.2 m, respectively) and %ISWT distance (5.1 vs 9%, respectively) compared with the Sham + cPR group (p < 0.05). Conclusion: The increase in exercise capacity is less important when NMES is used as an adjunct to the cPR.

Effect of pre-arrest and post-arrest mild hypothermia on myocardial function of ventricular fibrillation after restoration of spontaneous circulation in rabbits

To study the effect of pre-arrest and post-arrest mild hypothermia after restoration of spontaneous circulation (ROSC) on myocardial function, ultrastructure, apoptosis of myocardial cells in rabbits with ventricular fibrillation. Sixty-two male New Zealand rabbits were randomly allocated into five groups: namely normothermic control group (NTC group, n = 10), hypothermia control group (HTC group, n = 10), normothermic resuscitation group (NTR group, n = 14), hypothermia pre-arrest group (HPRA group, n = 14), and hypothermia post-arrest group (HPOA group, n = 14). The normal temperature was controlled at (39.0 ± 0.5) centigrade, and the hypothermia (33.5±0.5) centigrade. Ventricular fibrillation cardiac arrest (CA) was reproduced in rabbits by transcutaneous epicardium electrical stimulation. The parameters of hemodynamics were monitored dynamically for 4 hours in all the groups, including heart rate (HR), left ventricular end diastolic and systolic pressure (LVEDP/LVESP), maximal rate of increase/decrease in left ventricular pressure (±dp/dt max), and mean arterial pressure (MAP). The body temperature of rabbits in hypothermia groups was maintained by surface cooling for 4 hours followed by rewarming. The survived rabbits were sacrificed at 48 hours after resuscitation, and myocardial apical tissue was harvested for observation of ultrastructure with electronic microscope, and to observe apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining. (1) Resuscitation investigation: there was no significant difference in rate of ROSC, time of CPR and energy of defibrillation among HPRA, HPOA, and NTR groups [rate of ROSC: 85.71%, 71.43%, 71.43%; time of CPR (seconds): 45.3 ± 30.2, 61.2 ± 41.3, 82.3 ± 63.8; energy of defibrillation (J): 14.3 ± 8.9, 22.0 ± 15.5, 25.0 ± 15.8, all P > 0.05]. (2) Hemodynamics: compared with normal temperature groups, animals in hypothermia groups exhibited lower levels of HR (all P < 0.05). Compared with NTR group, HPRA group exhibited higher levels of LVESP (mmHg, 1 mmHg = 0.133 kPa) at 0.5, 1, 2 and 3 hours post ROSC (0.5 hour: 103.8 ± 14.3 vs. 91.6 ± 13.3, 1 hour: 107.2 ± 14.1 vs. 82.7 ± 8.5, 2 hours: 109.0 ± 16.9 vs. 88.8 ± 12.9, 3 hours: 109.1 ± 14.6 vs. 89.3 ± 14.3, all P < 0.05). Compared with NTR group and HPOA group, HPRA group exhibited lower levels of LVEDP (mmHg) at 0.5 hour post ROSC (3.70 ± 0.85 vs. 7.61 ± 2.73, 7.02 ± 3.12, both P < 0.05). Compared with NTR group, HPRA group exhibited lower levels of LVEDP at 1 hour post ROSC (4.34 ± 1.44 vs. 6.99±1.96, P < 0.05). In HPRA group, the level of +dp/dt max (mmHg/s) was higher than that of NTR group and HPOA group at 1 hour and 2 hours post ROSC (1 hour: 2 759.5 ± 321.6 vs. 2 123.0 ± 304.5, 2 283.7 ± 234.2, 2 hours: 2 730.6±425.1 vs. 2 221.5 ± 392.9, 2 252.6 ± 476.0, all P < 0.05). There were no significant differences in -dp/dt max and MAP levels among three CPR groups. (3) The survival rate at 48 hours post ROSC of NTR, HPRA and HPOA groups was 60%, 75%, and 100%, respectively. Compared with NTR group, higher survival rate was found in HPOA group at 48 hour post ROSC (P < 0.05). (4) Compared with NTR group, less damage to myocardial ultrastructure was found in HPRA and HPOA groups. Apoptosis index (AI) was lower in HPRA and HPOA groups than that in NTR group [(28.05 ± 9.82) %, (26.39 ± 8.98) % vs. (42.02 ± 13.36) %, both P < 0.05]. Our study shows that mild hypothermia has no effect on ROSC rate. Pre-arrest hypothermia can ameliorate myocardial systolic function of rabbit in early stage after ROSC, and it has no negative influence on diastolic function. Post-arrest mild hypothermia produces no negative influence on myocardial function of rabbit, but it improves 48 hours survival rate in ROSC rabbits. Both pre-arrest and post-arrest mild hypothermia therapy can attenuate myocardial injury in CA model of rabbits by ameliorating mitochondrial injuries and suppressing apoptosis of myocardial cells.

Doublet Vs Triplet Lenalidomide-Containing Regimens in Newly Diagnosed Myeloma Patients, Younger or Older Than 75 Years: Subgroup Analysis of a Phase III Study

Introduction : a formal comparison between Lenalidomide-Dexamethasone (Rd) and Lenalidomide-Prednisone plus Melphalan (MPR) or Cyclophosphamide (CPR) has not been performed yet. We compared Rd vs. MPR vs. CPR in newly diagnosed multiple myeloma (NDMM) patients ≥65 years old in a multicenter phase III trial. Per protocol, upfront dose reductions of Dexamethasone, Melphalan and Cyclophosphamide were performed, according to patients age ( ≤75 years vs. >75 years). The primary endpoint was progression-free survival (PFS).Methods : 662 patients with NDMM were randomized to receive nine 28-day cycles of Rd (n=222), MPR (n=218) or CPR (n=222). Rd: lenalidomide 25 mg/day for 21 days; dexamethasone 40 mg on days 1,8,15,22 in patients 65-75 years old and 20 mg in those >75 years; MPR: lenalidomide 10 mg/day for 21 days; melphalan orally 0.18 mg/Kg for 4 days in patients 65-75 years old and 0.13 mg/Kg in patients >75 years; prednisone 1.5 mg/Kg for 4 days; CPR: lenalidomide 25 mg/day for 21 days; cyclophosphamide orally 50 mg/day for 21 days in patients 65-75 years old and 50 mg every other day in patients >75 years; prednisone 25 mg every other day. After induction, patients were randomized to receive maintenance with lenalidomide alone (R) or with prednisone (RP).Results : Patients characteristics were well balanced. Eighty-three (37%) patients in the Rd, 86 (39%) in the MPR and 80 (36%) in the CPR groups were older than 75 years. In intention to treat analysis, after a median follow-up of 31 months, no difference in PFS and overall survival (OS) was observed. Median PFS was 23 months in Rd, 27 months in MPR and 23 months in CPR (Rd vs MPR p=0.216; Rd vs CPR p=0.872; MPR vs CPR p=0.148). Median OS was not reached and was 73% in Rd, 67% in MPR and 72% in CPR at 3 years (Rd vs MPR p=0.663; Rd vs CPR p=0.754; MPR vs CPR p=0.448). A subgroup analysis, according to age was performed. No difference in response rate was observed. In patients ≤75 years, median PFS was 23 in Rd, 30 in MPR and 23 months in CPR (Rd vs MPR, p<0.04; Rd vs CPR p=0.897; MPR vs CPR, p<0.05).Median OS was not reached and was 75% in Rd, 76% in MPR, 77% in CPR at 3 years (Rd vs MPR p=0.251; Rd vs CPR p=0.280; MPR vs CPR p=0.975). In patients >75 years, no PFS difference was noticed: median PFS was 22 in Rd, 18 in MPR, 21 months in CPR (Rd vs MPR p=0.572; Rd vs CPR p=0.699; MPR vs CPR p=0.914). An OS advantage was reported with Rd: median OS was not reached in Rd patients, and was 37 and 43 months in the MPR and CPR groups, respectively (Rd vs MPR p=0.04; Rd vs CPR p=0.430; MPR vs CPR p=0.323). The rate of at least one hematologic grade 3-4 adverse event was 29% in Rd, 66% in MPR, 33% in CPR patients ≤ 75 years and 29% in Rd, 70% in MPR, 33% in CPR patients > 75 years (MPR vs Rd/CPR p< 0.0001). No difference was observed in extra-hematologic adverse events: 25% in Rd, 24% in MPR and 25% in CPR patients ≤75 years; 29% in Rd, 35% in MPR, 34% in CPR patients >75 years.Conclusion : this trial compared for the first time Rd, MPR and CPR in elderly NDMM. In all patients, the addition of alkylating agent to Lenalidomide-steroid combination did not show any advantage on PFS and OS. In a subgroup analysis, safety and efficacy data suggest that triplet regimens may be indicated in patients ≤75 years, while a doublet regimens for those >75 years. The MPR combination showed a PFS advantage in patients ≤75 years, with a higher incidence of hematologic toxicity and SPM. In patients >75 years an OS advantage was reported with Rd, mainly due to a higher efficacy of salvage treatments. Updated results will be presented at the meeting. DisclosuresOff Label Use: Use of Lenalidomide as off label. Bringhen:Onyx: Consultancy; Merck Sharp & Dohme: Membership on an entity’s Board of Directors or advisory committees; Novartis: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria. Offidani:Mundipharma: Honoraria; Sanofi: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria; Amgen: Honoraria. Patriarca:Merck Sharp & Dohme: Honoraria; Janssen and Cilag: Honoraria; Celgene: Honoraria. Hajek:Janssen: Honoraria; Celgene: Consultancy, Honoraria; Merck: Consultancy, Honoraria. Boccadoro:Onyx: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Janssen and Cilag: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees. Palumbo:Onyx Pharmaceuticals: Consultancy, Honoraria; Millennium Pharmaceuticals, Inc.: Consultancy, Honoraria; Janssen-Cilag: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Genmab A/S: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Sanofi: Honoraria; Amgen: Consultancy, Honoraria; Array BioPharma: Honoraria.

Probucol prevents atrial remodeling by inhibiting oxidative stress and TNF-α/NF-κB/TGF-β signal transduction pathway in alloxan-induced diabetic rabbits.

Diabetes mellitus (DM) is an independent risk factor for atrial fibrillation (AF). However, the underlying mechanisms for the increased propensity for AF in the setting of DM and the potential effects of probucol on atrial remodeling remain unclear. Eighty Japanese rabbits were randomly assigned to normal/control group (Control, n = 20), alloxan-induced diabetic group (DM, n = 20), probucol-treated group (Control-P, n = 20), and probucol-treated diabetic group (DM-P, n = 20). Rabbits in the DPR and CPR groups were orally administered probucol (1,000 mg/day) for 8 weeks. Serum and left atrial tissue malonaldehyde (MDA), superoxide dismutase (SOD), myeloperoxidase (MPO), and catalase (CAT) levels were assessed. Isolated Langendorff perfused rabbit hearts were prepared to evaluate atrial refractory effective period (AERP) and its dispersion (AERPD), interatrial conduction time (IACT), and vulnerability to AF. Atrial interstitial fibrosis was also evaluated. The mRNA expression levels of TNF-α and TLR4 were analyzed. The protein expressions of NF-κB, HSP70, TGF-β, and ERK in left atrial tissue were analyzed by Western blot. Probucol administration decreased the inducibility of AF in diabetic rabbits and attenuated atrial interstitial fibrosis. The DM-P rabbits exhibited significant alleviation of oxidative stress, evidenced by reduced serum and tissue MDA, compared with diabetic rabbits. Moreover, NF-κB, TGF-β, and HSP70 protein expression and TNF-α mRNA expression were significantly downregulated by probucol treatment in alloxan-induced diabetic rabbits. Probucol prevents atrial remodeling and suppresses AF development in alloxan-induced diabetic rabbits. Its inhibitory effects on oxidative stress, NF-κB, TGF-β, and TNF-α overexpression may contribute to its antiremodeling effects.

GW24-e3518 Probucol prevents atrial remodeling by inhibiting reactive oxygen species production and NF-kappaB activation in alloxan-induced diabetic rabbits

ObjectivesThis study sought to assess the effects of probucol on atrial remodelling and atrial fibrillation (AF) promotion in alloxan-induced diabetic rabbits and to elucidate the underlying mechanisms.Methods40 Japanese rabbits were...

Abstract 315: Both Systemic and Cerebral Microcirculation Are Reduced During Hypothermia in a Porcine Model

Introduction: Mild hypothermia improves neurological outcomes after cardiac arrest. However, systemic microcirculation is reduced with the reduction of body temperature. We investigated the changes of cerebral (CM) and sublingual microcirculation (SM) during hypothermia in a porcine model during spontaneous circulation and following successful cardiopulmonary resuscitation. Hypothesis: We hypothesized that during spontaneous circulation and following CPR, SM is reduced with the progress of hypothermia. However, CM is preserved in the range of mild hypothermia. Methods: Ten domestic pigs weighing 34±1kg were randomized into spontaneous circulation control or CPR groups. The cerebral cortices were exposed for microcirculation measurement. In CPR group, ventricular fibrillation (VF) was induced and untreated for 5 mins. Defibrillation of 150J was attempted after 5 mins of CPR. Hypothermia was initiated after completion of animal preparation in control group and immediately following successful resuscitation in CPR group. The blood temperature was reduced from 37°C to 35°C, 33°C and 28°C with a cooling blanket. SM and CM was measured at each temperature point with the orthogonal polarization spectral imaging technique. Results: Microcirculatory blood flow index and perfused microvessel density of both SM and CM decreased with the progress of hypothermia in both groups. There was no statistical difference between the two groups. (Table) Conclusion: CM is reduced with the reduction of body temperature during spontaneous circulation and following CPR. The relationship between reduced CM during hypothermia and improved neurological outcomes following hypothermia remains to be investigated.

Chest compression alone CPR is associated with better long-term survival compared to standard CPRStatus: PendingCategory: CPR Quality

Background —Little is known about the long-term survival effects of type-specific bystander CPR in the community. We hypothesized that dispatcher instruction consisting of chest compression alone would be associated with better overall long-term prognosis compared to chest compression plus rescue breathing. Methods and Results —The investigation was a retrospective cohort study that combined 2 randomized trials comparing the short-term survival effects of dispatcher CPR instruction consisting either of chest compression alone or chest compression plus rescue breathing. Long-term vital status was ascertained using the respective National and State death records through 31st July 2011. We performed Kaplan Meier method and Cox regression to evaluate survival according to the type of CPR instruction. Of the 2496 subjects included in the current investigation, 1243 (50%) were randomized to chest compression alone and 1253 (50%) were randomized to chest compression plus rescue breathing. Baseline characteristics were similar between the two CPR groups. During the 1153.2 person-years of follow-up, there were 2260 deaths and 236 long-term survivors. Randomization to chest compression alone compared to chest compression plus rescue breathing was associated with a lower risk of death after adjustment for potential confounders (adjusted HR=0.91; 95% CI [0.83-0.99], p=0.02). Conclusions —The findings provide strong support for long-term mortality benefit of dispatcher CPR instruction strategy consisting of chest compression alone rather than chest compression plus rescue breathing among adult cardiac arrest patients requiring dispatcher assistance.

Growth hormone/insulin-like growth factor-1 axis: a possible non-nutritional factor for growth retardation in children with cerebral palsy

To assess growth hormone (GH)/insulin like growth factor-1 (IGF-1) axis as a possible non-nutritional factor for growth retardation in children with cerebral palsy (CP). A case-control study was conducted at a tertiary university hospital. Thirty children with CP (seven children with normal growth [CP-N] and 23 with retarded growth [CP-R]), 30 children with protein energy malnutrition (PEM), and 30 healthy children (REF group) underwent an assessment of growth parameters, serum IGF-1, basal GH, and peak GH after stimulation with insulin. PEM patients had higher basal GH levels than CP-N, CP-R and REF groups (p = 0.026, p < 0.001, and p < 0.001 respectively). After insulin stimulation, CP-N, CP-R, and PEM patients had lower GH levels compared to the REF group (p = 0.04, p = 0.007, and p = 0.036 respectively). IGF-1 levels were lower in CP-R group compared to CP-N and REF groups (p = 0.037 and p < 0.001 respectively), and in PEM group compared to CP-N and REF groups (p < 0.001 and p < 0.001 respectively). CP-R patients failed to demonstrate the same high basal GH response as PEM patients, and responded inadequately to the insulin stimulation test, but they had IGF-1 levels comparable to those of PEM patients. On the other hand, CP-N patients behaved as controls regarding their basal GH and IGF-1 levels, but failed to respond adequately to the insulin stimulation test. The PEM group presented high basal GH and low IGF-1 levels. These findings suggest that non-nutritional factors contribute to growth retardation in CP children.

Effects of sustained abdominal aorta compression on coronary perfusion pressures and restoration of spontaneous circulation during cardiopulmonary resuscitation in swine

Objectives The present study was undertaken to explore whether sustained abdominal aorta compression-cardiopulmonary resuscitation (SAAC-CPR), as a means, can raise coronary perfusion pressure (CPP) as well as restoration of spontaneous circulation (ROSC) during CPR. In the present study, we hypothesised that SAAC-CPR elevates CPP during CPR and improves ROSC, without causing liver laceration. Methods Animals were randomised into one of two groups (Standard CPR and SAAC-CPR). Ten domestic swine (22–25 kg) were anaesthetised, intubated and mechanically ventilated. Ventricular fibrillation was induced, and after 3 min of untreated ventricular fibrillation, the animals were treated with standard CPR (with simplex chest compression (SCC) and epinephrine) or SAAC-CPR (SCC with sustained abdominal aorta compression, without epinephrine). CPP and ROSC were compared. Results SCC with sustained abdominal aorta compression (SCC + SAAC) significantly increased CPP in comparison with SCC during CPR ( p < 0.05). The increase in CPP with SCC + SAAC is equivalent to that achieved with epinephrine ( p > 0.05). All animals in the standard CPR and SAAC-CPR groups restored spontaneous circulation. No liver damage was found in post-mortem examinations of the swine subjects. Conclusions During CPR, non-invasive SAAC can rapidly and reversibly raise the CPP as much as can epinephrine and is especially suitable for out-of-hospital CPR.