tbuckley/cabot-search huggingface dataset:
Abstract 197: Initial Base Deficit and Arterial Carbon Dioxide Level Associated with Survival in Postarrest Patients
Authors: David F Gaieski, Anne V Grossestreuer, Sarah M Perman, Marion Leary, Anthony M Napoli, Robert W Neumar, Lance B Becker, Benjamin S Abella
Journal: Circulation (2012)

Introduction: Serial arterial blood gases (ABG) are typically monitored in post-arrest patients treated with therapeutic hypothermia (TH). The relationship between arterial carbon dioxide (PaCO 2 ) levels, degree of base deficit (BD), neurologic outcome, and survival is unclear. Hypothesis: Lower PaCO 2 , as a surrogate for hyperventilation, and larger BD, correlating with ongoing acidosis, may be associated with decreased survival and worse neurologic outcomes in post-arrest TH patients. Methods: We conducted a retrospective chart review of post-arrest patients treated with TH from the PATH database representing 11 institutions. Demographic variables were analyzed using chi-square tests. Unadjusted logistic regression analyses were performed to assess the relationship between hypocapnea (PaCO 2 &lt; 30 mmHg), normocapnea (PaCO 2 30-45 mmHg), hypercapnea (PaCO 2 &gt; 45 mmHg), mean BD, with respect to mortality or neurologic outcome at 1 st post-arrest ABG and at 6 hrs, 12 hrs, and 24 hrs post-arrest. Results: A total of 179 patients were enrolled. Patients were 59.6 ± 16.4 years, 54% male, and VF/VT was present in 31% of patients. Sixty-six (37%) survived to discharge, of which 76% (50/66) had a good neurologic outcome (CPC 1 or 2). Survivors had a lower mean initial PCO 2 value than non-survivors (49.0 vs. 57.5 mmHg; p=0.03); survival was significantly higher in patients who had normocapnea (51%) on their initial ABG when compared to those who were hypocapneic (25%) or hypercapneic (28%) (p=0.007), however, there was no significant difference in survival at the other time points. When adjusting for gender and initial rhythm, hypocapnea and hypercapnea had lower odds for survival in comparison to normocapnea (OR 0.23, 95% CI 0.03-2.01, p=0.18 and OR 0.72, 95% CI 0.35-1.5, p=0.38). Survivors had less severe BD than non-survivors at initial ABG (-8.0 vs. -11.3; p=0.005) and at all subsequent time points. There was no difference between PCO 2 or BD values between patients with good vs. bad neurologic outcomes. Conclusions: Patients who were normocapneic on initial ABG had improved survival. Survivors had lower initial PaCO 2 levels and less severe BD than non-survivors. There was no difference in PaCO 2 or BD values in patients with good vs. poor neurologic outcomes.
Abstract 335: Outcomes Analysis for Direct Transport to Trauma Centers Versus Transfer After Stabilization at Other Hospitals: Nationwide Population-Based Research in Taiwan
Authors: Dorji Harnod, Mathew Huei-Ming Ma, Chu-Hui Chang
Journal: Circulation (2012)

Background: Major trauma remains a major disease with about ten-thousand death annually in Taiwan. Since Trunkey described the concept of “golden hour”, outcomes for trauma patients in different levels of hospitals and the influence of transferring to trauma centers after stabilization in first hospitals become of particular interest. Methods: From the claim data of one million beneficiaries of Taiwan National Health Insurance during the year of 2006 to 2008, all of the trauma patients were identified from the database by the ICD-9-CM system. ICD-MAP was used for calculating the Injury Severity Score as the variable controlling the disease severity. The patients of major trauma were defined as ISS more than fifteen. We used patients’ diagnosis in 2005 for calculating Charlson Comorbidity Index. And factors such as age, gender, preexisting co-morbidities and different hospital levels were adjusted in a logistic regression model for survival analysis. Results: There were 5912, 5611 and 5760 trauma patients admitted from emergency department from 2006 to 2008, and there were 2497 major trauma patients (ISS more then 15). The totally mortality rate was 12.49% (6.98% in the youngest group and 18.19% in the oldest group, P&lt;0.01). After controlling the age, genders, co-morbidity and injury severity, the difference of mortality rates were significant in hospital levels. Compared with the risk in trauma centers, the risk of mortality is 1.58 times in non- trauma centers (P&lt;0.01). In the oldest group (&gt;60 year-old), the risk of mortality is 1.89 times in non-trauma centers (P&lt;0.01). There is no significant difference in the mortality rates between transferred and non-transferred trauma patients. And, the mortality rates is higher in those areas without trauma centers (OR=1.72, P&lt;0.01) Conclusions: Our results suggest major trauma patients should be sent to trauma centers for care, especially the elderly patients. And based on the non-significant difference in mortality rates between transferred and non-transferred patients, major trauma patients should be transferred to trauma centers after initial stabilization.
Abstract 337: Plasma Oncotic Pressure Is Reduced in Transfused Trauma Patients
Authors: Elaheh Rahbar, Lisa A Baer, Bryan A Cotton, John B Holcomb, Charles E Wade
Journal: Circulation (2012)

Objective: Hemorrhagic shock is the leading cause of potentially preventable traumatic death. Many of these deaths are believed to be avoidable with appropriate resuscitation. We investigated the role of initial plasma colloid osmotic presure (COP, i.e. oncotic pressure) on outcomes in trauma patients. Methods: Plasma samples were collected from 10 healthy consented volunteers and 27 patients (TRPs) upon admission to the emergency department (ED). Biophysical properties of plasma including osmolality, COP, and serum protein were measured and correlated to clinical data. Initial vital signs, routine laboratory values, type and volume of resuscitative fluids were recorded 24 hours post-ED admission as was length of hospital stay. Results: COP was significantly reduced in TRPs compared to controls 17.7±2.6 vs 20.7±2.1 mmHg (p&lt;0.05). COP strongly correlated (R 2 =0.8) to serum protein values, 6.1±0.8 in TRPs compared to controls, 6.6±0.4 g/dL. COP in TRPs were further categorized into Low (L&lt;15.3 mmHg, N=7), Moderate (M=15.3-19.3 mmHg, N=13) and Normal COP (N&gt;19.3 mmHg, N=6) subgroups, based on the interquartile range. TRPs with low and moderate COP had similar heart rates, systolic and diastolic blood pressures (128/75 mmHg, HR=94); whereas TRPs with N COP had higher blood pressures (148/93 mmHg). TRPs with L COP also received more blood transfusions within the first 24 hours of admission (L=1340±1568 ml, M=131±316 ml, and N=0 ml). Crystalloid infusions during the first 24 hours were similar among all groups (L=1480±1051 ml, M=1130±1040 ml, N=1171±965 ml). TRPs with L COP had longer hospital stays than M and N COP groups (13.5 vs. 7 days). Conclusions: Reduced COP and protein levels in TRPs are indicative of injury and hemorrhage. TRPs with low COP were more likely to receive blood transfusions during the first 24 hours and had longer hospital stays despite having similar vital signs as the M and N COP groups. In the absence of significant alterations in blood pressures and heart rate, COP and protein levels were indicative of a requirement for blood transfusions. We believe that using COP and protein levels in conjunction with current protocols could potentially improve resuscitation strategies for trauma patients.
Abstract 294: The Effect of 1-Shock Protocol using Biphasic Defibrillators for Treatment of Out-of-Hospital Shockable Cardiac Arrest
Authors: Tsukasa Yagi, Ken Nagao, Eizo Tachibana, Kei Nishikawa, Naohiro Yonemoto, Shinichi Shirai, Morimasa Takayama, Hiroshi Nonogi, Takeshi Kimura
Journal: Circulation (2012)

BACKGROUND In recent guidelines for electrical therapy of cardiopulmonary resuscitation (CPR), there was insufficient evidence to recommend any specific biphasic waveform. When defibrillation is required, a single shock should be provided with immediate resumption of chest compressions after the shock (1-shock protocol). We investigated the effect of 1-shock protocol using biphasic defibrillators. METHODS From the data of the All-Japan Utstein Registry, a prospective, nationwide, population-based registry of out-of-hospital cardiac arrest, we extracted the patients who were persons 18 years of age or older with bystander-witnessed shockable cardiac arrest due to cardiac etiology in the years 2005 (the 3-shock protocol era), and 2008, 2009 and 2010 (the 1-shock protocol era). The study patients were divided into 4 groups according to the two shock protocols and the two AED waveforms. The primary endpoint was 30-day favorable neurological outcome after shockable arrest. RESULTS Of the 17,297 patients who met the inclusion criteria, 1,626 received 3-shock protocol using biphasic AEDs, 1,960 3-shock protocol using monophasic AEDs, 12,133 1-shock protocol using biphasic AEDs, and 1,578 1-shock protocol using monophasic AEDs. Figure showed comparisons of favorable neurological outcome between the 1-shock protocol and the 3-shock protocol groups, and between the biphasic AEDs and the monophasic AEDs groups. In the subgroups of patients who did not receive bystander CPR, the frequencies were similar to the results of all patients. Adjusted odds ratios for favorable neurological outcome were 2.5 (95% CI, 2.2 to 2.8) after 1-shock protocol and 1.3 (95% CI, 1.2 to 1.4) after biphasic AEDs in the whole cohort. CONCLUSION Single-shock protocol using biphasic AEDs was superior to the others, including 1-shock protocol using monophasic AEDs, 3-shock protocol using biphasic AEDs and 3-shock protocol using monophasic AEDs, in terms of neurological benefits.
Abstract 19275: T-type Calcium Channel Overexpression in Mice Attenuates Recovery from Bupivacaine-Induced Cardiac Arrest
Authors: Swapnil Khoche, Larry Barr, Hongyu Zhang, Catherine Makarewich, Sharven Taghavi, Steven Houser
Journal: Circulation (2012)

Background _ The cardiotoxicity from the local anesthetic bupivacaine is predominantly a result of sodium channel blockade, though calcium channel inhibition has been implicated as well. Mechanisms of reversal of this cardiotoxicity are unclear. We investigated the toxicity of bupivacaine on FVB isolated mouse hearts that were either wild type (WT) or overexpressors for T-type calcium channel (TTCC). We subsequently attempted reversal of cardiotoxicity with a combination of intralipid and epinephrine. We hypothesized that the increased calcium metabolism of the transgenic hearts would augment the adverse effects of bupivacaine. Methods and Results _ Hearts from anesthetized WT and transgenic FVB mice aged 4 months were excised and placed on a Langendorff perfusion apparatus. The left atrial auricle was excised, the mitral valve was perforated, and a fluid-filled balloon was placed in the left ventricle to capture left ventricular pressure and heart rate data. After 10 min of baseline perfusion at an EDP of 10mmHg, bupivacaine was added at 100μM, causing arrest of cardiac activity for both mouse lines. After 3 min of cardiac arrest, the heart was perfused with a solution of bupivacaine (30μM), intralipid (0.2%) and epinephrine (0.15μg/ml) with cardiac recovery following. At baseline, there were no differences in left ventricle function between WT and transgenic mice. After recovery, the left ventricle end diastolic pressure in the transgenic mice was significantly higher (29.18 ± 4.05 mm Hg) than in the WT mice (17.15 ± 0.83 mmHg), P=0.02). Furthermore, the left ventricle developed pressure was significantly reduced (P=0.03) in the transgenic mice (28.61 ± 5.966 mmHg) when compared to WT (57.17 ± 8.052 mmHg). When incorporating heart rate, the Rate Pressure Product (HR x LVESP) was significantly decreased (P=0.03) in the transgenic mice (6455 ± 748.3) versus the WT (11396 ± 1646). Electrophysiological analysis revealed significantly increased suppression of calcium current in the L Type Calcium Channel (P=0.03) Conclusions _ These data show that bupivacaine-induced cardiotoxicity is more difficult to reverse in hearts overexpressing TTCC, possibly reflecting a stronger inhibition of Calcium release from the Sarcoplasmic Reticulum in them.
Abstract 30: Therapeutic Hypothermia Suppresses Arrhythmogenic, Calcium-Mediated Delayed Afterdepolarizations
Authors: Hidehira Fukaya, Joseph S Piktel, Bradley N Plummer, Kenneth R Laurita, Lance D Wilson
Journal: Circulation (2012)

Background : Therapeutic hypothermia (TH) is recommended for patients with return of spontaneous circulation after resuscitation from cardiac arrest. Hypothermia is known to cause derangements in cellular calcium (Ca) cycling, leading to Ca overload; however, the effect of TH on Ca-mediated arrhythmogenic substrates remains unclear. We hypothesized abnormal Ca cycling during TH would promote spontaneous Ca release and delayed afterdepolarizations (DADs). Methods and Results : Transmural dual optical mapping of Ca transients and action potentials was performed in canine wedge preparations during normothermia (36ºC; N group, n=5) or TH (32ºC; n=6). Multicellular spontaneous Ca release events (mSCR) and resultant DADs were induced by rapid pacing. TH significantly slowed the kinetics of Ca cycling compared to normal controls, significantly prolonging the time to peak (60.4 ± 5.7 vs. 40.1 ± 2.6 ms), duration (401.2 ± 13.8 vs. 305.8 ± 12.4 ms) and rate of decay (247.4 ± 29.2 vs. 146.0 ± 12.6 ms, all p&lt;0.05) of full Ca transients. The maximal mSCR amplitude was not significantly different in TH (21.1 ± 6.0%) compared to normals (28.4 ± 1.9%, p=NS). However, the slope (mSCR amplitude/time to peak) of mSCR activity, an important determinant of triggered activity, was significantly slower in TH (14.3 ± 3.7 %/s) compared to N (29.9 ± 3.9%/s, p&lt;0.05). Importantly, DAD amplitude was also significantly lower in TH (4.1 ± 2.2%) compared to N (11.1 ± 1.5%, p&lt;0.05). Conclusion : Even though therapeutic hypothermia did not decrease the magnitude of spontaneous calcium release, it did significantly reduce the slope, which was associated with significantly lower DAD amplitude. These results suggest that TH could be antiarrhythmic, in part, by slowing the kinetics of spontaneous calcium release and, thus, decreasing delayed afterdepolarizations, an important cause of triggered activity and arrhythmias.
Abstract 19748: Predicting Outcome in Adult Congenital Heart Disease: Correlating the Seattle Heart Failure Model with peak VO2 from Cardiopulmonary Exercise Testing
Authors: Ada Stefanescu, Eric Macklin, Elaine Lin, David Dudzinski, Doreen Defaria Yeh, George Lui, Ami Bhatt
Journal: Circulation (2012)

Background : The adult congenital heart disease (ACHD) population continues to grow and has increased risk of mortality and morbidity, including heart failure. Currently, no model exists to identify high risk patients. Cardiopulmonary exercise testing (CPET) is used in risk stratification with peak VO2 (pVO2) as a surrogate marker for outcomes in ACHD. This measurement requires specific equipment and expertise, not widely available outside of tertiary centers. The Seattle Heart Failure Model (SHFM) is a validated prediction model that estimates total mortality in patients with heart failure by using commonly obtained clinical, laboratory, medication, and device variables. Hypothesis : The SHFM predicts CPET pVO2 in moderate and complex ACHD. Methods : We performed a retrospective IRB approved study of 106 individuals (&gt;18 years of age) with transposition of the great arteries (TGA), Ebstein anomaly, tetralogy of Fallot (TOF), double outlet right ventricle (DORV) and single ventricle (SV) with a clinically indicated CPET at the Massachusetts General Hospital (MA, USA) and Montefiore Medical Center (NY, USA) between 2008 and 2012. Clinical/laboratory data (within one year of CPET) were obtained for SHFM calculation. Results : Mean age was 35.6 years (range 18-64), 55.7% are female, average systemic ventricle ejection fraction was 56.3% (18-83%). Medication use: 9.4% of individuals on ACE-I/ARB, 34% beta-blockers, 23.6% diuretics. The mean SHFM 1 year survival was 93.9% (72.5-99.0%); mean pVO2 was 21.2 cc/kg/min (10.2-41.6). The SHFM 5-year model was able to predict an outcome of pVO2&lt;20 in the group as a whole with a C statistic of 0.69. In individuals with TGA (systemic right ventricle) and Ebstein, the predictive ability of the SHFM 5-year model had a C statistic of 0.86 and 0.87, respectively. Peak VO2 and SHFM predicted survival correlated strongly among TGA and Ebstein patients (r=0.65 and 0.57, p &lt; 0.03), but not among SV or TOF patients (r.= -0.02 and 0.12, p &gt; 0.4). Conclusion : The SHFM is able to offer an increased ability to discriminate among ACHD patients who have a pVO2 &lt; or &gt; 20cc/kg/min. This model is easily created using clinically obtained data. Targeted application of SHFM in the community may have predictive value and guide care in select populations.
Abstract 19009: Increased Endogenous C-kit <sup>+</sup> Cardiac Stem Cells Diminish Myocardial Infarction Damage in S-nitrosoglutathione Reductase Mice
Authors: Ellena C Paulino, Konstantinos E Hatzistergos, Lauro M Takeuchi, Rosemeire M Kanashiro-Takeuchi, Wayne Balkan, Joshua M Hare
Journal: Circulation (2012)

Background. Cardiac tissue has endogenous cardiac stem cells (CSCs), which proliferate after myocardial infarction (MI) to support cardiac repair. As mice deficient in S-nitrosoglutathione reductase (GSNOR −/− ), an enzyme regulating S-nitrosothiol turnover, have preserved cardiac function after MI, we hypothesized that GSNOR −/− mice have higher levels of endogenous c-kit + CSCs post-MI. Methods. GSNOR −/− and WT (C57BL/6) mice were infarcted by permanent occlusion of the left anterior descending coronary artery. Cardiac performance was assessed by serial echocardiography. Histological sections were analyzed for infarct size and endogenous c-kit + /CD45 - CSCs were quantified by immunostaining. Results. There was no difference in ejection fraction (EF%) or endocardial volume (EDV, ESV) at baseline or 1 week post-MI, but at 8 weeks, EF% was improved (30.4±2.2 vs. 21.4±2.8, p&lt;0.05) and EDV and ESV were preserved in GSNOR −/− mice compared with WT (ESV 72.7±6.0 vs. 139.6±19.7 ul; p&lt;0.001, and EDV, 102.1±7.0 vs. 169.7±19.0 ul; p&lt;0.001, respectively). In addition, GSNOR −/− mice exhibited smaller scar size (34.6±2.8 vs. 62.2±7.9%, p&lt;0.05). The number of c-kit + /CD45 - CSCs was greater in post-MI GSNOR −/− hearts vs WT, independent of the zone analyzed (infarct+border zone: 6.3±0.8 vs. 2.3±0.9 cells/mm 3 , p&lt;0.05; remote zone: 0.4±0.1 vs. 0.1±0.05 cells/mm 3 , p&lt;0.05). Conclusion. Following MI, GSNOR −/− mice have preserved cardiac function, decreased remodeling and infarct size and increased c-kit + /CD45 - CSCs population in cardiac tissue during the remodeling phase. Thus, c-kit + CSCs contribute to cardioprotection in GSNOR −/− mice following MI, and suggest that enhanced S-nitrosylation based signaling contributes to CSC function following injury.
Abstract 9901: Essential Function of Tmem100 for Endothelial Differentiation and Vascular Development Downstream of ALK1 Signaling
Authors: Satoshi Somekawa, Masahide Sakabe, Hisaki Hayashi, Genki E Sato, Ken Inada, Munehiro Ito, Shiro Uemura, Osamu Nakagawa, Yoshihiko Saito
Journal: Circulation (2012)

Introduction: Among members of the TGFβ superfamily, bone morphogenetic protein (BMP) 9 and BMP10 regulate vascular development through activation of activin receptor-like kinase 1 (ALK1/ACVRL1) receptor. ALK1-mediated intracellular signaling is implicated in the etiopathogenesis of human diseases, but functional proteins downstream of ALK1 signaling are largely unknown. We previously reported that TMEM100 , a gene encoding an intracellular transmembrane protein, is activated by BMP9 and BMP10 through ALK1 receptor. We further demonstrated that Tmem100 null mice showed embryonic lethality due to impaired differentiation of arterial endothelium and defects of vascular morphogenesis, which phenocopied most of vascular abnormalities observed in Alk1 null embryos. However, the mechanisms of vascular defects caused by the Tmem100 deficiency and responsible cell type remain to be investigated. Methods and Results: To clarify which vascular cell type is contributed to developmental defects by the Tmem100 deletion, we generated Tmem100 conditional knockout mice using the Cre-loxP system. The deletion of endothelial Tmem100 caused impairment of vascular morphogenesis and embryonic lethality, which was virtually identical to the phenotypes of global null mice. To understand the mechanisms of vascular defects, we performed a microarray analysis using the yolk sac. We observed a significant decrease in the expression of Notch- and Akt-downstream genes, such as Hrt1/Hey1 , Hrt2/Hey2 , Klf2 and eNos , in Tmem100 null yolk sac as well as embryos. Expression of activated Notch1 receptor, Notch ICD, and Akt phosphorylation were down regulated in Tmem100 null yolk sac and embryos. Notch and Akt signaling regulates arterial development, and dysregulation of these signaling pathways was also observed in Alk1 null embryos, suggesting that TMEM100 works for proper vascular development downstream of ALK1 signaling, at least in part, by the regulation of these signaling pathways. Conclusion: TMEM100 functions in endothelial cells play indispensable roles during vascular development and morphogenesis downstream of ALK1-mediated signaling.
Abstract 79: The Predictive Value of NT-pro BNP in Cardiac Arrest Patients Treated with Mild Hypothermia
Authors: Jung Hee Wee, Jeong Ho Park, Chun Song Youn, Kyu Nam Park, Seung Pill Choi
Journal: Circulation (2012)

Background There has not been accurate, independent biomarker to reliably predict neurological outcome in cardiac arrest survivors. B-type natriuretic peptide (BNP) has both prognostic and diagnostic value in heart diseases, and many studies showed NT-pro BNP had more accurate than BNP. We speculated that NT-pro BNP measured after restoration of spontaneous circulation (ROSC) may predict patient outcome. Methods &amp; Results A retrospective review of comatose survivors who were treated with mild therapeutic hypothermia after cardiac arrest due to cardiac origin to two tertiary general hospitals between June 2007 and May 2011 was performed. NT-pro BNP level was checked in 87 patients immediately after ROSC. 35 (40.0%) had a favorable neurological outcome (cerebral performance category 1, 2) and 53 (60.9%) showed survival discharge. The mean value of NT-pro BNP was 557.1±1327.9pg/ml and 5,541.7±9,758.9pg/ml in favorable and unfavorable outcome, respectively (p=0.001). The AUC for favorable neurological outcome was 0.747, and 0.720 for death. The NT-pro BNP cutoff value of 362.7pg/ml for a favorable neurological outcome had a sensitivity of 65% and a specificity of 69%. The cutoff value of 393.8pg/ml for mortality had a sensitivity of 71% and a specificity of 66%. Adjusted odds ratios for favorable neurological outcome at 6 months were 0.686 (95% CI 0.205-2.295), 0.267 (0.0765-0.930), 0.060 (0.11-0.328) compared to the lowest quartile, respectively (p&lt;0.001). Conclusion The measurement of NT-pro BNP had valuable information to predict the neurological outcome for comatose survivors treated with mild hypothermia after out-of-hospital cardiac arrest of cardiac etiology.