bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 350: Remote Ischemic Pre-Conditioning Reduce Myocardial Ischemic Injury During and Following Hemorrhage Shock in a Rat Model
Authors: Yang Zhengfei , Xu Jiefeng , Hu Xianwen , Qian Jie , Yang Min , Cahoon Jena , Sun Shijie , Tang Wanchun
Published: April 2024

Introduction:
Myocardial ischemic injury following severe hemorrhage shock is often represented by acute changes of ST-segment and fractional shortening (FS). In this study, we investigated whether remote ischemic pre-conditioning (RIPC) reduces myocardial ischemic injury by measuring changes in ST-segment and fractional shortening during and following severe hemorrhage shock in a rat model.

Hypothesis:
RIPC reduces myocardial ischemic injury during and following severe hemorrhage shock as measured by changes of ST-segment and FS.

Methods:
Fourteen male Sprague-Dawley rats were randomized to receive RIPC, or sham control. RIPC was induced by four cycles of 5 mins of limb ischemia, followed by 5 mins of reperfusion. Fifty percent of estimated blood volume was then removed over an interval of 1 hour. Thirty mins after bleeding was completed, the animals were resuscitated by reinfusion of shed blood within 30 mins. Electrocardiographic tracings, and haemodynamics were continuously recorded for up to 2 hours. FS was measured by echocardiography at baseline, bleeding 60 mins, 30 mins before and after reinfusion and 1 and 2 hours after resuscitation.

Results:
Depression of ST-segment was observed during hemorrhage and followed with elevation of ST-segment after infusion in all animals. However, depression of ST-segment during hemorrhage and subsequent elevation after resuscitation were significantly better in the RIPC group than in the Control group. The compensative capacity of FS was significantly greater in the RIPC group than the Control group during and following hemorrhage (Table).

Conclusion:
RIPC reduces myocardial ischemic injury during and following severe hemorrhage shock.
Abstract 354: Nitrate Improves Postresuscitation Myocardial Dysfunction by Preserving Myocardial Nitric Oxide and Phospholamban Protein
Authors: Huang Yu , He Qing
Published: April 2024

Objectives:
Sarcoplasmic reticulum (SR) Ca
2+
handling proteins have been shown to play an important role in myocardial dysfunction after acute ischemic/reperfusion injury. We assessed the hypothesis that nitrite would improve postresuscitation myocardial dysfunction by increasing NO generation, and the mechanism is related to the modulation of SR Ca
2+
handling proteins.

Methods:
We performed a randomized prospective animal study using male Sprague-Dawley rats. Cardiac arrest was induced by intravenous bolus of potassium chloride (40 μg/g). Nitrite (1.2nmol/g) or placebo was administered when chest compression was started. No cardiac arrest was induced in sham group. Hemodynamic parameters were monitored invasively for one hour after ROSC. Echocardiogram was performed to evaluate cardiac function. Myocardial sample was harvested 5 minutes and 1 hour after ROSC respectively. The expression of sarcoplasmic reticulum Ca
2+
ATPase (SERCA2a), phospholamban (PLB) and rynodine receptors (RyRs) were analyzed by Western blot analysis. Myocardial NO five minutes after ROSC were measured using Nitric Oxide Assay Kit.

Results:
Myocardial function measured as the maximal rate of LV pressure increase (dP/dtmax), the maximal rate of LV pressure decline (-dP/dtmax), ejection fraction, fractional shortening was significantly impaired in nitrite and placebo groups after resuscitation, and cardiac function in nitrite group was significantly greater than placebo group. Nitrite administration increased the level of nitric oxide in myocardium 5 min after resuscitation when compared to the other two groups. The levels of phosphorylated phospholamban were decreased after resuscitation, and nitrite preserved the phosphorylation of phospholamban in myocardium after resuscitation when compared to placebo group. No significant differences were found in the expressions of myocardial sarcoplasmic reticulum Ca
2+
ATPase and rynodine receptors after resuscitation.

Conclusions:
Nitrite administered during resuscitation improves postresusctation myocardial dysfunction as an exogenous donor of nitric oxide, and the modulation of phosphorylated phospholamban, an important SR Ca
2+
uptake protein, is involved in the mechanism.
Abstract 357: Treatment With Fibrinogen ?-chain Peptide-coated, Adenosine Diphosphate-encapsulated Liposomes as an Infusible Haemostatic Agent for Dilutional Coagulopathy
Authors: Hagisawa Kohsuke , Kinoshita Manabu
Published: April 2024

Background:
We developed a fibrinogen γ-chain (dodecapeptide HHLGGAKQAGDV, H12)-coated, adenosine-diphosphate (ADP)-encapsulated liposomes [H12-(ADP)-liposomes] that accumulate at bleeding site via interaction with activated platelets via GPIIb/IIIa and augment platelet aggregation by releasing ADP.

Objective:
To evaluate the haemostatic efficacy of H12-(ADP)-liposomes against active liver bleeding in dilutional thrombocytopenic rabbits following massive transfusion.

Methods:
Acute thrombocytopenia (platelets < 50 х 10
3
/μL) was induced in rabbits by repeated blood withdrawal and isovolemic transfusion of autologous washed red blood cells. In these thrombocytopenic rabbits, liver hemorrhage was made by penetrating liver injury. Subsequently, they received the astriction treatment against the liver hemorrhage for 5 min and were intravenously administered with H12-(ADP)-liposomes with platelet-poor plasma (PPP), platelet-rich plasma (PRP), PPP alone, H12-(PBS)-liposome/PPP or H12-(ADP)-liposomes/PPP + fibrinogen concentrate during the astriction.

Results:
Administration of H12-(ADP)-liposomes as well as PRP rescued 60% rabbits from the liver hemorrhage (PRP, 50%), although rabbits receiving PPP or H12-(PBS)-liposome/PPP showed 10 or 17% survival in the first 24 h, respectively. Administration of H12-(ADP)-liposomes as well as PRP potently reduced both bleeding volume and time from the liver injury site. H12-(ADP)-liposomes were observed at the bleeding site in the liver with thrombus formation, suggesting an induction of thrombi. Whereas, neither macro- nor micro-thrombi were detected in the lung, kidney or liver in rabbits treated with H12-(ADP)-liposomes. Supplementation of fibrinogen to H12-(ADP)-liposomes/PPP did not significantly improve rabbit survivals (40% survival).

Conclusions:
H12-(ADP)-liposomes may be a safe and effective therapeutic tool during damage control surgery for acute thrombocytopenic trauma patients with massive bleeding.
Abstract 362: Behavioral Testing With Morris Water Maze in Rats Resuscitated With Emergency Cardiopulmonary Bypass From 10 Min Ventricular Fibrillation Cardiac Arrest
Authors: Weihs Wolfgang , Ettl Florian , Magnet Ingrid A , Warenits Alexandra , Teubenbacher Ursula , Hilpold Andreas , Sipoetz Johann , Tiboldi Akos , Holzer Michael , Sterz Fritz , Janata Andreas
Published: April 2024

Background:
Rodent models of cardiac arrest help to investigate detailed pathophysiologic mechanisms of cerebral ischemia and reperfusion. Sensitive neurologic and behavioral tests would enhance the ability of such models to evaluate possible beneficial effects of protective therapies. The Morris Water Maze (MWM) is a procedure to study spatial learning and memory. The aim of this study was to investigate behavioral testing with the MWM in rats resuscitated from ventricular fibrillation (VF) cardiac arrest (CA) via emergency cardiopulmonary bypass (ECPB).

Methods:
Sprague-Dawley rats (450g, male, anesthetized) were put into VF CA. After 10 min of CA the animals were resuscitated with ECPB, epinephrine and defibrillations and cooled to mild hypothermia (33°C) . Ten surviving animals with favorable neurologic recovery were compared to 8 healthy rats. MWM was performed in each animal 2 times on 4 consecutive days for maximal 60 s with a hidden platform in a 22°C cold water tank and on day 7 and 14 with the platform removed for memory testing.

Results:
The latency time to find the hidden platform decreased in the CPB group and the control group from 60(IQR 39-60) s and 60(IQR 60-60) s to 9(IQR 6-29) s and 10(IQR 6-19) s respectively (p=0.46). After removal of the platform the time within the target sector on day 7 in 60 s was 17±6 s and 22±5 s (p=0.08) and on day 14 12±4 s and 13±4 s (p=0.76) respectively.

Conclusions:
Spatial learning and memory in clinical neurologically intact animals resuscitated from a 10 min VF CA cooled to mild hypothermia was comparable to normal healthy controls. With this MWM setup learning was performed well, the remembrance of platform position was kept for one week in both groups equally.
Abstract 14611: Phenotypic Modulation of SMCs and Related Inflammation in the Development of Experimental Obstructive Pulmonary Vasculopathy
Authors: Otsuki Shoichiro , Sawada Hirofumi , Yodoya Noriko , Shinohara Tsutomu , Kato Taichi , Ohashi Hiroyuki , Zhang Erquan , Yoshida-Imanaka Kyoko , Shimpo Hideto , Maruyama Kazuo , Komada Yoshihiro , Mitani Yoshihide
Published: April 2024

Shoichiro Otsuki, 2013 Finalist and Presenting Author
Abstract 13145: Latent Rheumatic Heart Disease: Outcomes Two Years after Echocardiographic Detection
Authors: Beaton Andrea , Okello Emmy , Aliku Twalib , Lubega Sulaiman , Lwabi Peter , Mondo Charles , McCarter Robert , Sable Craig
Published: April 2024

Andrea Beaton, 2013 Finalist and Presenting Author
Abstract 15606: Genome-wide loss-of-function screen identifies SNARE proteins as a central component of programmed cellular necrosis
Authors: Elrod John W. , Davis Greg , Carpenter April C. , Plassard Andrew J. , Karch Jason , Dwyer Timothy , Aronow Bruce J. , Molkentin Jeffery D.
Published: April 2024

John W. Elrod, 2013 Finalist and Presenting Author
Abstract 11404: Delayed Hospital Arrival Among Women with Acute Ischemic Stroke: Cognitive and Behavioral Responses to Symptoms
Authors: Beal Claudia C.
Published: April 2024

Claudia C. Beal, 2013 Finalist and Presenting Author
Abstract 14917: Endogenous c-kit dependent genetic lineage tracing shows definable but limited contribution to cardiomyocyte regeneration.
Authors: van Berlo Jop H. , Kanisicak Onur , Lin Suh-Chin J. , Rota Marcello , Leri Annarosa , Anversa Piero , Molkentin Jeffery D.
Published: April 2024

Jop H. Van Berlo, 2013 Finalist and Presenting Author
Abstract 12669: MicroRNA-181b inhibits endothelial NF-κB signaling, insulin resistance, and atherosclerosis
Authors: Sun Xinghui , He Shaolin , Wara AKM , Icli Basak , Shvartz Eugenia , Tesmenitsky Yevgenia , Blackwell Timothy S. , Sukhova Galina K. , Croce Kevin , Feinberg Mark W.
Published: April 2024

Xinghui Sun, 2013 Finalist and Presenting Author
Abstract 10981: Morphine Decreases Clopidogrel Concentration and Effects: A Randomized, Double Blind, Placebo-Controlled Trial
Authors: Hobl Eva-Luise , Stimpfl Thomas , Sunder-Plassmann Raute , Stohlawetz Petra Jilma , Schoergenhofer Christian , Derhaschnig Ulla , Ebner Josef , Jilma Bernd
Published: April 2024

Eva- Luise Hobl, 2013 Finalist and Presenting Author
Abstract 9: Remote Ischemic Pre- and Post-Conditioning Produce Similar Improvement of Myocardial and Cerebral Function in a Rat Model of Cardiac Arrest and Resuscitation
Authors: Xu Jiefeng , Sun Shijie , Lu Xiaoye , Hu Xianwen , Cahoon Jena , Tang Wanchun
Published: April 2024

Introduction:
Remote ischemic pre-conditioning (RPC) has been demonstrated to provide powerful protection of the heart and the brain against ischemia reperfusion injury. However, it is not a practical use in the clinical settings of cardiac arrest and resuscitation. We investigated the effects of remote ischemic post-conditioning (RpostC) on post-resuscitation myocardial and cerebral function in a rat model of cardiac arrest.

Hypothesis:
RpostC is as effective as RPC in reducing post-resuscitation myocardial and cerebral dysfunction in a rat model of cardiac arrest.

Methods:
Twenty-one male Spague Dawley rats were randomized into three groups: 1) RPC, initiated 40 mins before induction of ventricular fibrillation (VF); 2) RpostC, initiated 5 mins after successful resuscitation; 3) Control. Remote ischemic conditioning was induced by four cycles of 5 mins of limb ischemia, followed by 5 mins of reperfusion. VF was induced and untreated for 6 mins while defibrillation was attempted after 8 mins of CPR. The animals were then monitored for 4 hours and observed for an additional 68 hours.

Results:
Equally improved post-resuscitation myocardial and neurological function were observed in the RPC and the RpostC groups, which were significantly better than the Control group (Table).

Conclusion:
In a rat model of cardiac arrest and resuscitation, remote ischemic pre- and post-conditioning produced similar improvement of myocardial and cerebral function.
Abstract 91: Weekend Admission Following Non-Traumatic Out-of-Hospital Cardiac Arrest is a Prognosticator of Poor Outcome: Results from a Nationwide Database
Authors: Eid Shaker M , Abougergi Marwan S , Albaeni Aiham , Chandra-Strobos Nisha
Published: April 2024

Background:
In the United States, differences in outcome based on day of admission have been reported for several disease entities including in-hospital cardiac arrest. We investigated whether outcomes are similarly affected in patients with non-traumatic out-of-hospital cardiac arrest (OHCA).

Methods:
The 2010 Nationwide Inpatient Sample and Nationwide Emergency Department Sample are nationally representative databases containing data on 8 and 21 million discharges, respectively. We included all patients with an ICD-9 CM code for a principle diagnosis of cardiac arrest and excluded those with ICD-9 CM code for any diagnosis of trauma. We defined “weekend” as Saturday 12:01 am to Sunday 11:59 pm. The primary outcome was a composite endpoint of in-hospital death or discharge to hospice. Secondary outcomes are listed in the table. Poor neurologic outcome was a composite endpoint of coma, vegetative state or anoxic brain injury with feeding tube or tracheostomy placement in patients discharged alive. Adjusted odds ratios were calculated using multivariable regression analyses.

Results:
In 2010, 140,128 OHCA patients were admitted to an ED in the United States; 29.3% occurred on the weekend. Ventricular fibrillation was the presenting rhythm in 3.8% of emergency department OHCA visits. Overall survival to hospital admission and discharge were only 8.2% and 4.8% respectively. When adjusted for variables known to affect outcome (Table), total in-hospital mortality remained higher on weekends compared with weekdays. Other outcomes, including the use of hypothermia were similar between weekends and weekdays.

Conclusion:
Despite the many advances in resuscitation systems, the national survival to hospital admission and discharge for non-traumatic out-of-hospital cardiac arrest remains very low. Yet again, a weekend admission appears as an independent predictor of higher in-hospital mortality in this patient population.
Abstract 9337: Zofenopril is Cost Effective for Treatment of Patients With Left Ventricular Systolic Dysfunction After Acute Myocardial Infarction: A Post- Hoc Analysis of the SMILE-4 Study
Authors: Borghi Claudio , Ambrosioni Ettore , Omboni Stefano , Cicero Arrigo F , Bacchelli Stefano , Degli Esposti Daniela , Novo Salvatore , Vinereanu Dragos , Ambrosio Giuseppe , Reggiardo Giorgio , Zava Dario
Published: April 2024

Background and objective:
in the Survival of Myocardial Infarction Long-term Evaluation 4 Study (SMILE-4) zofenopril associated with ASA was superior to ramipril plus ASA in reducing the occurrence of major cardiovascular events, in patients with left ventricular dysfunction (LVD) following acute myocardial infarction (AMI). The present post-hoc analysis was performed to evaluate cost-effectiveness of zofenopril compared to ramipril.

Methods:
a total of 771 patients with LVD and AMI were randomized double-blind to zofenopril 60 mg/day (n=389) or ramipril 10 mg/day (n=382) plus ASA 100 mg/day and followed-up for 1 year. The primary study end-point was 1-year combined occurrence of death or hospitalization for cardiovascular causes. The economic analysis was based on the evaluation of cost of medications and hospitalizations and was applied to the intention-to-treat population (n=716). Cost data were drawn from the National Health Service databases of the European countries participating into the study. The incremental cost-effectiveness ratio (ICER) was used to quantify the cost per event prevented with zofenopril vs. ramipril.

Results:
zofenopril significantly (p=0.028) reduced the risk of the primary study end-point by 30% as compared to ramipril (95% confidence interval: 49%, 4%). The number needed to treat to prevent a major cardiovascular event with zofenopril was 13 less than with ramipril.

The cost of drug therapies was higher with zofenopril (328.78 Euros per patient per year, n=365) than with ramipril (165.12 Euros per patient per year, n=351). The cost related to the occurrence of major cardiovascular events requiring hospitalization, averaged 4983.64 Euros for zofenopril and 4850.01 Euros for ramipril. The ICER of zofenopril vs. ramipril was 2125.45 Euros per event prevented (worst- and best-case scenario in the sensitivity analysis: 3590.09 and 3243.96 Euros, respectively).

Conclusions:
zofenopril is a viable and cost-effective treatment for managing patients with LVD after AMI.
Abstract 9359: Effects of Pre-Hospital ECG Use and Patient Residence Distance From PCI Center on Time to Device Activation in ST Segment Elevation Myocardial Infarction: A Retrospective Analysis From the NCDR
Authors: Mumma Bryn E , Kontos Michael C , Peng S A , Diercks Deborah B
Published: April 2024

Objective:
American Heart Association guidelines recommend <90 minutes from first medical contact (FMC) to reperfusion for ST segment elevation myocardial infarction (STEMI) patients. Prehospital electrocardiograms (ECGs) reduce time to reperfusion, but the relative influence of patient distance from a percutaneous coronary intervention (PCI) center on this effect is unclear. We evaluated the relationship between patient distance from a PCI center, prehospital ECG use, and interval from FMC to device activation among patients with STEMI.

Methods:
We performed a retrospective cohort study including all STEMI patients in the ACTION Registry-Get With the Guidelines from 7/1/2008 to 9/30/2012 who were transported by ground emergency medical services (EMS) to a PCI center. Patient distance was defined as the driving distance from the patient’s home zip code to the PCI center address as calculated by Google Maps. Home zip code was used as a surrogate for EMS call location. Patient distance was classified into tertiles (16.3 mi), and simple linear regression was used to characterize the interaction between prehospital ECG use and patient distance with respect to time to device activation.

Results:
Of the 29,506 STEMI patients, 19,690 (67%) received a prehospital ECG. The median patient distance to PCI center was 11.0 mi among patients with a prehospital ECG and 9.9 mi among those without. Overall, a prehospital ECG reduced the FMC to device activation time by 10.9 minutes (p<0.001). This reduction in time from FMC to device was consistent across tertiles of distance (1st, median 11 minutes; 2nd, median 11 minutes; 3rd, median 10 minutes). The effect of prehospital ECG is attenuated by 0.8 minutes for every 10 mile increases in distance (interaction p=.0002). During off hours, median time from FMC to device activation was longer in each distance tertile when compared to work hours (86 vs 68, 86 vs 70, and 92 vs 77 minutes, respectively; p<0.001 for all).

Conclusion:
Prehospital ECGs are commonly used among STEMI patients and reduce the time from FMC to device activation by approximately 10 minutes. Patient distance from a PCI center was not associated with this time interval, but presentation during off hours was associated with longer times.
Abstract 9362: Senescence Marker Protein 30 has a Cardio-protective Role in Doxorubicin-induced Cardiac Dysfunction
Authors: Miyata Makiko , Suzuki Satoshi , Misaka Tomofumi , Takeishi Yasuchika
Published: April 2024

Background:
Senescence marker protein 30 (SMP30), which was originally identified as an aging marker protein, is assumed to act as a novel anti-aging factor in the liver, lungs and brain. Anthracyclines are the drugs most closely related to acute and late cardiac toxicity. One of the mechanisms responsible for doxorubicin (DOX) cardiotoxicity is the formation of reactive oxygen species (ROS) which can harm membrane lipids and other cellular components, leading to cardiomyocyte apoptosis and death. We hypothesized that SMP30 has cardio-protective function due to its anti-aging and anti-oxidant effects on doxorubicin (DOX)-induced cardiac dysfunction.

Methods and Results:
SMP30 knockout (SMP30 KO) mice, SMP30 transgenic (SMP30 TG) mice with cardiac-specific overexpression of SMP30 gene and wild-type (WT) littermate mice were given intra-peritoneal injections of DOX (20 mg/kg) or saline. Seven days after DOX injection, echocardiography revealed that left ventricular ejection fraction was more severely reduced in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but was preserved in the DOX-treated SMP30 TG mice. Generation of ROS and oxidative DNA damage in the myocardium were greater in the DOX-treated SMP30 KO mice than in the DOX-treated WT mice, but much less in the SMP30 TG mice. The number of deoxynucleotidyl transferase-mediated dUTP nick end-labeling positive cardiomyocytes was higher in the DOX-treated SMP30 KO mice and lower in the DOX-treated SMP30 TG mice compared to that in the DOX-treated WT mice. Caspase-3 activity was higher in the DOX-treated SMP30 KO mice and lower in the DOX-treated SMP30 TG mice compared with the DOX-treated WT mice. The ratio of Bax to Bcl-2 was higher in the DOX-treated SMP30 KO mice and lower in the DOX-treated SMP30 TG mice than in the DOX-treated WT mice. Phosphorylation activity of SAPK/JNK was increased in the DOX-treated SMP30 KO mice and was decreased in the DOX-treated SMP30 TG mice compared with the DOX-treated WT mice.

Conclusions:
SMP30 has a cardio-protective role by anti-oxidative and anti-apoptotic effects in DOX-induced cardiotoxicity, and can be a new therapeutic target to prevent DOX-induced heart failure.
Abstract 9409: DSR-85955, a Novel Mineralocorticoid Receptor Antagonist With Carbonic Anhydrase Inhibitory Activity, Exhibits Low Hyperkalemia Risk in Rats
Authors: Kato Hiroshi , Mori Masaya , Masakazu Shintome , Nariai Tetsuro , Katayama Seiji , Hori Seiji , Hasegawa Futoshi , Suzuki Kuniko , Fujita Katsuya
Published: April 2024

Background:
Mineralocorticoid receptor (MR) antagonists, such as spironolactone and eplerenone, are useful for the treatment of hypertension and heart failure. However, these antagonists should be used carefully not to cause hyperkalemia as they can interfere with sodium/potassium exchange and reduce urinary potassium excretion. We hypothesized that increase in urinary potassium excretion can reduce elevated plasma potassium level, and accordingly identified DSR-85955 as a safe and orally effective MR antagonist with low hyperkalemia risk. We present the unique
in vitro / in vivo
profile of DSR-85955.

Methods and Results:
Using reporter gene assay, we first determined DSR-85955 selectivity for MR and compared it to that for androgen, progesterone, and glucocorticoid steroid receptors. DSR-85955 exhibited high selectivity for MR with an IC50 value of 0.39±0.1 uM (11±2.3 uM for the androgen / progesterone receptor, and 36±4.7 uM for the glucocorticoid receptor). To clarify DSR-85955 low risk for hyperkalemia, we focused on the hypokalemic side effect of other classes of diuretics. We found that DSR-85955, but not spironolactone or eplerenone, inhibits carbonic anhydrase involved in carbon dioxide transport. Next, we compared the effects of DSR-85955, spironolactone, and eplerenone on sodium excretion in deoxycorticosterone acetate-treated rats and plasma potassium levels in potassium-loaded rats. DSR-85955 (30 - 300 mg/kg) reversed sodium excretion without increasing plasma potassium level. Spironolactone and eplerenone, on the other hand, reversed sodium excretion at doses that increased plasma potassium level. In another experiment, 2-week-treatment with DSR-85955 (10 - 100 mg/kg) reduced systolic blood pressure in both uninephrectomized rats treated with aldosterone/salt (UN-Ald/Salt) and spontaneous hypertensive rats. DSR-85955 also decreased urinary albumin excretion in UN-Ald/Salt rats and heart weight in spontaneous hypertensive rats. The anti-hypertensive and organ protective effects of DSR-85955 were 2 to 3 times stronger than those of eplerenone.

Conclusion:
We have identified DSR-85955, a selective MR antagonist with CA inhibitory activity, as a hopeful antihypertensive candidate with low hyperkalemia risk.
Abstract 9543: βArrestin1 Genetic Deletion Improves Cardiac Function and Adverse Remodeling in Heart Failure
Authors: Lymperopoulos Anastasios , Rengo Giuseppe , Siryk Ashley , Dabul Samalia , Gao Erhe , Koch Walter J
Published: April 2024

Introduction:
Chronic heart failure (HF) is characterized by enhanced circulating cardiotoxic hormones, including catecholamines and aldosterone, which contribute to the increased morbidity and mortality associated with myocardial infarction (MI). Cardiac ß-adrenergic receptor (AR) desensitization is a hallmark molecular abnormality in HFand is due to the concerted action of cardiac G protein-coupled receptor kinase-2 (GRK2), together with its co-factors in receptor desensitization, the ßarrestins (ßarrs). We have also recently established that ßarr1 promotes angiotensin II-dependent aldosterone production in the adrenal cortex, and this leads to elevated circulating aldosterone levels in vivo, both under normal conditions and during post-MI HF progression.

Hypothesis:
Herein, we sought to investigate the effects of genetic deletion of ßarr1 on post-MI cardiac function and structure in mice progressing to HF.

Methods:
We utilized the global ßarr1 knockout (KO) mouse model and studied these mice at 4 weeks after surgically induced MI, in parallel with C57/Bl6 wild type (WT) controls. Cardiac function was assessed by echocardiography and in vivo catheterization. Plasma hormones were measured by ELISA. Adverse remodeling markers` mRNA expression was assessed by real time PCR.

Results:
Cardiac function is markedly improved in ßarr1KO`s at 4 weeks post-MI compared to WT mice (ejection fraction: 41.5±2.8% vs. 21.8±2.4%, respectively, n=9, p<0.0001). Isoproterenol-induced contractility is also enhanced. Additionally, cardiac dimensions are significantly reduced compared to WT`s, as are levels of adverse remodeling markers, indicating attenuation of adverse cardiac remodeling. Importantly, plasma circulating aldosterone and catecholamine levels are significantly lowered and cardiac ßAR signaling and function appear elevated in post-MI ßarr1KO`s compared to control WT`s.

Conclusions:
Genetic deletion of ßarr1 substantially improves cardiac function, adverse remodeling, neurohormonal status and ßAR function during post-MI HF progression. The underlying mechanism appears to be attenuation of both cardiac ßAR desensitization and adrenal cardiotoxic hormone production, both ßarr1-dependent phenomena.
Abstract 9607: Factors Associated With Cognitive Deficits in Heart Failure Differ by Gender
Authors: Riegel Barbara , Pressler Susan
Published: April 2024

Background:
In 2005 Bennett proposed a conceptual model of cognitive deficits (CD) in heart failure (HF). The purpose of this study was to test the model and to identify if results differ by gender.

Methods:
Data from 280 HF patients were analyzed using generalized linear modeling to predict CD measured as the number of neuropsychological tests on which participants scored in the abnormal range. Five tests (Trail-Making Tests A and B, Digit Symbol-Substitution, Probed-Recall Memory, Letter Number Sequencing) were used; the number on which subjects scored below their age-based norm was used as the measure of CD (0-5 range). Predictors entered into the model were age, sex, education, Charlson Comorbidity score, hypertension (yes/no), depression measured with the PHQ-9, HF type (systolic/mixed or diastolic), HF etiology (ischemic/nonischemic), ejection fraction, NYHA functional class, duration since diagnosis, and number of medications taken daily. Only oxygen saturation proposed in the original model was unavailable.

Results:
Overall, the model was adequate to describe CD but several of the variables were poor predictors so the model was rerun separately in men (n=180, mean age 63±12.3, 33% black) and women (n=100, mean age 60±12.7, 36% black). In men the model fit well (p=0.005) but not in women (p=0.969). In men the best indicators of CD were older age, less education, and poor functional class; these variables explained 36.3% of the variance in CD. In women, a new model was proposed that focused on behavior (smoking, drinking, exercise, medication adherence, taking vitamins, body weight, sleep hygiene), symptoms (NYHA functional class, sleep quality, fatigue, daytime sleepiness, depression), and social support. Demographic characteristics of age and education were included, as these are known to predict CD. In women the best predictors of CD were older age, lower medication adherence, worse NYHA functional class, and less social support. These 4 variables explained 55.9% of the variance in CD in women. When the new model was tested in men, only NYHA class was associated with CD, explaining 1.5% of the variance.

Conclusion:
Different factors are associated with cognitive decline in men and women. Different interventions targeting CD may be needed.
Abstract 9678: Clinical Profile of Patients With Coronary Chronic Total Occlusions at a Tertiary Veterans Affairs Medical Center
Authors: Jeroudi Omar M , Alomar Mohammed E , Michael Tesfaldet T , El Sabbagh Abdallah , Patel Vishal G , Mogabgab Owen , Fuh Eric , Sherbet Daniel , Lo Nathan , Roesle Michele , Rangan Bavana V , Abdullah Shuaib , Hastings Jeffrey L , Grodin Jerrold , Banerjee Subhash , Brilakis Emmanouil S
Published: April 2024

Introduction:
The clinical profile of patients with coronary chronic total occlusions (CTO) has received limited study. We sought to examine the characteristics of patients presenting with CTOs in a contemporary veteran population.

Methods:
We collected clinical and angiographic data on 1,699 consecutive patients that underwent coronary angiography at our institution between January 2011 and December 2012. Coronary artery disease (CAD) was defined as ≥50% diameter stenosis in ≥1 coronary artery. CTO was defined as total coronary artery occlusion of ≥3 month duration. Patients with prior coronary artery bypass graft surgery (CABG) were excluded from analysis.

Results:
At least one CTO was identified in 319 of 1,015 patients (31%) with significant CAD. Compared to non-CTO patients, patients with a CTO were significantly more likely to have cardiac and non-cardiac comorbidities such as diabetes mellitus, peripheral arterial disease, congestive heart failure, prior myocardial infarction, and prior stroke. CTO patients presented more frequently with stable angina (37% vs. 30%,
p
=0.03) and had more extensive CAD (
p
<0.001).

Conclusions:
In a contemporary veteran population, the presence of a coronary CTO was strongly associated with more extensive cardiac and non-cardiac comorbidities, CAD risk factors, and more extensive CAD.
Abstract 9689: Left Ventricular Mass Normalized to Lean Body Mass in Children May Obscure the Effect of Hypertension on the Heart
Authors: Mahgerefteh Joseph , Hsu Daphne , Chambers Sarah , Gonzalez Jennifer , Lopez Leo
Published: April 2024

Purpose:
In order to make comparisons of left ventricular mass (LVM) measurements among children, several methods of LVM normalization for body size have been developed. LVM has been hypothesized to correlate best with lean body mass (LBM). In addition, hypertension is a known risk factor for left ventricular hypertrophy. This study evaluates the agreement between LVM normalized to LBM (LVM
L
) and LVM normalized to body surface area (LVM
B
) or height (LVM
H
). In addition the study evaluates the relationship between each method and systemic blood pressure. Our hypothesis is that LVM normalization to LBM will obscure the effect of hypertension on the LVM.

Methods:
Echocardiograms performed from 2009-2010 in 206 children (118 males, age 4 to 18 years) with no structural heart disease or systemic disorders other than hypertension and obesity were analyzed. LVM was calculated from M mode images using the prolate ellipsoid formula. LVM Z scores were calculated using 3 different published nomograms adjusting for height, BSA, and LBM. Intraclass correlation coefficients (ICC) with absolute agreement of single measures were used to assess concordance between LVM
L
Z score with the LVM
B
and LVM
H
Z scores. Pearson correlation was done to assess the associations.

Results:
Among the 206 patients, 21% had hypertension, 38% were obese, and 10% were obese and hypertensive. Mean BMI Z score was 1.1 ± 1.2, systolic BP Z score 0.6 ± 1.2, and diastolic BP Z score 0.1 ± 0.9. The ICC between LVM
L
and LVM
B
Z scores was 0.81 (95
th
% CI: 0.73-0.86, p < 0.001) and between LVM
L
and LVM
H
Z scores was 0.73 (95
th
% CI: 0.29-0.87, p < 0.001). Correlations of the 3 LVM Z scores with BP, weight, and BMI Z scores are shown in the table.

Conclusion:
LVM
L
has a better correlation with LVM
B
compared to LVM
H
. Elevated systolic BP associate with higher LVM
H
. There was no significant relationship between systolic BP and LVM
L
or LVM
B
, suggesting that these methods of LVM normalization may mask the effect of hypertension on LVM.
Abstract 9857: Inhibition of Endoplasmic Reticulum Stress Prevents Cardiac Rupture and Attenuates Cardiac Remodeling by Alleviating Mitochondrial Apoptosis and Nlrp3 Inflammasome Activation
Authors: Luo Tao , Chen Baihe , Wang Xianbao , Wang Nisha , Wang Yanping , Zhang Chao
Published: April 2024

Background:
Endoplasmic reticulum (ER) stress is involved in myocardial ischemia, but its role and underlying mechanism in the pathogenesis of post-infarct cardiac rupture and remodeling remain unclear. It is known that mitochondrial apoptosis and NLRP3 inflammasome activation are associated with tissue necrosis and fibrosis, which are crucial for cardiac rupture and remodeling. Here we hypothesized that ER stress promotes cardiac rupture and remodeling by increasing mitochondrial apoptosis and NLRP3 inflammation activation.

Methods and Results:
Left coronary ligation was used to produce myocardial infarction (MI) in C57BL/6 mice. There was 37.5% cardiac rupture rate in the control group during the early phase of MI (2-7 days). The survivals underwent cardiac remodeling and formed ventricular aneurysm with impaired systolic and diastolic functions at the end of 4 weeks. The rupture rate was significantly decreased to 20% in the 4-PBA intraperitoneal injection group (20 mg/kg/day) and the heart functions were improved at the end of 4 weeks. Furthermore, the ventricular aneurysm and myocardial fibrosis were much smaller. Western blot showed that the ER stress markers, mitochondrial bax, caspase 3, NLRP3, TGFβ1 and Smad 2 in the heart tissues of control group were significantly increased after MI, in which mitochondrial bax and caspase 3 were increased markedly in the early phase of MI (3 days), while NLRP3, TGFβ1 and Smad 2 were increased obviously in the late phase of MI (3-28 days). 4-PBA decreased those protein levels in the early and late phases of MI respectively. Then ER stress was induced in neonatal rat’s cardiomyocytes and fibroblasts by 3% hypoxia stimulation for 3 days. Calcein plus CoCL
2
, flow cytometry for JC-1 and western blot for mitochondrial bax and caspase 3 indicated that 4-PBA (0.5 mM) pretreatment protects the cardiomyocytes against mitochondrial-dependent apoptosis induced by hypoxia. Meanwhile, western blot showed that the expression of NLRP3, TGFβ1 and Smad 2 in the fibroblasts were increased by hypoxia stimulation but decreased by 4-PBA.

Conclusion:
Inhibition of ER stress is a novel therapeutic strategy for preventing post-infarct cardiac rupture and attenuating cardiac remodeling.
Abstract 9916: Potent Antithrombotic Effect of a Small-molecule, Reversible and Direct Inhibitor of Factor XIa With Minimum Bleeding Time Effect In Rabbit Models of Arterial Thrombosis and Hemostasis
Authors: Wong Pancras C , Quan Mimi , Watson Carol , Crain Earl , Wexler Ruth , Seiffert Dietmar
Published: April 2024

BMS-654457 ((+) 3’-(6-carbamimidoyl-4-methyl-4-phenyl-1,2,3,4-tetrahydro-quinolin-2-yl)-4-carbamoyl-5’-(3-methyl-butyrylamino)-biphenyl-2-carboxylic acid). is a potent, reversible and direct factor XIa (FXIa) inhibitor. It inhibits human FXIa with K
i
of 0.2 nM and with >1000 fold selectivity over most of the relevant serine proteases. We conducted an in vivo proof of concept study and characterized the antithrombotic and bleeding time (BT) effects of BMS-654457 in rabbits. The direct thrombin inhibitor melagatran was included as a reference agent. BMS-654457 and melagatran were studied in rabbit models of electrically-induced carotid arterial thrombosis and cuticle bleeding. Compounds were given as an IV bolus plus infusion 30 min or IV infusion 60 min before the initiation of thrombosis or cuticle transection. Integrated carotid blood flow over 90 min (iCBF, % control) was used as a marker of the antithrombotic effect. Ex vivo clotting times were measured by using a commercial hemostasis analyzer. BMS-654457 at 0.011+0.008, 0.037+0.027, 0.11+0.08, 0.37+0.27 and 1.1+0.8 mg/kg+mg/kg/h IV increased iCBF to 17±3, 46±6*, 48±9*, 87±10* and 96±5%*, respectively,
vs
. 16 ± 3% in the vehicle-treated group (n=6 per group, *P<0.05,
vs
. vehicle). The antithrombotic EC
50
(concentration that increased iCBF by 50% of the control, μM) was 0.28 for BMS-654457 and 0.15 for melagatran. At their top equivalent antithrombotic doses, BMS-654457 and melagatran increased BT by 1.33±0.08 and 6.7±0.3-fold, respectively (n=6 per group). As expected for a FXIa inhibitor, BMS-654457 increased ex vivo activated partial thromboplastin time (aPTT) without changing prothrombin time and thrombin time. The antithrombotic effect of BMS-654457 was significantly correlated with its ex vivo aPTT, supporting ex vivo aPTT as a pharmacodynamic biomarker. This study demonstrated that BMS-654457 is as effective as melagatran in the prevention of arterial thrombosis in rabbits, and prolonged BT less than melagatran. These findings suggest that inhibition of FXIa, with a small-molecule, reversible and direct inhibitor, may represent a promising antithrombotic therapy with a wide therapeutic index.
Abstract 10259: Echocardiographic Predictors of Mortality in Adults With a Fontan Circulation
Authors: Cordina Rachael , von Klemperer Katherine , Kempny Aleksander , Senior Roxy , Celermajer David S , Babu-Narayan Sonya , Gatzoulis Michael , Li Wei
Published: April 2024

Introduction:
Transthoracic echocardiographic (TTE) parameters that predict mortality have not been well-defined in Fontan-adults. Atrioventricular valve systolic to diastolic duration ratio (AVV S:D) is an echocardiographic indice that reflects global cardiac performance but has not been studied in this setting. AVV S:D may be useful in this heterogeneous group as it does not rely on geographic assumption or segmental analysis.

Methods:
Fontan-adults (≥18 years) in sinus or A-paced V-sensed rhythm seen at our institution since 2005 were studied prospectively. Clinical data were recorded from time of index TTE. Subjects were censored at death or most recent review. Nil had cardiac transplant.

Results:
In total, 128 patients (64 male) were included, mean age was 27 ± 8 years, 107 had dominant left ventricle (LV), 18 had dominant right ventricle (RV) and 3 were biventricular with large ventricular septal defect. Forty-eight had atriopulmonary connection (APC), 64 had total cavopulmonary connection (TCPC) and 16 had TCPC conversion. Time since first repair was 22 ± 7 years. Mean NYHA Class was 1.4 ± 0.6. During mean follow-up of 4.3 ± 2.8 years, 12 patients died (1 dominant RV, 11 dominant LV). Eight deaths were due to heart failure, 2 were sudden death and 2 were due to liver failure. In univariate analysis the strongest TTE predictors of mortality were AVV S:D, presence of restrictive filling using pulse and tissue Doppler parameters, subjective grade of systolic ventricular function, fractional area change and moderate to severe AVV regurgitation. Results with p ≤ 0.2 are shown in Figure 1. Cox regression analysis suggested NYHA Class and AVV S:D were independent predictors of mortality (p<0.0001 for both).

Conclusions:
TTE indices are predictive of mortality in Fontan-adults. Ventricular performance assessed by AVV S:D was the most important parameter and should be incorporated into routine clinical assessment of these patients.
Abstract 10283: Motivational Interviewing Decreases Readmissions in Adults With Heart Failure
Authors: Riegel Barbara , Masterson Creber Ruth , Hill Julia , Stawnychy Michael , Chittams Jesse , Hoke Linda
Published: April 2024

Introduction:
In chronic heart failure (HF), 70% of patients are readmitted to the hospital within 12 months. At least 63% of these readmissions are for a condition other than HF.

Hypothesis:
We hypothesized that motivational interviewing (MI) would be effective in decreasing readmissions unrelated to HF in HF patients.

Methods:
Hospitalized adults with HF were enrolled if they were symptomatic (NYHA class II-IV), spoke and read English, lived in a setting where they could independently engage in self-care, and were cognitively intact. We enrolled 100 HF patients (mean age 60 ± 14.3 years; 57% Black, 33% female, 85% NYHA class III/IV symptoms, 64% were educated ≤ high school level) into a randomized controlled trial, using minimization to balance group assignment on NYHA class and gender. Participants in both groups received educational materials emphasizing self-care behavior change. The intervention group received MI emphasizing self-care (e.g. adherence, symptom monitoring) and tailored to individual goals. The intervention was provided by a nurse in a single home visit with 3-4 follow-up phone calls. Participants were followed for 3 months. For the primary outcome, readmission unrelated to HF, a multiple variable regression model was constructed using a backward variable elimination approach.

Results:
Over 3 months, 25% of the sample had a HF-readmission and 15% had a readmission unrelated to HF. There was an absolute difference of 21% (9 vs 30) in readmissions unrelated to HF between the MI intervention and control groups (p=0.006). The MI group had 94% lower odds of having a readmission unrelated to HF (p=0.001). Each additional unit of hemoglobin was associated with 48% lower odds of having a readmission unrelated to HF (p=0.006). For each additional year of age, the odds of having a readmission unrelated to HF were 7% lower. Participants with diabetes had 6.7 times the odds (p=0.012) of having a readmission unrelated to HF.

Conclusion:
An MI intervention emphasizing self-care and tailored to individual goals significantly reduced readmissions unrelated to HF in adults with HF, even after accounting for the influence of anemia, age, and diabetes.
Abstract 10363: Cardio-Protective Effects of Pentraxin 3 Produced From Bone Marrow-Derived Cells Against Ischemia/Reperfusion Injury
Authors: Shimizu Takeshi , Suzuki Satoshi , Sato Akihiko , Nakamura Yuichi , Saitoh Shu-ichi , Mantovani Alberto , Shishido Tetsuro , Kubota Isao , Takeishi Yasuchika
Published: April 2024

Background:
Pentraxin 3 (PTX3), produced in response to inflammatory signals, acts as a humoral arm of the innate immunity. Although a cardio-protective role of PTX3 against myocardial ischemia/reperfusion (I/R) injury has been reported experimentally, the origins of PTX3 functioning for protection of myocardium remain unclear. We examined the role of PTX3 produced from bone marrow (BM)-derived cells in myocardial I/R injury. Methods and Results: PTX3 deficient (PTX3
-/-
) and wild-type littermate (WT) mice were lethally irradiated and injected with BM cells, generating 4 types of mice (WT/WT BM, WT/PTX3
-/-
BM, PTX3
-/-
/WT BM and PTX3
-/-
/PTX3
-/-
BM). Six weeks after BM transplantation, the myocardial I/R procedure was performed. Infarct size was greater in WT and PTX3
-/-
mice with BM from PTX3
-/-
donor (WT/PTX3
-/-
BM and PTX3
-/-
/PTX3
-/-
BM) compared with WT and PTX3
-/-
mice with BM from WT donor (WT/WT BM and PTX3
-/-
/WT BM) (P<0.05 and P<0.01, respectively). Localization of PTX3 was observed in neutrophils and macrophages in WT and PTX3
-/-
mice with BM from WT donor (WT/WT BM and PTX3
-/-
/WT BM), while only in endothelial cells in WT mice with BM from PTX3
-/-
donor (WT/PTX3
-/-
BM). Infiltration of neutrophils and generation of reactive oxygen species (ROS) at ischemic border zones were greater in PTX3
-/-
mice with BM from PTX3
-/-
donor (PTX3
-/-
/PTX3
-/-
BM) than PTX3
-/-
mice with BM from WT donor (PTX3
-/-
/WT BM) (P<0.01 and P<0.01, respectively). Plasma levels and cardiac expressions of IL-6 were higher in PTX3
-/-
mice with BM from PTX3
-/-
donor (PTX3
-/-
/PTX3
-/-
BM) than PTX3
-/-
mice with BM from WT donor (PTX3
-/-
/WT BM) (P<0.05 and P<0.05, respectively). However, no significant differences in infarct size, infiltration of neutrophils, generation of ROS and production of IL-6 were observed between WT and PTX3
-/-
mice with BM from WT donor and between WT and PTX3
-/-
mice with BM from PTX3
-/-
donor. These results indicate that the lack of PTX3 produced from BM-derived cells, but not from cardiac resident cells, contributes to neutrophil infiltration, ROS generation and IL-6 production in response to I/R, resulting in the increment of infarct size.

Conclusion:
PTX3 produced from BM-derived cells plays a crucial role in cardiac protection against myocardial I/R injury.