Ventilation during continuous compressions or at 30:2 compression-to-ventilation ratio results in similar arterial oxygen and carbon dioxide levels in an experimental model of prolonged cardiac arrest

Background: In refractory out-of-hospital cardiac arrest, transportation to hospital with continuous chest compressions (CCC) from a chest compression device and ventilation with 100% oxygen through an advanced airway is common practice. Despite this, many patients are hypoxic and hypercapnic on arrival, possibly related to suboptimal ventilation due to the counterpressure caused by the CCC. We hypothesized that a compression/ventilation ratio of 30:2 would provide better ventilation and gas exchange compared to asynchronous CCC during prolonged experimental cardiopulmonary resuscitation (CPR).Methods: We randomized 30 anaesthetized domestic swine (weight approximately 50 kg) with electrically induced ventricular fibrillation to the CCC or 30:2 group and bag-valve ventilation with a fraction of inspired oxygen (FiO(2)) of 100%. We started CPR after a 5-min no-flow period and continued until 40 min from the induction of ventricular fibrillation. Chest compressions were performed with a Stryker Medical LUCAS (R) 2 mechanical chest compression device. We collected arterial blood gas samples every 5 min during the CPR, measured ventilation distribution during the CPR using electrical impedance tomography (EIT) and analysed post-mortem computed tomography (CT) scans for differences in lung aeration status.Results: The median (interquartile range [IQR]) partial pressure of oxygen (PaO2) at 30 min was 110 (52-117) mmHg for the 30:2 group and 70 (40-171) mmHg for the CCC group. The median (IQR) partial pressure of carbon dioxide (PaCO2) at 30 min was 70 (45-85) mmHg for the 30:2 group and 68 (42-84) mmHg for the CCC group. No statistically significant differences between the groups in PaO2 (p =0.40), PaCO2 (p = 0.79), lactate (p = 0.37), mean arterial pressure (MAP) (p = 0.47) or EtCO2 (p = 0.19) analysed with a linear mixed model were found. We found a deteriorating trend in PaO2, EtCO2 and MAP and rising PaCO2 and lactate levels through the intervention. There were no differences between the groups in the distribution of ventilation in the EIT data or the post-mortem CT findings.Conclusions: The 30:2 and CCC protocols resulted in similar gas exchange and lung pathology in an experimental prolonged mechanical CPR model.Peer reviewe

Niacin Cures Systemic NAD(+) Deficiency and Improves Muscle Performance in Adult-Onset Mitochondrial Myopathy

NAD(+) is a redox-active metabolite, the depletion of which has been proposed to promote aging and degenerative diseases in rodents. However, whether NAD(+) depletion occurs in patients with degenerative disorders and whether NAD(+) repletion improves their symptoms has remained open. Here, we report systemic NAD(+) deficiency in adult-onset mitochondrial myopathy patients. We administered an increasing dose of NAD(+) booster niacin, a vitamin B3 form (to 750-1,000 mg/day; clinicaltrials.gov NCT03973203) for patients and their matched controls for 10 or 4 months, respectively. Blood NAD(+) increased in all subjects, up to 8-fold, and muscle-NAD(+) of patients reached the level of their controls. Some patients showed anemia tendency, while muscle strength and mitochondrial biogenesis increased in all subjects. In patients, muscle metabolome shifted toward controls and liver fat decreased even 50%. Our evidence indicates that blood analysis is useful in identifying NAD(+) deficiency and points niacin to be an efficient NAD(+) booster for treating mitochondrial myopathy.Peer reviewe

Nicotinamide riboside improves muscle mitochondrial biogenesis, satellite cell differentiation, and gut microbiota in a twin study

Nicotinamide adenine dinucleotide (NAD(+)) precursor nicotinamide riboside (NR) has emerged as a promising compound to improve obesity-associated mitochondrial dysfunction and metabolic syndrome in mice. However, most short-term clinical trials conducted so far have not reported positive outcomes. Therefore, we aimed to determine whether long-term NR supplementation boosts mitochondrial biogenesis and metabolic health in humans. Twenty body mass index (BMI)- discordant monozygotic twin pairs were supplemented with an escalating dose of NR (250 to 1000 mg/day) for 5 months. NR improved systemic NAD(+) metabolism, muscle mitochondrial number, myoblast differentiation, and gut microbiota composition in both cotwins. NR also showed a capacity to modulate epigenetic control of gene expression in muscle and adipose tissue in both cotwins. However, NR did not ameliorate adiposity or metabolic health. Overall, our results suggest that NR acts as a potent modifier of NAD(+) metabolism, muscle mitochondrial biogenesis and stem cell function, gut microbiota, and DNA methylation in humans irrespective of BMI.Peer reviewe

Meta-analysis of Genome-Wide Association Studies for Extraversion: Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Meta-analysis of genome-wide association studies for extraversion:Findings from the Genetics of Personality Consortium

Extraversion is a relatively stable and heritable personality trait associated with numerous psychosocial, lifestyle and health outcomes. Despite its substantial heritability, no genetic variants have been detected in previous genome-wide association (GWA) studies, which may be due to relatively small sample sizes of those studies. Here, we report on a large meta-analysis of GWA studies for extraversion in 63,030 subjects in 29 cohorts. Extraversion item data from multiple personality inventories were harmonized across inventories and cohorts. No genome-wide significant associations were found at the single nucleotide polymorphism (SNP) level but there was one significant hit at the gene level for a long non-coding RNA site (LOC101928162). Genome-wide complex trait analysis in two large cohorts showed that the additive variance explained by common SNPs was not significantly different from zero, but polygenic risk scores, weighted using linkage information, significantly predicted extraversion scores in an independent cohort. These results show that extraversion is a highly polygenic personality trait, with an architecture possibly different from other complex human traits, including other personality traits. Future studies are required to further determine which genetic variants, by what modes of gene action, constitute the heritable nature of extraversion

Oxygenation and ventilation during prolonged experimental cardiopulmonary resuscitation with either continuous or 30:2 compression-to-ventilation ratios together with 10 cmH20 positive end-expiratory pressure

Background: In refractory out-of-hospital cardiac arrest, the patient is commonly transported to hospital with mechanical continuous chest compressions (CCC). Limited data are available on the optimal ventilation strategy. Accordingly, we compared arterial oxygenation and haemodynamics during manual asynchronous continuous ventilation and compressions with a 30:2 compression-to-ventilation ratio together with the use of 10 cmH2O positive end-expiratory pressure (PEEP). Methods: Intubated and anaesthetized landrace pigs with electrically induced ventricular fibrillation were left untreated for 5 min (n = 31, weight ca. 55 kg), after which they were randomized to either the CCC group or the 30:2 group with the the LUCAS® 2 piston device and bag-valve ventilation with 100% oxygen targeting a tidal volume of 8 ml/kg with a PEEP of 10 cmH2O for 35 min. Arterial blood samples were analysed every 5 min, vital signs, near-infrared spectroscopy and electrical impedance tomography (EIT) were measured continuously, and post-mortem CT scans of the lungs were obtained. Results: The arterial blood values (median + interquartile range) at the 30-min time point were as follows: PaO2: 180 (86–302) mmHg for the 30:2 group; 70 (49–358) mmHg for the CCC group; PaCO2: 41 (29–53) mmHg for the 30:2 group; 44 (21–67) mmHg for the CCC group; and lactate: 12.8 (10.4–15.5) mmol/l for the 30:2 group; 14.7 (11.8–16.1) mmol/l for the CCC group. The differences were not statistically significant. In linear mixed models, there were no significant differences between the groups. The mean arterial pressures from the femoral artery, end-tidal CO2, distributions of ventilation from EIT and mean aeration of lung tissue in post-mortem CTs were similar between the groups. Eight pneumothoraces occurred in the CCC group and 2 in the 30:2 group, a statistically significant difference (p = 0.04). Conclusions: The 30:2 and CCC protocols with a PEEP of 10 cmH2O resulted in similar gas exchange and vital sign outcomes in an experimental model of prolonged cardiac arrest with mechanical compressions, but the CCC protocol resulted in more post-mortem pneumothoraces.Peer reviewe