Recurrence of ventricular fibrillation in out-of-hospital cardiac arrest: Clinical evidence and underlying ionic mechanisms.

Defibrillation remains the optimal therapy for terminating ventricular fibrillation (VF) in out-of-hospital cardiac arrest (OHCA) patients, with reported shock success rates of ∼90%. A key persistent challenge, however, is the high rate of VF recurrence (∼50-80%) seen during post-shock cardiopulmonary resuscitation (CPR). Studies have shown that the incidence and time spent in recurrent VF are negatively associated with neurologically-intact survival. Recurrent VF also results in the administration of extra shocks at escalating energy levels, which can cause cardiac dysfunction. Unfortunately, the mechanisms underlying recurrent VF remain poorly understood. In particular, the role of chest-compressions (CC) administered during CPR in mediating recurrent VF remains controversial. In this review, we first summarize the available clinical evidence for refibrillation occurring during CPR in OHCA patients, including the postulated contribution of CC and non-CC related pathways. Next, we examine experimental studies highlighting how CC can re-induce VF via direct mechano-electric feedback. We postulate the ionic mechanisms involved by comparison with similar phenomena seen in commotio cordis. Subsequently, the hypothesized contribution of partial cardiac reperfusion (either as a result of CC or CC independent organized rhythm) in re-initiating VF in a globally ischaemic heart is examined. An overview of the proposed ionic mechanisms contributing to VF recurrence in OHCA during CPR from a cellular level to the whole heart is outlined. Possible therapeutic implications of the proposed mechanistic theories for VF recurrence in OHCA are briefly discussed.

Real-Time Cardiopulmonary Resuscitation Feedback and Targeted Training Improve Chest Compression Performance in a Cohort of International Healthcare Providers.

BACKGROUND: Optimal cardiopulmonary resuscitation (CPR) performance is the foundation of successful cardiac arrest resuscitation. However, health care providers perform inadequate compressions. Better training techniques and real-time CPR feedback may improve compression performance. OBJECTIVE: We sought to evaluate the impact of a targeted training program combined with real-time defibrillator CPR feedback on chest compression performance in an international cohort of health care providers. METHODS: Physicians, nurses, respiratory therapists, and technicians from 6 hospitals in 5 countries (Taiwan, Singapore, China, Bahrain, and Kuwait) participated in a standardized resuscitation workshop. Chest compression was measured before and after didactics and activation of CPR feedback. Compressions were performed for 1 min on standard CPR manikins placed on a hospital bed and backboard and measured using ZOLL R Series defibrillators. The percentage of compressions meeting target values for depth and rate were compared before and after the workshop and activation of real-time CPR feedback. No depth maximum was defined to allow for mattress compression. RESULTS: Chest compressions were more likely to meet targets for depth (71-95%, odds ratio [OR] 8.61 [95% confidence interval {CI} 4.42-16.77], p < 0.001), rate (41-81%, OR 6.4 [95% CI 4.2-9.8], p < 0.001), and both depth and rate (5-42%, OR 2.4 [95% CI 6.7-22.9], p < 0.001) after the workshop and activation of real-time CPR feedback. CONCLUSIONS: A targeted training intervention combined with real-time CPR feedback improved chest compression performance among health care providers from various countries.

Characterization of Pediatric In-Hospital Cardiopulmonary Resuscitation Quality Metrics Across an International Resuscitation Collaborative.

OBJECTIVES: Pediatric in-hospital cardiac arrest cardiopulmonary resuscitation quality metrics have been reported in few children less than 8 years. Our objective was to characterize chest compression fraction, rate, depth, and compliance with 2015 American Heart Association guidelines across multiple pediatric hospitals. DESIGN: Retrospective observational study of data from a multicenter resuscitation quality collaborative from October 2015 to April 2017. SETTING: Twelve pediatric hospitals across United States, Canada, and Europe. PATIENTS: In-hospital cardiac arrest patients (age < 18 yr) with quantitative cardiopulmonary resuscitation data recordings. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: There were 112 events yielding 2,046 evaluable 60-second epochs of cardiopulmonary resuscitation (196,669 chest compression). Event cardiopulmonary resuscitation metric summaries (median [interquartile range]) by age: less than 1 year (38/112): chest compression fraction 0.88 (0.61-0.98), chest compression rate 119/min (110-129), and chest compression depth 2.3 cm (1.9-3.0 cm); for 1 to less than 8 years (42/112): chest compression fraction 0.94 (0.79-1.00), chest compression rate 117/min (110-124), and chest compression depth 3.8 cm (2.9-4.6 cm); for 8 to less than 18 years (32/112): chest compression fraction 0.94 (0.85-1.00), chest compression rate 117/min (110-123), chest compression depth 5.5 cm (4.0-6.5 cm). "Compliance" with guideline targets for 60-second chest compression "epochs" was predefined: chest compression fraction greater than 0.80, chest compression rate 100-120/min, and chest compression depth: greater than or equal to 3.4 cm in less than 1 year, greater than or equal to 4.4 cm in 1 to less than 8 years, and 4.5 to less than 6.6 cm in 8 to less than 18 years. Proportion of less than 1 year, 1 to less than 8 years, and 8 to less than 18 years events with greater than or equal to 60% of 60-second epochs meeting compliance (respectively): chest compression fraction was 53%, 81%, and 78%; chest compression rate was 32%, 50%, and 63%; chest compression depth was 13%, 19%, and 44%. For all events combined, total compliance (meeting all three guideline targets) was 10% (11/112). CONCLUSIONS: Across an international pediatric resuscitation collaborative, we characterized the landscape of pediatric in-hospital cardiac arrest chest compression quality metrics and found that they often do not meet 2015 American Heart Association guidelines. Guideline compliance for rate and depth in children less than 18 years is poor, with the greatest difficulty in achieving chest compression depth targets in younger children.

Quantification of ventilation volumes produced by compressions during emergency department cardiopulmonary resuscitation.

BACKGROUND: Clinical investigations have shown improved outcomes with primary compression cardiopulmonary resuscitation strategies. It is unclear whether this is a result of passive ventilation via chest compressions, a low requirement for any ventilation during the early aspect of resuscitation or avoidance of inadvertent over-ventilation. OBJECTIVES: To quantify whether chest compressions with guideline-compliant depth (>2 in) produce measurable and substantial ventilation volumes during emergency department resuscitation of out-of-hospital cardiac arrest. METHODS: This was a prospective, convenience sampling of adult non-traumatic out-of-hospital cardiac arrest patients receiving on-going cardiopulmonary resuscitation in an academic emergency department from June 1, 2011 to July 30, 2013. Cardiopulmonary resuscitation quality files were analyzed using R-Series defibrillator/monitors (ZOLL Medical) and ventilation data were measured using a Non-Invasive Cardiac Output monitor (Philips/Respironics, Wallingford, CT). RESULTS: cardiopulmonary resuscitation quality data were analyzed from 21 patients (17 males, median age 59). The median compression depth was 2.2 in (IQR = 1.9, 2.5) and the median chest compression fraction was 88.4% (IQR = 82.2, 94.1). We were able to discern 580 ventilations that occurred during compressions. The median passive tidal volume recorded during compressions was 7.5 ml (IQR 3.5, 12.6). While the highest volume recorded was 45.8 ml, 81% of the measured tidal volumes were <20 ml. CONCLUSION: Ventilation volume measurements during emergency department cardiopulmonary resuscitation after out-of-hospital cardiac arrest suggest that chest compressions alone, even those meeting current guideline recommendations for depth, do not provide physiologically significant tidal volumes.

The influence of scenario-based training and real-time audiovisual feedback on out-of-hospital cardiopulmonary resuscitation quality and survival from out-of-hospital cardiac arrest.

STUDY OBJECTIVE: We assess whether an initiative to optimize out-of-hospital provider cardiopulmonary resuscitation (CPR) quality is associated with improved CPR quality and increased survival from out-of-hospital cardiac arrest. METHODS: This was a before-after study of consecutive adult out-of-hospital cardiac arrest. Data were obtained from out-of-hospital forms and defibrillators. Phase 1 included 18 months with real-time audiovisual feedback disabled (October 2008 to March 2010). Phase 2 included 16 months (May 2010 to September 2011) after scenario-based training of 373 professional rescuers and real-time audiovisual feedback enabled. The effect of interventions on survival to hospital discharge was assessed with multivariable logistic regression. Multiple imputation of missing data was used to analyze the effect of interventions on CPR quality. RESULTS: Analysis included 484 out-of-hospital cardiac arrest patients (phase 1 232; phase 2 252). Median age was 68 years (interquartile range 56-79); 66.5% were men. CPR quality measures improved significantly from phase 1 to phase 2: Mean chest compression rate decreased from 128 to 106 chest compressions per minute (difference -23 chest compressions; 95% confidence interval [CI] -26 to -19 chest compressions); mean chest compression depth increased from 1.78 to 2.15 inches (difference 0.38 inches; 95% CI 0.28 to 0.47 inches); median chest compression fraction increased from 66.2% to 83.7% (difference 17.6%; 95% CI 15.0% to 20.1%); median preshock pause decreased from 26.9 to 15.5 seconds (difference -11.4 seconds; 95% CI -15.7 to -7.2 seconds), and mean ventilation rate decreased from 11.7 to 9.5/minute (difference -2.2/minute; 95% CI -3.9 to -0.5/minute). All-rhythms survival increased from phase 1 to phase 2 (20/231, 8.7% versus 35/252, 13.9%; difference 5.2%; 95% CI -0.4% to 10.8%), with an adjusted odds ratio of 2.72 (95% CI 1.15 to 6.41), controlling for initial rhythm, witnessed arrest, age, minimally interrupted cardiac resuscitation protocol compliance, and provision of therapeutic hypothermia. Witnessed arrests/shockable rhythms survival was 26.3% (15/57) for phase 1 and 55.6% (20/36) for phase 2 (difference 29.2%; 95% CI 9.4% to 49.1%). CONCLUSION: Implementation of resuscitation training combined with real-time audiovisual feedback was independently associated with improved CPR quality, an increase in survival, and favorable functional outcomes after out-of-hospital cardiac arrest.

A new defibrillator mode to reduce chest compression interruptions for health care professionals and lay rescuers: a pilot study in manikins.

BACKGROUND: Chest compression interruptions are detrimental during the resuscitation of cardiac arrest patients, especially immediately prior to shock delivery. OBJECTIVE: To evaluate the effect of use of a new defibrillator technology, which filters compression-induced artifact and provides reliable rhythm analysis with automatic defibrillator charging during chest compressions, on preshock chest compression interruption. METHODS: Thirty subjects (20 basic life support [BLS]; 10 advanced life support [ALS]) worked in pairs to perform two randomly ordered simulated cardiac resuscitations with the defibrillator operating in either standard mode (ALS = manual; BLS = automated external defibrillator [AED]) or the new Analysis and Charging during CPR (AC-CPR) mode. During each resuscitation simulation, rescuers switched roles as chest compressor and defibrillator operator every two segments of CPR (one segment = 2 minutes of chest compressions, rhythm analysis, and shock delivery, if appropriate), for eight total segments. The participants rested ≥30 minutes between trials and received brief AC-CPR training (BLS = 30 seconds; ALS = 5 minutes). Heart rate and perceived exertion were measured with pulse oximetry and the Borg scale, respectively. RESULTS: Mean (± standard deviation) preshock chest compression pause time was considerably shorter in each CPR segment with AC-CPR versus standard defibrillator operation (2.13 ± 0.99 sec vs. 10.93 ± 1.33, p < 0.0001), demonstrating effective use of AC-CPR with minimal training. Despite reduced chest compression interruption with AC-CPR, rescuer fatigue and perceived exertion did not differ in any CPR segment with standard defibrillator operation versus AC-CPR (p = 0.2-1.0). CONCLUSIONS: Preshock pause time is reduced by 80% utilizing a novel technology that employs automated analysis and charging during chest compression. Although chest compression pause time is reduced with the use of the new technology, participants do not excessively fatigue.

Higher resuscitation guideline adherence in paramedics with use of real-time ventilation feedback during simulated out-of-hospital cardiac arrest: A randomised controlled trial.

OBJECTIVES: To investigate whether real-time ventilation feedback would improve provider adherence to ventilation guidelines. DESIGN: Non-blinded randomised controlled simulation trial. SETTING: One Emergency Medical Service trust in Copenhagen. PARTICIPANTS: 32 ambulance crews consisting of 64 on-duty basic or advanced life support paramedics from Copenhagen Emergency Medical Service. INTERVENTION: Participant exposure to real-time ventilation feedback during simulated out-of-hospital cardiac arrest. MAIN OUTCOME MEASURES: The primary outcome was ventilation quality, defined as ventilation guideline-adherence to ventilation rate (8-10 bpm) and tidal volume (500-600 ml) delivered simultaneously. RESULTS: The intervention group performed ventilations in adherence with ventilation guideline recommendations for 75.3% (Interquartile range (IQR) 66.2%-82.9%) of delivered ventilations, compared to 22.1% (IQR 0%-44.0%) provided by the control group. When controlling for participant covariates, adherence to ventilation guidelines was 44.7% higher in participants receiving ventilation feedback. Analysed separately, the intervention group performed a ventilation guideline-compliant rate in 97.4% (IQR 97.1%-100%) of delivered ventilations, versus 66.7% (IQR 40.9%-77.9%) for the control group. For tidal volume compliance, the intervention group reached 77.5% (IQR 64.9%-83.8%) of ventilations within target compared to 53.4% (IQR 8.4%-66.7%) delivered by the control group. CONCLUSIONS: Real-time ventilation feedback increased guideline compliance for both ventilation rate and tidal volume (combined and as individual parameters) in a simulated OHCA setting. Real-time feedback has the potential to improve manual ventilation quality and may allow providers to avoid harmful hyperventilation.

Corrigendum to "Higher resuscitation guideline adherence in paramedics with use of real-time ventilation feedback during simulated out-of-hospital cardiac arrest: A randomised controlled trial" [Resuscitation Plus 5 (2021) 100082].

[This corrects the article DOI: 10.1016/j.resplu.2021.100082.].

Effect of Amplitude Spectral Area on Termination of Fibrillation and Outcomes in Pediatric Cardiac Arrest.

Background Amplitude spectral area (AMSA) predicts termination of fibrillation (TOF) with return of spontaneous circulation (ROSC) and survival in adults but has not been studied in pediatric cardiac arrest. We characterized AMSA during pediatric cardiac arrest from a Pediatric Resuscitation Quality Collaborative and hypothesized that AMSA would be associated with TOF and ROSC. Methods and Results Children aged <18 years with cardiac arrest and ventricular fibrillation were studied. AMSA was calculated for 2 seconds before shock and averaged for each subject (AMSA-avg). TOF was defined as termination of ventricular fibrillation 10 seconds after defibrillation to any non-ventricular fibrillation rhythm. ROSC was defined as >20 minutes without chest compressions. Univariate and multivariable logistic regression analyses controlling for weight, current, and illness category were performed. Primary end points were TOF and ROSC. Secondary end points were 24-hour survival and survival to discharge. Between 2015 and 2019, 50 children from 14 hospitals with 111 shocks were identified. In univariate analyses AMSA was not associated with TOF and AMS-Aavg was not associated with ROSC. Multivariable logistic regression showed no association between AMSA and TOF but controlling for defibrillation average current and illness category, there was a trend to significant association between AMSA-avg and ROSC (odds ratio, 1.10 [1.00‒1.22] P=0.058). There was no significant association between AMSA-avg and 24-hour survival or survival to hospital discharge. Conclusions In pediatric patients, AMSA was not associated with TOF, whereas AMSA-avg had a trend to significance for association in ROSC, but not 24-hour survival or survival to hospital discharge. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02708134.

Protein expression in vascular endothelial cells obtained from human peripheral arteries and veins.

Studying molecular mechanisms of vascular endothelial function in humans is difficult in part because of limited access to arteries. Access to peripheral veins is more practical. We determined if differences in protein expression of endothelial cells (EC) collected from a peripheral artery are reflected in measurements made on EC obtained from peripheral veins. EC were collected from the brachial artery and an antecubital vein of 106 healthy adults (60 men and 46 women, age 18-77 years). Quantitative immunofluorescence was used to measure protein expression of endothelial nitric oxide synthase (eNOS), Ser-1177 phosphorylated eNOS, manganese superoxide dismutase, nitrotyrosine, xanthine oxidase and nuclear factor-kappaB p65. Protein expression in EC obtained from brachial artery and antecubital vein sampling was moderately to strongly related (r = 0.59-0.81, all p < 0.0001, mean r = 0.70). Moreover, differences between subgroups in the lowest and highest tertiles of protein expression in EC obtained from arterial samples were consistently reflected in EC obtained from venous collections. These findings indicate that interindividual and group differences in expression of several proteins involved in nitric oxide production, oxidant production, antioxidant defense and inflammatory signaling in EC obtained from brachial artery sampling are consistently reflected in EC obtained from venous samples. Thus, EC collected from peripheral veins may provide a useful surrogate for EC obtained from arteries for measurements of EC protein expression in humans.

Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase.

To determine whether impaired endothelium-dependent dilation (EDD) in older adults is associated with changes in the expression of major vasoconstrictor or vasodilator proteins in the vascular endothelium, endothelial cells (EC) were obtained from the brachial artery and peripheral veins of 56 healthy men, aged 18-78 yr. Brachial artery EC endothelin-1 (ET-1) [0.99 +/- 0.10 vs. 0.57 +/- 0.10 ET-1/human umbilical vein EC (HUVEC) intensity, P = 0.01] and serine 1177 phosphorylated endothelial nitric oxide synthase (PeNOS) (0.77 +/- 0.09 vs. 0.44 +/- 0.07 PeNOS/HUVEC intensity, P < 0.05) (quantitative immunofluorescence) were greater, and EDD (peak forearm blood flow to intrabrachial acetylcholine) was lower (10.2 +/- 0.9 vs. 14.7 +/- 1.7 ml.100 ml(-1).min(-1), P < 0.05) in older (n = 18, 62 +/- 1 yr) vs. young (n = 15, 21 +/- 1 yr) healthy men. EDD was inversely related to expression of ET-1 (r = -0.39, P < 0.05). Brachial artery EC eNOS expression did not differ significantly with age, but tended to be greater in the older men (young: 0.23 +/- 0.03 vs. older: 0.33 +/- 0.07 eNOS/HUVEC intensity, P = 0.08). In the sample with venous EC collections, EDD (brachial artery flow-mediated dilation) was lower (3.50 +/- 0.44 vs. 7.68 +/- 0.43%, P < 0.001), EC ET-1 and PeNOS were greater (P < 0.05), and EC eNOS was not different in older (n = 23, 62 +/- 1 yr) vs. young (n = 27, 22 +/- 1 yr) men. EDD was inversely related to venous EC ET-1 (r = -0.37, P < 0.05). ET-1 receptor A inhibition with BQ-123 restored 60% of the age-related impairment in carotid artery dilation to acetylcholine in B6D2F1 mice (5-7 mo, n = 8; 30 mo, n = 11; P < 0.05). ET-1 expression is increased in vascular EC of healthy older men and is related to reduced EDD, whereas ET-1 receptor A signaling tonically suppresses EDD in old mice. Neither eNOS nor PeNOS is reduced with aging. Changes in ET-1 expression and bioactivity, but not eNOS, contribute to vascular endothelial dysfunction with aging.

Direct evidence of endothelial oxidative stress with aging in humans: relation to impaired endothelium-dependent dilation and upregulation of nuclear factor-kappaB.

Aging is associated with impaired vascular endothelial function, as indicated in part by reduced endothelium-dependent dilation (EDD). Decreased EDD with aging is thought to be related to vascular endothelial cell oxidative stress, but direct evidence is lacking. We studied 95 healthy men: 51 young (23+/-1 years) and 44 older (63+/-1 years). EDD (brachial artery flow-mediated dilation) was approximately 50% lower in older versus young men (3.9+/-0.3% versus 7.6+/-0.3%, P<0.01; n=42 older/n=51 young). Abundance of nitrotyrosine (quantitative immunofluorescence), an oxidatively modified amino acid and marker of oxidative stress, was higher in endothelial cells (ECs) obtained from the brachial artery (1.25+/-0.12 versus 0.61+/-0.11 nitrotyrosine intensity/human umbilical vein EC [HUVEC] intensity, P=0.01; n=11 older/n=11 young) and antecubital veins (0.55+/-0.04 versus 0.34+/-0.03, P<0.05; n=19 older/n=17 young) of older men. Flow-mediated dilation was inversely related to arterial EC nitrotyrosine expression (r=-0.62, P=0.01; n=22). In venous samples, EC expression of the oxidant enzyme NAD(P)H oxidase-p47(phox) was higher in older men (0.71+/-0.05 versus 0.57+/-0.05 NAD[P]H oxidase-p47(phox) intensity/HUVEC intensity, P<0.05; n=19 older/n=18 young), whereas xanthine oxidase and the antioxidant enzymes cytosolic and mitochondrial superoxide dismutase and catalase were not different between groups. Nuclear factor-kappaB p65, a component of the redox-sensitive nuclear transcription factor nuclear factor-kappaB, was elevated in both arterial (0.73+/-0.07 versus 0.53+/-0.05 NF-kappaB p65 intensity/HUVEC intensity, P<0.05; n=9 older/n=12 young) and venous (0.65+/-0.07 versus 0.34+/-0.05, P<0.01; n=13 older/n=15 young) EC samples of older men and correlated with nitrotyrosine expression (r=0.51, P<0.05 n=16). These results provide direct support for the hypothesis that endothelial oxidative stress develops with aging in healthy men and is related to reductions in EDD. Increased expression of NAD(P)H oxidase and nuclear factor-kappaB may contribute to endothelial oxidative stress with aging in humans.

The hazards of providing care in emergency vehicles: an opportunity for reform.

The risk of occupational death is disproportionately high for emergency medical services (EMS) personnel, largely as a consequence of the high incidence of transportation-related fatalities. The purpose of this narrative review is twofold: to raise awareness in the EMS community by examining the various factors that contribute to vehicular EMS injuries and fatalities and to outline practical strategies for mitigating these risks to EMS professionals. This review describes three main categories of factors that contribute to personnel risk during ambulance transport: the inherent risks of driving/riding in an ambulance, poor ambulance safety standards and design, and increased provider vulnerability to injury while delivering critical patient care in the back of a moving ambulance. Specific educational, technologic, regulatory, and behavioral strategies for mitigating these risks are offered in hopes of improving ambulance safety practices.

The impact of real-time chest compression feedback increases with application of the 2015 guidelines.

BACKGROUND: Cardiac arrest survival depends upon chest compression quality. Real-time audiovisual feedback may improve compression guideline adherence, particularly with the more specific 2015 guidelines. METHODS: Subjects included healthcare providers from multiple U.S. hospitals. Compression rate and depth were recorded using standard manikins and real-time audiovisual feedback defibrillators (ZOLL R Series). Subjects were enrolled before (n = 756) and after (n = 995) release of the 2015 guidelines, which define narrower compression targets. Subjects performed 2 min of continuous compressions before and after activation of feedback. The percentage of compressions meeting appropriate rate/depth targets was determined before and after release of the 2015 guidelines. RESULTS: An increase in compression guideline adherence was observed with use of feedback before [68.7% to 96.3%, p < .001] and after [16.6% to 94.1%, p < .001] release of the 2015 guidelines. The proportion of subjects requiring feedback to achieve adherence was higher for the 2015 guidelines [28.6% vs. 78.5%, OR 9.12, 95% CI 7.33-11.35, p < .001]. CONCLUSIONS: The use of real-time audiovisual feedback increases adherence to chest compression guidelines, particularly with application of the narrower 2015 guidelines targets for compression depth and rate.

Chest compression release velocity factors during out-of-hospital cardiac resuscitation.

BACKGROUND: Higher chest compression release velocity (CCRV) has been associated with better outcomes after out-of-hospital cardiac arrest (OHCA), and patient factors have been associated with variations in chest wall compliance and compressibility. We evaluated whether patient sex, age, weight, and time in resuscitation were associated with CCRV during pre-hospital resuscitation from OHCA. METHODS: Observational study of prospectively collected OHCA quality improvement data in two suburban EMS agencies in Arizona between 10/1/2008 and 12/31/2016. Subject-level mean CCRV during the first 10 min of compressions was correlated with categorical variables by the Wilcoxon rank-sum test and with continuous variables by the Spearman's rank correlation coefficient. Generalized estimating equation and linear mixed-effect models were used to study the trend of CCRV over time. RESULTS: During the study period, 2535 adult OHCA cases were treated. After exclusion criteria, 1140 cases remained for analysis. Median duration of recorded compressions was 8.70 min during the first 10 min of CPR. An overall decline in CCRV was observed even after adjusting for compression depth. The subject-level mean CCRV was higher for minutes 0-5 than for minutes 5-10 (mean 347.9 mm/s vs. 339.0 mm/s, 95% CI of the difference -12.4 to -5.4, p < 0.0001). Males exhibited a greater mean CCRV compared to females [344.4 mm/s (IQR 307.3-384.6) vs. 331.5 mm/s (IQR 285.3-385.5), p = 0.013]. Mean CCRV was negatively correlated with age and positively correlated with patient weight. CONCLUSION: CCRV declines significantly over the course of resuscitation. Patient characteristics including male sex, younger age, and increased weight were associated with a higher CCRV.

Overweight and obese humans demonstrate increased vascular endothelial NAD(P)H oxidase-p47(phox) expression and evidence of endothelial oxidative stress.

BACKGROUND: Obesity may alter vascular endothelial cell protein expression (VECPE) of molecules that influence susceptibility to atherosclerosis. METHODS AND RESULTS: Quantitative immunofluorescence was performed on vascular endothelial cells collected from 108 men and women free of clinical disease who varied widely in adiposity (body mass index 18.4 to 36.7 kg/m2; total body fat 5.8 to 55.0 kg; waist circumference: 63.0 to 122.9 cm). All 3 expressions of adiposity were positively associated with VECPE of the oxidant enzyme subunit NAD(P)H oxidase-p47(phox) (part correlation coefficient [r(part)] 0.22 to 0.24, all P < 0.05) and the antioxidant enzyme catalase (r(part) = 0.71 to 0.75, all P < 0.001). Total body fat was positively associated with VECPE of nitrotyrosine (r(part) = 0.36, P = 0.003), a marker of protein oxidation, and, in men, with Ser1177-phosphorylated endothelial nitric oxide synthase (r(part) = 0.46, P = 0.02), an activated form of endothelial nitric oxide synthase. Overweight/obese subjects (body mass index > or = 25 kg/m2) had 35% to 130% higher VECPE of NAD(P)H oxidase-p47(phox), nitrotyrosine, catalase, and the cytosolic antioxidant CuZn superoxide dismutase (all P < 0.05), as well as a 56% greater VECPE of the potent local vasoconstrictor endothelin-1 (P = 0.05) than normal-weight subjects (body mass index < 25 kg/m2). Nuclear factor-kappaB protein expression was approximately 60% to 100% greater in the most obese adults than in the leanest adults (P < or = 0.01). These relations were independent of sex but were selectively reduced after accounting for the influence of plasma C-reactive protein, fasting glucose-insulin metabolism, or serum triglycerides. CONCLUSIONS: Compared with their normal-weight peers, overweight and obese adults demonstrate increased vascular endothelial expression of NAD(P)H oxidase-p47(phox) and evidence of endothelial oxidative stress, with selective compensatory upregulation of antioxidant enzymes and Ser1177-phosphorylated endothelial nitric oxide synthase. Endothelin-1 and nuclear factor-kappaB protein expression also appear to be elevated in obese compared with lean adults. These findings may provide novel insight into the molecular mechanisms linking obesity to increased risk of clinical atherosclerotic diseases in humans.

Predictive value of reactive hyperemia for cardiovascular events in patients with peripheral arterial disease undergoing vascular surgery.

OBJECTIVE: Reactive hyperemia is the compensatory increase in blood flow that occurs after a period of tissue ischemia, and this response is blunted in patients with cardiovascular risk factors. The predictive value of reactive hyperemia for cardiovascular events in patients with atherosclerosis and the relative importance of reactive hyperemia compared with other measures of vascular function have not been previously studied. METHODS AND RESULTS: We prospectively measured reactive hyperemia and brachial artery flow-mediated dilation by ultrasound in 267 patients with peripheral arterial disease referred for vascular surgery (age 66+/-11 years, 26% female). Median follow-up was 309 days (range 1 to 730 days). Fifty patients (19%) had an event, including cardiac death (15), myocardial infarction (18), unstable angina (8), congestive heart failure (6), and nonhemorrhagic stroke (3). Patients with an event were older and had lower hyperemic flow velocity (75+/-39 versus 95+/-50 cm/s, P=0.009). Patients with an event also had lower flow-mediated dilation (4.5+/-3.0 versus 6.9+/-4.6%, P<0.001), and when these 2 measures of vascular function were included in the same Cox proportional hazards model, lower hyperemic flow (OR 2.7, 95% CI 1.2 to 5.9, P=0.018) and lower flow-mediated dilation (OR 4.2, 95% CI: 1.8 to 9.8, P=0.001) both predicted cardiovascular events while adjusting for other risk factors. CONCLUSIONS: Thus, lower reactive hyperemia is associated with increased cardiovascular risk in patients with peripheral arterial disease. Furthermore, flow-mediated dilation and reactive hyperemia incrementally relate to cardiovascular risk, although impaired flow-mediated dilation was the stronger predictor in this population. These findings further support the clinical relevance of vascular function measured in the microvasculature and conduit arteries in the upper extremity.

Cardiac rhythm analysis during ongoing cardiopulmonary resuscitation using the Analysis During Compressions with Fast Reconfirmation technology.

BACKGROUND: Pauses in chest compressions (CCs) have a negative association with survival from cardiac arrest. Electrocardiographic (ECG) rhythm analysis and defibrillator charging are significant contributors to CC pauses. OBJECTIVE: Accuracy of the Analysis During Compressions with Fast Reconfirmation (ADC-FR) algorithm, which features automated rhythm analysis and charging during CCs to reduce CC pauses, was retrospectively determined in a large database of ECGs from 2701 patients with out-of-hospital cardiac arrest. METHODS: The ADC-FR algorithm generated a total of 7264 advisories, of which 3575 were randomly assigned to a development data set and 3689 to a test data set. With ADC-FR, a high-pass digital filter is used to remove CC artifacts, while the underlying ECG rhythm is automatically interpreted. When CCs are paused at the end of the 2-minute cardiopulmonary resuscitation interval, a 3-second reconfirmation analysis is performed using the artifact-free ECG to confirm the shock/no-shock advisory. The sensitivity and specificity of the ADC-FR algorithm in correctly identifying shockable/nonshockable rhythms during CCs were calculated. RESULTS: In both data sets, the accuracy of the ADC-FR algorithm for each ECG rhythm exceeded the recommended performance goals, which apply to a standard artifact-free ECG analysis. Sensitivity and specificity were 97% and 99%, respectively, for the development data set and 95% and 99% for the test data set. CONCLUSION: The ADC-FR algorithm is highly accurate in discriminating shockable and nonshockable rhythms and can be used to reduce CC pauses.

Impaired flow-mediated dilation with age is not explained by L-arginine bioavailability or endothelial asymmetric dimethylarginine protein expression.

Aging is associated with a decline in vascular endothelial function, manifesting in part as impaired flow-mediated arterial dilation (FMD), but the underlying mechanisms are uncertain. Impaired FMD may be mediated in part by a decrease in synthesis of nitric oxide by endothelial nitric oxide synthase, and in clinical populations this has been attributed to competitive inhibition of l-arginine binding sites by asymmetric dimethylarginine (ADMA). If this mechanism is involved in the age-associated decline in FMD, increasing l-arginine concentration may swing the competitive balance in favor of l-arginine binding, restoring nitric oxide synthesis, and enhancing FMD in older humans. To test this hypothesis, we measured FMD (brachial ultrasound) in 10 younger (21 +/- 1 yr) and 12 older healthy men and women (60 +/- 2 yr) following infusion of vehicle or vehicle + l-arginine. Baseline FMD in the older subjects was only approximately 60% of that in the younger subjects (P = 0.002). l-Arginine did not significantly increase FMD in either group despite 23-fold (older) and 19-fold (younger) increases in plasma l-arginine concentrations (P < 0.0001 vs. control). Protein expression (immunofluorescence) in vascular endothelial cells showed that ADMA and the enzyme isoform that controls its degradation, dimethylarginine dimethylaminohydrolase II, were not different in the younger and older subjects. Endothelium-independent vasodilation (sublingual nitroglycerine) was not different between age groups or conditions. We conclude that acutely increasing plasma concentrations of l-arginine do not significantly improve brachial artery FMD in healthy older subjects and thus does not restore the age-associated loss of FMD. Together with the finding that endothelial cell ADMA protein expression was not increased in older adults, these findings suggest that competitive inhibition of l-arginine binding sites on endothelial nitric oxide synthase by ADMA is not an important mechanism contributing to impaired conduit artery endothelium-dependent dilation with aging in healthy humans.

The association between chest compression release velocity and outcomes from out-of-hospital cardiac arrest.

BACKGROUND: Previous studies have demonstrated significant relationships between cardiopulmonary resuscitation (CPR) quality metrics and survival to hospital discharge from out-of-hospital cardiac arrest (OHCA). Recently, it has been suggested that a new metric, chest compression release velocity (CCRV), may be associated with improved survival from OHCA. METHODS AND RESULTS: We performed a retrospective review of all treated adult OHCA occurring over a two year period beginning January 1, 2012. CPR metrics were abstracted from accelerometer measurements during each resuscitation. Multivariable regression analysis was used to examine the impact of CCRV on survival to hospital discharge. Secondary outcome measures were the impact of CCRV on return of spontaneous circulation (ROSC) and neurologically intact survival (MRS ≤ 3). Among 1800 treated OHCA, 1137 met inclusion criteria. The median (IQR) age was 71.6 (60.6, 82.3) with 724 (64%) being male. The median (IQR) CCRV (mm/s) amongst 96 survivors was 334.5 (300.0, 383.2) compared to 304.0 (262.6, 354.1) in 1041 non survivors (p < 0.001). When adjusted for Utstein variables, the odds of survival to hospital discharge for each 10 mm/s increase in CCRV was 1.02 (95% CI: 0.98, 1.06). Similarly the odds of ROSC and neurologically intact survival were 1.01 (95% CI: 0.99, 1.03) and 1.02 (95% CI: 0.98, 1.06), respectively. CONCLUSIONS: When adjusted for Utstein variables, CCRV was not significantly associated with outcomes from OHCA. Further research in other EMS systems is required to clarify the potential impact of this variable on OHCA survival.