bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract P84: The Outcome of Cardiac Arrest the Years Before and After Introduction of Lucas in the Ambulances
Authors: Olsson Paul , Steen S , Kongstad P , Sjöberg T
Published: July 2021

Purpose:
Evaluate the outcome of OHCA (Out of Hospital Cardiac Arrest) in the ambulance station of Lund before and after the introduction of LUCAS
™
in the prehospital setting.

Material and method:
The district area is 767 km
2
and has a population of 186 000 inhabitants. LUCAS was introduced in 2002 and has gradually been the method of choice for CPR. From a database including all pre-hospital missions, the OHCA cases with resuscitation attempt were retrospectively collected for a period of 7 years (2000 –2006). Period I includes years 2000 –2002 (n=85) and is regarded as a period without LUCAS-CPR. Period II (n=187) including years 2003–2006 is regarded as a period with LUCAS-CPR. In Period I, 11% of the OHCA patients admitted to the emergency department received LUCAS-CPR and in Period II it was 85%.

Result:
The mean incidence of OHCA per 10.000 inhabitants was 6.7 during Period I and 6.8 during Period II. Compared with Period I, the number of patients with resuscitation attempt increased with 68% (from 28.3/year to 46.8/year) and patients admitted to the emergency department increased with 63% (from 14/year to 22.5/year) during Period II. The number of patients surviving >30 days increased by 77%, from 3.0 per year (Period I) to 5.3 per year (Period II). If the OHCA took place more than 10 km from the hospital no patient survived >30 days during Period I whereas 9 patients survived >30 days during Period II.

Conclusion:
LUCAS markedly enhances the number of CPR treatments and makes it possible to bring victims to the hospital with vital circulation even if the distance to hospital is over 10 km. The introduction of LUCAS, improved education, changes of CPR-algorithm, in-hospital handling (body cooling) and in some cases causal treatment (PCI, bypass surgery) increase the >30 day survival by 77%.
Abstract P94: Pre-hospital Care of Patients with St-elevation Myocardial Infarction in Two Different European Regions: Data from Two Regional, Pre-hospital Registries, Concerning Myocardial Infarction in Ile-de-france and Andalusia
Authors: Bataille Sophie , Ozguler Anna , Ortiz Fernando Rosell , Perea-Milla Emilio , del Aguila Jose Javier Garcia , Govantes Luis Olavarria , Lambert Yves , Baer Michel
Published: July 2021

The European HESCULAEP project’s objective is the evaluation of pre-hospital practice in Europe; HESCULAEP identified 2 regional ST-elevation myocardial infarction (STEMI) registries: e-MUST (Paris area, France, 11 million inhabitants) and PEFEX (Andalusia, Spain, 8 million inhabitants). The objective of this study is to compare these 2 registries, taking into account territorial, population and methodological differences. A comparison of common target population and common variables was performed. Population study was patients having a typical chest pain, lasting less than 24 hours in year 2006. In 2006, e-MUST included 1618 patients, versus 725 in PEFEX. Patients were more often men (77%) in both registries. They were younger in France (61 years old versus 63), p<10
−3
. Cardio-vascular risk factors were quite different: there were more often smokers and dylispemia in France, and more often High Blood Pressure and diabetes in Spain. Emergency teams arrived faster after onset of symptoms in Spain. Patients with Killip 1 were 90% in both registries. In e-MUST, 93% benefited from repermeabilisation decision by the ALS emergency team, versus 46% in PEFEX. Repermeabilisation consisted in thrombolysis in 27% in e-MUST versus 85% in PEFEX. This was performed earlier in France: 130 minutes after onset of chest pain, versus 155 minutes. Apart from Aspirin used in 93% of cases in both registries, adjuvant treatment was also quite different: antithrombotic and anticoagulant were less used in PEFEX than in e-MUST (respectively 17% versus 42% and 51% versus 91%). This was the opposite for nitrates and analgesics. In-hospital mortality was 6.6% in France versus 3.7% in Spain with no significant difference. Despite, regional, patients’ baseline characteristics and pre-hospital care differences in these 2 registries, in-hospital mortality was quite similar. At a further step, it is important to deeply analyze added-information and consequently improve patients’ management based on this pilot study.
Abstract P105: Safety of Beta Blockers in the Acute Management of Cocaine-associated Chest Pain
Authors: Ibrahim Morhaf , Maselli Diego , Merza Housin , Alhadi Mohammad Manar Abd , Fanari Zaher , Badawi Yazan , Hamilton Andrew
Published: July 2021

Cocaine is the most abused illegal drug in patients presenting to emergency rooms with chest pain, accounting for almost 40% of all drug related visits. It is not known whether all â Blockers (BB) and α1-Selective agents (α1-BB) or mixed α1/β-adrenergic antagonists (α1/β-BB) are safe in the acute management of cocaine-associated chest pain, due to fears of unopposed alpha-receptor activity resulting in coronary artery spasm and hypertensive urgency.

Methods:
378 patients presenting to the emergency rooms (ER) in two different hospitals with chest pain who tested positive for cocaine, were evaluated by retrospective chart review. We reviewed the presence and type of BB used in relation to peak elevation in troponin T and troponin I. Troponin elevation was defined as a troponin I >0.6 and troponin T >0.1 if creatinine was <2 mg/dl.

Results:
The 378 patients comprised African Americans (77%), Hispanics (11%), Caucasian (9%). Of these 12% had typical chest pain, 22% had history of coronary artery disease, 56% had hypertension, and 21% had diabetes mellitus. The admission EKG showed changes (ST elevation, ST depression or new T wave inversion) in 43%. BBs were used in 43%. Troponin became elevated in 9.9% of all patients. There was no difference in the number of patients with troponin rise in the BB and non-BB groups 21/165 vs 16/213 (p=0.1). There was no difference in mean peak troponin levels in patients with troponin rise who were treated with BB vs. no BB 6.7 vs. 5.7 (p=0.6). There was no difference in mean peak troponin levels in patients with troponin rise who were treated with a β1-BB vs. a α1/β-BB 7.5 vs. 4.1 (p=.4). No cases of hypertensive urgency were identified after taking any BB.

Conclusion:
Troponin rise is not uncommon in patients with cocaine associated chest pain and occurs in 10%. In patients with cocaine-associated chest pain BBs did not appear to change the incidence of troponin rise. â1 Selective BBs did not appear to worsen troponin levels compared to mixed α1/â-adrenergic antagonists. There were no cases of unopposed alpha activity reported.
Abstract P115: Higher Threshold and Dose of Coronary Perfusion Pressure are Associated with ROSC in Prolonged Swine Cardiac Arrest
Authors: Reynolds Joshua C , Salcido David D , Menegazzi James J
Published: July 2021

Introduction:
The amount of myocardial perfusion required for successful defibrillation after prolonged cardiac arrest is not known. Coronary perfusion pressure (CPP) is a surrogate for myocardial perfusion. One limited clinical study reported that a threshold of 15mmHg was necessary for return of spontaneous circulation (ROSC), and that CPP was predictive of ROSC. A distinction between threshold and dose of CPP has not been reported.

Hypothesis:
Animals that achieve ROSC will have higher mean CPP and higher area under the CPP curve (AUC) than no-ROSC swine.

Methods:
Data from 4 similar swine cardiac arrest studies were retrospectively pooled. Animals had undergone 8 –11 minutes of untreated ventricular fibrillation, 2 minutes of mechanical CPR, administration of drugs, and 3 more minutes of CPR prior to the first shock. Mean CPP ± standard error was derived from the last 20 compressions of each 30 second epoch of CPR and compared between ROSC/no-ROSC groups by RM-ANOVA. AUC for all compressions delivered over the 5 minutes was calculated by direct summation and compared by Kruskal-Wallis test. Prediction of ROSC was assessed by logistic regression.

Results
: During 5 minutes of CPR (n=80), mean CPP ± SEM was higher in animals with ROSC (n=63) (p < 0.001). Animals with ROSC received more total flow than animals without ROSC (p < 0.001). Two regression models identified CPP (OR 1.11; 95% CI 1.05, 1.18) and AUC (OR 1.10; 95% CI 1.05, 1.16) as predictors of ROSC. Experimental protocol also predicted ROSC in each model (OR 1.70; 95% CI 1.15, 2.50) and (OR 1.59; 95% CI 1.12, 2.25), respectively.

Conclusion
: Higher CPP threshold and dose are associated with and predictive of ROSC.
Abstract P121: Post-resuscitation Ionized Hypocalcemia Revisited
Authors: Heyming Ted , Youngquist Scott , Rosborough John P , Niemann James T
Published: July 2021

Objective
: Hypocalcemia during cardiac arrest has been reported. However, hypotheses for the decrease in ionized calcium (iCa) vary and its importance unknown. The objective of this study was to assess the relationships of iCa, pH, and base excess (BE) in two porcine cardiac arrest models, and to determine the effect of exogenous calcium on postresuscitation hemodynamics.

Methods
: Swine were instrumented and VF was induced either electrically (EVF, n=49) or spontaneously, ischemically induced (IVF) with balloon occlusion of the LAD (n=37). Animals were resuscitated after 7 minutes of VF. BE, iCa, and pH, were determined prearrest and at 15, 30, 60 min after ROSC. Arterial lactate was also measured in 10 pigs. In three animals, 1 gm of CaCl
2
was infused over 20 min after ROSC.

Results:
iCa, BE, and pH declined significantly over the 60 min following ROSC, regardless of VF type (figure

). Lactate was strongly correlated with BE (r = −0.83, p<0.0001). In a multivariate generalized linear mixed model, iCa was 0.007 mg/dL higher for every one unit increase in BE (95% CI 0.005– 0.008, p<0.0001), while controlling for type of induced VF. CaCl
2
improved post-ROSC hemodynamics when compared to saline infusion (figure

).

Conclusions
: Ionized hypocalcemia occurs following ROSC. This may be due to binding by lactate as evidenced by its strong association with the decline in base excess. CaCl
2
improves post-ROSC hemodynamics suggesting that hypocalcemia may play adial dysfunction.
Abstract P123: Vasopressin, but not Norepinephrine, causes Ventriculoarterial Mismatch in Experimental Post Ischemic Cardiogenic Shock
Authors: How Ole-Jakob , Røsner Assami , Gjessing Petter , Hermansen Stig E , Myrmel Truls
Published: July 2021

Introduction In agreement with existing guidelines, inotropic and vasopressor support is given routinely in cardiogenic shock (CS). However, there is a lack of scientific evidence supporting the efficacy and safety of such treatment.

Hypothesis Vasoconstrictors given in cardiogenic shock will increase the ventriculoarterial mismatch and thus lead to reduced cardiac output

Methods In a closed chest pig model we tested the inodilator (dobutamine, Dobut) alone and combined with either an inoconstrictor (norepinephrine, NE) or a pure vasopressor (arginine vasopressin, AVP). In anesthetized animals, CS was induced by coronary microembolization under fluoroscopic guidance. Hemodynamic indices were obtained by Swan-Ganz catheters, left ventricular pressure-volume catheters and echocardiography, and the ventriculoarterial coupling calculated.

Results In the normal heart, Dobut (2ug/kg/min) enhanced ventriculoarterial energy transfer, shown as a decreased Ea/Ees (ratio of arterial and ventricular elastance), 1.0 ± 0.1 to 0.8 ± 0.1, and an increased preload recruitable stroke work (PRSW), 53 ± 5 to 63 ± 2. This was further enhanced by NE (100 ng/kg/min) to 0.7 ± 0.1 and 79 ± 6. In contrast, adding AVP (0.001 u/kg/min) resulted in an increased Ea/Ees (1.0 ± 0.1) and decreased PRSW (56 ± 8) compared to Dobut alone (a two fold increase in systemic vascular resistance (SVR), concomitant with no elevation in contractility). In post ischemic CS, energy transfer from the ventricle to the arterial system (Ea/Ees 1.8 ± 0.2, PRSW 26 ± 2 and Ejection fraction 42 ± 6 %) was partly restored by Dobut (1.4 ± 0.2, 46 ± 2 and 47 ± 6%) unaffected by further adding NE (1.5 ± 0.2, 53 ± 2 and 45 ± 5%), but impaired after adding AVP (2.0 ± 0.1, 43 ± 1 and 34 ± 4%). Consequently, Dobut improved the shock by increasing cardiac output (CO) and SVO2 from 74 ± 3 ml/kg and 37 ± 2% to 103 ± 8 ml/kg and 49 ± 3%. Adding NE resulted in a further improvement of CO (125 ± 9 ml/kg) and SVO2 (59 ± 4%). In contrast AVP further worsened the shock state by decreasing CO (70 ± 6 ml/kg) and SVO2 (45 ± 5%) compared to Dobut alone.

Conclusion A pure afterload increasing substance in acute ischemic hearts with cardiogenic shock aggravate the shock state by causing a ventriculoarterial mismatch.
Abstract P133: Role of Akt and p38 in Oxidant Stress Injury and Hypothermic Protection in Murine Cardiomyocytes
Authors: Wojcik Kimberly R , Shao Zuo-Hui , Li Chang-Qing , Hamann Kimm J , Hoek Terry L Vanden
Published: July 2021

Cardiac arrest is an ischemia/reperfusion (I/R) disease characterized by oxidant generation, inflammation, and cell death; and hypothermia (HT) has been shown to improve post-cardiac arrest reperfusion injury. We developed a neonatal mouse cardiomyocyte model of I/R (90 min I + 3 hr R) that demonstrates cell injury associated with increased reactive oxygen species (ROS) generation at reperfusion (as measured by DCFH). Mild HT (32°C) protects mouse cardiomyocytes from I/R injury, and we hypothesize that this protection may be related to the activation of the survival kinase Akt. The Akt inhibitor API-2 (10 ìM) reversed HT protection [32.4 ± 7.1% vs 65.7 ± 6.3% with API-2, p< .01(as measured by PI)] to cell death levels commensurate with normothermic I/R injury (60.7 ± 6.0%). Phospho-Akt (pAkt) levels declined during ischemia, and while both Ser473 and Thr308 were phosphorylated in normothermia and HT within 15 min reperfusion, HT showed an augmented level of pAkt at Thr308. Furthermore, this increase was sustained for the first 30 min of reperfusion. To further study this relationship, murine cardiomyocytes were exposed to exogenous H2O2 to mimic the oxidant stress associated with I/R. Mouse cardiomyocytes demonstrated a dose- and time-dependent activation of Akt to H2O2 that showed maximal activation of both the Ser473 and Thr308 sites within 30 min with 200 ìM H2O2. As in I/R-stimulated cells, the Thr308 site declined to near baseline levels within 1 hr while Ser473 remained elevated. Based on recent findings linking Akt and ROS with p38, we examined the effect of I/R and H2O2 on p38. Mouse cardiomyocytes demonstrated a rapid activation of p-p38 (Thr10/Tyr182) in the context of both stresses. Further, we studied the effect of the Akt inhibitor, API-2, as well as the p38 inhibitor, SB 203580, in H2O2-stimulated cells. As in I/R, API-2 blocked H2O2-induced pAkt, but this inhibitor did not have any effect on p-p38. However, when p38 activation was blocked using SB 203580, pAkt levels decreased by 2 hr. These data suggest that HT is, in part, mediated through Akt and that p38 lies upstream of Akt in the context of oxidant stress. These kinases may act as triggers for the initiation of survival pathways in cardiomyocytes to combat potential damage induced by ROS generation.
Abstract P136: Tracheal Temperature for Monitoring Core Temperature during Mild Hypothermia in Pigs
Authors: Krizanac Danica , Haugk Moritz , Weihs Wolfgang , Holzer Michael , Bayegan Keywan , Janata Andreas , Sterz Fritz , Herkner Harald , Losert Udo , Laggner Anton , Behringer Wilhelm
Published: July 2021

Purpose of the stud
y: Early out-of-hospital induction of mild hypothermia after cardiac arrest needs an easy to use and accurate core temperature monitoring, which might be achievable with tracheal temperature measurement. The aim of the study was to evaluate which tracheal temperature site (Ttra) reflects best pulmonary artery temperature (Tpa) during the induction of mild hypothermia.

Methods:
Eight pigs (29 –38 kg) were anesthetized and intubated with a specially designed endotracheal tube with three temperature probes: Ttra1 was attached to the wall of the tube, 1 cm proximal to the cuff-balloon, without contact to the mucosa; Ttra2 and Ttra3 were placed on the cuff-balloon with tight contact to the mucosa, whereas Ttra3 was covered by a plastic tube to protect the mucosa. Core temperature was measured with a pulmonary artery catheter (Tpa). Pigs were cooled with a new surface cooling device (Emcoolspad®, Vienna, Austria). Data are presented as mean (±SD), and mean differences (95% CI).

Results:
Emcoolspad® decreased Tpa from 38.5°C to 33°C in 31±10 min, which translates into a cooling rate of 11.9±3.8°C/h. Overall mean differences of tracheal temperatures to pulmonary artery temperature (Tpa) are shown in table 1

. Ttra 1 showed the least difference to Tpa, followed by Ttra 2 and Ttra 3. There was a significant difference in temperature differences (Ttra-Tpa) related to temperature measurement site on the tracheal tube (p<0.007).

Conclusions:
The temperature probe proximal of the cuff (Ttra 1) reflects best pulmonary artery temperature. It seems to be an accurate surrogate for core temperature during the induction of mild hypothermia. The industry is asked to provide a tracheal tube with a temperature sensor for simple temperature monitoring during fast cooling to facilitate the implementation of mild hypothermia after cardiac arrest in the out-of-hospital setting.
Abstract P141: Electrocardiogram Waveform Analysis Reveals Probability of Return of Spontaneous Circulation in Both Swine and Human Subjects
Authors: Sherman Lawrence D , Niemann James T , Rea Thomas D , Rosborough John P , Waters James D , Menegazzi James J
Published: July 2021

Background:
The Logarithm of the Absolute Correlations (LAC) is a measure which estimates VF duration based on the fractal dimension of the waveform. We hypothesized that the LAC measures the underlying physiology of the myocardium and would enable identification of those who would have return of spontaneous circulation (ROSC) in response to the initial shock. We tested this hypothesis in a swine model and among humans treated for out-of-hospital cardiac arrest

Methods:
20 swine were placed in VF either by electrical stimulation (n=10) or through ischemia produced by percutaneous balloon occlusion of the left anterior descending artery (n=10). After 7 minutes of VF, CPR was performed for 1 min followed by defibrillation. Response to shock was recorded as ROSC if a BP of 60 mm Hg was present. The LAC was calculated for five second intervals during VF. In the human cohort, the AED ECG recordings of 165 subjects were analyzed. The average interval from 9 –1–1 call to EMS scene arrival was 5 minutes. Response to shock was recorded as ROSC if an organized rhythm corresponded with a palpable BP as determined by review of audio and written EMS report. The LAC was calculated on the 6 seconds of VF preceding the initial shock. In both the swine and human experience, we compared the mean LAC between those with and without ROSC. We calculated receiver operating characteristic (ROC) curves and measured the area under the curve to assess the diagnostic ability of the LAC.

Results:
In the swine model, the mean LAC differed significantly between swine with and without ROSC following the initial shock (with ROSC: 5.17±0.19 [n=6] versus without ROSC: 4.88±0.27 [n=14]: p = 0.033). The AUC for the LAC measure was 0.80. In the human cohort, the LAC also differed significantly between those with and without ROSC following the initial shock (5.21±0.34 [n=36] versus 4.81±0.47 [n=129], p < 0.0001). The AUC for the LAC measure was 0.76.

Conclusions:
The LAC measure predicts ROSC in both swine and human VF and can be used to guide resuscitation care. Swine ischemic VF is similar to that seen in humans.
Abstract P144: Bioinformatic Profiling of the Transcriptional Response of Adult Porcine Bone Marrow Stem Cell during Exposure to Hypoxia
Authors: Wang Suna , Zhou Yifu , Xu Xiuli , Hunt Timothy , Hoyt Robert F , Horvath Keith A
Published: July 2021

Background: Cell-based transplantation therapy in a large animal model has been shown to improve angiogenesis and function of ischemic myocardium. These improvements may be due to the endothelial progenitor cells from bone marrow derived stem cells (BMC) generated under ischemic or hypoxic conditions. However the molecular activities of porcine BMC (PBMC) are largely unknown. Thus, a comprehensive gene expression pattern for PBMC is needed to advance the preclinical work necessary for future human treatment.

Methods: Fifteen PBMC were cultured in the medium of EGM 2 for 4 weeks, and then incubated either in a monitored hypoxic chamber (1% O2, 5% CO2) (H) or in normal culture conditions (normoxia, N) for 6, 12, 24 and 48 hrs. Twenty RNAs comprising 5 Ns and 15 Hs (6, 12 and 24hr) were hybridized to Affymetrix Porcine arrays. An additional 40 samples were prepared for data confirmation by qRTPCR and Western blot. Data normalization and pattern recognition in each of these subgroups were achieved using R package 2.4 and GeneSpringGX. Homologous gene search and functional classification based on NCBI Pig Genomic Resources and DAVID Bioinformatics Resources 2007.

Results: Significant gene expression levels among the four groups were identified. The patterns of three hypoxia (H) groups were clearly distinct from that of normoxia (N) group. However, the expression pattern of 12hr H was more similar to 24hr H than that of 6hr H. Of 23,928 probes, 394 genes were statistically regulated rapidly in 6hr Hs vs. Ns, including HIF2alpha, VEGFA, PDGFA, ANGPT2, CXCL14 and PGD. Only 182 genes were modulated in 12hr Hs, but 84% (152/182) of the genes appeared either with 6hr or 24hr H groups. 227 genes were significantly over- or down- regulated in 24hr Hs, among the 94 genes were overlapped with 6hr and 12hr Hs. Notably, the 94 genes were the most differentially modulated in all three H groups, some of the genes were known involving in the processes of hypoxic stress, response to inflammatory, wounding, apoptosis and angiogenesis. The 94 genes are considered as hypoxic targets for further study.

Conclusions: Our results confirmed the role of several genes involved in hypoxic or ischemic states, and captured a set of genes that associated the PBMC response to hypoxic or ischemic surroundings.
Abstract P150: Chest Compression Depth is Influenced by Compression Rate and Gender
Authors: Peberdy Mary Ann , Silver Annemarie , Ferland Lisa , Faulkenberry Phyllis , Ornato Joseph
Published: July 2021

Purpose:
Quality of chest compressions (CC) is an important determinant of resuscitation outcome for cardiac arrest patients. The purpose of this study was to characterize the quality of CC performed by hospital personnel and to evaluate for predictors of CC performance.

Methods:
A total of 754 individuals (488 nurses, 178 other healthcare professionals, 36 nursing students, and 52 non-healthcare professionals) participated in a CPR quality improvement challenge at 31 U.S. hospitals. Participants performed 2 minutes of CC on a manikin with an accelerometer-based system for measuring both rate (CC/min, cpm) and depth (in) of CC using the AED Plus (ZOLL Medical). Real-time audiovisual feedback normally available on the AED was disabled.

Results:
The mean depth of compressions was below AHA minimum guidelines (<1.5 in) for 34% of participants (1.30±0.14 in, n=255) and above maximum guidelines (>2.0 in) for 12% of participants (2.20±0.22 in, n=93). CC depth related inversely to CC rate (r=−0.37, p<0.0001), suggesting that excessive CC rate can contribute to insufficient CC depth. Male participants performed CC of greater depth compared with female participants [1.72±0.33 in (n=187) vs.1.60±0.31 (n=534), p<0.0001]. There were no differences in CC depth between ACLS, BCLS, and non-CPR certified participants [1.64±0.33 in (n=392) vs. 1.63±0.31 (n=278) vs. 1.58±0.23 (n=34); p=0.6]. However, depth of CC was greater for non-healthcare professionals compared with healthcare professionals [1.74±0.33 in (n=52) vs. 1.63±0.32 (n=702)]. CC depth varied slightly with rescuer age [<20yr= 1.82±0.27 in (n=8); 21–30 yr= 1.66±0.31 (n=177); 31–40 yr= 1.65±0.31 (n=204); 41–50 yr= 1.62±0.32 (n=196); 51–60yr= 1.54±0.29 (n=109); 61–70 yr= 1.63±0.47 (n=13), p=0.009]. Multivariate linear regression revealed that CC rate (r
part
=−0.37, p<0.001) and gender (r
part
= 0.15, p=0.001) were predictors of CC depth.

Conclusions:
Many hospital personnel do not perform CC within AHA guideline recommendations for depth. Depth of CC may be compromised when rescuers provide CC of excessive rate. Males provide CC of greater depth compared with females.
Abstract P169: Patients with an AED Applied by a Bystander in a Public Setting have a Strikingly Higher Frequency of VT/VF Than Observed Cardiac Arrests in the Home
Authors: Weisfeldt Myron L , Sitlani Colleen , Rea Thomas , Atkins Dianne , Aufderheide Tom P , Bigham Blair , Brooks Steven , Foerster Christopher , Ornato Joseph P , Powell Judy , Van Ottingham Lois , Morrison Laurie J
Published: July 2021

Introduction:
The overall incidence of ventricular tachycardia/ventricular fibrillation (VT/VF) as the first recorded electrical rhythm in out of hospital cardiac arrest (OOHCA) has declined from ~70% to ~25% over the last 30 years. This change has been attributed to primary and secondary prevention of cardiovascular disease and VT/VF. We evaluated whether the incidence of VT/VF as first recorded rhythm differed by location among bystander AED applied patients and EMS witnessed cardiac arrests.

Methods:
Prospective cohort study of non-traumatic cardiac arrest from December 2005 to April 2007 in the Resuscitation Outcomes Consortium database from 10 US and Canadian sites. The incidence of an initial shockable rhythm on AED or documented VT/VF was compared among bystander applied AED patients and EMS witnessed arrests in public versus private settings.

Results:
The first rhythm was known in 13,235 of 14,059 (94%) adult EMS-treated cardiac arrests. Of the 13,235 with known rhythms, 3436 (26%) had VT/VF. Among 1115 EMS-witnessed arrests, 61/161 (38%) had VT/VF in public settings and 224/954 (23%) in private settings. Similarly, for bystander AED applied in the private setting 39/114 (34%) were shocked. But, in contrast, 125/159 (79%) (P<.001 vs all other) were shocked by the AED in the public setting. Witnessed arrests in both the private setting (vs public) and in EMS witnessed cases (vs bystander AED applied) were more likely to occur in older subjects and females. After adjusting for age and gender via logistic regression models, a significant difference in the odds of having a shockable rhythm in public versus private location of arrest remained in EMS-witnessed arrests (P<0.005). The difference also remained in bystander AED applied arrests (P<0.001) after adjusting for age, gender, and bystander-witnessed status.

Conclusions:
The incidence of VT/VF is far greater in the public setting particularly for bystander witnessed AED applied arrests. Patients in the private home setting, even for EMS observed arrests, are far less likely to benefit from AED application than bystander witnessed patients in the public setting. CPR strategies may need to be tailored by arrest location.
Abstract P172: What Facilities Reserve Public Access Defibrillation Programs? A Suvey from a Japanese Metropolis
Authors: Kaneko Hiroshi , Hatanaka Tetsuo , Nagase Aki , Noguchi Hiroko , Sakamoto Tetsuya , Marukawa Seishiro
Published: July 2021

Previous reports have described several facility categories as important locations for public access defibrillation (PAD) program. However, in decision-making process as to what specific facilities may deserve PAD programs, each facility needs to estimate the number of shockable cardiac arrest (CA). Such estimation depends not only on the expected number of visitors/workers but also on the profile of the visitors/workers, which may vary among types of facilities.

[Methods]
Nagoya City has a population of 2.2 million with ~2,000 CA annually. Locations of CA were abstracted from data collected by Nagoya FD from 2003 through 2007. Types of public facilities were tallied and grouped into 36 categories consistent with Ordinance for Enforcement of Fire Service Act, and the number of CA within each category was determined. Data on the number of visitors/workers in each category were collected from governmental databases on metropolitan statistics. The incidence rate was calculated as numbers of all CA and CA with VF per 1 billion person.year.

[Results]
In 8 location categories, the databases for CA and the database for numbers of visitors/workers coincided in the categorization rules of the locations. The incidence rates are shows in the table

.

[Discussion]
The incidence rate of shockable CA varies substantially among the location categories, presumably reflecting the variations of age distribution, average length of stay and intensity of physical activities of people who gather there. Schools (teachers) and factories have the highest incidence of shockable CA. However, our data may indicate that a school with small numbers of workers (teachers) may have a low priority of a PAD program. On the contrary, a station with low incidence rate of 0.05 may be a preferred target of a PAD program if a large number of travelers are expected to pass through. Thus our study provides fundamental data to detect important and cost-effective target locations of a PAD program.

Number of CA per 1 billion preson.year
Abstract P182: Usefulness of Mobile Telemedicine System in Real-time Transmission of Out-of-hospital 12-lead ECG
Authors: Nonogi Hiroshi , Yokoyama Hiroyuki , Otsuka Yoritaka , Kasahara Yoichiro , Kataoka Yu , Kokubu Nobuaki , Sase Kazuhiro
Published: July 2021

[Purpose] AHA/ACC guidelines recommend routine use of 12-lead ECG and advance notification for patients with acute coronary syndrome. However, transmission of out-of-hospital 12-lead ECG to emergency department is still not spread and ECG interpretation on the prehospital and emergency department is not established. Therefore, we have developed and tested the clinical usefulness of the mobile telemedicine system to transmit 12-lead ECG between moving ambulances and physicians in cardiovascular emergency.

[Method] We set up the mobile telemedicine using the third-generation digital mobile phone to promote communications between an ambulance and diverse hospital. Compatibility issue among device vendors was solved by the implementation of open-standard medical waveform encoding rule with motion noise-reduction system. Real time 12-lead ECG was transferred together with vital signs and live video during transfer the patient by an ambulance. The performance of the mobile telemedicine system in the field-test was checked to transfer 12-lead ECG in different scenarios such as transferred ECG from a volunteer moving hand or leg, coughing or twisting body in an ambulance driving on common road or highway. In the next step, we set up the mobile telemedicine on an ambulance to promote communications between moving 5 ambulances in Suita-city and National Cardiovascular Center since 2008 June 2. To establish the efficacy of real-time transmission of out-of-hospital 12-lead ECG, the time-line from the onset of acute myocardial infarction to reperfusion is analyzed.

[Results] Totally 36 patters of 12-lead ECG were checked in the field test and all of them were comparable than those original one in the ambulance. Time-delay for transmission of 12 lead ECG was within 10seconds and for one-lead ECG monitoring and vital signs including BP, HR and oxygen saturation was 1 second without the difficulties for the interpretation.

[Conclusion] Those results indicate the usefulness and reliability of transmission of 12-lead ECG using the mobile telemedicine system from the ambulance. Further investigation is on-going to determine the efficacy in clinical conditions to reduce the treatment delay for acute myocardial infarction.
Abstract 210: αMyHC-mCherry-LC3 Transgenic Mice is a New and Useful Tool to Examine the Role of Autophagy in Cardiomyocytes
Authors: Terada Mai , Nobori Kiyoshi , Munehisa Yoshiko , Kakizaki Manabu , Ohba Takayoshi , Koyama Takashi , Takahashi Yoichiro , Ishida Masaru , Iino Kenji , Kosaka Toshimitsu , Watanabe Hiroyuki , Hasegawa Hitoshi , Ito Hiroshi
Published: July 2021

Autophagy is an intracellular process in which proteins and organelles are transported in double-membrane vesicles called autophagosomes through the cytoplasm to lysosomes for degradation. The autophagosome acquires hydrolytic enzymes by fusing with the lysosome to generate an autolysosome. Constitutive autophagy in the heart under baseline conditions is a homeostatic mechanism for maintaining cardiomyocyte size and global cardiac structure and function. Upregulation of autophagy in various heart diseases, including cardiac hypertrophy and heart failure, is an adaptive response for protecting cells from hemodynamic stress. However, the detailed roles of autophagy in the heart remain unclear. LC3 is localized on the autophagosome membrane. Exogenously expressed GFP fused to LC3 (GFP-LC3) serves as an ideal molecular marker for autophagosome. Transgenic mice expressing GFP-LC3 (CAG-GFP-LC3) have been used to detect autophagy systemically. However, CAG-GFP-LC3 mice cannot distinguish autophagy-positive cardiomyocytes from other cells such as fibroblasts and smooth muscles in the heart and cannot detect autolysosome because GFP-LC3 loses fluorescence due to lysosomal acidic and degradative conditions. To resolve these problems, we have generated transgenic mice (αMyHC-mCherry-LC3) expressing mCherry fused to LC3 under the control of αmyosin heavy chain promoter instead of CAG promoter to detect autophagy only in cardiomyocytes. mCherry is an improved-monomeric red-fluorescence protein and does not lose fluorescence under acidic condition. Thus, αMyHC-mCherry-LC3 mice can detect not only autophagosome before fusion with lysosome but also autophagosome after fusion with lysosome. Moreover, we have crossed αMyHC-mCherry-LC3 mice with CAG-GFP-LC3 mice. Green signals showed autophagosome in non-cardiomyocytes. On the other hand, red signals showed autolysosome and double positive signals showed autophagosome in cardiacmyocytes. In conclusion, we have generated αMyHC-mCherry-LC3 mice to detect both autophagosome and autolysosome. The double transgenic mice cannot only detect autophagosome and autolysosome but also distinguish between them. This is an innovative method to examine the role of autophagy in cardiomyocytes.
Abstract 222: Oxidative Modification of Extracellular Matrix Proteins Alters the Hsp90 Interactome in Human Umbilical Vein Endothelial Cells
Authors: Xu Hao , Wang Weiling , Wakim Basam , Pritchard Kirkwood A
Published: July 2021

Lipid peroxidation increases the production of thiol-reactive α, β-unsaturated aldehydes such as 4-hydroxy-2-nonenal (4-HNE). Exposure of endothelial cells (EC) to 4-HNE impairs cell function. Interestingly, heat shock protein 90 (hsp90), which interacts with a multitude of client proteins, is upregulated under conditions that promotes oxidative stress. However, to our knowledge no one has examined the effects of oxidative modification of matrix proteins on cell function. Here we hypothesize that oxidative modification of matrix perturbs EC function with respect to the hsp90 interactome. To test this hypothesis, we treated gelatin-coated culture dishes with 10 μM Linoleic Acid (LA) under conditions that promoted oxidation. Dishes were washed free of excess LA and seeded with human umbilical vein EC. Native dishes without LA treatment were used as control. The hsp90 client proteins were identified by immunoprecipitation of hsp90 and nanoLC-MS/MS analysis. Oxidative modification of gelatin caused a marked shift in the hsp90-interactome (n = 4). EC maintained on LA-treated gelatin expressed more hsp90 (1.5 X) than controls. Only ~33% of the proteins were present in both groups at similar levels. Hsp90 client proteins in EC maintained on LA-treated gelatin also had increased levels of DNA repair protein BRCA2, protein kinase Tec, protein phosphatase RPTP-rho, ubiquitin ligase Pellino 3, chaperone protein nucleophosmin, retinoic acid receptor, 2 histone deacetylases (e.g. Sin3b), 4 transcription factors (e.g. Prox1), 5 cytoskeleton protein and stress fibers (e.g. tubulin), 9 ribosomal proteins. GO analysis revealed that most of these proteins are involved in stress responses such as protein synthesis, degradation, stress fiber formation, transcription repression, DNA repair and senescence. These data show that EC enter into a stress-response status with marked alterations in the hsp90 interactome upon sensing oxidative modification of extracellular matrix proteins. Such changes may play a role in impaired anti-atherogenic responses in the vessel wall.
Abstract 223: S-glutathiolation Uncouples Endothelial Nitric Oxide (NO) Synthase, Switching Enzyme from NO to Superoxide Production
Authors: Chen Chun-An , Druhan Lawrence J , Wang Tse-Yao , Chen Yeong-Renn , Zweier Jay L
Published: July 2021

Overproduction of superoxide (•O
2
−
) and •O
2
−
-derived oxidants increases cellular oxidative stress. This can lead to cell death, via apoptosis or necrosis. An important response of protein thiols to oxidative stress is reversible formation of protein mixed disulfides via S-glutathiolation. This redox based protein modification is thought to play an important role as an adaptive response to oxidative injury in cells, or alternatively in controlling cellular signaling in a manner similar to phosphorylation. Protein S-glutathiolation is increased in the post-ischemic heart. Human eNOS, which is of critical importance in maintaining cardiovascular function, contains 29 cysteinyl residues. To investigate the effects of S-glutathiolation on the regulation of eNOS function and its relation to cardiovascular diseases, eNOS functional alterations induced by S-glutathiolation were studied. Additionally, LC/MS/MS was used to determine the precise residues of eNOS involved in this redox-dependent thiol modification. S-glutatiolation significantly reduced NO production from heNOS, with a 63% decrease induced by incubation with 2 mM GSSG in
vitro
. This process was reversible by addition of DTT. Alkylation of the cysteinyl residues with N-ethylmaleimide (NEM) completely inhibited NO production. S-glutathiolation of an uncoupled heNOS increased •O
2
−
generation (> 70%), and this increase was only partially blocked by L-NAME, implicating the reductase site as the source for the increased •O
2
−
generation. When the cysteinyl residues were all alkylated with NEM, the •O
2
−
generation from eNOS was dramatically increased (+2.4-fold), and this increase was not inhibited by L-NAME. We have identified three cysteine residues, C
382
, C
689
and C
908
as sights of S-glutathiolation in heNOS, all three of which are conserved in all known mammalian eNOS enzymes. Therefore, cysteinyl residues are critical for the regulation of eNOS coupling, and S-glutatiolation of specific residues switches eNOS from an NO producing to a •O
2
−
generating enzyme, by inducing electron leakage from the reductase domain. As such, S-glutathiolation provides a novel mechanism for the regulation of heNOS, defining a unique pathway for the redox regulation of cardiovascular function.

This research has received full or partial funding support from the American Heart Association, AHA Great Rivers Affiliate (Delaware, Kentucky, Ohio, Pennsylvania & West Virginia).
Abstract 237: Acute Activation of eNOS by Lovastatin Involves Scavenger Receptor-B1
Authors: Datar Rahul , Kaesemeyer Wayne H , Fulton David J , Caldwell Robert W
Published: July 2021

Statins (HMG CoA reductase inhibitors) have beneficial vascular effects independent of their ability to reduce cholesterol synthesis. We and others have previously shown that statins acutely activate endothelial cell NOS (eNOS). Our present study characterized signaling pathways by which statins activate NOS using cultured bovine aortic endothelial cells (BAEC) and COS 7 cells. It also examined involvement of scavenger receptor - B1 (SR-B1), which is expressed in endothelial cells and maintains caveolae cholesterol concentration and eNOS localization. BAEC were exposed to lovastatin (LOV, 10
−6
M) for 2–5 min after pretreatment with the end product of HMG CoA reductase (mevalonic acid, 5×10
−4
M), a Gi protein inhibitor (pertussis toxin, 10
−4
M), a PLC inhibitor (U-73122, 10
−5
M), a receptor tyrosine kinase (RTK) inhibitor (tyrphostine 51A, 2×10
−6
M) or intracellular and extracellular calcium chelators -BAPTA-AM (10
−5
M) and EGTA (10
−4
M), respectively, and levels of NO production were determined. LOV alone acutely increased NO production by 67%. NO production in response to LOV was not blocked by mevalonic acid indicating that it occurs independent of HMG CoA reductase inhibition. Inhibition of Gi protein, PLC, and RTK almost completely blocked the LOV-induced NO generation. Removal of extracellular Ca
++
prevented statin-induced NO production by 90%, while intracellular Ca
++
chelation with BAPTA-AM reduced NO production by 45%. COS 7 cells transfected with eNOS did not show increased NO production to LOV or HDL, indicating NOS activation occurs through an endothelial cell receptor. In COS 7 cells, co-transfected with eNOS and the endothelial SR-B1, LOV or HDL (10
−5
M), a known agonist of SR-B1, increased NO production by over 200%. In COS 7 cells transfected with eNOS alone or co-transfected with the bradykinin B2 receptor, neither LOV nor HDL increased NO production, indicating effects specific for the SR-B1 receptor. In conclusion, our study shows LOV acutely activates eNOS independently of HMG CoA reductase inhibition. eNOS activation appears to involve an endothelial Gi protein receptor and subsequent activation of PLC and RTK pathways, leading to entry of extracellular calcium. Furthermore, LOV can activate eNOS via the SR-B1 receptor.
Abstract 238: Toll-Like Receptor 4-Deficiency Improves Ischemic Cardiomyocytes Contractile Dysfunction via Augmentation of AMPK Activation
Authors: Zhao Peng , He Leilei , Ma Heng , Li Jing , Wang Jingying , Zhu Xinglei , Ren Jun , Li Ji
Published: July 2021

Myocardial ischemia/reperfusion injury involves a robust inflammatory response especially activation of toll-like receptor 4 (TLR4), a proximal signaling receptor in innate immune responses to lipopolysaccharide of Gram-negative pathogens. TLR4 is expressed in the heart and vasculature, the deficiency of which was shown to protect the heart against ischemia/reperfusion injury. However, the molecular mechanisms behind TLR4 deficiency-induced cardioprotection against ischemic damage remain unclear. The AMP-activated protein kinase (AMPK), an intracellular energy gauge, plays an important role in limiting cardiac damage following by ischemia, thus we hypothesized that AMPK maybe a mediator of TLR4-deficiency cardioprotection against ischemic injury. To test this hypothesis,
In vivo
regional ischemia was induced by occlusion of the left anterior descending (LAD) coronary artery in wild type (WT) C3H/HeN and TLR4-deficient C3H/HeJ mice, which carry a natural mutation of TLR4. Immunoblotting analysis was performed to assess the activation of AMPK and TLR4 downstream signal, the mitogen-activated protein kinase (MAPK). The endoplasmic reticulum (ER) chaperons, Grp78/BiP and Gadd153/CHOP, and ER integral membrane protein IRE1α were also monitored. The results demonstrated that C3H/HeJ hearts had impaired ischemic MAPK and AMPK activation compared to WT C3H/HeN hearts, i.e. activation of p38 MAPK and JNK was blunted, while ERK and AMPK signaling pathways were augmented during ischemia in C3H/HeJ hearts. Intriguingly, ischemia-stimulated ER stress was higher in WT C3H/HeN hearts than that in C3H/HeJ as demonstrated by up-regulation of Grp78/BiP, Gadd153/CHOP and IRE1α. Caspase-3 activity and TUNEL staining results showed that WT C3H/HeN hearts have more damages than those of C3H/HeJ hearts. Moreover, isolated cardiomyocytes from C3H/HeJ hearts showed resistance to ischemia-induced contractile dysfunction compared to WT C3H/HeN hearts. These findings suggest that the cardioprotective effects against ischemic injury of TLR4-deficient hearts may mediated through augmentation of AMPK and ERK while alleviation of p38 MAPK and JNK inflammatory signaling pathways.

This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 246: Global Analysis of Differentially Expressed Genes in the Aortae of Apoe-deficient Mice Infused with Insulin-like Growth Factor I: Novel Mechanisms of the Anti-atherogenic Effect of IGF-1
Authors: Vaughn Charlotte E , Titterington Jane S , Sukhanov Sergiy , Delafontaine Patrick
Published: July 2021

We have previously shown that insulin like growth factor-I (IGF-1) suppresses atherosclerosis progression in ApoE-null mice. To determine mechanisms, ApoE-null mice were chronically infused with IGF-1 (1.5 mg/kg/d, 12 weeks) or saline (control) or treated short-term with IGF-1 (0.4 mg/kg/d, i.p., 1 week) or saline (control). Aortic gene expression of 84 atherosclerosis-related genes-of-interest was analyzed with RT-PCR arrays. Chronic IGF-1 infusion decreased expression levels of pro-apoptotic molecules (Bax, 0.62, BID, 0.26), adhesion molecules (integrin β2, 0.32, integrin α2, 0.28, VCAM-1, 0.43), pro-inflammatory cytokines (TNFα, 0.22, interferon γ, 0.30) and lipoprotein lipase (LPL, an enzyme mediating lipid hydrolysis and tissue uptake of oxidized low density lipoprotein (OxLDL), 0.69). These changes in gene expression correlated with a reduction in atherosclerotic plaque burden (Oil Red-positive aortic valve lesion area, ×000 pixels
2
, IGF-1, 228±13, saline, 268±22), suppression of plaque apoptosis (% apoptotic cells per plaque, IGF-1, 3.4±0.7, saline, 5.8±0.5, P<0.05, TUNEL assay), decrease in plaque TNFα levels (58% reduction vs. saline, P<0.05, immunostaining), and inhibition of serum LPL activity (IGF-1, 1.1±0.2, saline, 3.7±0.4, P<0.05, fluorescence assay). Short-term IGF-1 treatment similarly decreased mRNA levels of Bax (0.68), BID (0.61), integrin β2 (0.62), TNFα (0.50), interferon γ (0.37), LPL (0.42) and also downregulated a group of scavenger receptors (CD36, 0.44, MSR-1, 0.48, MSR-2, 0.52). To further characterize the effect of IGF-1 on LPL we exposed THP-1-derived macrophages to OxLDL (80 ug/ml, 16 h) in the presence or absence of IGF-1. OxLDL increased LPL activity in conditioned media (>5 fold, P<0.01), but pre-treatment with IGF-1 (25 ng/ml, 24 h) reversed LPL upregulation by 52% and suppressed lipid internalization by 88% (P<0.05, Oil Red staining). In summary IGF-1 reduces pro-inflammatory cytokines, pro-apoptotic molecules, adhesion molecules, scavenger receptors, and lipoprotein lipase expression in ApoE-null mice and markedly blunts OxLDL-induced upregulation of LPL and lipid uptake in THP-derived macrophages. These data provide major insights into mechanisms whereby IGF-1 is atheroprotective.