Spinal and corticospinal excitability in response to reductions in skin and core temperature via whole-body cooling

Cold stress impairs fine and gross motor movements. Although peripheral effects of muscle cooling on performance are well understood, less is known about central mechanisms. This study characterized corticospinal and spinal excitability during surface cooling, reducing skin (Tsk) and core (Tes) temperature. Ten subjects (3 female) wore a liquid-perfused suit and were cooled (9°C perfusate, 90 min) and rewarmed (41°C perfusate, 30 min). Transcranial magnetic stimulation [eliciting motor evoked potentials (MEPs)], as well as transmastoid [eliciting cervicomedullary evoked potentials (CMEPs)] and brachial plexus [eliciting maximal compound motor action potentials (Mmax)] electrical stimulation, were applied at baseline, every 20 min during cooling, and following rewarming. Sixty minutes of cooling, reduced Tsk by 9.6°C (P<0.001) but Tes remained unchanged (P=0.92). Tes then decreased ~0.6℃ in the next 30 minutes of cooling (P<0.001). Eight subjects shivered. During rewarming, shivering was abolished, and Tsk returned to baseline while Tes did not increase. During cooling and rewarming, Mmax, MEP, and MEP/Mmax were unchanged from baseline. However, CMEP and CMEP/Mmax increased during cooling by ~85% and 79% (P<0.001) respectively, and remained elevated post-rewarming. Results suggest that spinal excitability is facilitated by reduced Tsk during cooling, and reduced Tes during warming, while corticospinal excitability remains unchanged. ClinicalTrials.gov ID NCT04253730 Novelty: • This is the first study to characterize corticospinal, and spinal excitability during whole body cooling, and rewarming in humans. • Whole body cooling did not affect corticospinal excitability. • Spinal excitability was facilitated during reductions in both skin and core temperatures.

Keeping Cool

Measurement of giraffe body temperature has shown that it is ~38.5oC but it can vary by ~5oC over the course of a day. Body heat is derived from fermentation of browse, other metabolic processes and radiant heat. Heat loss mechanisms partly depend on body surface area. Despite their unusual shape the body surface area of giraffes is similar to that in other equivalent body mass mammals: a shorter trunk is offset by a longer neck and legs. Heat loss by radiation is constant, by conduction rare and minimal. Their long, slender legs and neck are an advantage for convective and evaporative heat loss from the skin: heat transfer is inversely proportional to the square root of diameter. Evaporation from the respiratory system occurs through the nasal mucosa, the surface area of which in giraffes is large. Cooling of the nasal mucosa and blood follows and cool blood drains in to the jugular vein and contributes to whole body cooling and cooling of the blood supplying the brain by heat exchange in the carotid rete. Similar heat exchange may occur across the surface of the ossicones. Behavior changes when ambient temperature exceeds skin temperature. Giraffes re-orientate their bodies to minimize radiant heat gain and seek shade. A unique arrangement of blood vessels supplying blood to skin patches allows patches to act as thermal windows through which heat can be lost an arrangement enhanced by evaporation: sweat gland density in the skin of patches is greater than it is elsewhere.

Effects of passive heat stress and recovery on human cognitive function: An ERP study

Using event-related potentials (ERPs), we investigated the effects of passive heat stress and recovery on the human cognitive function with Flanker tasks, involving congruent and incongruent stimuli. We hypothesized that modulation of the peak amplitude and latency of the P300 component in ERP waveforms would differ with task difficulty during passive heat stress and recovery. Subjects performed the Flanker tasks before (Pre), at the end of whole body heating (Heat: internal temperature increase of ~1.2°C from the pre-heat baseline), and after the internal temperature had returned to the pre-heat baseline (Recovery). The internal temperature was regulated by a tube-lined suit by perfusing 50°C water for heat stress and 25°C water for recovery immediately after the heat stress. Regardless of task difficulty, the reaction time (RT) was shortened during Heat rather than Pre and Recovery, and standard deviations of RT (i.e., response variability) were significantly smaller during Heat than Pre. However, the peak amplitudes of the P300 component in ERPs, which involved selective attention, expectancy, and memory updating, were significantly smaller during Heat than during Pre, suggesting the impairment of neural activity in cognitive function. Notably, the peak amplitudes of the P300 component were higher during Recovery than during Heat, indicating that the impaired neural activity had recovered after sufficient whole-body cooling. An indicator of the stimulus classification/evaluation time (peak latency of P300) and the RT were shortened during Heat stress, but such shortening was not noted after whole-body cooling. These results suggest that hyperthermia affects the human cognitive function, reflected by the peak amplitude and latency of the P300 component in ERPs during the Flanker tasks, but sufficient treatment such as whole-body cooling performed in this study can recover those functions.

Exogenous Ketone Salt Supplementation and Whole-Body Cooling Do Not Improve Short-Term Physical Performance

Exogenous ketone supplementation and whole-body cooling (WBC) have shown to independently influence exercise metabolism. Whether readily available ketone salts, with and without WBC, would provide similar metabolic benefits during steady-state aerobic and time-trial performances was investigated. Nine active males (VO2peak: 56.3 ± 2.2 mL·kg−1·min−1) completed three single-blind exercise sessions preceded by: (1) ingestion of placebo (CON), (2) ketone supplementation (0.3 g·kg−1 β-OHB) (KET), and (3) ketone supplementation with WBC (KETCO). Participants cycled in steady-state (SS, 60% Wmax) condition for 30-min, immediately followed by a 15-min time trial (TT). Skin and core temperature, cardio-metabolic, and respiratory measures were collected continuously, whereas venous blood samples were collected before and after supplementation, after SS and TT. Venous β-OHB was elevated, while blood glucose was lower, with supplementation vs. CON (p &lt; 0.05). TT power output was not different between conditions (p = 0.112, CON: 190 ± 43.5 W, KET: 185 ± 40.4 W, KETCO: 211 ± 50.7 W). RER was higher during KETCO (0.97 ± 0.09) compared to both CON (0.88 ± 0.04, p = 0.012) and KET (0.88 ± 0.05, p = 0.014). Ketone salt supplementation and WBC prior to short-term exercise sufficiently increase blood β-OHB concentrations, but do not benefit metabolic shifts in fuel utilization or improve time trial performance.

Subcutaneous fat necrosis (SCFN) secondary to therapeutic hypothermia with persistent leucocytosis in a neonate

We report a term male neonate, born to consanguineous parents through a difficult labour who needed resuscitation at birth, followed by ventilation for respiratory distress. In view of suspected Hypoxic Ischemic Injury, he was started on whole body cooling for 72 hours. He was treated as suspected sepsis with 5 days of intravenous antibiotics. On day 6, he was noted to have hard, painless skin nodules of his back and left arm which was clinically diagnosed as subcutaneous fat necrosis. His serum calcium and phosphate levels remained normal throughout hospital stay. His full blood counts and bone profile were monitored regularly. During follow-up at 6 weeks, his white cell counts continued to be high with 69% lymphocytes. To our knowledge, this is the first case of SCFN of a neonate associated with persistent leucocytosis. Haematological and metabolic complications should be closely monitored in a neonate with subcutaneous fat necrosis.

Outcome of Infants with Hypoxic-Ischemic Encephalopathy Treated by Whole Body Cooling and Magnesium Sulfate

Therapeutic hypothermia (TH) either by selective head cooling or whole-body cooling decreases brain damage and provide neuroprotection and reduced mortality rate in cases of moderate-to-severe hypoxia-ischemia encephalopathy (HIE) of newborns, especially if started at first 6 hours after birth. Also, management with adjuvant therapies like magnesium sulfate (MS) provides more neuroprotection. The interventional randomized controlled research aimed to assess short-term actions of TH as sole therapy and in combination with MS as a neuroprotective agent for the treatment of HIE newborn infants. A total of 36 full-terms and near-term infants delivered at Assiut University Children's Hospital and fulfilled HIE criteria were enrolled. They were divided equally into three groups; Group 1 (n = 12) received whole body cooling during first 6 hours of life as a sole therapy; Group 2 (n = 12) received whole body cooling in addition to MS as adjuvant therapy; Group 3 (n = 12) received supportive intensive care measures as a control. TH plus MS group (group 2) had a significantly good short-term outcomes as short period of respiratory support and mechanical ventilation (p-value =0.001), less in incidence of convulsion (p-value = 0.001) and early in feeding initiation (p-value = 0.009), compared with other groups managed by TH (group 1) or by supportive treatment (group 3). In conclusion, whole body cooling in addition to MS as adjunctive therapy for the treatment of HIE neonates is safe therapy that improves short-term outcome both clinically and radiologically.

Methods for personal cooling in hot environment used in clothing and wearables

The use of an efficient personal cooling system in hot environments is becoming increasingly popular, as the increased air temperature provokes thermophysiological discomfort, heat stress, reduced productivity and could lead to several health issues. Different methods and devices for personal and local cooling have been developed over the years. The paper summarises the cooling methods applied in clothing and wearable items: phase-change materials, Peltier elements, evaporative cooling, water cooling and hybrid cooling. The local vs total (of the whole body) cooling is examined. The passive and active colling are analysed in terms of advantages, disadvantages and application.

The nitric oxide dependence of cutaneous microvascular function to independent and combined hypoxic cold exposure

When separated from local cooling, whole body cooling elicited cutaneous reflex vasoconstriction via mechanisms independent of nitric oxide removal. Hypoxia elicited cutaneous vasodilatation via mechanisms mediated primarily by nitric oxide synthase, rather than xanthine oxidase-mediated nitrite reduction. Cold-induced vasoconstriction was blunted by the opposing effect of hypoxic vasodilatation, whereas the underpinning mechanisms did not interrelate in the absence of local cooling. Full vasoconstriction was restored with nitric oxide synthase inhibition.

An injectable refrigerated hydrogel for Inducing local hypothermia and neuroprotection against traumatic brain injury

Hypothermia is a promising therapy for Traumatic brain injury (TBI) in the clinic. However, the neuroprotective outcomes of hypothermia-treated TBI are not consistent in clinical studies due to several severe side effects. Here, an injectable refrigerated hydrogel is designed to deliver 3-iodothyronamine (T1AM) to achieve a longer period of local hypothermia for TBI treatment. The hydrogel has four advantages: (1) It can be injected into injured site after TBI, where it forms a hydrogel and avoids the side effects of whole-body cooling. (2) The hydrogel can biodegrade and be used for controlled drug release. (3) Released T1AM can bind to trace amine-associated receptor 1 (TAAR1) to produce cyclic adenosine monophosphate (cAMP), which induces hypothermia. (4) This hydrogel has an increased medical value due to its simple operation and ability to achieve timely treatment. This hydrogel is able to cool the brain to 30.25 ± 2.25 °C for 12 hours while maintaining the body temperature at 36.80 ± 1.75 °C after TBI. More importantly, the hypothermia induced by this hydrogel leads to the maintenance of blood-brain barrier (BBB) integrity, the prevention of cell death, the reduction of the inflammatory response and brain edema, and the promotion of functional recovery after TBI. This cooling method can potentially be developed as a new approach for hypothermia treatment in TBI.