bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18285: ARI-3037MO, a Novel Niacin Analog, Significantly Improves Plasma Lipid Levels in the Hyperlipidemic Golden Syrian Hamster
Authors: Connolly Beth A , O'Connell Daniel P , LeBlanc Daniel F , Kuang Yu-Lin , Schaefer Ernst J , Lamon-Fava Stefania , Benedict Claude R , Kiritsy Christopher P , Bachovchin William W
Published: April 2024

Introduction:
ARI-3037MO is a once-a-day structural analog of niacin currently in Phase I clinical trials for treatment of dyslipidemia. In preclinical studies in multiple species, ARI-3037MO did not induce cutaneous flushing, an adverse event that is commonplace with existing niacin preparations.

Hypotheses:
We hypothesized that ARI-3037MO would significantly improve the lipoprotein profile of hamsters with diet-induced hyperlipidemia.

Methods:
Golden Syrian hamsters (n=30, 111-120 g, 56-61 days old) were fed a diet consisting of 11.5% corn oil, 11.5% coconut oil, 0.5% cholesterol, and 0.25% deoxycholate and were provided water containing 10% fructose for 20 days. Animals remained on the atherogenic diet and were dosed P.O. with either vehicle (n=12), 1200 mg/kg/day (9.8 mmol/kg/day) niacin (n=9), or 1400 mg/kg/day (5.8 mmol/kg/day) ARI-3037MO (n=9) for 18 days. At the end of the dosing period, hamsters were sacrificed via CO2 asphyxiation, blood was collected via cardiac puncture, and tissues were harvested.

Results:
Compared to vehicle, ARI-3037MO significantly reduced plasma levels of TC (mean±SEM; 857±122 vs. 343±66 mg/dL, -60%, p<0.01), LDL-C (253±24 vs. 114±30 mg/dL, -55%, p<0.001), TG (1065±140 vs. 138±28 mg/dL, -87%, p<0.001), and free fatty acids (FFA) (1.96±0.16 vs. 0.75±0.05 mmol/L, -62%, p<0.001). Niacin, administered at a higher molar dose than ARI-3037MO, showed a less pronounced lipid modulating effect (TC, -39%, p=0.05; LDL-C, -33%, p<0.05; no significant changes in TG or FFA). Compared to vehicle, the increase in plasma HDL-C with ARI-3037MO was borderline significant (139±9 vs. 186±25 mg/dL, +33%, p=0.06); however, fast pressure liquid chromatography analysis of pooled plasma indicated an increase in the HDL-C fraction of the ARI-3037MO treated animals. Also, relative to vehicle, ARI-3037MO significantly increased liver Apo-A1 and ATP-Binding Cassette Transporter (ABC) A1 mRNA levels (+66%, p<0.001 and +55%, p<0.01, respectively).

Conclusions:
Relative to vehicle, ARI-3037MO was more effective than niacin at significantly reducing pro-atherogenic lipoproteins in the hyperlipidemic hamster. In addition, ARI-3037MO increased the proportion of HDL-C, possibly through liver apoAI- and ABCA1-mediated mechanisms.
Abstract 18298: Trafficking-Deficient hERG K+ Channels Linked to Long QT Syndrome are Regulated by a Quality Control Compartment in the ER
Authors: Smith Jennifer L , Reloj Allison R , Nataraj Parvathi , Anderson Corey L , January Craig T , Delisle Brian P
Published: April 2024

The human Ether-a-go-go Related Gene (hERG) encodes the pore-forming voltage-gated K+ channel (Kv) α-subunit that underlies the rapidly-activating delayed-rectifier current in cardiomyocytes. hERG is synthesized in the Endoplasmic Reticulum (ER) as “immature” 135 kDa asparagine-linked (N-linked) glycoprotein & is terminally glycosylated in the Golgi apparatus (Golgi) to form a “mature” 155 kDa glycoprotein. Most hERG missense mutations linked to Long QT syndrome Type 2 (LQT2) reduce terminal glycosylation & functional expression. E-4031 is a class III anti-arrhythmic that binds to hERG & blocks current (IhERG), & can increase terminal glycosylation & functional expression for many “trafficking-deficient” LQT2 mutations (pharmacological correction). Treating HEK293 cells expressing the trafficking-deficient LQT2 mutation G601S-hERG in 10 uM E-4031 (E4) for 6 or 12 hours showed a time-dependent increase in maximal IhERG after drug washout, Western blot analyses showed similar increase in the fractional density (FD) of terminally glycosylated G601S-hERG. Treating cells in 0.2mg/ml cycloheximide (cyclo), that inhibits protein translation, did not alter the E4 induced increase in terminally glycosylated G601S-hERG, suggesting pharmacological correction occurs post-translationally. Immunocytochemistry & colocalization analyses showed that in control conditions G601S-hERG primarily colocalized w/ BAP31, an itinerant ER protein that moves between the peripheral ER and perinuclear ER. G601S-hERG weakly colocalized w/ other ER proteins, like lecithin chaperone calnexin, ERAD complex protein Derlin, or transitional ER marker Sec31. Treating cells in E4 decreased G601S-hERG and BAP31 colocalization after 6 hrs & 12 hr. Treatment with microtubular depolymerizing agent nocodazole (10 uM) for 2 hrs increased G601S-hERG colocalization with BAP31 & caused them to accumulate into peripheral ER compartments. We conclude that in control conditions, G601S-hERG is an itinerant ER protein that moves between the peripheral and perinuclear ER via a microtubule-dependent mechanism, & pharmacological correction with E-4031 prevents this by allowing transport to the Golgi & cell surface membrane.
Abstract 18326: p38MAPK is a Novel Negative Regulator for Smooth Muscle Differentiation
Authors: Long Xiaochun , Cowan Sarah , Miano Joseph
Published: April 2024

p38MAPK belongs to members of the MAPK family which can be activated by various environmental stressors and inflammatory cytokines. While more and more studies have defined the critical roles of p38MAPK in different biological processes involving cell growth, differentiation and apoptosis, its actual contribution to smooth muscle cell (SMC) phenotypic modulation is largely unexplored. Using the mouse complete carotid artery ligation model, we found both total p38 and phosphorylated p38 to be predominantly located in the neointima of the vessel wall where SMCs undergo hyper-proliferation and SMC differentiation is compromised, suggesting a negative regulatory role of p38MAPK in SMC differentiation. To test this hypothesis, we applied siRNA studies in primary human coronary artery SMC (HCASM) cultures and examined SMC contractile gene expression. Depletion of p38MAPK evoked a dramatic increase in SMC contractile gene expression. The stimulatory effect of SMC contractile gene expression upon knockdown of p38MAPK was reproduced in a variety of SMC culture models including human aortic SMCs, rat aortic SMCs, PAC1 cells and primary human myofibroblasts. Consistent with the siRNA studies, cotransfecting p38 with its upstream kinase MKK3 or MMK6 abolished promoter activity of several SMC-restricted genes, while little effect was found with the dominant negative mutants of p38. Furthermore, adenovirus carrying the constitutively active MKK6 completely abrogated TGF-beta1 induced SMC differentiation as assessed by Western blotting and immunfluorescence mirocsopy, indicating that phosphorylated p38 is required for the repressive effect of p38MAPK in SMC differentiation. Interestingly, in HCASMs, we found myocardin-related transcription factor A (MRTFA) was mainly located in the nucleus when the endogenous p38MAPK was knocked down; conversely, over-expression of constitutively active MKK6 was found to shift the majority of MRTFA to the cytoplasm of HCASMs, suggesting that phosphorylated p38MAPK is able to block nuclear import of MRTFA in SMCs. Taken together, our studies revealed an unexpected role for p38MAPK in the negative regulation of SMC differentiation.
Abstract 18327: Early Estrogen Replacement After Ovariectomy Limits Liver DAG and Promotes Insulin Sensitivity in a Manner That Requires Hepatic Estrogen Signaling
Authors: Zhu Lin , McGuinness Owen P , Stafford John M
Published: April 2024

The cardiovascular effects of postmenopausal estrogen replacement have been controversial. Estrogen replacement at the time of menopause may protect from cardiovascular disease, due to improvements in the complications of obesity. We designed studies to define mechanisms by which estrogen replacement may alter the impact of high-fat feeding, when given at the time of surgical menopause by ovariectomy (OVX) in C57/B6 mice. OVX-mice had a 2-fold increase in adiposity after 5 weeks of high-fat diet feeding, compared with sham mice (sham 16.5±1.2% vs. OVX 32.4±3.1% adiposity). The weight gain and increased adiposity were prevented with subcutaneous replacement of estradiol (E2) at the time of OVX (OVX-E2 5.4±0.4% vs OVX 32.4±3.1% adiposity). We defined the impact of OVX and E2 replacement on insulin sensitivity with hyperinsulinemic-euglycemic clamp studies. For OVX mice, insulin sensitivity was reduced 25% compared with sham mice, while OVX-E2 mice had a 2.2-fold increase in insulin sensitivity (sham 694±51; OVX 519±125; OVX-E2 1584.0±197 mg•ml•[kg•min•mU]-1). Compared to OVX, after hyperinsulinemia, in the liver of OVX-E2 mice, we found: 1) increased phosphorylation of ACC (inactive form), increased protein amounts of DGAT 2 (promotes TG synthesis from DAG). This potential increase in fatty-acid oxidation, coupled with increased TG synthesis was associated with reduced liver DAG content in OVX-E2 mice (OVX 4.0±0.7 vs. OVX-E2 1.74±0.53 µg•mg-1), and increased phosphorylation of ser473-AKT (insulin-signaling activated). In order to define the requirement of liver estrogen signaling in the protective effects of E2 replacement, we performed a parallel study with OVX and E2 replacement in mice with liver estrogen receptor alpha knockout (LKO). While E2 replacement reduced adiposity in LKO mice similar to controls, E2 replacement in LKO mice failed to improve whole-body insulin resistance (746±138 mg•ml•[kg•min•mU]-1), and failed to prevent liver DAG accumulation (3.2±1.1 µg•mg-1) compared to OVX mice. This study demonstrates that estrogen replacement at the time of OVX promotes insulin sensitivity by increasing TG synthesis, thereby limiting liver DAG content, and lipotoxicity. This protective effect requires hepatic estrogen signaling.
Abstract 18334: Prolonged Use of Clopidogrel and Risk of Death and Myocardial Infarction 4 Years after Coronary Stenting in Diabetes: the VA DES Study
Authors: Kinlay Scott , Gaziano Michael , Young Melissa , Lawler Elizabeth , Faxon David P
Published: April 2024

Clopidogrel is recommended with aspirin for up to one year after coronary drug-eluting stent (DES) placement but the value beyond this time is controversial. Patients with diabetes mellitus (DM) are at higher risk of cardiovascular events than patients without DM, and may benefit from more prolonged clopidogrel treatment.

Methods:
We assessed all DM patients in the National VA Healthcare System who received a coronary stent from 2002- 2006. Baseline factors and comorbities, pharmacy data, and adverse events during follow-up were collected. We estimated crude and adjusted hazard ratios for prolonged versus 12 or less months of clopidogrel on the risk of death, and death or myocardial infarction (MI), stroke, major bleeding, and repeat revascularization up to 4 years after stenting using Cox proportional hazards. We used a landmark analysis that excluded all events up to 12 months after stenting with DES or bare-metal stents (BMS).

Results:
Of 42,254 patients who received a coronary stent, 13,657 had diabetes on treatment. 2,808 received a DES and 2,782 a BMS. 39% of DES pts and 23% of BMS pts were on clopidogrel >12months. The results of the landmark analysis showed no differences for stroke, major bleeding or repeat revascularization in either group.

Conclusion:
In this large unrestricted veteran population, prolonged clopidogrel use of more than 12 months in patients with diabetes receiving coronary stenting associated with lower risk of death and death and MI particularly after DES. These data suggest that prolonged use more than one year may be of benefit in DM patients receiving a DES.
Figure:
Risk of Outcomes After the 12 Month Landmark for Prolonged vs 12 or Less Months Clopidogrel Use
†
Adjusted for age, diabetes, ACS during index admission, hypertension, PVD, heart failure, warfarin within 7-days of index discharge, year of stent, occurrence of another outcome within 12-months of index procedure
Abstract 18366: Cutoff of 1.0 cm
2
For Severe Aortic Stenosis? A Case for Redefining this Cutoff Based on Eccentricity of LVOT Geometry
Authors: Mehrotra Praveen , Mak Gary , Jansen Katrijn , Zeng Xin , Flynn Aidan , Passeri Jon , Hung Judy
Published: April 2024

Background:
Current guidelines define severe aortic stenosis (AS) as aortic valve area (AVA) of <1.0 cm
2
. This cutoff is based on the assumption of a circular left ventricular outflow tract (LVOT) cross sectional area (CSA) for the continuity equation (CE). However, patients with AS have chronic pressure load and may have remodeling of the LVOT geometry from circular to elliptical. An elliptical LVOT with a smaller dimension in the anterior-posterior plane would result in a lower calculated AVA. Many patients have discrepant indices of severe AS where AVA by CE is severe (<1.0 cm
2
) yet peak velocity (V2) and mean gradient (MG) are in the moderate or mild range. We hypothesized that discordance of AS severity by AVA versus V2 or MG may be due to inaccurate circular LVOT CSA assumption in patients with AS where chronic pressure load results in an elliptical LVOT geometry.

Methods:
We assessed LVOT geometry by direct planimetry using 3D transesophageal echo (TEE) and calculated an eccentricity index (ratio of two orthogonal linear measurements and also ratio of CSA direct planimetry/CSA by circular LVOT assumption) in 54 patients with severe AS undergoing TTE and TEE within one month of each other. We compared AVA by elliptical LVOT (AVA
LVOT
) to conventional circular LVOT CE. We then applied a correction factor for AVA underestimation based on the measured LVOT eccentricity index in a separate cohort of 49 patients with discrepant AS indices (AVA <1.0 cm
2
but MG <30 mmHg).

Results:
LVOT shape was elliptical in 53 of 54 (98%) patients with a mean eccentricity index of 0.88 ± 0.06 by 3D TEE. The mean LVOT CSA assuming circular geometry underestimated the true CSA determined by direct planimetry by approximately 14% (3.25 vs. 3.71 cm
2
, p<0.001). AVA
LVOT
was higher than AVA by conventional CE (0.71 vs. 0.61 cm
2
, p=0.003). After multiplying the LVOT CSA by correction factor of 1.14 (to account for 14% underestimation of LVOT area) in 49 patients with discrepant severe AS (mean AVA, V2 and MG of 0.88 cm
2
, 3.2 m/s and 23 mmHg, respectively), the mean AVA increased to 1.0 cm
2
.

Conclusions:
The LVOT geometry in patients with AS is predominantly elliptical with an eccentricity index of 0.88. The cutoff for severe AS valve area by conventional CE should be 0.8 cm
2
to adjust for elliptical LVOT geometry.
Abstract 18373: Validating ARMYDA-PRO/BLEEDS: a Therapeutic Window in Platelet Reactivity for Patients Undergoing Elective Percutaneous Coronary Intervention
Authors: Mangiacapra Fabio , Patti Giuseppe , Peace Aaron J , Gatto Laura , De Bruyne Bernard , Barbato Emanuele , Wijns William , Di Sciascio Germano
Published: April 2024

Aims.
Platelet reactivity has been shown to be an important determinant of both thrombotic and bleeding events in patients undergoing percutaneous coronary intervention (PCI). Recently, the ARMYDA-PRO study has shown that a threshold of P2Y12 reaction units (PRU) >240, measured with the VerifyNow assay, is associated with increased risk for thrombotic events at 30 days, while the ARMYDA-BLEEDS study has shown that a threshold of PRU <189 is associated with a increased risk of bleeding events. We aimed at validating the aforementioned PRU thresholds in an independent population of 640 patients taking clopidogrel and aspirin and undergoing elective PCI.

Methods and results.
Platelet reactivity was measured immediately before the procedure with the VerifyNow P2Y12 assay. Primary end point was the 30-day incidence of net adverse clinical events (NACE), defined as the occurrence of major adverse cardiac events (MACE) or major bleeding/significant entry site complications, in relation to the PRU distribution. Patients were divided in 3 groups on the basis of PRU values: low-PRU (240). At 30-day follow-up, patients in the low-, medium- and high-PRU groups presented an incidence of MACE of 4.6%, 5.0% and 14.6%, respectively (p for trend <0.001), and an incidence of major bleeding or significant entry site complications of 8.8%, 2.2% and 1.5%, respectively (p for trend <0.001). The incidence of NACE was 13.4% in the low-PRU group, 7.2% in the medium-PRU group (p=0.040 vs. low-PRU group), and 15.1% in the high-PRU group (p=0.016 vs. medium-PRU group). At multivariate analysis, a pre-PCI PRU value in the low- or high-PRU group was an independent predictor of increased occurrence of NACE at 30 days.

Conclusions.
A therapeutic window in platelet reactivity can be identified using validated thresholds that define a group of patients at lower risk for both thrombotic and bleeding events. Tailoring antiplatelet therapy in order to obtain platelet reactivity levels within this range could result in a net lowering of adverse events after PCI.
Abstract 18393: Survival after Post-Arrest Therapeutic Hypothermia: Secondary Analysis of The Strategies for Post-Arrest Care (SPARC) Stepped-Wedge Trial
Authors: Morrison Laurie J , Dorian Paul , Dainty Katie N , Brooks Steven C , Thorpe Kevin , Zhan Cathy , Scales Damon C
Published: April 2024

Introduction:
Current guidelines recommend early institution of therapeutic hypothermia (TH) in survivors of out of hospital cardiac arrest (OHCA) regardless of initial rhythm. This was based on trials employing concurrent or historical controls since the original randomized trials restricted the analysis to OHCA presenting with ventricular fibrillation (VF) or ventricular tachycardia (VT). We sought to measure the survival of patients after application of these recommended guidelines during a stepped-wedge randomized trial that compared KT strategies to improve TH in a network of 36 hospitals.

Methods:
After a baseline period of 12 months, 4 wedges of 8 to 10 hospitals were randomized to receive 12 months of passive KT followed by 4 months of active KT. We measured the secondary outcome of survival to hospital discharge in patients that had received therapeutic hypothermia. We used multilevel modeling to calculate odds ratios (OR) for survival after adjusting for time and the Utstein factors.

Results:
During the study, 4,742 OHCA patients were transported to hospital; 1,963 (39%) achieved ROSC and 1,104 (56%) of these were eligible for TH. 638 (58%) of the eligible patients had cooling initiated and 223 (35%) were cooled to 34 degrees within 6 hours. No survival advantage of cooling was observed for all eligible patients (cooling ever vs never, OR adjusted for time only 1.04, 95% CI 0.74-1.47; OR adjusted for prehospital variables (Utstein) 0.80, 95% CI 0.53-1.20). Similar findings were observed when the analyses were restricted to the 516 eligible patients that presented with VF/VT (OR adjusted for time only 0.74, 95% CI 0.44-1.24; OR adjusted for Utstein variables 0.84, 95% CI 0.52-1.37).

Conclusions:
During a stepped wedge knowledge translation randomized trial, we were unable to confirm the survival advantage associated with cooling after OHCA.
Abstract 18409: Long-Term Mortality Following On- and Off-Pump Coronary Artery Bypass Graft Surgery
Authors: Wu Chuntao , Camacho Fabian , Hannan Edward L
Published: April 2024

Background:
There are limited data on the relative survival following on- and off-pump coronary artery bypass graft (CABG) surgery during follow-up periods longer than 5 years.

Objectives:
To examine the difference in 7-year mortality after on- and off-pump isolated CABG surgery.

Methods:
A total of 5,940 on-pump and 2,640 off-pump isolated CABG patients discharged between October 1 and December 31, 2000 were identified using the New York State's Cardiac Surgery Reporting System. The patients' vital statuses through the end of 2007 were determined by matching to the National Death Index. We fit a logistic regression model that used the baseline patient characteristics to predict the probability (propensity) of receiving off-pump procedure. Using a 1:1 ratio, we then matched on- and off-pump CABG patients based on the propensity of receiving off-pump procedure. We compared the Kaplan-Meier survival curves for on- and off-pump CABG using the matched data, and fit a Cox proportional hazards model to obtain the hazard ratio for death for off-pump in comparison to on-pump procedures. We also conducted subgroup analysis and tested the significances of interactions between treatment (on- or off-pump) and a number of baseline risk factors.

Results:
A total of 2,634 off-pump patients were matched to on-pump patients. During the follow-up until the end of 2007, 727 on-pump and 780 off-pump patients died. The respective 7-year survival rates for off- and on-pump were 71.3% and 73.1% (P=0.09), and the hazard ratio for death (off- vs. on-pump) was 1.11 (95% confidence interval: 1.00 to 1.24, P=0.06). In addition, there were no differences in 7-year mortality between off- and on-pump CABG surgery in the subgroups of patients defined by age, sex, the number of diseased coronary arteries, left main coronary disease, ejection fraction, history of myocardial infarction, and comorbidities such as cerebrovascular disease, peripheral vascular disease, congestive heart failure, and diabetes.

Conclusions:
There was no difference in long-term morality between on- and off-pump CABG surgery.
Abstract 189: Potential Negative Effects of Epinephrine on Carotid Blood Flow and ETCO
2
During Active Compression-Decompression CPR Utilizing an Impedance Threshold Device
Authors: Burnett Aaron M , Salzman Joshua G , Segal Nicolas , Frascone Ralph J , McKnite Scott
Published: April 2024

Objectives:
This study examined the effects of IV epinephrine administration on carotid blood flow and end tidal CO
2
(ETCO2) production of a swine undergoing active compression-decompression CPR with an impedance threshold device (ACD-CPR + ITD).

Methods:
Six female swine (32±1Kg) were anesthetized, intubated and mechanically ventilated. Intracranial, thoracic aorta and right atrial pressures were recorded via indwelling catheters. Carotid blood flow (CBF) was recorded via Doppler. ETC02, Sp02 and EKG were monitored. V-fib was induced and went untreated for 6 minutes. 3 minutes each of standard CPR (STD), STD-CPR+ITD and ACD-CPR+ITD was preformed. At minute 9 of the resuscitation, 40µg/Kg of IV Epinephrine was administered and ACD-CPR+ITD was continued for 1 minute. Statistical analysis was performed with a Paired t test.

Results:
Aortic pressure and calculated cerebral and carotid perfusion pressures increased from STD < STD+ITD < ACD-CPR < ACD-CPR+ITD (p=<.001). Epinepherine administered during ACD-CPR+ITD signficantly increased mean aortic (29±5vs42±12, p=0.01) cerebral (12±5 vs 22±10, p=0.01), and coronary perfusion pressures (8±7 vs 17±4, p=0.02); however, mean CBF and ETCO
2
decreased (respectively 29±15 vs 14±7.0, p=0.03; 20±7 vs 18±6, p=0.04).

Conclusions:
The administration of epinepherine during ACD-CPR+ITD signficantly increased markers of macrocirculation, while significantly decreasing ETCO
2
, a proxy for organ perfusion. While the calculated cerebral perfusion pressures increased, the directly measured CBF decreased. This calls into question the ability of calculated perfusion pressures to accurately reflect blood flow and oxygen delivery to end organs.
Abstract 190: Potential Mechanism for Improved Neurological Survival After Cardiac Arrest After Treatment with Active Compression-Decompression Cardiopulmonary Resuscitation Combined with Augmentation of Negative Intrathoracic Pressure
Authors: Metzger Anja , McKnite Scott , Yannopoulos Demetris , Lurie Keith
Published: April 2024

Objective:
Active compression decompression (ACD) CPR with augmentation of negative intrathoracic pressure using an impedance threshold device (ITD) has been previously shown to enhance refilling of the heart and improve neurologically intact survival when compared with standard (S) CPR. To study the neuroprotective effects of ACD CPR + ITD, we tested the hypothesis that this new approach improves brain perfusion by reducing intracranial pressure (ICP) during the decompression phase of CPR, thereby lowering resistance to forward flow.

Methods:
Following 8.5 minutes of untreated ventricular fibrillation in 9 anesthetized (100 ug/kg/min propofol) female farm pigs (29.2 ± 1.3 kg), ACD CPR + ITD or SCPR was initiated in random order for 5 minutes followed by 5 additional minutes of CPR with the alternate method.

Results:
Cerebral perfusion pressures (mmHg) were improved with ACD CPR + ITD (21.9 ± 1.2) versus SCPR (8.9 ± 0.8, p<0.0001). The effects of the CPR on the absolute ICP values and the rate of ICP change during the decompression phase are shown in Table 1. Mean carotid blood flow (ml/min) in the ACD CPR + ITD group was also higher (12.0 ± 2.2 versus 8.0 ± 1.5, p=0.008).

Conclusions:
The increase in cerebral perfusion pressures and carotid blood flow observed with ACD CPR + ITD was associated with lower diastolic ICP values and a more rapid decrease in ICP during the decompression phase of CPR compared with SCPR. These findings support a dual mechanism for neuroprotection with ACD CPR + ITD: increased forward brain flow and decreased intracerebral resistance, allowing more time for cerebral perfusion.
Abstract 191: Mechanical Postconditioning with Chest Compression Pauses at the Initiation of CPR Prevents Neurological Dysfunction at 24 Hours in Pigs After 15 Minutes of Untreated Ventricular Fibrillation
Authors: Yannopoulos Demetris , Segal Nicolas , Caldwell Emily , McKnite Scott , Garcia Santiago , Becker Lance , Aufderheide Tom P , Lurie Keith G
Published: April 2024

Background:
Mechanical post conditioning (PC) with intermittent initiation of flow (“stutter” reperfusion) has been shown to decrease infarction size in ST elevation infarction and decrease ischemic stroke size in animals. We hypothesize that when using sodium nitroprusside-enhanced cardiopulmonary resuscitation (SNPeCPR) mechanical post conditioning with stutter CPR (20-second CPR pauses), begun immediately on SNPeCPR initiation, will improve 24-hour cerebral function compared to 12 hours of therapeutic hypothermia (TH) post resuscitation.

Methods:
14 anesthetized and intubated pigs underwent 15 minutes of untreated VF followed by 5 minutes of SNPeCPR comprised of active compression decompression CPR plus an inspiratory impedance threshold device combined with abdominal binding. 2 mg of sodium nitroprusside (SNP) were given IV at minute 1 and 1 mg at minute 3 of CPR. All animals received in addition 0.5 mg of epinephrine at minute 5, 30 seconds before the first defibrillation attempt. Six animals (PC group), were treated with 40 seconds of SNPeCPR and the first dose of SNP, then followed by 20-second pauses (cessation of perfusion) and 20 seconds of SNPeCPR with a total of 4 cycles for up to 3 minutes. After that, animals had uninterrupted SNPeCPR until defibrillation at minute 5. The other 8 animals (TH group) had SNPeCPR for a total of 5 minutes without interruptions. The TH group received 12 hours of TH (core temp=33°C). The PC group received no TH. Cerebral performance category (CPC) was scored at 24 hours by a veterinarian blinded to the treatment group.

Results:
During SNPeCPR, there were no hemodynamic differences except for a significantly higher aortic pressure response to epinephrine at min 5 (SBP/DBP; 148±12/78±7 in the PC group versus 110±9/62±5 mmHg in the TH group, p<0.05). Both groups had 100% return of spontaneous circulation rates and 24-hour survival. CPC was significantly lower in the PC group (1±0 = normal) versus the TH group (2.4±0.8 = mild to moderate disability), p<0.01.

Conclusion:
In this porcine model of cardiac arrest and SNPeCPR, mechanical PC with pauses in compressions at the initiation of the resuscitation efforts prevented 24-hour neurological dysfunction after 15 minutes of untreated VF and was superior to TH.
Abstract 194: A Combination of Metabolic Strategies and Cardiopulmonary Bypass Allows Improved Short-Term Resuscitation from Prolonged Lethal Cardiac Arrest
Authors: Boller Manuel , Jung Sung K , Odegaard Silje , Katz Joseph M , Muehlmatt Amy , Becker Lance B
Published: April 2024

Background:
The metabolic or late phase of cardiac arrest is highly lethal. Emergency cardiopulmonary bypass (ECPB) can resuscitate many patients even after prolonged cardiac arrest and provides immediate vascular access for correction of metabolic derangement during the reperfusion process. We developed a rodent model of ECPB resuscitation which showed the superiority of ECPB over conventional CPR, especially when combined with hypothermia. For this study we examined a metabolic strategy against ischemia/reperfusion (MS-I/R) injury that included: leukoreduction, low Ca2+, Mg, buffered pH, red blood cells and a colloid. We tested whether ECPB plus MS-I/R and/or hypothermia reduced reperfusion injury and showed better outcomes compared to our standard ECPB reperfusate.

Methods:
Using a 2x2 factorial design we tested ECPB with (a) MS-I/R versus standard solution, and (b) hypothermia versus normothermia in our rat model (n=38). The four reperfusion strategies included: (1) MS-I/R reperfusate plus hypothermia, (2) MS-I/R with normothermia, (3) standard plasmalyte reperfusate plus hypothermia, or (4) plasmalyte plus normothermia. Animals underwent 12 min of untreated asphyxial arrest and were resuscitated with ECPB with one of the strategies for 30 min. Thereafter ECPB was stopped and ICU-like support was provided for 3 hours, while hemodynamic, perfusion and other metrics were serially measured.

Results:
All rats achieved ROSC with ECPB. Significant differences emerged after 3 hrs, the best outcomes were in animals with MS-I/R perfusate plus hypothermia (lactate: 1.0±0.3 mmol/L; MAP: 84±12 mm Hg, seizures: 0/10), while the worst outcomes were with standard plasmalyte reperfusate and normothermia (lactate: 8.8±4.3 mmol/L, MAP: 36±13 mm Hg, seizures: 7/10, P<0.001). The outcomes of the other two groups (hypothermia only; MS-I/R reperfusate only) were intermediate. Both hypothermia and MS-I/R reperfusate independently improved outcome.

Conclusions:
While most human ECPB is applied without a MS-I/R reperfusate, we observed that in rodents the addition of a MS-I/R reperfusate plus hypothermia to ECPB resuscitation resulted in short-term benefit after prolonged arrest. Future long-term and translational survival studies are warranted.
Abstract 203: Insulin Alleviates Cardiac Dysfunction After Mechanical Trauma by Inhibiting TNF-α--Mediated ROS Generation via the PI3K/Akt Pathway
Authors: Li Jia , Liu Yi , Feng Ya F , Wang De X , Liu Wen C , Cai Xiao Q , Gao Feng
Published: April 2024

Background:
Intensive insulin treatment protects injured myocardium and reduces mortality in surgical critically ill patients but the mechanisms involved remain unclear. This study was designed to investigate whether insulin may alleviate cardiac dysfunction after mechanical trauma (MT) and the underlying mechanisms.

Methods and Results:
Male adult rats were subjected to non-lethal MT (Noble-Collip drum trauma, 35 r/m, 200 r) and randomly received different treatments. Non-lethal MT increased cardiac TNF-α (13.8±2.4
vs
. 5.7±2.7 pg/mg protein,
P
<0.01) and reactive oxygen species (ROS) production 0.5 h after trauma, resulted in immediate cardiac dysfunction 0.5 h post-trauma with subsequent myocardial injury as evidenced by increased serum troponin I (cTnI) and significant cardiomyocyte apoptosis 2 h post-trauma (n=6, all
P
<0.01). Administration of GIK (250 g/L glucose, 60 U/L insulin, 80 mmol/L potassium) markedly inhibited TNF-α and ROS overproduction together with reduced myocardial injury and alleviated cardiac dysfunction at 1 h, 2 h, 3 h and 4 h after trauma. However, MT had no effect on blood glucose level compared with the sham-operated group and there was no difference in blood glucose between the GIK-treated and vehicle-treated rats during the 4-h experiment (n=6,
P
>0.05). Blockade of TNF-α with etanercept (a fusion protein blocker of TNF-α, 16 mg/kg,
i.p
.) attenuated ROS generation and preserved cardiac function after MT (n=6, both
P
<0.01). Furthermore, combining GIK and etanercept treatment did not exert any additive effects on these two parameters. In addition, pretreatment with Tempol (30 mg/kg,
i.v
.), a ROS scavenger, enhanced cardiac functional recovery after MT. Interestingly, cotreatment with the PI3K inhibitor wortmannin completely abolished the anti-TNF-α, anti-oxidative and cardioprotective effects afforded by GIK.

Conclusions:
These results demonstrated for the first time that insulin alleviates myocardial dysfunction after trauma by inhibiting TNF-α-mediated ROS generation via the PI3K/Akt pathway. The anti-inflammatory and anti-oxidative properties elicited by insulin may prevent cardiac dysfunction and improve outcomes in surgical critically ill patients.
Abstract 206: Distribution of ETCO
2
Values in Out-of-Hospital Cardiac Arrest Patients
Authors: Idris Ahamed H , Babaeizadeh Saeed , Daya Mohamud , Edelson Dana , Firoozabadi Reza , Helfenbein Eric , Zhou Sophia
Published: April 2024

Background
The American Heart Association 2010 guidelines recommend that capnography be used to verify tracheal tube placement and monitor CPR quality as well as detect ROSC during resuscitation. Capnography has been rapidly adopted by EMS in out-of-hospital CPR. Though capnography has been well understood in hospital patient care, the EtCO2 distribution in the population of interest has not been well studied.

Objective
Determine the distribution of EtCO2 levels during CPR in out-of-hospital cardiac arrest (OHCA) patients.

Methods
Recordings from 107 OHCA patients with capnogram waveforms were collected from 2008 to 2010 in two EMS agencies based in Oregon and Texas. Experts manually annotated all the recordings for breathing cycles and EtCO2 values. The histogram was generated using only the segments with active chest compression (total of 33 hours, 19,444 breath cycles). Each patient had chest compressions for an average of 19.8 ± 14.2 minutes. Chest compressions had an average rate of 108 ± 12 compressions-per-minute and average depth of 3.7 ± 0.7 centimeters.

Results
The figure below shows the distribution of the EtCO2 values in the OHCA patients. EtCO2 values varied from 0.5 to 99 mmHg, had a median value of 26 mmHg, and had an average value of 29 ± 18 mmHg.

Conclusion
In OHCA populations, EtCO2 values during CPR vary widely. EtCO2 values below 10 mmHg occurred in 13% of breaths and almost 60% of values were below 30 mmHg. Recommendations that make use of EtCO2 values in OHCA should consider this distribution.
Abstract 210: Facilitators to Learning Cardiopulmonary Resuscitation in High-Risk Neighborhoods
Authors: Sasson Comilla , Moreno Emily , King Renee , Colbert Susan , Bond-Zielinski Cindy , Rabe Marilyn , Sayre Michael , Heisler Michele
Published: April 2024

Background:
Previous research in Columbus, Ohio has identified three high-risk neighborhoods, comprised primarily of African-American residents and with a median household income of <$30,000, where the incidence of OHCA is high and bystander cardiopulmonary (CPR) is low.

Objectives:
To identify 1) facilitators to learning CPR and 2) perceived attributes of people most likely to learn CPR in high-risk neighborhoods.

Methods:
Five focus groups, lasting 90-120 minutes, were conducted in January-February 2011 in the three identified neighborhoods in Columbus. We utilized purposeful and snowball sampling to recruit 42 residents to participate. A qualitative study design using grounded theory was used to develop codes, categories and themes in an iterative process. The focus groups were audiotaped and transcribed verbatim. Three reviewers independently read through each transcript and discussed major themes to develop a conceptual framework.

Results:
Three main thematic areas were identified as facilitators for residents to learn CPR: family/self-preservation, emotional factors and economic incentives (Table 1). The importance of showing how learning CPR might save the lives of family members was the most consistent theme. Participants felt that tying CPR instruction to basic first aid, especially in the setting of traumatic arrest was very important due to the high rates of interpersonal violence in the community. Obtaining academic credit and job skills through CPR training were also important. The participants perceived certain attributes of people likely to learn CPR: self-motivated, concerned and people with prior medical training.

Conclusion:
Linking CPR instruction to saving the lives of family members and saving the life of a violent crime victim were consistent themes. Future work will be conducted with residents from these neighborhoods to implement and measure the success of a community-based approach to CPR training based on this research.
Abstract 214: Which American Heart Association Guidelines---2005 or 2010---Are Associated with Better Skills Retention?
Authors: Miotto Heberth C , Ribeiro Cristiano V , Silva Felipe R , Miotto Isadora Z , Barroso Pedro M , Oliveira Raphael R , Goulart Eugenio M , Moreira Maria C
Published: April 2024

Background:
The major difference between 2005 and 2010 statements for CPR is simplification of the ABCD primary sequence (CAB instead of ABC). Little is known about which one is associated with better skills retention.

Objective:
To determine which guidelines is associated with better skills retention we conducted a randomized controlled trial comparing guideline 2005 and 2010.

Methods:
We selected paramedics to participate voluntarily in the study and divided them into two groups: Group A received CPR training based in 2005 AHA guidelines, and group B received CPR training based in 2010 AHA guidelines. All training sessions occurred in the same way using manikins (Brad - Laerdal Company ®) after demonstration of the CPR sequence (CAB or ABC). Just after and after 30 days they were evaluated using Resuscianne Skillmeter®. At the same time they were recorded for posterior scoring by experienced BLS instructors using BLS/ACLS check list. Correct ventilations, tidal volume, minute ventilations, compression depth, compressions per minute, compression rate, wrong hand position compressions, too shallow compressions and incomplete released compressions were compared. Continuous variables were analyzed by the t-student test, and when necessary, the non-parametric Kruskall-Wallis test and the chi square for comparison between proportions.

Results:
Group A (41 paramedics) and B (23 paramedics) were similar (age, gender, body mass index, past trainings and antidepressant or sedative drugs use). Tidal volume and minute ventilation were not different in both groups (p>0.05) but, number of correct ventilation were better in group A after 30 days (p=0.002). Compression depth was better in group B immediately and 30 days after (p=0.022 and p=0.04 respectively). Compression rate, wrong hand position compressions, too shallow compressions and incomplete released compressions was similar in both groups (p>0.05). Practical video scored evaluation were similar in both groups (p>0.05).

Conclusions:
In 30 days providers trained with 2010 AHA guidelines was associated with better CPR quality based in the maintenance of good compression depth.
Abstract 24: Postresuscitation Care Practices Following Cardiac Arrest at 6 Regional Interventional Cardiology Centers in the United States, 2007-2011
Authors: Seder David , Mooney Michael , Patel Nainesh , McPherson John , McMullen John , Kern Karl B , Unger Barb , Browning J , Nanda S , Hacobian Melkon , Kelley M B , Nielsen Niklas
Published: April 2024

Background:
We characterized post-resuscitation care practices in cardiac arrest (CA) survivors at six regional PCI centers in the United States.

Methods:
Demographics, hospital course, and treatments of 663 cardiac arrest survivors were retrospectively and prospectively entered into a secure, web-based registry (INTCAR). Interhospital variability was evaluated, and group practices compared to AHA guidelines.

Results:
Mean age was 61 (+14.9) years, 69.2% male, 58.8% VT/VF, 23.5 (+16.3) minutes from arrest to return of spontaneous circulation (ROSC), 31.1% had shock and 26% STEMI at admission. 50% patients were received in transfer, at estimated mean distance of 37.2 miles and 72.4 (+26.6) minutes from initial ED presentation to destination. Overall, 38.6% underwent urgent cardiac catheterization and 20.2% urgent PCI. 98% patients received therapeutic hypothermia (TH), using a surface cooling device (98.6%), cold fluids (18%), ice packs (29.7%), or an intravascular cooling device (1.2%). 74.9% patients received neuromuscular blockade during hypothermia. Mean time from ROSC to initiation of TH was 178 (+142) minutes, and ROSC to target temperature 375 (+197) minutes. The highest volume center had shorter time from ROSC to onset of therapeutic hypothermia (97+87 vs 178+142 minutes, P<0.001) and target temperature (314+346 vs. 375+197 minutes, P<0.001) than the group mean. 15.5% patients underwent MRI, 41.7% head CT, 33.6% continuous EEG monitoring, 16.5% IABP, and 9.5% AICD placement. Urgent coronary angiography at admission varied from 15-58%; this and other differences in treatment were incompletely explained by case mix (% STEMI admissions).

Conclusions:
Standard post-resuscitation care practices approximated AHA guidelines for comprehensive cardiac arrest centers, but with substantial variability of practice among institutions. Where such variability exists, such as the utilization of urgent coronary angiography and revascularization in unresponsive patients at the time of hospital admission, future research should scientifically define best practices.
Abstract 248: Utility of Central Telemetry Monitoring in 2011
Authors: Rehman Shuja ur , Kovacs Richard J
Published: April 2024

Introduction:
ECG monitoring via central telemetry (TECG) is commonly used in modern hospitals. Guidelines for the application of TECG are infrequently updated, and the value of TECG in an era of concern over escalating costs is not known. Our institution is critically examining the role of TECG in overall patient safety and needed baseline data on the outcomes of patients undergoing TECG.

Objective:
Describe the frequency of clinically important events in patients undergoing TECG.

Methods:
During a 3 month period in 2011, 11,520 patient-days of telemetry were surveyed in a large urban multihospital network with central telemetry staffed by trained technicians. Those patients that required a call from a telemetry technician to a nurse and subsequent intervention were included in the study. Subsequent interventions included additional diagnostic testing, drug administration, and transfer to a higher acuity of care, rapid response team intervention or code 99.

Results:
3 months of TECG monitoring yielded a total of 280 telemetric events and 62 (22.1%) required intervention. The most common arrhythmias requiring intervention were atrial fibrillation (N=27), ventricular tachycardia (N =7) and supra ventricular tachycardia (N=5) (figure 1). One case of Torsade de Pointes was detected. The most common interventions were drug administration (N=26), additional diagnostic testing ordered (N=36) and code 99, transfer to higher acuity of care or rapid response team intervention (N=11).

Conclusion:
Our results suggest that central telemetry monitoring in a modern hospital results in a substantial number of interventions in response to telemetry findings. We intend to use these data in further studies assessing the utility of central telemetry compared to local monitoring techniques.
Abstract 254: Comparison of Cold Crystalloid and Colloid Infusions for Induction of Therapeutic Hypothermia in a Porcine Model of Cardiac Arrest
Authors: Truhlar Anatolij , Skulec Roman , Turek Zdenek , Parizkova Renata , Cerny Vladimir
Published: April 2024

Introduction:
Cold crystalloids have been used for induction of therapeutic hypothermia after cardiac arrest but so far the effectiveness of cold colloids has not been evaluated. This prospective study investigates the cooling effect of rapid intravenous infusion of cold crystalloid compared to colloid in a porcine model of ventricular fibrillation (VF).

Methods:
VF was electrically induced in twenty-two anesthetized domestic pigs (33 ± 2 kg). Defibrillation was attempted after 15 min CPR using the AutoPulse (Zoll Medical, USA) and artificial ventilation. After spontaneous circulation was restored, the animals were randomized to receive either 1500 mL of 1°C cold Voluven [6% hydroxyethyl starch 130/0.4 in 0.9% NaCl] within 25 min using a Zoll Power Infuser (group A; n = 9), or 1500 mL of 1°C cold normal saline (group B; n = 9), or no infusion (group C; n = 4). The animals were observed for 90 min following infusion. Cerebral, rectal, intramuscular, pulmonary artery, and subcutaneous fat body temperatures (BT) were continuously recorded using GES 130 temperature probes and GMH 3250 digital thermometers with logger function (Greisinger Electronic, Germany). Data were analyzed with JMP 3.2 software (SAS Institute, USA) and are expressed as a mean ± SD.
P
< 0.05 was considered statistically significant.

Results:
45.6 ± 2.7 mL·kg
-1
of cold colloid was infused in group A, and 46.8 ± 3.1 mL·kg
-1
of crystalloid in group B. The animals treated with cold fluids achieved a significant decrease of BT in all measurement sites while there was a spontaneous increase in group C. At the time of finishing infusion there was a greater decrease in cerebral and pulmonary artery temperatures in group B compared to group A (-1.7 ± 0.4 vs. -1.1 ± 0.3 °C,
P
< 0.05, and -2.1 ± 0.3 vs. -1.6 ± 0.2 °C,
P
< 0.05 respectively). Area under the curve (AUC) analysis of the decrease in intra-cerebral BT revealed a more vigorous cooling effect in group B compared to A (-91 ± 30 vs. -62 ± 32 °C·min,
P
= 0.06). There was also a higher calculated amount of absorbed heat for crystalloids compared to colloids (33.9 ± 5.7 vs. 26.6 ± 3.4 cal,
P
< 0.05).

Conclusion:
Cold crystalloid infusions resulted in a more intense cooling effect than colloid infusions of the same temperature and infusion rate in this porcine model of cardiac arrest.
Abstract 255: Therapeutic Hypothermia Ameliorates Sepsis-Induced Myocardial Mitochondrial Dysfunction
Authors: Hsu Chiung-Yuan , Huang Chien-Hua , Tsai Min-Shan , Chen Huei-Wen , Chen Wen-Jone
Published: April 2024

Introduction:
Mitochondrial dysfunction play an important roles during the sepsis induce organ failure. Therapeutic hypothermia can protect mitochondrial dysfunction during injury. How the therapeutic hypothermia acts on septic myocardial mitochondria is still not well explored.

Hypothesis:
Therapeutic hypothermia is beneficial sepsis induced myocardial mitochondrial dysfunction and survival.

Methods:
Sepsis was induced in 10-12 week specific-pathogen-free bred male adult Sprague-Dawley rats by cecal ligation and tube insertion. Rats were randomized into controlled normothermia (36-37.5°C) or therapeutic hypothermia (32-34°C) at sepsis induced 6 hours later. The animal heart was harvested at 1 hour after temperature control and mitochondrial was isolated by differential centrifugation.

Results:
Therapeutic Hypothermia group (n=18) can significantly improve 72 hours survival than the Normothermia group (n=20, p= 0.0031< 0.05). Mitochondrial membrane potential has trend to deteriorat in sepsis (n=13) compared to Sham.( n=18, p=0.062 >0.05). Temperature management did not maintained the membrane potential (Normothermia n= 7, Hypothermia n=5, sepsis vs. normothermia p= 0.98; sepsis vs. hypothermia p=0.88). Myocardial mitochondria oxidative phosphorylation complexes activity including Complex I+III, Complex II+III and Complex IV were worse in sepsis (n=9) compared to Sham (n=14) group. Temperature control can significantly improved the activity either in therapeutic hypothermia ( n=4) and normothermia groups (n=6) except Complex I+II in therapeutic hypothermia group. (Figure)

Conclusion:
Therapeutic hypothermia preserves mitochondrial oxidative phosphorylation complexes activity in sepsis myocardium and indeed benefit for sepsis prognosis.