Effects of hyperthermia and acidosis on mitochondrial production of reactive oxygen species.

Exercise is associated with the development of oxidative stress, but the specific source and mechanism of production of pro-oxidant chemicals during exercise has not been confirmed. We used equine skeletal muscle mitochondria to test the hypothesis that hyperthermia and acidosis affect mitochondrial oxygen consumption and production of reactive oxygen species (ROS). Skeletal muscle biopsies were obtained at rest, after an acute episode of fatiguing exercise, and after a 9-wk conditioning program to increase aerobic fitness. Mitochondrial oxygen consumption and ROS production were measured simultaneously using high-resolution respirometry. Both hyperthermia and acidosis increased nonphosphorylating (LEAK) respiration (5.8× and 3.0×, respectively, P < 0.001) and decreased efficiency of oxidative phosphorylation. The combined effects of hyperthermia and acidosis resulted in large decreases in phosphorylating respiration, further decreasing oxidative phosphorylation efficiency from 97% to 86% (P < 0.01). Increased aerobic fitness reduced the effects of acidosis on LEAK respiration. Hyperthermia increased and acidosis decreased ROS production (2× and 0.23×, respectively, P < 0.001). There was no effect of acute exercise, but an aerobic conditioning program was associated with increased ROS production during both nonphosphorylating and phosphorylating respiration. Hyperthermia increased the ratio of ROS production to O2 consumption during phosphorylating respiration, suggesting that high-temperature impaired transfer of energy through the electron transfer system despite relatively low mitochondrial membrane potential. These data support the role of skeletal muscle mitochondria in the development of exercise-induced oxidative stress, particularly during forms of exercise that result in prolonged hyperthermia without acidosis.NEW & NOTEWORTHY The results of this study provide evidence for the role of mitochondria-derived ROS in the development of systemic oxidative stress during exercise as well as skeletal muscle diseases such as exertional rhabdomyolysis.

Are American transplant centers willing to transplant prisoners.

INTRODUCTION: The United Network for Organ Sharing (UNOS) is tasked with ensuring fair and equitable access to organs for patients seeking transplant. Despite UNOS' position statement clearly stating that prisoner status should not preclude transplant evaluation, prisoners continue to face significant barriers. The goal of this survey was to discover how many American transplant centers are willing to evaluate, list, and transplant prisoners. MATERIALS AND METHODS: All adult kidney transplant centers listed as active on the UNOS website were contacted to participate in a survey asking if they were willing to evaluate, list, and transplant prisoners, and why or why not. RESULTS: A total of 122 centers responded. Forty-nine were willing to evaluate, 43 willing to list, and 42 willing to transplant prisoners. Fourteen centers said yes, but on a case-by-case basis only. Things they reported considering were type of crime, length of sentence, and likelihood of release. Frequently cited reasons for not treating inmates were: inadequate follow up (28), insurance/funding (16), transportation (12), medication compliance (9), security (8), patient safety (8), and lack of social support (5). Twenty-four centers refused to disclose their policy or did not have one. CONCLUSIONS: Prisoners continue to face barriers to evaluation, listing, and receiving kidney transplants. A lack of understanding of contraindications to transplant or a lack of knowledge about the prisoner system on behalf of transplant centers may contribute to these barriers. We feel as transplant professionals it is our responsibility to assist vulnerable patients in overcoming barriers to transplantation and work to ensure equitable access to organs, regardless of prisoner status.

Biomarkers of heatstroke-induced organ injury and repair.

NEW FINDINGS: What is the topic of this review? The status and potential role of novel biological markers (biomarkers) that can help identify the patients at risk of organ injury or long-term complications following heatstroke. What advances does it highlight? Numerous biomarkers were identified related to many aspects of generalized heatstroke-induced cellular injury and tissue damage, and heatstroke-provoked cardiovascular, renal, cerebral, intestinal and skeletal muscle injury. No novel biomarkers were identified for liver or lung injury. ABSTRACT: Classic and exertional heatstroke cause acute injury and damage across numerous organ systems. Moreover, heatstroke survivors may sustain long-term neurological, cardiovascular and renal complications with a persistent risk of death. In this context, biomarkers, defined as biological samples obtained from heatstroke patients, are needed to detect early organ injury, and predict outcomes to develop novel organ preservation therapeutic strategies. This narrative review provides preliminary insights that will guide the development and future utilization of these biomarkers. To this end, we have identified numerous biomarkers of widespread heatstroke-associated cellular injury, tissue damage and repair (extracellular heat shock proteins 72 and 60, high mobility group box protein 1, histone H3, and interleukin-1α), and other organ-specific biomarkers including those related to the cardiovascular system (cardiac troponin I, endothelium-derived factors, circulation endothelial cells, adhesion molecules, thrombomodulin and von Willebrand factor antigen), the kidneys (plasma and urinary neutrophil gelatinase-associated lipocalin), the intestines (intestinal fatty acid-binding protein 2), the brain (serum S100ß and neuron-specific enolase) and skeletal muscle (creatine kinase, myoglobin). No specific biomarkers have been identified so far for liver or lung injury in heatstroke. Before translating the identified biomarkers into clinical practice, additional preclinical and clinical prospective studies are required to further understand their clinical utility, particularly for the biomarkers related to long-term post-heatstroke health outcomes.

Orthopedic and ultrasonographic examination findings in 128 shoulders of 64 ultra-endurance Alaskan sled dogs.

OBJECTIVE: To determine the location and periarticular shoulder-muscle-abnormalities detected via orthopedic examinations and ultrasonography in ultra-endurance Alaskan sled-dogs, returned from an ultra-endurance sled-dog-race prior to finishing it. STUDY DESIGN: Prospective clinical study. SAMPLE POPULATION: Sixty-four dogs (128 shoulders). METHODS: Dogs were classified based on clinical evidence of shoulder pain (SP versus control). Orthopedic examination findings, shoulder-abduction-angles (SAA; before- and during-anesthesia), and ultrasonographic findings were recorded. Relationships between orthopedic and ultrasonographic abnormalities were compared. RESULTS: Pain was elicited on 55/128 shoulders; 73 shoulders were pain-free. The most common painful structures included the biceps-tendon (BT; 30%), triceps-muscle (28%), and infraspinatus-muscle (25%). SAA ranged between 25° and 75° among groups, including pain-free shoulders in dogs without lameness. SAA was greater when dogs were anesthetized (46.3° ± 14.0° vs. 47.8° ± 12.0°; p = .03), especially in SP (mean increase of 3.49° ± 8.85°) compared to control (0.03° ± 7.71°, p = .009). Overall, 103 ultrasonographic abnormalities were detected (SP: 44; control: 59). The most common ultrasonographic abnormality was fluid surrounding the biceps tendon, similarly distributed between groups (SP: 39/44; control: 57/59). Most chronic ultrasonographic abnormalities affected the BT (15/103 abnormalities). No associations were detected between ultrasonographic abnormalities and clinical findings. CONCLUSION: Shoulder abduction varied greatly and reached up to 75° in normal joints. Ultrasonographic shoulder-muscle abnormalities were common but did not seem associated with clinical findings. CLINICAL SIGNIFICANCE: Interpretation of shoulder abduction warrants caution, and the presence of fluid around the BT may reflect a physiologic adaptation to racing, rather than a pathologic change in ultra-endurance Alaskan sled-dogs.

Evaluating injuries and illnesses that occurred during the Yukon Quest International sled dog race, 2018-2020.

Introduction: The purpose of this study was to evaluate medical record data from the 2018-2020 Yukon Quest International Sled Dog race to examine injury patterns and risk factors for dogs competing in multi-day ultra-endurance events. Specifically, we summarized injuries and illnesses that resulted in canine athletes being removed ("dropped") from competition, and in orthopedic injuries diagnosed in both dropped and finished dogs. Methods: The records of 989 dogs that started the race were examined, but only records from dogs in teams that went on to finish the race were included, for a total of 711 records. Results and discussion: Three hundred and sixty five dogs (51.3%) were noted to have at least one abnormal finding in their veterinary medical record during the race. Orthopedic injuries were most common, and 291 injuries were ultimately diagnosed in 234 dogs (32.9%). Ultimately, 206 dogs (29%) were dropped from competition, for any reason. The most common reasons for dropping dogs were orthopedic injuries (156 dogs; 188 injuries), gastrointestinal illness (22 dogs), and cardiorespiratory disease (7 dogs). Most orthopedic injuries in dropped dogs occurred in the thoracic limb (n = 121 dogs; 151 injuries). Of those, injuries to the shoulder were most common (n = 77), followed by injuries to the carpus (n = 59), and injury to the pelvic limb (n = 32). Carpal injuries were the most prevalent injury diagnosed in dogs that went on to finish the race (71 of 85 injuries). Carpal injuries were the most prevalent injuries overall in 2018 (51%) and 2019 (52%). In 2020, shoulder injuries were most prevalent (27%), suggesting that trail conditions may have differed between years. The majority of dogs with an orthopedic injury ultimately were removed from competition (156 of 234, or 66.6%), but the likelihood of finishing the race with an injury depended on the type of injury sustained; 71 of 130 dogs (54.6%) with a carpal injury went on to finish the race, whereas only 9 of 86 dogs with a shoulder injury (10.5%) went on to finish. The results of this study can assist mushers and veterinarians in preparing for races, and in decision making during endurance sled dog races.

Early growth response 1 and fatty acid synthase expression is altered in tumor adjacent prostate tissue and indicates field cancerization.

BACKGROUND: Field cancerization denotes the occurrence of molecular alterations in histologically normal tissues adjacent to tumors. In prostate cancer, identification of field cancerization has several potential clinical applications. However, prostate field cancerization remains ill defined. Our previous work has shown up-regulated mRNA of the transcription factor early growth response 1 (EGR-1) and the lipogenic enzyme fatty acid synthase (FAS) in tissues adjacent to prostate cancer. METHODS: Immunofluorescence data were analyzed quantitatively by spectral imaging and linear unmixing to determine the protein expression levels of EGR-1 and FAS in human cancerous, histologically normal adjacent, and disease-free prostate tissues. RESULTS: EGR-1 expression was elevated in both structurally intact tumor adjacent (1.6× on average) and in tumor (3.0× on average) tissues compared to disease-free tissues. In addition, the ratio of cytoplasmic versus nuclear EGR-1 expression was elevated in both tumor adjacent and tumor tissues. Similarly, FAS expression was elevated in both tumor adjacent (2.7× on average) and in tumor (2.5× on average) compared to disease-free tissues. CONCLUSIONS: EGR-1 and FAS expression is similarly deregulated in tumor and structurally intact adjacent prostate tissues and defines field cancerization. In cases with high suspicion of prostate cancer but negative biopsy, identification of field cancerization could help clinicians target areas for repeat biopsy. Field cancerization at surgical margins on prostatectomy specimen should also be looked at as a predictor of cancer recurrence. EGR-1 and FAS could also serve as molecular targets for chemoprevention.

Glucocentric Metabolism in Ultra-Endurance Sled Dogs.

The total energy expenditure of a racing sled dog can exceed 500 kcal/kg bodyweight during typical events spanning a week or more. Based on early research, as well as practical considerations, modern commercial diets are formulated to meet these energy requirements using fat and protein. However, more recent research provides a clear picture of a canine athlete with glucocentric metabolism, including many conditioning-induced adaptations oriented toward sustaining submaximal exercise with glucose as the primary metabolic fuel despite the consumption of fat as the primary dietary energy source. The specific strategies used by racing sled dogs to maintain a robust supply of glucose during exercise, as well as the possible role of fat in facilitating that metabolic priority, is the subject of ongoing research.

Effect of conditioning and physiological hyperthermia on canine skeletal muscle mitochondrial oxygen consumption.

Exercise often causes skeletal muscle hyperthermia, likely resulting in decreased efficiency of mitochondrial respiration. We hypothesized that athletic conditioning would improve mitochondrial tolerance to hyperthermia. Skeletal muscle biopsies were obtained from six Alaskan sled dogs under light general anesthesia before and after a full season of conditioning and racing, and respiration of permeabilized muscle fibers was measured at 38, 40, 42, and 44°C. There was no effect of temperature on phosphorylating respiration, and athletic conditioning increased maximal phosphorylating respiration by 19%. Leak respiration increased and calculated efficiency of oxidative phosphorylation decreased with increasing incubation temperature, and athletic conditioning resulted in higher leak respiration and lower calculated oxidative phosphorylation efficiency at all temperatures. Conditioning increased skeletal muscle expression of putative mitochondrial leak pathways adenine nucleotide transporter 1 and uncoupling protein 3, both of which were correlated with the magnitude of leak respiration. We conclude that athletic conditioning in elite canine endurance athletes results in increased capacity for mitochondrial proton leak that potentially reduces maximal mitochondrial membrane potential during periods of high oxidative phosphorylation. This effect may provide a mechanistic explanation for previously reported decreases in exercise-induced muscle damage in well-conditioned subjects.NEW & NOTEWORTHY Athletic conditioning is expected to increase exercise capacity through improved function of cardiopulmonary and musculoskeletal tissues. Our finding of decreased calculated efficiency of skeletal muscle mitochondria in one of the premier mammalian athletes suggests that this mandate for improved function may take the form of sacrificing capacity for maximal oxidative phosphorylation to minimize exercise-induced muscle damage caused by mitochondrial oxidative stress.

Initial Presentation and Outcomes of Testicular Cancer among Different Racial and Ethnic Groups at a Tertiary Care Facility in New Mexico.

INTRODUCTION: This study explored differences in testicular cancer presentation, treatment, compliance and outcomes among ethnicities in New Mexico. METHODS: A retrospective review of patients with testicular cancer treated between 2002 and 2015 was performed. Data included demographics, stage, delays in care, treatments, insurance status and nonadherence rates. RESULTS: Of 186 patients Hispanics and Native Americans presented at higher stage (p <0.01) and delayed treatment (p=0.02). Retroperitoneal lymph node dissection for stage I disease was 28% while stage II was 30%, compared to 18% and 58% nationally, respectively. Of stage II in Hispanic patients 24.5% received retroperitoneal lymph node dissection compared to 41.3% of Caucasians (p <0.05). Regarding chemotherapy Caucasian patients at stage I were more likely than Hispanics to receive chemotherapy (p <0.05). Hispanics had higher rates of nonadherence (p <0.01). Insurance rates did not differ among groups. However, insurance increased the likelihood for receiving chemotherapy/retroperitoneal lymph node dissection only for Caucasians. Lack of insurance increased active surveillance rates for stage I in Hispanics. The incidence of testicular cancer in Hispanics rose by 58% after 2009 (p <0.05). CONCLUSIONS: Minority groups presented at higher stages and delayed treatment. Retroperitoneal lymph node dissection rates differed nationally compared to this cohort with Hispanic patients at higher stage being less likely to receive retroperitoneal lymph node dissection. Meanwhile, Hispanics with stage I are less likely to obtain chemotherapy. Insurance rates did not differ among ethnicities but having insurance did not increase rates of chemotherapy/retroperitoneal lymph node dissection for Hispanics unlike for Caucasians. Meanwhile, lack of insurance increased stage I rates of active surveillance suggesting cultural/financial factors contribute to treatment decisions. Increased health literacy, outreach and access may aid in alleviating these disparities.

Contrast therapy: Tissue heating and cooling properties within the equine distal limb.

BACKGROUND: Rehabilitation of tendon injuries in horses often involves cryotherapy to reduce inflammation and occasionally tissue heating to increase collagen extensibility. The application of alternating cold and hot (ie contrast therapy) is widely used in human physical therapy; however, its utility in equine rehabilitation is largely unknown. OBJECTIVES: The objectives of this study were to (a) assess if the equipment could achieve therapeutic tissue temperatures (<15 and >40°C) at different tissue depths relative to the digital flexor tendons and (b) evaluate the time-temperature profiles during serial heating and cooling cycles using a contrast therapy device. STUDY DESIGN: In vivo experiment. METHODS: In 4 adult horses with normal forelimb digital flexor tendons, fine-wire temperature probes were placed superficially on the skin and implanted subcutaneously, deep to the superficial digital flexor tendon (SDFT) and deep to the deep digital flexor tendon (DDFT). Temperatures were recorded over three complete thermal (hot-cold) cycles. Minimum and maximum temperatures were recorded and the rate of temperature changes and the areas underneath the time-temperature curves (ie thermal load) were calculated. RESULTS: Minimum and maximum tissue temperatures (°C) included: superficial skin [12.6 ± 1.0; 42.4 ± 2.4], subcutaneous tissues [14.1 ± 0.8; 42.3 ± 2.2], deep to the SDFT [15.6 ± 0.8; 41.7 ± 2.6] and deep to DDFT [25.1 ± 2.0; 38.0 ± 3.5]. An initial rapid rate of tissue temperature change between 3.2 and 4.3°C/min occurred within tissues to the depth of the DDFT. Tissue thermal loads during heating ranged from 255 to 607°C*second and from 309 to 780°C*second during tissue cooling, with the lower values noted deep to the DDFT. MAIN LIMITATIONS: Unknown clinical efficacy in diseased tissues. CONCLUSIONS: The applied contrast therapy was consistently able to induce cooling and heating of tissues to the depth of the DDFT.

Acylcarnitine profile in Alaskan sled dogs during submaximal multiday exercise points out metabolic flexibility and liver role in energy metabolism.

Alaskan sled dogs develop a particular metabolic strategy during multiday submaximal exercise, allowing them to switch from intra-muscular to extra-muscular energy substrates thus postponing fatigue. Specifically, a progressively increasing stimulus for hepatic glycogenolysis and gluconeogenesis provides glucose for both fueling exercise and replenishing the depleted muscle glycogen. Moreover, recent studies have shown that with continuation of exercise sled dogs increase their insulin-sensitivity and their capacity to transport and oxidize glucose and carbohydrates rather than oxidizing fatty acids. Carnitine and acylcarnitines (AC) play an essential role as metabolic regulators in both fat and glucose metabolism; they serve as biomarkers in different species in both physiologic and pathologic conditions. We assessed the effect of multiday exercise in conditioned sled dogs on plasma short (SC), medium (MC) and long (LC) chain AC by tandem mass spectrometry (MS/MS). Our results show chain-specific modification of AC profiles during the exercise challenge: LCACs maintained a steady increase throughout exercise, some SCACs increased during the last phase of exercise and acetylcarnitine (C2) initially increased before decreasing during the later phase of exercise. We speculated that SCACs kinetics could reflect an increased protein catabolism and C2 pattern could reflect its hepatic uptake for energy-generating purposes to sustain gluconeogenesis. LCACs may be exported by muscle to avoid their accumulation to preserve glucose oxidation and insulin-sensitivity or they could be distributed by liver as energy substrates. These findings, although representing a "snapshot" of blood as a crossing point between different organs, shed further light on sled dogs metabolism that is liver-centric and more carbohydrate-dependent than fat-dependent and during prolonged submaximal exercise.

Organ-wide telomeric status in diseased and disease-free prostatic tissues.

BACKGROUND: Telomere attrition occurs early in the development of prostatic adenocarcinoma. However, little is known about either telomere status in benign prostatic hyperplasia (BPH), or the spatial and organ-wide distribution of potential telomere aberrations throughout all areas of prostatic glands affected by cancer or BPH. METHODS: Slot blot titration assay was used to determine telomere DNA content (TC), a proxy for telomere length, in macrodissected tissue consisting of 54 normal samples from 5 disease-free prostates, 128 BPH samples from 4 non-cancerous prostates, and 45 tumor, 73 BPH, and 4 prostatic intraepithelial neoplasia (PIN) samples from 5 cancerous prostates. RESULTS: Compared to TC in normal prostate samples (n = 54; TC mean = 0.98), tumor samples displayed telomere attrition (n = 45; TC mean = 0.67). TC in PIN samples was similar to tumors. TC in BPH samples from cancerous prostates was similar to TC in tumors and also displayed telomere shortening (n = 73; TC mean = 0.76), whereas BPH samples from non-cancerous prostates displayed longer telomeres (n = 128; TC mean = 1.06). In prostates affected by adenocarcinoma, areas of potential telomere attrition occurred in histologically normal tissues through the entire gland. However, three-dimensional zoning revealed a pattern of increasing TC as a function of distance from the primary (index) tumor. CONCLUSIONS: Spatial distributions of TC in prostate specimens indicate a complex "field effect" with varying contributions from both cancer and BPH. The observation that telomere length variations occur in fields of histologically normal tissues surrounding the tumor is of clinical importance, as it may have implications for the diagnosis and focal therapy of prostate cancer.

Comparison of Postexercise Cooling Methods in Working Dogs.

BACKGROUND: Overheating is a common form of injury in working dogs. The purpose of this study was to evaluate the relative efficacy of three postexercise cooling methods in dogs with exercise-induced heat stress. METHODS: Nine athletically conditioned dogs were exercised at 10kph for 15 minutes on a treadmill in a hot environmental chamber (30°C) three times on separate days. After exercise, the dogs were cooled using one of three methods: natural cooling, cooling on a 4°C cooling mat, and partial immersion in a 30°C water bath for 5 minutes. RESULTS: Time-weighted heat stress was lower for immersion cooling compared with the cooling mat and the control. The mean time required to lower gastrointestinal temperature to 39°C was 16 minutes for immersion cooling, 36 minutes for the cooling mat, and 48 minutes for control cooling. CONCLUSION: Water immersion decreased postexercise, time-weighted heat stress in dogs and provided the most rapid cooling of the three methods evaluated, even with the water being as warm as the ambient conditions. The cooling mat was superior to cooling using only fans, but not as effective as immersion. The placement of simple water troughs in working- dog training areas, along with specific protocols for their use, is recommended to reduce the occurrence of heat injury in dogs and improve the treatment of overheated dogs.

Assessment of alterations in triglyceride and glycogen concentrations in muscle tissue of Alaskan sled dogs during repetitive prolonged exercise.

OBJECTIVE: To assess changes in muscle glycogen (MG) and triglyceride (MT) concentrations in aerobically conditioned sled dogs during prolonged exercise. ANIMALS: 54 Alaskan sled dogs fed a high-fat diet. PROCEDURES: 48 dogs ran 140-km distances on 4 consecutive days (cumulative distance, up to 560 km); 6 dogs remained as nonexercising control animals. Muscle biopsies were performed immediately after running 140, 420, or 560 km (6 dogs each) and subsequently after feeding and 7 hours of rest. Single muscle biopsies were performed during recovery at 28 hours in 7 dogs that completed 560 km and at 50 and 98 hours in 7 and 6 dogs that completed 510 km, respectively. Tissue samples were analyzed for MG and MT concentrations. RESULTS: In control dogs, mean +/- SD MG and MT concentrations were 375 +/- 37 mmol/kg of dry weight (kgDW) and 25.9 +/- 10.3 mmol/kgDW, respectively. Compared with control values, MG concentration was lower after dogs completed 140 and 420 km (137 +/- 36 mmol/kgDW and 203 +/- 30 mmol/kgDW, respectively); MT concentration was lower after dogs completed 140, 420, and 560 km (7.4 +/- 5.4 mmol/kgDW; 9.6 +/- 6.9 mmol/kgDW, and 6.3 +/- 4.9 mmol/kgDW, respectively). Depletion rates during the first run exceeded rates during the final run. Replenishment rates during recovery periods were not different, regardless of distance; only MG concentration at 50 hours was significantly greater than the control value. CONCLUSIONS AND CLINICAL RELEVANCE: Concentration of MG progressively increased in sled dogs undergoing prolonged exercise as a result of attenuated depletion.

Effects of training and strenuous exercise on hematologic values and peripheral blood leukocyte subsets in racing sled dogs.

OBJECTIVE: To determine the effects of training and sustained submaximal exercise on hematologic values in racing sled dogs. DESIGN: Cohort study. ANIMALS: 39 Alaskan sled dogs bred for endurance racing. Procedures-Blood samples were collected prior to initiation of a 7-month training regimen (n=39), after completion of the training regimen (19), and after completion of an 1,100-mile race (9), and a CBC, differential cell count, and flow cytometry for leukocyte surface antigens were performed. RESULTS: Both training and exercise caused significant decreases in PCV and hemoglobin concentration and significant increases in total WBC count. In contrast, training and exercise were not found to have significant effects on absolute numbers or fractions of CD4+ or CD8+ lymphocytes, other than a significant increase in the fraction of CD8+ lymphocytes associated with training. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested that training and exercise induced changes in several hematologic values in racing sled dogs. Extracellular fluid volume expansion was the likely explanation for the training-induced decrease in PCV, and acute blood loss secondary to gastrointestinal tract bleeding was likely responsible for the decrease in PCV associated with acute exercise.

Effect of Endurance Conditioning on Insulin-mediated Glucose Clearance in Dogs.

INTRODUCTION: Physical activity has been shown to improve insulin sensitivity in subjects with insulin resistance, but the effect of athletic conditioning on subjects with normal insulin sensitivity has received less scrutiny. Because strenuous exercise can be limited by the availability of substrates, it is reasonable to hypothesize that conditioning would increase the capacity for muscle uptake of substrates like glucose and to the extent that improvement in this process would include upregulation of the portions of the glucose uptake pathway in muscle, this increased capacity would also be reflected in insulin sensitivity. Therefore, we tested the hypothesis that conditioning for endurance exercise would result in increased insulin sensitivity using elite racing sled dogs. METHODS: A frequent-sampled intravenous glucose tolerance test was performed on these dogs before and after a full 7-month season of conditioning in preparation for a 1600-km race. RESULTS: Compared with the results in unconditioned dogs, conditioned dogs rapidly cleared the intravenous glucose bolus through increases in both glucose mediated (7.6%·min ± 3.4%·min vs 3.0%·min ± 2.2%·min, P = 0.008) and insulin-mediated (36.3 ± 18.4 × 10 L·min·mU vs 11.5 ± 8.0 × 10 L·min·mU, P = 0.007) mechanisms. The more modest increase in serum insulin after the intravenous glucose bolus in conditioned dogs failed to suppress lipolysis and serum concentrations of nonesterified fatty acids remained constant in the conditioned dogs throughout the 4-h test. CONCLUSIONS: These results, in particular the increase in insulin-independent peripheral uptake of glucose, describe novel alterations in metabolism induced by athletic conditioning that arguably result in near-continuous provision of oxidizable substrates to peripheral muscle in support of sustained muscular work typical of these dogs.

Advanced Resuscitative Care in Tactical Combat Casualty Care: TCCC Guidelines Change 18-01:14 October 2018.

TCCC has previously recommended interventions that can effectively prevent 4 of the top 5 causes of prehospital preventable death in combat casualties-extremity hemorrhage, junctional hemorrhage, airway obstruction, and tension pneumothorax- and deaths from these causes have been markedly reduced in US combat casualties. Noncompressible torso hemorrhage (NCTH) is the last remaining major cause of preventable death on the battlefield and often causes death within 30 minutes of wounding. Increased use of whole blood, including the capability for massive transfusion, if indicated, has the potential to increase survival in casualties with either thoracic and/or abdominopelvic hemorrhage. Additionally, Zone 1 Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) can provide temporary control of bleeding in the abdomen and pelvis and improve hemodynamics in casualties who may be approaching traumatic cardiac arrest as a result of hemorrhagic shock. Together, these two interventions are designated Advanced Resuscitative Care (ARC) and may enable casualties with severe NCTH to survive long enough to reach the care of a surgeon. Although Special Operations units are now using whole blood far-forward, this capability is not routinely present in other US combat units at this point in time. REBOA is not envisioned as care that could be accomplished by a unit medic working out of his or her aid bag. This intervention should be undertaken only by designated teams of advanced combat medical personnel with special training and equipment.

Efficacy of famotidine for the prevention of exercise-induced gastritis in racing Alaskan sled dogs.

BACKGROUND: Omeprazole reduces the severity of exercise-induced gastritis but not the prevalence of gastric lesions in sled dogs. The frequent feeding of sled dogs during competition likely results in decreased absorption of omeprazole and, thereby, decreased efficacy. HYPOTHESIS: Famotidine, a histamine-2 blocker with good bioavailability in the presence of food, would reduce the incidence and severity of exercise-induced gastric disease in sled dogs. ANIMALS: Sixteen fit Alaskan sled dogs (4 female, 12 male, all intact, age 2-6 years). METHODS: Dogs were randomly assigned to treatment (22 mg famotidine PO q24h) or control groups (n = 8 per group). Famotidine was administered with a meal to the treatment group once daily for 7 days before a challenge and once during exercise. Control dogs were fed an identical diet as the principal group. The 16 dog team completed a 100-mile exercise challenge in 18 hours. A gastroscopy was performed 24 hours after the challenge. The appearance of the mucosa was scored by an individual by using a scoring system. RESULTS: Treatment with famotidine significantly reduced the severity score compared with control (P = .0004). No adverse effects of treatment were reported. CONCLUSIONS AND CLINICAL RELEVANCE: Famotidine is effective in reducing the severity of exercise-induced gastric disease in racing Alaskan sled dogs, with minimal to no adverse effects, and may be recommended for prophylactic use in short distance races.

Effect of strenuous exercise on urine concentrations of homovanillic acid, cortisol, and vanillylmandelic acid in sled dogs.

OBJECTIVE: To determine whether prolonged exercise by conditioned sled dogs affects urine concentrations of homovanillic acid (a metabolite of dopamine), vanillylmandelic acid (a metabolite of norepinephrine and epinephrine), and cortisol. ANIMALS: 24 conditioned Alaskan sled dogs (2 to 8.5 years old) that were in training for a multiday endurance race. PROCEDURES: Voided urine samples were collected from 4 groups of dogs (randomly selected from 54 dogs) after no exercise (control group; n = 6 dogs), completion of a 160km run (group A; 3), completion of a 420-km run (group B; 7), and completion of a 560-km run (group C; 6). Urine cortisol concentrations were determined by use of an immunoassay technique; urine vanillylmandelic acid and homovanillic acid concentrations were measured via high-performance liquid chromatography. RESULTS: Compared with the control group, urine cortisol concentration in groups A, B, and C was significantly different (5.33 x 10(4) +/- 2.62 x 10(4) microg/dL vs 1.04 x 10(4) +/- 2.31 x 10(5) microg/dL, 8.88 x 10(4) +/- 5.49 x 10(4) microg/dL, and 6.31 x 10(4) +/- 5.09 x 10(4) microg/dL, respectively). Urine homovanillic acid concentration did not differ among the 4 groups. Vanillylmandelic acid was not detected in any urine samples. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that prolonged exercise by sled dogs did not affect urine homovanillic acid concentration but did increase urinary cortisol secretion, which is indicative of adrenocortical stimulation. The apparent lack of vanillylmandelic acid in voided urine samples requires further investigation.

Influx of neutrophils and persistence of cytokine expression in airways of horses after performing exercise while breathing cold air.

OBJECTIVE: To determine effects of exercise performed while breathing cold air on expression of cytokines and influx of neutrophils in airways of horses. ANIMALS: 9 adult horses. PROCEDURES: In a crossover study, bronchoalveolar lavage fluid (BALF) was obtained 24 and 48 hours after each of 2 submaximal exercise sessions performed by horses while breathing warm (25 degrees C) or cold (-5 degrees C) air. Total and differential nucleated cell counts were determined for each BALF sample. Relative mRNA expression of cytokines in BALF cells was quantified by use of a reverse transcription-PCR assay. RESULTS: Horses had a modest but significant influx of neutrophils into the airways 24 hours after a single exercise session while breathing cold air. No other cell types were increased at 24 or 48 hours after exercising while breathing cold air. Continued increases in expression of cytokines interleukin (IL)-5 and-10 as well as proinflammatory cytokines IL-1, -6, and -8 were detected 24 hours after exercising while breathing cold air. Forty-eight hours after exercising while breathing cold air, expression of IL-10 was still higher than that for IL-10 after horses exercised while breathing warm air. Expression of tumor necrosis factor-alpha was significantly increased at 48 hours after exercising while breathing cold air. CONCLUSIONS AND CLINICAL RELEVANCE: Exposure of intrapulmonary airways to cold air alters immunologic responses of horses for at least 48 hours. The increased expression of cytokines that suppress cell-mediated immunity may predispose athletes to viral infections of the respiratory tract following exercise in cold weather.