Cardiovascular effects of a continuous rate infusion of lidocaine in calves anesthetized with xylazine, midazolam, ketamine and isoflurane

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Limit on gamma(pi-0-]nu-nu-bar) from SN1987A

We consider the possible neutrino emission from SN1987A generated through the process γγ→π0→νν, which is permitted when the neutrinos have a right-handed component. This energy-loss mechanism is consistent with the supernova neutrino observations if the decay rate I (π0→νν̄) < (0.15-6.3) × 10-13 eV. When the reaction π0→νν̄ is mediated by weak gauge bosons the limit on the decay rate allows us to obtain constraints on neutrino masses, mv<5-27 keV, depending on the core temperature.

Reductions in systemic and skeletal muscle blood flow and oxygen delivery limit maximal aerobic capacity in humans

[EN] BACKGROUND: A classic, unresolved physiological question is whether central cardiorespiratory and/or local skeletal muscle circulatory factors limit maximal aerobic capacity (VO2max) in humans. Severe heat stress drastically reduces VO2max, but the mechanisms have never been studied. METHODS AND RESULTS: To determine the main contributing factor that limits VO2max with and without heat stress, we measured hemodynamics in 8 healthy males performing intense upright cycling exercise until exhaustion starting with either high or normal skin and core temperatures (+10 degrees C and +1 degrees C). Heat stress reduced VO2max, 2-legged VO2, and time to fatigue by 0.4+/-0.1 L/min (8%), 0.5+/-0.2 L/min (11%), and 2.2+/-0.4 minutes (28%), respectively (all P<0.05), despite heart rate and core temperature reaching similar peak values. However, before exhaustion in both heat stress and normal conditions, cardiac output, leg blood flow, mean arterial pressure, and systemic and leg O2 delivery declined significantly (all 5% to 11%, P<0.05), yet arterial O2 content and leg vascular conductance remained unchanged. Despite increasing leg O2 extraction, leg VO2 declined 5% to 6% before exhaustion in both heat stress and normal conditions, accompanied by enhanced muscle lactate accumulation and ATP and creatine phosphate hydrolysis. CONCLUSIONS: These results demonstrate that in trained humans, severe heat stress reduces VO2max by accelerating the declines in cardiac output and mean arterial pressure that lead to decrements in exercising muscle blood flow, O2 delivery, and O2 uptake. Furthermore, the impaired systemic and skeletal muscle aerobic capacity that precedes fatigue with or without heat stress is largely related to the failure of the heart to maintain cardiac output and O2 delivery to locomotive muscle.

Studio dei ritmi circadiani in pazienti in stato vegetativo

Objective: To study circadian rhythms (sleep-wake, body core temperature and melatonin circadian rhythms) in patients in vegetative state (VS) in basal condition and after nocturnal blue light exposure. Methods: Eight patients in VS underwent two experimental sessions of 48 consecutive hours polysomnography with body core temperature (BCT) measurement separated by a 1-week interval. For a week between the two experimental sessions, patients underwent nocturnal blue light exposure (470 nm; 58 μW/cm2 for 4 hours from 11.30 p.m. to 3.30 a.m.). Brain MRI, Level of Cognitive Functioning Scale (LCF) and Disability Rating Scale (DRS) were assessed just before polysomnography. Results: In all patients LCF and DRS confirmed vegetative state. All patients showed a sleep-wake cycle. All patients showed spindle or spindle-like activities. REM sleep was detected in only 7 patients. Patients displayed a greater fragmentation of nocturnal sleep due to frequent awakenings. Mean nocturnal sleep efficiency was significantly reduced (40±22 vs. 74±17) in VS patients respect to controls. A significantly increasing of phase 1 and a significantly reduction of phase 2 and phase 3 were observed too. A modification of diurnal sleep total time and of diurnal duration of REM sleep were found after 1-week nocturnal blue light exposure. All patients displayed a normal BCT 24-h rhythm in basal condition and after nocturnal blue light exposure. A reduction of mean nocturnal melatonin levels in basal condition were observed in VS patients. Melatonin suppression after blue light exposure was observed in only 2 patients in VS. Conclusions: We found disorganized sleep-wake cycle and a normal BCT rhythm in our patients in VS. A reduction of mean nocturnal melatonin levels in basal condition were observed too.

Resistive-Polymer Versus Forced-Air Warming: Comparable Efficacy in Orthopedic Patients

BACKGROUND: Several adverse consequences are caused by mild perioperative hypothermia. Maintaining normothermia with patient warming systems, today mostly with forced air (FA), has thus become a standard procedure during anesthesia. Recently, a polymer-based resistive patient warming system was developed. We compared the efficacy of a widely distributed FA system with the resistive-polymer (RP) system in a prospective, randomized clinical study. METHODS: Eighty patients scheduled for orthopedic surgery were randomized to either FA warming (Bair Hugger warming blanket #522 and blower #750, Arizant, Eden Prairie, MN) or RP warming (Hot Dog Multi-Position Blanket and Hot Dog controller, Augustine Biomedical, Eden Prairie, MN). Core temperature, skin temperature (head, upper and lower arm, chest, abdomen, back, thigh, and calf), and room temperature (general and near the patient) were recorded continuously. RESULTS: After an initial decrease, core temperatures increased in both groups at comparable rates (FA: 0.33 degrees C/h +/- 0.34 degrees C/h; RP: 0.29 degrees C/h +/- 0.35 degrees C/h; P = 0.6). There was also no difference in the course of mean skin and mean body (core) temperature. FA warming increased the environment close to the patient (the workplace of anesthesiologists and surgeons) more than RP warming (24.4 degrees C +/- 5.2 degrees C for FA vs 22.6 degrees C +/- 1.9 degrees C for RP at 30 minutes; P(AUC) <0.01). CONCLUSION: RP warming performed as efficiently as FA warming in patients undergoing orthopedic surgery.

Millennial and sub-millennial scale climatic variations recorded in polar ice cores over the last glacial period

Since its discovery in Greenland ice cores, the millennial scale climatic variability of the last glacial period has been increasingly documented at all latitudes with studies focusing mainly on Marine Isotopic Stage 3 (MIS 3; 28–60 thousand of years before present, hereafter ka) and characterized by short Dansgaard-Oeschger (DO) events. Recent and new results obtained on the EPICA and NorthGRIP ice cores now precisely describe the rapid variations of Antarctic and Greenland temperature during MIS 5 (73.5–123 ka), a time period corresponding to relatively high sea level. The results display a succession of abrupt events associated with long Greenland InterStadial phases (GIS) enabling us to highlight a sub-millennial scale climatic variability depicted by (i) short-lived and abrupt warming events preceding some GIS (precursor-type events) and (ii) abrupt warming events at the end of some GIS (rebound-type events). The occurrence of these sub-millennial scale events is suggested to be driven by the insolation at high northern latitudes together with the internal forcing of ice sheets. Thanks to a recent NorthGRIP-EPICA Dronning Maud Land (EDML) common timescale over MIS 5, the bipolar sequence of climatic events can be established at millennial to sub-millennial timescale. This shows that for extraordinary long stadial durations the accompanying Antarctic warming amplitude cannot be described by a simple linear relationship between the two as expected from the bipolar seesaw concept. We also show that when ice sheets are extensive, Antarctica does not necessarily warm during the whole GS as the thermal bipolar seesaw model would predict, questioning the Greenland ice core temperature records as a proxy for AMOC changes throughout the glacial period.

Ondansetron does not reduce the shivering threshold in healthy volunteers

BACKGROUND: Ondansetron, a serotonin-3 receptor antagonist, reduces postoperative shivering. Drugs that reduce shivering usually impair central thermoregulatory control, and may thus be useful for preventing shivering during induction of therapeutic hypothermia. We determined, therefore, whether ondansetron reduces the major autonomic thermoregulatory response thresholds (triggering core temperatures) in humans. METHODS: Control (placebo) and ondansetron infusions at the target plasma concentration of 250 ng ml(-1) were studied in healthy volunteers on two different days. Each day, skin and core temperatures were increased to provoke sweating; then reduced to elicit peripheral vasoconstriction and shivering. We determined the core-temperature sweating, vasoconstriction and shivering thresholds after compensating for changes in mean-skin temperature. Data were analysed using t-tests and presented as means (sds); P<0.05 was taken as significant. RESULTS: Ondensetron plasma concentrations were 278 (57), 234 (55) and 243 (58) ng ml(-1) at the sweating, vasoconstriction and shivering thresholds, respectively; these corresponded to approximately 50 mg of ondansetron which is approximately 10 times the dose used for postoperative nausea and vomiting. Ondansetron did not change the sweating (control 37.4 (0.4) degrees C, ondansetron 37.6 (0.3) degrees C, P=0.16), vasoconstriction (37.0 (0.5) degrees C vs 37.1 (0.3) degrees C; P=0.70), or shivering threshold (36.3 (0.5) degrees C vs 36.3 (0.6) degrees C; P=0.76). No sedation was observed on either study day. CONCLUSIONS: /b>. Ondansetron appears to have little potential for facilitating induction of therapeutic hypothermia.

Meperidine and skin surface warming additively reduce the shivering threshold: a volunteer study

INTRODUCTION: Mild therapeutic hypothermia has been shown to improve outcome for patients after cardiac arrest and may be beneficial for ischaemic stroke and myocardial ischaemia patients. However, in the awake patient, even a small decrease of core temperature provokes vigorous autonomic reactions-vasoconstriction and shivering-which both inhibit efficient core cooling. Meperidine and skin warming each linearly lower vasoconstriction and shivering thresholds. We tested whether a combination of skin warming and a medium dose of meperidine additively would reduce the shivering threshold to below 34 degrees C without producing significant sedation or respiratory depression. METHODS: Eight healthy volunteers participated on four study days: (1) control, (2) skin warming (with forced air and warming mattress), (3) meperidine (target plasma level: 0.9 mug/ml), and (4) skin warming plus meperidine (target plasma level: 0.9 mug/ml). Volunteers were cooled with 4 degrees C cold Ringer lactate infused over a central venous catheter (rate asymptotically equal to 2.4 degrees C/hour core temperature drop). Shivering threshold was identified by an increase of oxygen consumption (+20% of baseline). Sedation was assessed with the Observer's Assessment of Alertness/Sedation scale. RESULTS: Control shivering threshold was 35.5 degrees C +/- 0.2 degrees C. Skin warming reduced the shivering threshold to 34.9 degrees C +/- 0.5 degrees C (p = 0.01). Meperidine reduced the shivering threshold to 34.2 degrees C +/- 0.3 degrees C (p < 0.01). The combination of meperidine and skin warming reduced the shivering threshold to 33.8 degrees C +/- 0.2 degrees C (p < 0.01). There were no synergistic or antagonistic effects of meperidine and skin warming (p = 0.59). Only very mild sedation occurred on meperidine days. CONCLUSION: A combination of meperidine and skin surface warming reduced the shivering threshold to 33.8 degrees C +/- 0.2 degrees C via an additive interaction and produced only very mild sedation and no respiratory toxicity.

Postmortem quantitative 1.5-T MRI for the differentiation and characterization of serous fluids, blood, CSF, and putrefied CSF.

The purpose of the present study was to investigate whether serous fluids, blood, cerebrospinal fluid (CSF), and putrefied CSF can be characterized and differentiated in synthetically calculated magnetic resonance (MR) images based on their quantitative T 1, T 2, and proton density (PD) values. Images from 55 postmortem short axis cardiac and 31 axial brain 1.5-T MR examinations were quantified using a quantification sequence. Serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF were analyzed for their mean T 1, T 2, and PD values. Body core temperature was measured during the MRI scans. The fluid-specific quantitative values were related to the body core temperature. Equations to correct for temperature differences were generated. In a 3D plot as well as in statistical analysis, the quantitative T 1, T 2 and PD values of serous fluids, fluid blood, sedimented blood, blood clots, CSF, and putrefied CSF could be well differentiated from each other. The quantitative T 1 and T 2 values were temperature-dependent. Correction of quantitative values to a temperature of 37 °C resulted in significantly better discrimination between all investigated fluid mediums. We conclude that postmortem 1.5-T MR quantification is feasible to discriminate between blood, serous fluids, CSF, and putrefied CSF. This finding provides a basis for the computer-aided diagnosis and detection of fluids and hemorrhages.

Minimally invasive extracorporeal circulation resuscitation in hypothermic cardiac arrest.

Current guidelines for the treatment of hypothermic cardiocirculatory arrest recommend extracorporeal life support and rewarming, using cardiopulmonary bypass or extracorporeal membrane oxygenation circuits. Both have design-related shortcomings which may result in prolonged reperfusion time or insufficient oxygen delivery to vital organs. This article describes clear advantages of minimally invasive extracorporeal circulation systems during emergency extracorporeal life support in hypothermic arrest. The technique of minimally invasive extracorporeal circulation for reperfusion and rewarming is represented by the case of a 59-year-old patient in hypothermic cardiocirculatory arrest at 25.3°C core temperature, with multiple trauma. With femoro-femoral cannulation performed under sonographic and echocardiographic guidance, extracorporeal life support was initiated using a minimally invasive extracorporeal circulation system. Perfusing rhythm was restored at 28°C. During rewarming on the mobile circuit, trauma surveys were completed and the treatment initiated. Normothermic weaning was successful on the first attempt, trauma surgery was completed and the patient survived neurologically intact. For extracorporeal resuscitation from hypothermic arrest, minimally invasive extracorporeal circulation offers all the advantages of conventional cardiopulmonary bypass and extracorporeal membrane oxygenation systems without their shortcomings.

Molecular properties of gases of ODP Leg 204 sites

The recognition of finely disseminated gas hydrate in deep marine sediments heavily depends on various indirect techniques because this mineral quickly decomposes upon recovery from in situ pressure and temperature conditions. Here, we discuss molecular properties of closely spaced gas voids (formed as a result of core recovery) and gas hydrates from an area of relatively low gas flux at the flanks of the southern Hydrate Ridge offshore Oregon (ODP Sites 1244, 1245 and 1247). Within the gas hydrate occurrence zone (GHOZ), the concentration of ethane (C2) and propane (C3) in adjacent gas voids shows large variability. Sampled gas hydrates are enriched in C2 relative to void gases but do not contain C3. We suggest that the observed variations in the composition of void gases is a result of molecular fractionation during crystallization of structure I gas hydrate that contains C2 but excludes C3 from its crystal lattice. This hypothesis is used to identify discrete intervals of finely disseminated gas hydrate in cored sediments. Variations in gas composition help better constrain gas hydrate distribution near the top of the GHOZ along with variations in pore water chemistry and core temperature. Sediments near the base of the gas hydrate stability zone are relatively enriched in C2+ hydrocarbon gases. Complex and poorly understood geological and geochemical processes in these deeper sediments make the identification of gas hydrate based on molecular properties of void gases more ambiguous. The proposed technique appears to be a useful tool to better understand the distribution of gas hydrate in marine sediments and ultimately the role of gas hydrate in the global carbon cycle.

Gas content, composition of gas hydrate and volumetric gas/water ratios of ODP and DSDP sites

Gas hydrate samples were recovered from four sites (Sites 994, 995, 996, and 997) along the crest of the Blake Ridge during Ocean Drilling Program (ODP) Leg 164. At Site 996, an area of active gas venting, pockmarks, and chemosynthetic communities, vein-like gas hydrate was recovered from less than 1 meter below seafloor (mbsf) and intermittently through the maximum cored depth of 63 mbsf. In contrast, massive gas hydrate, probably fault filling and/or stratigraphically controlled, was recovered from depths of 260 mbsf at Site 994, and from 331 mbsf at Site 997. Downhole-logging data, along with geochemical and core temperature profiles, indicate that gas hydrate at Sites 994, 995, and 997 occurs from about 180 to 450 mbsf and is dispersed in sediment as 5- to 30-m-thick zones of up to about 15% bulk volume gas hydrate. Selected gas hydrate samples were placed in a sealed chamber and allowed to dissociate. Evolved gas to water volumetric ratios measured on seven samples from Site 996 ranged from 20 to 143 mL gas/mL water to 154 mL gas/mL water in one sample from Site 994, and to 139 mL gas/mL water in one sample from Site 997, which can be compared to the theoretical maximum gas to water ratio of 216. These ratios are minimum gas/water ratios for gas hydrate because of partial dissociation during core recovery and potential contamination with pore waters. Nonetheless, the maximum measured volumetric ratio indicates that at least 71% of the cages in this gas hydrate were filled with gas molecules. When corrections for pore-water contamination are made, these volumetric ratios range from 29 to 204, suggesting that cages in some natural gas hydrate are nearly filled. Methane comprises the bulk of the evolved gas from all sites (98.4%-99.9% methane and 0%-1.5% CO2). Site 996 hydrate contained little CO2 (0%-0.56%). Ethane concentrations differed significantly from Site 996, where they ranged from 720 to 1010 parts per million by volume (ppmv), to Sites 994 and 997, which contained much less ethane (up to 86 ppmv). Up to 19 ppmv propane and other higher homologues were noted; however, these gases are likely contaminants derived from sediment in some hydrate samples. CO2 concentrations are less in gas hydrate than in the surrounding sediment, likely an artifact of core depressurization, which released CO2 derived from dissolved organic carbon (DIC) into sediment. The isotopic composition of methane from gas hydrate ranges from d13C of -62.5 per mil to -70.7 per mil and dD of -175 per mil to -200 per mil and is identical to the isotopic composition of methane from surrounding sediment. Methane of this isotopic composition is mainly microbial in origin and likely produced by bacterial reduction of bicarbonate. The hydrocarbon gases here are likely the products of early microbial diagenesis. The isotopic composition of CO2 from gas hydrate ranges from d13C of -5.7 per mil to -6.9 per mil, about 15 per mil lighter than CO2 derived from nearby sediment.

Hipotermia terapêutica no traumatismo crânio-encefálico

Enquadramento – A hipotermia terapêutica consiste na redução controlada da temperatura central dos doentes com objetivos terapêuticos pré-definidos, assumindo-se actualmente como uma mais-valia no tratamento clínico de vítimas com TCE. Objetivos – Avaliar a eficácia da HT intra-hospitalar na redução da morbilidade e mortalidade do adulto vítima de TCE. Métodos – Foi realizada uma revisão sistemática da literatura sobre a eficácia da HT intrahospitalar na redução da morbilidade e mortalidade do adulto vítima de TCE. Efetuou-se uma pesquisa na PUBMED, The Cochrane Library, Scielo e Google Académico de estudos publicados entre 1 de janeiro de 2012 a 31 de agosto de 2014. Partindo dos critérios de inclusão previamente definidos, os estudos selecionados foram posteriormente avaliados. Dois revisores avaliaram a qualidade dos estudos a incluir, utilizando a grelha para a avaliação crítica de um estudo de Ascenção et al. (2008). Resultados – Quatro artigos preencheram os critérios de inclusão, tendo-se constituído como corpus amostral. Como metasíntese e seleção da análise dos artigos, inferiu-se que os potenciais benefícios neuroprotetores da hipotermia terapêutica, sem efeitos colaterais negativos, deve ser implementada como parte do quotidiano de tratamento e controlo das vítimas de TCE e não como terapia de resgate. Contudo, a validação das implicações práticas da HT carece de mais estudos, cuja indução seja fator neuroprotetor, independentemente do valor da PIC, individualizando a duração da indução da hipotermia. Conclusão – Os benefícios da HT em adultos vítimas de TCE são ainda alvo de debate, requerendo a realização de mais metanálises e ensaios clínicos, visando a atualização das suas recomendações. Palavras-chave – Hipotermia terapêutica; traumatismo crânio-encefálico; eficácia

Impact of acute weight loss and/or thermal stress on rowing ergometer performance

Purpose: The impact of acute weight loss on rowing performance was assessed when generous nutrient intake was provided in 2 h of recovery after making weight. Methods: Competitive rowers (N = 17) completed four ergometer trials, each separated by 48 h. Two trials were performed after a 4% body mass loss in the previous 24 h (WT) and two were performed after no weight restrictions, that is, unrestricted (UNR). In addition, two trials (I X WT, I X UNR) were in a thermoneutral environment (NEUTRAL, mean 21.1 +/- SD 0.7 degrees C, 29.0 +/- 4.5% RH) and two were in the heat (HOT 32.4, +/- 0.4 degrees C, 60.4 +/- 2.7% RH). Trials were performed in a counterbalanced fashion according to a Latin square design. Aggressive nutritional recovery strategies (WT 2.3 g(.)kg(-11) carbohydrate, 34 mg-kg(-1) Na, 28.4 mL(.)kg(-1) fluid; UNR ad libitum) were employed in the 2 h after weigh-in. Results: Both WT (mean 2.1, 95% CI 0.7-3.4 s; P = 0.003) and HOT (4.1, 2.7 - 5.4 s; P < 0.001) compromised 2000-m time-trial performance. Whereas WT resulted in hypohydration, the associated reduction in plasma volume explained only part of the performance compromise observed (0.2 s for every 1% decrement) Moreover, WT did not influence core temperature or indices of cardiovascular function. Conclusions: Acute weight loss compromised performance, despite generous nutrient intake in recovery, although the effect was small. Performance decrements were further exacerbated when exercise was performed in the heat.

Leukocyte subset responses during exercise under heat stress with carbohydrate or water intake

Purpose: This study investigated leukocyte subset responses to moderate-intensity exercise under heat stress, with water (W) or carbohydrate (CHO) drink ingestion. Methods: In repeated trials, 13 soldiers consumed either a W or CHO drink during 3 h of walking at 4.4 km center dot h(-1) with a 5% gradient (15 min rest per hour) under heat stress (35 C and 55% relative humidity). The soldiers wore combat uniforms and carried water bottles and dummy rifles and ammunition, altogether weighing about 11.5 +/- 1.0 kg. Results: Plasma glucose concentration was significantly higher with CHO than W ingestion during exercise (p < 0.01). There were no significant differences between W and CHO conditions in exercise performance, plasma cortisol concentration, heart rate, or core temperature. CHO ingestion significantly moderated the increases in leukocyte (83% in W, 28% in CHO; p < 0.001), monocyte (60% in W, 34% in CHO; p < 0.05), and granulocyte counts (120% in W, 30% in CHO; p < 0.001), but not in lymphocyte count (41% in W, 25% in CHO). Conclusions: The increases in leukocyte and subset counts during moderate-intensity exercise under heat stress may be comparable to those observed during intense exercise in cool conditions. The response of immune cell counts is blunted by CHO intake during moderate-intensity exercise in the heat, and may not occur through the cortisol pathway.