Nitric Oxide in Selective Cerebral Perfusion Could Enhance Neuroprotection During Aortic Arch Surgery

BackgroundHypothermic circulatory arrest (HCA) in aortic arch surgery has a significant risk of neurological injury despite the newest protective techniques and strategies. Nitric oxide (NO) could exert a protective role, reduce infarct area and increase cerebral perfusion. This study aims to investigate the possible neuroprotective effects of NO administered in the oxygenator of selective antegrade cerebral perfusion (SCP) during HCA.MethodsThirty male SD adult rats (450–550 g) underwent cardiopulmonary bypass (CPB), cooling to 22°C body core temperature followed by 30 min of HCA. Rats were randomized to receive SCP or SCP added with NO (20 ppm) administered through the oxygenator (SCP-NO). All animals underwent CPB-assisted rewarming to a target temperature of 35°C in 60 min. At the end of the experiment, rats were sacrificed, and brain collected. Immunofluorescence analysis was performed in blind conditions.ResultsNeuroinflammation assessed by allograft inflammatory factor 1 or ionized calcium-binding adapter molecule 1 expression, a microglia activation marker was lower in SCP-NO compared to SCP (4.11 ± 0.59 vs. 6.02 ± 0.18%; p < 0.05). Oxidative stress measured by 8oxodG, was reduced in SCP-NO (0.37 ± 0.01 vs. 1.03 ± 0.16%; p < 0.05). Brain hypoxic area extent, analyzed by thiols oxidation was attenuated in SCP-NO (1.85 ± 0.10 vs. 2.74 ± 0.19%; p < 0.05). Furthermore, the apoptotic marker caspases 3 was significantly reduced in SCP-NO (10.64 ± 0.37 vs. 12.61 ± 0.88%; p < 0.05).ConclusionsNitric oxide administration in the oxygenator during SCP and HCA improves neuroprotection by decreasing neuroinflammation, optimizing oxygen delivery by reducing oxidative stress and hypoxic areas, finally decreasing apoptosis.

Influence of Soldiers’ Cardiorespiratory Fitness on Physiological Responses and Dropouts During a Loaded Long-distance March

ABSTRACT Introduction In military service, marching is an important, common, and physically demanding task. Minimizing dropouts, maintaining operational readiness during the march, and achieving a fast recovery are desirable because the soldiers have to be ready for duty, sometimes shortly after an exhausting task. The present field study investigated the influence of the soldiers’ cardiorespiratory fitness on physiological responses during a long-lasting and challenging 34 km march. Materials and Methods Heart rate (HR), body core temperature (BCT), total energy expenditure (TEE), energy intake, motivation, and pain sensation were investigated in 44 soldiers (20.3 ± 1.3 years, 178.5 ± 7.0 cm, 74.8 ± 9.8 kg, body mass index: 23.4 ± 2.7 kg × m−2, peak oxygen uptake ($\dot{\rm{V}}$O2peak): 54.2 ± 7.9 mL × kg−1 × min−1) during almost 8 hours of marching. All soldiers were equipped with a portable electrocardiogram to record HR and an accelerometer on the hip, all swallowed a telemetry pill to record BCT, and all filled out a pre- and post-march questionnaire. The influence of aerobic capacity on the physiological responses during the march was examined by dividing the soldiers into three fitness groups according to their $\dot{\rm{V}}$O2peak. Results The group with the lowest aerobic capacity ($\dot{\rm{V}}$O2peak: 44.9 ± 4.8 mL × kg−1 × min−1) compared to the group with the highest aerobic capacity ($\dot{\rm{V}}$O2peak: 61.7 ± 2.2 mL × kg−1 × min−1) showed a significantly higher (P < .05) mean HR (133 ± 9 bpm and 125 ± 8 bpm, respectively) as well as peak BCT (38.6 ± 0.3 and 38.4 ± 0.2 °C, respectively) during the march. In terms of recovery ability during the break, no significant differences could be identified between the three groups in either HR or BCT. The energy deficit during the march was remarkably high, as the soldiers could only replace 22%, 26%, and 36% of the total energy expenditure in the lower, middle, and higher fitness group, respectively. The cardiorespiratory fittest soldiers showed a significantly higher motivation to perform when compared to the least cardiorespiratory fit soldiers (P = .002; scale from 1 [not at all] to 10 [extremely]; scale difference of 2.3). A total of nine soldiers (16%) had to end marching early: four soldiers (21%) in the group with the lowest aerobic capacity, five (28%) in the middle group, and none in the highest group. Conclusion Soldiers with a high $\dot{\rm{V}}$O2peak showed a lower mean HR and peak BCT throughout the long-distance march, as well as higher performance motivation, no dropouts, and lower energy deficit. All soldiers showed an enormous energy deficit; therefore, corresponding nutritional strategies are recommended.

Shear Stress Induced by Acute Heat Exposure Is Not Obligatory to Protect Against Endothelial Ischemia-reperfusion Injury in Humans

Acute heat exposure protects against endothelial ischemia-reperfusion (I/R) injury in humans. However, the mechanism/s mediating this protective effect remain unclear. We tested the hypothesis that inhibiting the increase in shear stress induced by acute heat exposure would attenuate the protection of endothelial function following I/R injury. Nine (3 women) young healthy participants were studied under 3 experimental conditions: 1) thermoneutral control; 2) whole-body heat exposure to increase body core temperature by 1.2 °C; 3) heat exposure + brachial artery compression to inhibit the temperature-dependent increase in shear stress. Endothelial function was assessed via brachial artery flow-mediated dilatation before (pre-I/R) and after (post-I/R) 20 min of arm ischemia followed by 20 min of reperfusion. Brachial artery shear rate was increased during heat exposure (681 ± 359 s-1), but not for thermoneutral control (140 ± 63 s-1; P < 0.01 vs. heat exposure) nor heat + brachial artery compression (139 ± 60 s-1; P < 0.01 vs. heat exposure). Ischemia-reperfusion injury reduced flow-mediated dilatation following thermoneutral control (pre-I/R, 5.5 ± 2.9 % vs. post-I/R, 3.8 ± 2.9 %; P = 0.06), but was protected following heat exposure (pre-I/R, 5.8 ± 2.9 % vs. post-I/R, 6.1 ± 2.9 %; P = 0.5) and heat + arterial compression (pre-I/R, 4.4 ± 2.8 % vs. post-I/R, 5.8 ± 2.8 %; P = 0.1). Contrary to our hypothesis, our findings demonstrate that shear stress induced by acute heat exposure is not obligatory to protect against endothelial I/R injury in humans.

Night-Restricted Feeding Improves Gut Health by Synchronizing Microbe-Driven Serotonin Rhythm and Eating Activity-Driven Body Temperature Oscillations in Growing Rabbits

The circadian misalignment of the gut microbiota caused by unusual eating times in adult animals is related to disease development. However, whether the composition and diurnal rhythm of gut microbiota can be optimized by synchronizing the window period of eating with natural eating habits to reduce the risk of diarrhea remains unclear, especially in growing animals. In this study, 108 5-week-old weaned rabbits (nocturnal animals) were randomly subjected to daytime feeding (DF) and night-restricted feeding (NRF). At age 12 weeks, six rabbits were selected from each group, and caecum and cecal contents, as well as serum samples were collected at 4-h intervals during 24 h. Overall, NRF was found to reduce the risk of diarrhea in growing rabbits, improved the diurnal rhythm and abundance of beneficial microorganisms, along with the production of beneficial metabolites, whereas reduced the abundance of potential pathogens (Synergistes, Desulfovibrio, and Alistipes). Moreover, NRF improved diurnal rhythm of tryptophan hydroxylase isoform 1 and serotonin. Furthermore, NRF strengthened the diurnal amplitude of body core temperature, and promoted the diurnal expression of intestinal clock genes (BMAL1, CLOCK, REV-ERBα, and PER1), and genes related to the regulation of the intestinal barrier (CLAUDIN-1), and intestinal epithelial cell self-proliferation and renewal (BMI1). In vitro simulation experiments further revealed that synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, which are important zeitgebers, could promote the diurnal expression of clock genes and CLAUDIN-1 in rabbit intestinal epithelial cells (RIEC), and enhance RIEC proliferation. This is the first study to reveal that NRF reprograms the diurnal rhythm of the gut microbiome, promotes the diurnal expression of clock genes and tight junction genes via synchronization of microbial-driven serotonin rhythm and eating activity-driven body temperature oscillations, thereby improving intestinal health and reducing the risk of diarrhea in growing rabbits. Collectively, these results provide a new perspective for the healthy feeding and management of growing animals.

Impact of a Cold Environment on the Performance of Professional Cyclists: A Pilot Study

The practice of physical activity in a variable climate during the same competition is becoming more and more common due to climate change and increasingly frequent climate disturbances. The main aim of this pilot study was to understand the impact of cold ambient temperature on performance factors during a professional cycling race. Six professional athletes (age = 27 ± 2.7 years; height = 180.86 ± 5.81 cm; weight = 74.09 ± 9.11 kg; % fat mass = 8.01 ± 2.47%; maximum aerobic power (MAP) = 473 ± 26.28 W, undertook ~20 h training each week at the time of the study) participated in the Tour de la Provence under cold environmental conditions (the ambient temperature was 15.6 ± 1.4 °C with a relative humidity of 41 ± 8.5% and the normalized ambient temperature (Tawc) was 7.77 ± 2.04 °C). Body core temperature (Tco) was measured with an ingestible capsule. Heart rate (HR), power, speed, cadence and the elevation gradient were read from the cyclists’ onboard performance monitors. The interaction (multivariate analysis of variance) of the Tawc and the elevation gradient has a significant impact (F(1.5) = 32.2; p < 0.001) on the variables (cadence, power, velocity, core temperature, heart rate) and on each individual. Thus, this pilot study shows that in cold environmental conditions, the athlete’s performance was limited by weather parameters (ambient temperature associated with air velocity) and race characteristics. The interaction of Tawc and elevation gradient significantly influences thermal (Tco), physiological (HR) and performance (power, speed and cadence) factors. Therefore, it is advisable to develop warm-up, hydration and clothing strategies for competitive cycling under cold ambient conditions and to acclimatize to the cold by training in the same conditions to those that may be encountered in competition.

Hypothermia modulates myeloid cell polarization in neonatal hypoxic–ischemic brain injury

Background Neonatal encephalopathy due to hypoxia–ischemia (HI) is a leading cause of death and disability in term newborns. Therapeutic hypothermia (HT) is the only recommended therapy. However, 30% still suffer from neurological deficits. Inflammation is a major hallmark of HI pathophysiology with myeloid cells being key players, participating either in progression or in resolution of injury-induced inflammation. In the present study, we investigated the impact of HT on the temporal and spatial dynamics of microglia/macrophage polarization after neonatal HI in newborn mice. Methods Nine-day-old C57BL/6 mice were exposed to HI through occlusion of the right common carotid artery followed by 1 h hypoxia. Immediately after HI, animals were cooled for 4 h or kept at physiological body core temperature. Analyses were performed at 1, 3 and 7 days post HI. Brain injury, neuronal cell loss, apoptosis and microglia activation were assessed by immunohistochemistry. A broad set of typical genes associated with classical (M1) and alternative (M2) myeloid cell activation was analyzed by real time PCR in ex vivo isolated CD11b+ microglia/macrophages. Purity and composition of isolated cells was determined by flow cytometry. Results Immediate HT significantly reduced HI-induced brain injury and neuronal loss 7 days post HI, whereas only mild non-significant protection from HI-induced apoptosis and neuronal loss were observed 1 and 3 days after HI. Microglia activation, i.e., Iba-1 immunoreactivity peaked 3 days after HI and was not modulated by HT. However, ex vivo isolated CD11b+ cells revealed a strong upregulation of the majority of M1 but also M2 marker genes at day 1, which was significantly reduced by HT and rapidly declined at day 3. HI induced a significant increase in the frequency of peripheral macrophages in sorted CD11b+ cells at day 1, which deteriorated until day 7 and was significantly decreased by HT. Conclusion Our data demonstrate that HT-induced neuroprotection is preceded by acute suppression of HI-induced upregulation of inflammatory genes in myeloid cells and decreased infiltration of peripheral macrophages, both representing potential important effector mechanisms of HT.

Comparative Analysis of Temperature Measurement Methods based on Degree of Agreement

Many sports have a high risk of climatic ailments, such as hypothermia, hyperthermia, and heatstroke. The measurement of a sportsperson's body core temperature (Tc) may have an impact on their performances and it assists them to avoid injuries as well. To avoid complications like electrolyte imbalances or infections, it's essential to precisely measure the core body temperature during targeted temperature control when spontaneous circulation has returned. Previous approaches on the other hand, are intrusive and difficult to use. The usual technique, an oesophageal thermometer, was compared to a disposable non-invasive temperature sensor that used the heat flux methodology. This research indicates that, non-invasive disposable sensors used to measure core body temperature are very reliable when used for targeted temperature control after overcoming a cardiac arrest successfully. The non-invasive method of temperature measurement has somewhat greater accuracy than the invasive approach. The results of this study must be confirmed by more clinical research with various sensor types to figure out if the bounds of agreement could be increased. This will ensure that the findings are accurate based on core temperature.

Brain thermal kinetics at brain-eyelid thermal tunnels overcoming COVID-19 thermometry limitations for automated asymptomatic infection detection in concert with physical and biological principles

For centuries, temperature measurement deficiencies attributable to biological barriers and low thermo-conductivity (k) have precluded accurate surface-based fever assessment. At this stage of the pandemic, infection detection in children (who due to immature immune system may not effectively respond to vaccines) is critical because children can be readily infected and also become a large mutation reservoir. We reveal hitherto-unrecognized worldwide body temperature measurements (T°), in children and adults, over tissue typified by low-k similar to wood that may reach 6.8°C in thermal variability, hampering thereby COVID-19 control. Brain-eyelid thermal tunnels’ (BTT) integration of low-k and high-k regions creating a thermal pathway for undisturbed heat transmission from hypothalamus to high-k skin eliminates current shortcomings and makes the brain indispensable for defeating COVID-19 given that brain thermoregulatory signals are not limited by mutations. Anatomo-histologic, emissive, physiologic, and thermometric bench-to-bedside studies characterized and overcome biophysical limitations of thermometry through high-k eyelid-enabled brain temperature measurements in children and adults. BTT eyelid features fat-free skin (~900 µm) and unique light emission through a blood/fat configuration in the underlying tunnel. Contrarily, forehead features variable and thick dermis (2000–2500 µm) and variable fat layers (1100–2800 µm) resulting in variable low-k as well as temperatures 1.97 °C lower than BTT temperature (BTT°). Highest emission present in only ~3.1% of forehead averaged 1.08±0.49 °C (mean±SD) less than BTT° (p=0.008). Environmental and biological impacts during fanning revealed thermal imaging limitations for COVID-19 screening. Comparison of paired measurements for 100 pediatric patients showed that in the children subgroup above 37°C, BTT° exceeded body core temperature (Core°) in 60/72 patients; the average difference in the 72 patients was 0.62±0.7°C (p<0.001 by unpaired t-test); and in the subgroup beyond 37.5°C, BTT° exceeded Core° in 30/32 patients. Delineating hypothalamic activity in children facilitates early infection detection, which is essential because children’s immunogenicity prevents effective vaccination and causes accelerated viral evolution. Capturing hypothalamic thermal signals from BTT was further supported by brain thermal kinetics via BTT using wearables during anesthesia, sedation, sleep, brain injury, exercise, and asymptomatic infection, which revealed brain/core discordance and enabled automated noninvasive afebrile infection detection for interrupting asymptomatic human-to-human transmission. BTT-based spot-check thermometry can be harmlessly implemented for children worldwide without undue burden and costs; meanwhile, continuous brain-eyelid T° in concert with biological and physical principles affords a new dimension for combating pandemics. The “detection–vaccination” pair solution presented is required to mitigate COVID-19 from spreading indefinitely through mutations and vaccine evasion while opening a viable path for eradicating COVID-19.

Core Temperature Measurement—Principles of Correct Measurement, Problems, and Complications

Core temperature reflects the temperature of the internal organs. Proper temperature measurement is essential to diagnose and treat temperature impairment in patients. However, an accurate approach has yet to be established. Depending on the method used, the obtained values may vary and differ from the actual core temperature. There is an ongoing debate regarding the most appropriate anatomical site for core temperature measurement. Although the measurement of body core temperature through a pulmonary artery catheter is commonly cited as the gold standard, the esophageal temperature measurement appears to be a reasonable and functional alternative in the clinical setting. This article provides an integrative review of invasive and noninvasive body temperature measurements and their relations to core temperature.