bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P58: Impact of 2005 AHA Guidelines on OOHCA Survival
Authors: White Lynn J , Sayre Michael R , Cantrell Sarah A , Hiestand Brian C , Cudnik Michael , Koser Shawn C , Keseg David P 
Published: July 2021

Objective: To describe changes in out-of-hospital sudden cardiac arrest (OOHCA) survival before and after the release of the 2005 AHA guidelines for CPR and ECC.
Methods: Analysis of survival data from a pre-established Utstein style OOHCA registry was conducted for 1923 adult cases of OOHCA treated by EMS between April 1, 2004 and December 31, 2007. These data represented all adult cases treated by one EMS system in a large metropolitan area (population 711,432). The primary endpoint was survival to hospital discharge. A convenience sample of 69 electronic ECG recordings was also analyzed using impedence waveform analysis to assess CPR quality parameters during corresponding time periods. Intervention: Implementation of the 2005 AHA Guidelines for CPR and ECC in Spring 2006.
Results: Annual OOHCA incidence rate was 72/100,000, and VF incidence rate was 15/100,000. Bystander CPR rates were 27%, and 8% of arrests occurred in a public location. PAD AED use was 2% over the entire study period and few patients received hypothermia therapy. Unadjusted OOHCA survival rates were significantly higher in the post-guidelines period 8.2% (n=1055) than in the pre-guidelines period 5.3% (n=868) despite similarities in all major predictors of outcome (OR 1.6; 95% CI 1.05–1.69). Bystander witnessed OOHCA survival for victims with VF on EMS arrival was 18 of 89 (20%) pre-guidelines vs. 31 of 110 (28%) post-guidelines (OR 1.55; 95% CI 0.8 –3.0). CPR quality measures showed significant improvement in the post-guideline period. The mean no-flow fraction (NFF) in the pre-guidelines group was 0.46 (95% CI 0.41– 0.51), while the mean NFF in the post-guidelines group was 0.34 (95% CI 0.29 – 0.40). Multivariate regression analysis controlling for significant predictors of survival showed that OOHCA in the post-guidelines time period were associated with 1.75 greater odds of survival than those in the pre-guidelines time period (95% CI 1.17–2.62).
Conclusion: Substantial improvement occurred in overall OOHCA survival rates following the implementation of the 2005 AHA Guidelines for CPR and ECC. These changes are associated with improvements in the quality of CPR.
Abstract P82: Implementation Of New Resuscitation Guidelines Takes One-and-a-half Year
Authors: Berdowski Jocelyn , Schmohl Andra , Koster Rudolph W 
Published: July 2021

Objective- In November 2005, updated resuscitation guidelines were introduced world-wide, and will be revised again in 2010. This study aims to determine how long it takes to implement new guidelines.
Methods- This was a prospective observational study. From July 2005 to January 2008, we included all patients with a non traumatic out-of-hospital cardiac arrest. Ambulance paramedics sent all continuous ECG registrations with impedance signal by modem. We excluded ECGs from patients with Return Of Spontaneous Circulation at arrival, incomplete ECG registrations, ECGs with technical deficits or with continuous chest compressions. The same guidelines needed to be used in over 75% of the registration time in order to be labeled. We classified ECGs as guidelines 2000 if the c:v ratio was 15:2, shock blocks were present and there was rhythm analysis after each shock; guidelines 2005 if the c:v ratio was 30:2, a single shock protocol was used and chest compressions was immediately resumed after shock or rhythm analysis in a no shock scenario. We accepted 10% deviations in the amount of compressions (13–17 for 2000 guidelines, 27–33 for 2005).

Results- Of the 1703 analyzable ECGs, we classified 827 (48.6%) as guidelines 2000 and 624 (36.6%) as guidelines 2005. In the remaining 252 ECGs (14.8%) 31 used guidelines 1992, 137 applied guidelines 2000 with c:v ratio of 30:2 and 84 did not show distinguishable guideline usage. Since the introduction in November 2005, it took 17 months to apply new guidelines in over 80% of the cases (figure 1

).

Conclusion- Guideline changes are slowly implemented by professionals. This needs to be taken in consideration when new guideline revisions are considered.
Abstract P93: Heart Rate Variability Analysis using Wavelet Transform to Predict Hemorrhage Severity
Authors: Ji Soo-Yeon , Ward Kevin , Ryan Kathy , Najarian Kayvan 
Published: July 2021

Introduction: The Pulse Initiative on resuscitation identified the need to develop biosensing for detection of critical limitations of blood flow. The ability to rapidly detect the severity of hemorrhage based on heart rate has been limited. Use of heart rate variability (HRV) is problematic. We used a number of new defined ECG features based on discrete wavelet transformation (DWT) that may be used to estimate blood loss severity. The features are defined based on the energy of detail coefficients of Daubecies DWT.
Methods: The performance of DWT was tested using ECG data from a human model of hemorrhage using lower body negative pressure (LBNP). LBNP consisted of a 5-minute rest period (0 mm Hg) followed by 5 minutes of chamber decompression of the lower body to −15, −30, −45, and −60 mm Hg and additional increments of −10 mm Hg every 5 minutes until the onset of cardiovascular collapse. These levels were divided into 3 classes (mild: −15 to −30 mmHg; moderate: −45 to −60 mmHg; severe: over −60 mmHg). These levels correspond to estimated blood losses of 400 –550 cc, 500 –1000 cc and greater than 1000 cc respectively. The ECG DWT features of subjects were used for classification of each ECG recording during volume loss levels. Before classification in order to eliminate redundancy among the features, principal component analysis is applied to the feature set. Machine learning algorithms (SVM, AdaBoost, C4.5) were then applied to analyze the processed features and predict the severity of blood loss.
Results: A 219 sample set was used to classify groups by using machine learning algorithms with 10-fold cross validation. C4.5 outperformed other algorithms with a prediction accuracy of 74.4%. The average precision and recall (sensitivity) for the three classes were 77.4% and 76.1%, respectively. In particular, 30 out of 39 cases in the severe class were correctly classified by C4.5. These results required sampling rates of only 125 Hz.
Conclusion: This is the first reported use of an ECG analysis method to classify volume loss. The DWT method described may have the ability to rapidly determine the degree of volume loss from hemorrhage providing for more rapid triage and decision making. This may be particularly helpful for remote monitoring of war fighters or for mass casualty care.
Abstract 1499: Angiotensin And Endothelin Systems - Important Players In Urotensin II Induced Myocardial Distensibility
Authors: Fontes-Sousa Ana P , Pires Ana L , Monteiro-Cardoso Vera , Leite-Moreira Adelino F 
Published: July 2021

Objective: Urotensin II (U-II) is a vasoactive peptide with important actions in the cardiovascular system. It was recently shown that it acutely decreases myocardial stiffness. Although angiotensin II (AngII) and endothelin-1 (ET-1) also modulate myocardial diastolic properties, their interaction with U-II at this level has not yet been investigated.
Methods: Effects of increasing concentrations of U-II (10 – 8–10 – 6M) were studied in rabbit papillary muscles immersed in a modified Krebs solution (0.6Hz;1.8mM Ca2+;35°C) in the absence (n=12) and in presence of losartan, a selective competitive antagonist of AngII receptor type 1 (10 – 6M;n=8) or PD-145065, a nonselective endothelin receptor antagonist (10 – 6M;n=6). Calculated parameters: passive tension (PT), active tension (AT), maximum velocity of tension rise and decline (dT/dtmax and dT/dtmin, respectively) and muscle length. Results presented as mean±SEM (p<0.05).
Results: U-II induced a concentration dependent negative inotropic and lusitropic effects, decreasing at 10 – 6M 15.8±5.6%AT, 13.5±5.4%dT/dtmax and 18.1±4.5%%dT/dtmin. This effect was inhibited by losartan or PD-145065. Additionally, U-II induced a concentration dependent increase in passive muscle length of 1.0081±0.002L/ Lmax. Restoring muscle length to Lmax decreased 19.5±3.5%PT, indicating increased myocardial distensibility. In the presence of PD-145065, the maximal concentration of U-II only increased muscle length to 1.004±0.002%L/Lmax, which corresponded to a decrease of PT of just 11.6±2.7%. With losartan these effects of U-II were abolished.
Conclusion: The acute increase in myocardial distensibility induced by U-II is attenuated by ET-1 receptor blockade and completely abolished in the presence of an AT1 antagonist. This interaction between U-II, AngII and ET-1 is a novel finding with potential pathophysiologic and therapeutic implications in heart failure that deserves further investigation.
Abstract 1511: Gap Junction Internalization and Autophagic Degradation in the Failing Heart
Authors: Hesketh Geoffrey G , Shah Manish H , Kass David A , Van Eyk Jennifer E , Tomaselli Gordon F 
Published: July 2021

INTRODUCTION Gap junctions (GJs) mediate electrical coupling between cardiomyocytes, and are required for coordinated electrical activation and contraction of the heart. GJs are remodeled in diseased myocardium, resulting in impaired intercellular coupling and a predisposition to life threatening arrhythmias. To understand the mechanisms of GJ remodeling in heart failure (HF), we examined the ultrastructure of GJs in failing canine myocardium.
METHODS and RESULTS Using transmission electron microscopy, we observed the formation of GJs between lateral membranes of ventricular myocytes in rapid pacing induced heart failure (HF) in dogs. Lateral GJs exhibited complex membrane bending and extensive internalization. Lateral GJs were frequently adjacent to mitochondria and internalized GJs often formed concentric ring structures surrounding cellular debris. Internalized GJ membranes were associated with multi-lamellar membrane structures, with features characteristic of autophagosomes. Connexin43 (Cx43) and the autophagosome marker GFP-LC3 were extensively co-localized when expressed in HeLa cells. A hyperphosphorylated form of Cx43 previously associated with GJ degradation co-fractionated with LC3-II (autophagosome targeted form) in a Triton-insoluble and buoyant fraction of ventricular tissue. The hyperphosphorylated/buoyant population of Cx43 as well as LC3-II were both significantly increased (n=5 each, p=0.011 and p=0.016 respectively), and whole tissue levels of Cx43 were significantly decreased (n=5, p=0.01), in pacing-induced HF.
CONCLUSION We show that structurally heterogeneous GJs are present at the lateral membranes of cardiomyocytes in HF, suggesting aberrant targeting of GJs. Internalized GJs are degraded via autophagy, which involves a hyperphosphorylated form of Cx43, and is enhanced in HF. These findings reveal a novel pathway of GJ targeting and degradation in HF, and suggest potential therapeutic targets for HF-related conduction slowing and arrhythmias.
Abstract 1610: Repetitive Ischemia Elicits a Third Window of Ischemic Preconditioning
Authors: Yan Lin , Depre Christophe , Shen You-Tang , Jain Komal , Tian Bin , Vatner Dorothy E , Vatner Stephen F 
Published: July 2021

Ischemic preconditioning (IPC), following 1 or 2 episodes of coronary occlusion (CO) is the most powerful mechanism of cardioprotection, but it remains unclear whether IPC occurs clinically. Since patients with coronary disease experience episodes of repetitive ischemia (RI), we hypothesized that a pattern of RI would provide more clinically relevant cardioprotection. Conscious, chronically instrumented pigs (6/group) were submitted to RI induced by 6 episodes, 12 hrs apart, of coronary stenosis for 90 min (RCS) and compared to pigs submitted to second window IPC (SWIPC) induced by 2 episodes of 10 min CO / 24 hr reperfusion (CR) and to shams. Lethal ischemia, induced by 60 min CO, resulted in an infarct size/area at risk (IS/AAR) of 42±4% in shams, and significantly less, p<0.05, after RCS (6±3%) and after SWIPC (16±4%). SWIPC showed 2–3-fold increases, p<0.05, in translocation of PKCepsilon and the inducible isoform of nitric oxide synthase (NOS), which were not found in RCS. Pretreatment with the NOS inhibitor L-NNA (35 mg/kg) prevented the protection by SWIPC but not by RCS. Microarrays were performed to further elucidate the differences in molecular mechanisms between the SWIPC and RCS models. The number of genes significantly regulated was greater in RCS (5739) than in SWIPC (2394). Of the 5739 genes regulated in RCS, only 31% were also regulated in SWIPC. Since another difference between the two models is that one involves CS and the other complete CO, we examined another group of RI pigs (n=5) with 6 episodes, 12 hrs apart, of 2–10 min periods of CO, which showed reduced IS/AAR with 60 min CO after RI (14±4%); similar to RCS the cardioprotection was still observed after L-NNA. Both RI models, in further contrast to SWIPC, demonstrated downregulation of genes involved in mitochondrial function, and upregulation of genes involving autophagy (such as cathepsins B and D), endoplasmic reticulum stress (Grp78) and cell cycle (E2F1). These results were confirmed at the protein level by western blotting. Therefore, RI, over a time course of several days, provides a NOS-independent “third window” of protection, which is as effective as traditional SWIPC, but is mechanistically distinct.
This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 1693: Effect of Pitavastatin on Serum Concentrations of Endothelial Lipase and High-Density Lipoprotein Cholesterol in Humans
Authors: Sun Li , Ishida Tatsuro , Yoko Kojima , Yasuda Tomoyuki , Fukuda Akira , Kureha Fumie , Hirata Kenichi 
Published: July 2021

[Purpose] Endothelial lipase (EL) is a novel phospholipase which regulates serum high-density lipoprotein cholesterol (HDL-C) levels. In the present study, we have measured serum levels of EL in human subjects, and examined the effect of statins on serum HDL levels and EL mass.
[Methods and Results] A sandwich ELISA for human EL was established using two monoclonal antibodies against amino- or carboxy-terminus of human EL. Serum EL concentrations were measured and compared with the serum lipid profile in 237 patients with cardiovascular diseases. There was no significant correlation between serum EL mass and age or gender. Serum EL levels were negatively associated with serum HDL-C levels, but not with serum LDL-C, total cholesterol, or triglyceride levels. Forty-eight patients with hypercholesterolemia were treated with pitavastatin for 6 months, and serum EL mass was evaluated before and after the pitavastatin treatment. Pitavastatin treatment significantly reduced serum EL levels by 15% and increased HDL-C levels by 12%. Complimentary cell culture experiments revealed that pitavastatin suppressed basal and cytokine-induced EL expression and phospholipase activities in endothelial cells, which is reversed by the concomitant treatment with mevalonate or geranylgeranylpyrophosphate. Also, overexpression of RhoA T19N, a dominant negative mutant of RhoA, decreased the EL expression.
[Conclusion] EL is a determinant of serum HDL-C levels in humans. Pitavastatin reduced EL expression through the protein isoprenylation and inhibition of Rho activity, and raised serum HDL-C levels. Thus, EL would be a target molecule for the HDL-raising pharmaceutical interventions.
Abstract 1749: Endothelial Progenitor Cells and Vascular Endothelial Function Follow a Parallel Circadian Pattern
Authors: Mheid Ibhar Al , Aznaouridis Konstantinos , Patel Riyaz , Shirazi Farheen , Sutcliffe Diane J , Taylor W. R , Alexander R. W , Quyyumi Arshed 
Published: July 2021

Background: Endothelial Progenitor Cells (EPCs) are mobilized in response to endothelial injury and their counts correlate with endothelial function and cardiovascular risk burden. This rare cell population can be characterized by either flow cytometric analysis or mononuclear cell culture and colony counting, however, the 24-hour circadian variation and inter-relation of EPC measures with endothelial function remain unknown. We hypothesized that EPC levels and endothelial function will have a similar circadian variation.
Methods: In 12 healthy subjects (8 men, 42 ± 18 yrs), we investigated the circadian variation of: 1-circulating cells positive for:

CD34,

CD133 andCD34,

the number of colonies formed by culturing mononuclear cells utilizing a 7-day assay and

flow-mediated vasodilation utilizing brachial artery reactivity at 8am, noon, 4pm, 8pm, midnight, 4am and 8am.

Results: ANOVA for repeated measures over 24 hours indicated significant changes in the number of colony counts (p < .001, highest at midnight). Similarly, flow-mediated vasodilation was highest at midnight (p < .001). In contrast, CD34+ and dual positive CD34+ /CD133+ cell counts peaked a little earlier at 8 pm (8 pm vs.8 am p = .07 and .01 for paired t-tests, respectively). (Figure

)

Conclusion: Endothelial function and EPCs estimated as colony forming units peak at midnight and are lower at other times of the day. The highest counts of circulating progenitors are seen at 8pm. There is a parallel change in circulating EPCs and vascular endothelial function during a 24-hour period, with lower levels in the morning hours.
Abstract 1771: Serum And Glucocorticoid-induced Kinase-1 (SGK-1) Dynamically Regulates Cardiac Fibrosis In A CTGF- Independent Manner
Authors: Rosenberg Michael A , Das Saumya , Pinzon Pablo Quintero , Xiao Chunyang , Banerjee Sucharita , Rosenzweig Anthony 
Published: July 2021

Intro: We previously reported that the mineralcorticoid-responsive kinase, SGK-1, is activated in cardiac hypertrophy and regulates cardiomyocyte (CM) growth and survival. SGK-1 has also been implicated in renal fibrosis through transcriptional induction of connective tissue growth factor (CTGF). In this study, we examined the role of CM SGK-1 activation in the development of cardiac fibrosis.
Methods: We studied histology and electrophysiology in transgenic mice with cardiac-specific overexpression of constitutively-activated (SGK-CA) and kinase-dead (SGK-KD) SGK-1 protein. Protein and RNA expression were measured by Western blot and QRT-PCR, respectively, and SGK-KD mice were studied following transverse aortic constriction (TAC).

Results: EKG analysis revealed QRS prolongation in SGK-CA mice compared with wild type (WT) littermates (22.3±6.6 ms vs. 15.7±4.3 ms, p<0.05), which correlated with increasing age (R
2
0.44, p<0.05). Histologically, SGK-CA mice displayed increased fibrosis on Mason’s trichrome stain compared with WT mice. Protein expression of connexin43 (Cx43) was decreased 33% in SGK-CA ventricles (p<0.05), without a change in Cx43 RNA, consistent with post-transcriptional downregulation secondary to fibrosis. TGF-β RNA expression was increased in SGK-CA mice 1.44 fold (p<0.05), as was the fibrosis marker fibronectin (1.22 fold, p<0.05), while CTGF RNA expression was not significantly different between SGK-CA mice and wild type littermates. Following TAC, the SGK-KD mice displayed decreased cardiac fibrosis compared with TAC WT mice. Paradoxically, SGK-KD had increased expression of CTGF RNA vs. WT both at baseline (1.26 fold, p<0.05), as well as after TAC (1.52 fold, p<0.05), with both groups having > 3 fold increase in CTGF RNA after TAC. TGF- β RNA expression also increased about 1.5 fold in each group with TAC, although there was no significant difference between SGK-KD and WT mice either at baseline or after TAC.

Conclusion: Cardiomyocyte SGK-1 activation appears to play a dynamic role in the development of cardiac fibrosis as well as subsequent conduction disease. Our finding of a disconnect between fibrosis and induction of CTGF or TGF- β in SGK mice suggests that it works at least in part through independent pathways.
Abstract 1783: Pro-Apoptotic Bnip3 Mediates Permeabilization of Mitochondria and Release of Cytocrome c via a Novel Mechanism
Authors: Quinsay Melissa N , Rikka Shivaji , Sayen M Richard , Molkentin Jeffery D , Gottlieb Roberta A , Gustafsson Asa B 
Published: July 2021

Bnip3 is a member of the BH3-only subfamily of pro-apoptotic Bcl-2 proteins and is associated with mitochondrial dysfunction and cell death in the myocardium. The pro-apoptotic Bcl-2 proteins mediate mitochondrial dysfunction independent of the mitochondrial permeability transition pore (mPTP). However, Bnip3 has been reported to mediate cell death via the mPTP. In this study, we investigated the mechanism(s) by which Bnip3 causes mitochondrial dysfunction. Using a mitochondrial swelling assay to assess pore opening, we found that addition of 200 microM Ca2+ to mitochondria isolated from rat hearts induced rapid swelling of mitochondria and release of cytochrome c (cyto c). Bnip3 also induced mitochondrial swelling and cyto c release, but always at a slower rate and to a greater degree, suggesting that Bnip3 mediates swelling via a different mechanism. Cyclosporin A (CsA), an inhibitor of mPTP opening, prevented Ca2+-induced swelling and cyto c release, but had no effect on Bnip3. Another BH3-only protein, tBid, caused release of cyto c but failed to induce swelling of mitochondria. Interestingly, Bnip3, but not Ca2+ and tBid, induced release of the matrix protein MnSOD. Cyclophilin D (cycD) is an essential component of the mPTP and heart mitochondria isolated from cycD−/− mice were resistant to Ca2+-, but not to Bnip3-induced swelling and cyto c release. Also, tBid caused cyto c release without mitochondrial swelling in the absence of cycD. To further explore the mPTP as a downstream effector of Bnip3-mediated cell death, we assessed cell death in mouse embryonic fibroblasts (MEFs) isolated from wild type (wt) and cycD−/− mice. Infection with an adenovirus expressing Bnip3 caused significant cell death in wt (52.8±1.8%) and cycD−/− (61.8±6.1%) MEFs as measured by LDH release. In addition, both Bnip3 and opening of the mPTP have been reported to initiate upregulation of autophagy. Monitoring of GFP-LC3 incorporation into autophagosomes by fluorescence microscopy revealed that Bnip3 infection induced autophagy in wt (86.5±6.6%) and cycD−/− (96.4±1.4%) MEFs (n=3, p<0.05). Thus, these studies suggest that Bnip3 mediates permeabilization of the inner and outer mitochondrial membranes via a novel mechanism that is different from other BH3-only proteins.
This research has received full or partial funding support from the American Heart Association, AHA National Center.