Prevalence and severity of exercise-induced pulmonary hemorrhage in 2-year-old Thoroughbred racehorses and its relationship to performance.

BACKGROUND: Little has been reported regarding the prevalence and severity of exercise-induced pulmonary hemorrhage (EIPH) in 2-year-old Thoroughbred racehorses. OBJECTIVES: Evaluate EIPH prevalence and severity and its association with performance, speed index, furosemide administration, race distance, and track surface. ANIMALS: A total of 830 2-year-old Thoroughbreds. METHODS: Prospective blinded observational study. Videoendoscopy was performed 30 to 60 minutes postrace at 15 American racetracks. Three blinded observers independently assigned an EIPH grade (0-4) to each video, and prevalence and severity of EIPH were determined. Relationships of EIPH grade to performance, speed index, race distance, track surface, and prerace administration of furosemide were evaluated using Pearson's chi-squared test for categorical variables and analysis of variance (ANOVA) for numerical variables. Multivariable logistic regression assessed relationships between EIPH prevalence and severity, respectively, and the aforementioned independent variables. A P < .05 was considered significant. RESULTS: A total of 1071 tracheoendoscopies were recorded. The EIPH prevalence was 74% and for EIPH grade ≥3 was 8%. Speed index (P = .02) and finishing place (P = .004) were lower with EIPH ≥3. The EIPH prevalence and severity were lower at 2 tracks where postrace tracheoendoscopy was mandatory rather than voluntary (P < .001). Probability of observing EIPH was negatively associated with speed index (P = .01) at tracks where postrace tracheoendoscopy was mandatory. Prerace furosemide administration decreased the probability of EIPH occurrence (P = .007) and severity (P = .01) where study participation was voluntary. CONCLUSIONS AND CLINICAL IMPORTANCE: Prevalence and severity of EIPH in 2-year-old racehorses were consistent with that of older racehorses. An EIPH grade ≥3 was associated with decreased performance. Prerace furosemide administration was associated with a decreased likelihood, but not severity, of EIPH at most tracks.

Atrial fibrillation as a risk factor for exercise-induced pulmonary haemorrhage following a standardised exercise test.

BACKGROUND: Atrial fibrillation (AF) has been proposed as a risk factor for exercise-induced pulmonary haemorrhage (EIPH) due to increased pressure in the left atrium. OBJECTIVE: To evaluate if AF was associated with EIPH following a standardised exercise test (SET) to fatigue. STUDY DESIGN: Two-arm controlled experiment. METHODS: Ten untrained Standardbred mares mean (standard deviation [SD]) age 6 (2) years performed a SET on the treadmill in sinus rhythm (SR) (SET1) and 25-44 days after induction of self-sustained AF (SET2). AF was induced by tachypacing using a pacing device. Endoscopy, including tracheal wash and bronchoalveolar lavage (BAL), was performed 48-72 h before and 24 h after the two SETs. In addition, endoscopic grading of tracheal blood was performed 2 h after each SET. RESULTS: After SET1, none of the horses showed blood in the trachea, and two horses showed erythrophagocytosis. Following SET2, two horses had grade 1 blood in the trachea and free erythrocytes and erythrophagocytosis in the BAL, while another two horses had erythrophagocytosis in the BAL. In SET2, the overall performance on the treadmill was decreased with a lower maximum velocity (SET1 10.3 ± 0.8 m/s vs. SET2 8.9 ± 0.9 m/s, p = 0.004), a higher heart rate (284 ± 21 vs. 221 ± 18 bpm, p = 0.003) and more abnormal QRS complexes (p < 0.001) compared with SET1. CONCLUSIONS: Two horses showed signs of EIPH, resulting in visible blood in the trachea, when exercising in AF compared with SR. However, a possible link between EIPH, pulmonary pressure and AF needs to be further elucidated.

Associations between postrace atrial fibrillation and measures of performance, racing history and airway disease in horses.

BACKGROUND: Atrial fibrillation (AF) is the most common performance limiting arrhythmia in racehorses. High dose exercise and airway disease promote AF in humans. Few studies have investigated epidemiological factors associated with AF in horses. OBJECTIVES: Explore variables relating to performance, exercise volume and postrace endoscopic findings in horses with AF. ANIMALS: A total of 164 horses with poor race performance and postrace AF were compared to 321 horses with poor performance without AF (PP) and 314 horses performing to expectation (TE). METHODS: Horse-level and race-level variables for horses racing in Australia and Hong Kong from 2009 to 2021 were compared using univariable and multivariable logistic regression. Postrace endoscopic exercise-induced pulmonary hemorrhage (EIPH) and tracheal mucus accumulation (TMA) grades for AF and PP horses were compared using chi-squared analysis. RESULTS: Variables that were significant in the multivariable model of AF compared to TE were distance (lengths) behind the winner, (odds ratio [OR]; 95% confidence interval [95% CI], 1.41 [1.32-1.51], P < .0001), cumulative prize money per start before the event (OR [95% CI] 1.02 [1.01-1.03], P = .01) and age (OR [95% CI] 0.72 [0.55-0.92], P = .01). More AF horses had EIPH grade ≥ 3 (23/109; 21.1%) than PP horses (7/213; 3.3%; OR [95%CI] 7.9 [3.3-20.2], P < .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: Acute race performance was substantially impaired by AF but career earnings before the event were not inferior. Exercise volume did not promote AF. Higher grades of EIPH found in AF horses suggests a mechanistic relationship between these conditions.

Assessment of gastrointestinal health in racing Alaskan sled dogs using capsule endoscopy and inflammatory cytokines.

OBJECTIVES: Exercise-induced gastrointestinal syndrome occurs in dogs and people and might compromise athlete performance by increasing intestinal permeability and causing gastrointestinal erosions. Racing sled dogs often receive acid suppressant prophylaxis which decreases the incidence of gastric erosions induced by exercise. The objectives were to quantify intestinal injury by measuring serum pro-inflammatory cytokine concentrations before and after exercise and to evaluate gastrointestinal mucosa using video capsule endoscopy after exercise. MATERIALS AND METHODS: Prospective study of 12 racing Alaskan sled dogs receiving approximately 1 mg/kg omeprazole once daily from the day before the race until race completion. Blood was drawn before and 8 to 10 hours after an endurance race for the quantification of cytokines. Gastrointestinal tract mucosa was assessed with video capsule endoscopy immediately post-race. RESULTS: Eight of nine dogs (89%; 95% confidence interval 52 to 100%) had gastric erosions; all dogs (100%, 95% confidence interval 63 to 100%) had small intestinal erosions. Most of the dogs (seven of nine) had straw or foreign material present. Cytokine levels were not different from before to after the race. CLINICAL SIGNIFICANCE: Video capsule endoscopy identified gastrointestinal tract mucosal erosions after exercise in all dogs receiving once-daily omeprazole treatment, though other causes for the lesions besides exercise are possible.

Pharmacokinetics of aminocaproic acid in thoroughbred horses.

The antifibrinolytic agent aminocaproic acid (ACA) is occasionally used prior to episodes of intense training in racehorses suffering from exercise-induced pulmonary hemorrhage. Although a previous study indicated that the drug is cleared rapidly in horses, some racetrack practitioners claim that recent adverse analytical findings for ACA in postrace samples were from ACA administrations 5-7 days before the race. The purpose of this study was to re-examine the pharmacokinetics of ACA in horses to address this apparent conundrum. Eight exercise-conditioned thoroughbred horses were administered 5 g of ACA IV, and blood and urine samples were collected at pre-determined time points prior to drug administration and for up to 168 h after dosing. Concentrations of ACA in the serum and urine samples were determined by LC-MS/MS. The pharmacokinetics of ACA in serum were best described by a three-compartment model with a terminal elimination half-life of 24.2 ± 2.9 h. After dosing, ACA was above the lower limit of detection (1 ng/mL for serum and 10 ng/mL for urine) in all serum and urine samples at all time points. In a similar manner, ACA was above the lower limit of quantification (LLOQ; 10 ng/mL for serum and 100 ng/mL for urine) in all serum and urine samples collected from all horses from 0.5 to 120 h post dosing. In six of the eight horses, ACA was above the LLOQ 168 h after dosing in serum and urine samples. LC-MS/MS methodology is the industry standard for testing of samples collected from racehorses with the purpose of controlling the use of medications and performance altering substances. The improved sensitivity of the analytical procedure used in the present study allowed the detection of a prolonged terminal elimination phase of ACA in horses that had not previously been described. Currently, most racing jurisdictions have not adopted a permitted concentration or threshold for ACA in postrace samples, and therefore veterinarians need to allow for an extended withdrawal time of a minimum of 11 days after the administration of ACA to racehorses to substantially reduce the risk of adverse analytical findings of ACA in postrace samples.

Management of Injuries in Agility Dogs.

Agility is a physically demanding sport, and injuries are common. An understanding of the common clinical presentations, frequent injuries, and risk factors for injury is critical when seeing this population of patients in practice. Shoulder injuries and other soft tissue injuries including iliopsoas muscle strains are commonly seen. The Border Collie seems to be at higher risk of developing agility-related injuries. The key to rehabilitation of the agility dog is accurate and expedient diagnosis of the injury, which often involves advanced diagnostics such as musculoskeletal ultrasound, arthroscopy, and/or MRI.

Free Swimming and Exercise-Induced Pulmonary Hemorrhage in Endurance Horses: A Preliminary Study.

Swimming is used for rehabilitation of musculoskeletal injuries and for conditioning to improve equine fitness. However, there are anecdotal reports that suggest that tethered swimming can induce epistaxis, likely secondary to exercise-induced pulmonary hemorrhage (EIPH). The objective of this observational, prospective study was to investigate if EIPH occurs during intensive free-swimming training sessions (5 × 70m) using 15 endurance horses. On tracheo-bronchoscopic evaluations following swimming, low grade mucus scores were observed, but no tracheal blood was observed. Bronchoalveolar lavage fluid analysis revealed a low cellularity, and the median red blood cell count (RBCs) was 271 cells/µL (interquartile range 150-363 cells/µL), which is much lower than the threshold of RBCs >1,000 cells/µL for horses to be considered positive for EIPH. Therefore, free swimming does not seem to predispose endurance horses to EIPH following a typical free-swimming training session.

A review of equine tibial fractures.

Equine tibial fractures are relatively infrequent in racing and non-racing sport horses, but limitations in successful treatment of tibial fractures in adult horses result in relatively high mortality compared with other musculoskeletal injuries. The aetiology of tibial fracture can be classified into two general categories: traumatic impact or fatigue failure. Tibial stress fractures, also known as fatigue fractures, are often rated as the second most common stress fracture in racing Thoroughbreds; young age, early stage in race training, and initiation of training after a period of rest are the reported risk factors. Both impact and fatigue fracture propagation are dependent on the magnitude of force applied and on the local composition/alignment of mineralised collagen in the tibial lamella. Extensive research has characterised the pattern of strain distribution and stress remodelling within the equine tibia, but in vivo measurement of load and angular moments are currently not feasible. Further research is warranted to correlate biomechanical theory of tibia fatigue fracture propagation with current histopathological data. Preventative measures for fatigue fractures aim to optimise diagnostic efficiency, reduce the interval between injury and diagnosis and modify racing and training conditions to reduce non-specific fracture risk. Treatment options for complete tibial fractures in adult horses are limited, but with careful case selection, successful outcomes have been reported after open reduction and internal fixation. On the other hand, tibial stress fractures and minimally displaced incomplete fractures are typically treated conservatively and have good prognosis for athletic recovery. This review aims to describe the current literature regarding tibial fracture aetiology, prevalence, risk factors, fracture biomechanics, treatment, prognosis and prevention.

Effect of acupuncture pretreatment on inflammatory response of exercise-induced skeletal muscle damage in rats based on TLR9/MyD88/NF-κB signaling pathway. / 基于TLR9/MyD88/NF­κBä¿¡å·é€šè·¯æŽ¢è®¨é’ˆåˆºé¢„å¤„ç†å¯¹è¿åŠ¨æ€§éª¨éª¼è‚ŒæŸä¼¤å¤§é¼ ç‚Žæ€§ååº”çš„å½±å“.

OBJECTIVES: To observe the effects of acupuncture pretreatment on toll-like receptor 9/myeloid differentiation factor 88/nuclear factor-κB (TLR9/MyD88/NF-κB) signaling pathway and inflammatory response in the rats with exercise-induced skeletal muscle damage (EIMD) and explore the underlying mechanism of this pretreatment for EIMD. METHODS: A total of 88 male SD rats were randomly divided into a blank group (8 rats), a model group (40 rats) and an acupuncture pretreatment group (40 rats). In the model group and the acupuncture pretreatment group, 5 subgroups were randomized according to the sampling time of 0, 12, 24, 48 and 72 h of modeling, with 8 rats in each one, respectively. Before modeling, in the acupuncture pretreatment group, acupuncture was delivered at bilateral "Zusanli" (ST 36) and "Guanyuan" (CV 4) for 20 min, once daily for consecutive 7 days. By one-time intermittent downhill centrifugal exercise on animal experimental treadmill, EIMD model was established in the model group and the acupuncture pretreatment group. The ultrastructure of gastrocnemius muscle was observed under transmission electron microscope. The levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in the serum were detected by ELISA. The protein and mRNA expression of TLR9, MyD88 and NF-κB p65 in the gastrocnemius tissue of rats was detected by the Western blot and real-time PCR, respectively. RESULTS: Compared with the blank group, the gastrocnemius ultrastructure in the model group showed the damage of different degrees, with myofilaments disarranged and twisted, mitochondria obviously swollen and mitochondrial crista partially defected. Compared with the model group, the injury was mild, most of muscle fibers were arranged neatly and the number of mitochondria increased remarkably in the acupuncture pretreatment group. Compared with the blank group, in the model group, the serum IL-6 levels increased at 0, 12, 24 and 48 h after modeling in the rats (P<0.01), and TNF-α levels were elevated at each time point after modeling (P<0.05, P<0.01). In the acupuncture pretreatment group, the serum IL-6 levels were reduced at 12, 24 and 48 h after modeling (P<0.01, P<0.05), and the TNF-α levels decreased at 24, 48 and 72 h after modeling (P<0.01) when compared with those in the model group at the same time points separately. The serum IL-6 and TNF-α levels ascended and then tended to decline in the model group and the acupuncture pretreatment group. Compared with the blank group, the protein and mRNA expression of TLR9 and NF-κB p65 in the gastrocnemius tissue increased at 12, 24, 48 and 72 h after modeling (P<0.01, P<0.05), and the protein and mRNA expression levels of MyD88 in the gastrocnemius tissue at each time point after modeling were elevated (P<0.05, P<0.01) in the model group. When compared with the model group at the same time points, in the acupuncture pretreatment group, the protein expression of TLR9 in the gastrocnemius tissue decreased at 12, 24, 48 and 72 h after modeling (P<0.05, P<0.01), and the mRNA expression of TLR9 was declined at 24, 48 and 72 h after modeling (P<0.01, P<0.05); the protein and mRNA expression of MyD88 in the gastrocnemius decreased at 24, 48 and 72 h after modeling (P<0.01, P<0.05), and that of NF-κB p65 was reduced at 24 h and 48 h after modeling (P<0.01). The protein and mRNA expression of TLR9, MyD88 and NF-κB p65 in the gastrocnemius tissue showed a trend of decrease after increase in the model group and the acupuncture pretreatment group. CONCLUSIONS: Acupuncture pretreatment can alleviate exercise-induced skeletal muscle damage, which may be related to modulating the expression of TLR9/MyD88/NF-κB signaling pathway to inhibit the inflammatory response.

Diagnostic Value of Tracheal Wash Cytology for Monitoring Exercise-Induced Pulmonary Hemorrhage in Thoroughbred Racehorses.

Lower airway cytology has been proposed as a complementary diagnostic method to confirm the presence and quantifying the severity of exercise-induced pulmonary hemorrhage (EIPH). Bronchoalveolar lavage is usually preferred over tracheal wash (TW), yet the need for sedation imposes as a limitation for active sport horses in addition to be a highly invasive technique. This study aims to evaluate the diagnostic value of TW with Total Hemosiderin Score (THS) for monitoring EIPH in active Thoroughbred racehorses. A sampling of 47 randomly selected Thoroughbreds were endoscopically examined for EIPH grading 30 to 60 minutes after competing in an official race and then classified as Group 1 (EIPH-negative), Group 2 (EIPH-positive) or Group 3 (furosemide users). Tracheal wash fluids (TWFs) were collected from 24 to 30 hours later and smears were stained for differential cell count and hemosiderophage grading and counting to calculate THS. Differential cell counts were compared by the median test. Comparisons between mean THS values by EIPH grade and by group were compared by the Mann-Whitney test and ANOVA, respectively. Test performance criteria were determined with a contingency table. It was not possible to establish a THS cut-off point but statistical results showed that, at THS stand view, all groups had similar results despite their EIPH grades. Most animals showed no signs of neutrophilic inflammation, but haemosiderophages were found even on a first-time runner from Group 1. Thus, TW can detect evidence of lung bleeding even on horses with no history of EIPH. The implementation of TW analysis to diagnose EIPH in racehorses is promising, as TW is both low-cost and a less invasive tool.

[The role of clock gene BMAL1 in exercise-induced skeletal muscle injury recovery].

Objective: To investigate the role of clock gene BMAL1 in exercise-induced skeletal muscle injury recovery. Methods: Two hundred and eight 8-week-old SD rats were randomly divided into the control group (Group C, n=104) and the exercise group (Group E, n=104). Group E performed a 90-minute downhill run on the treadmill. After exercise, the gastrocnemius muscle of 8 rats in Group C and Group E were collected at 0 h, 6 h, 12 h, 18 h, 24 h, 30 h, 36 h, 42 h, 48 h, 54 h, 60 h, 66 h and 72 h. The expression of skeletal muscle core clock gene, BMAL1 was measured by real-time fluorescence quantitative PCR. The parameters of fitting cosine curve were obtained by cosine analysis software circacompare (R package), and the change trend of rhythmic oscillation was analyzed. The ultrastructure of skeletal muscle fibers was observed by transmission electron microscope. The expressions of skeletal muscle BMAL1 and DESMIN were detected by Western blot; Immunofluorescence was used to observe the localization and contents of BMAL1 and DESMIN. Results: In Group C, three complete circadian rhythm cycles of mRNA BMAL1 were observed within 72 hours; in Group E, the circadian rhythm of BMAL1 mRNA disappeared at 0 h～24 h. Compared with Group C, the expression level of BMAL1 mRNA was significantly increased at 0 h, 6 h, 12 h, and 18 h after exercise in Group E (P＜0.05), and the expression of BMAL1 protein was significantly increased at 0 h and 12 h after exercise(P＜0.05), and recovered to the level of that in Group C from 24 h to 72 h(P＞0.05). The expression of DESMIN protein was decreased at 0 h and 12 h after exercise(P＜0.05), gradually increased at 24 h, increased significantly at 48 h(P＜0.01), and recovered to the control level at 72 h (P＞0.05). In Group E, BMAL1 and DESMIN were co-localized at 0 h, 12 h, and 24 h after exercise; the colocalization at 0 h～24 h showed a trend of first decreasing and then increasing, and the fluorescence intensity at 24 h reached the highest value. Conclusion: The post-exercise clock gene BMAL1 may be involved in the enhanced synergy of regulating the cytoskeletal protein DESMIN, it is thus related to the promotion of muscle fiber structure recovery.

Pulmonary bleeding in racehorses: A gross, histologic, and ultrastructural comparison of exercise-induced pulmonary hemorrhage and exercise-associated fatal pulmonary hemorrhage.

Exercise-induced pulmonary hemorrhage (EIPH) is a common condition of Thoroughbred racehorses that is usually responsible for reduced performance, while exercise-associated fatal pulmonary hemorrhage (EAFPH) is characterized by severe pulmonary bleeding of unknown pathogenesis resulting in sudden death during strenuous exercise. The aim of the study was to characterize and compare anamnestic data together with pulmonary gross, histologic, and ultrastructural findings in racehorses with EIPH (n = 10), EAFPH (n = 10), and control horses (n = 5). No differences in anamnesis were identified between the 3 groups. Grossly cranial lobe reddening and edema scores were significantly more prevalent and severe in the EAFPH group compared with the EIPH and control groups. Histologically, hemorrhage scores were higher in the EAFPH group, while hemosiderophages, iron encrustations of collagen and elastin fibers, and vascular remodeling scores were significantly higher in EIPH group compared with the EAFPH and control groups. In all groups, caudal lung locations exhibited a significantly higher score for vascular remodeling, hemosiderophage accumulation, iron encrustation, and type II pneumocyte hyperplasia when compared with cranial, dorsal, and ventral locations. Ultrastructural analysis of perivascular collagen showed fibrils with significantly larger diameters in the EAFPH group compared with the EIPH group but not compared with the control group. This study demonstrates that lungs of horses that experienced EAFPH show significantly less vascular remodeling and other long-term pulmonary abnormalities that characterize horses with EIPH.

Exercise Causes Arrhythmogenic Remodeling of Intracellular Calcium Dynamics in Plakophilin-2-Deficient Hearts.

BACKGROUND: Exercise training, and catecholaminergic stimulation, increase the incidence of arrhythmic events in patients affected with arrhythmogenic right ventricular cardiomyopathy correlated with plakophilin-2 (PKP2) mutations. Separate data show that reduced abundance of PKP2 leads to dysregulation of intracellular Ca2+ (Ca2+i) homeostasis. Here, we study the relation between excercise, catecholaminergic stimulation, Ca2+i homeostasis, and arrhythmogenesis in PKP2-deficient murine hearts. METHODS: Experiments were performed in myocytes from a cardiomyocyte-specific, tamoxifen-activated, PKP2 knockout murine line (PKP2cKO). For training, mice underwent 75 minutes of treadmill running once per day, 5 days each week for 6 weeks. We used multiple approaches including imaging, high-resolution mass spectrometry, electrocardiography, and pharmacological challenges to study the functional properties of cells/hearts in vitro and in vivo. RESULTS: In myocytes from PKP2cKO animals, training increased sarcoplasmic reticulum Ca2+ load, increased the frequency and amplitude of spontaneous ryanodine receptor (ryanodine receptor 2)-mediated Ca2+ release events (sparks), and changed the time course of sarcomeric shortening. Phosphoproteomics analysis revealed that training led to hyperphosphorylation of phospholamban in residues 16 and 17, suggesting a catecholaminergic component. Isoproterenol-induced increase in Ca2+i transient amplitude showed a differential response to ß-adrenergic blockade that depended on the purported ability of the blockers to reach intracellular receptors. Additional experiments showed significant reduction of isoproterenol-induced Ca2+i sparks and ventricular arrhythmias in PKP2cKO hearts exposed to an experimental blocker of ryanodine receptor 2 channels. CONCLUSIONS: Exercise disproportionately affects Ca2+i homeostasis in PKP2-deficient hearts in a manner facilitated by stimulation of intracellular ß-adrenergic receptors and hyperphosphorylation of phospholamban. These cellular changes create a proarrhythmogenic state that can be mitigated by ryanodine receptor 2 blockade. Our data unveil an arrhythmogenic mechanism for exercise-induced or catecholaminergic life-threatening arrhythmias in the setting of PKP2 deficit. We suggest that membrane-permeable ß-blockers are potentially more efficient for patients with arrhythmogenic right ventricular cardiomyopathy, highlight the potential for ryanodine receptor 2 channel blockers as treatment for the control of heart rhythm in the population at risk, and propose that PKP2-dependent and phospholamban-dependent arrhythmogenic right ventricular cardiomyopathy-related arrhythmias have a common mechanism.

Training related risk factors for exercise induced pulmonary haemorrhage in British National Hunt racehorses.

BACKGROUND: Exercise induced pulmonary haemorrhage (EIPH) is an important condition of horses performing high intensity exercise, with reported prevalence among racehorses of up to 95%, based on the detection of blood on tracheobronchoscopy. Previously identified risk factors include age, sex, season, race type, years spent in racing and lower airway inflammation. OBJECTIVES: To estimate the prevalence of EIPH in British National Hunt racehorses as indicated by two outcome measures: presence of tracheal blood on tracheobronchoscopy, and presence of moderate-large (significant) proportions of haemosiderophages in tracheal wash (TW) fluid; and to identify training-related risk factors for these indicators of EIPH. STUDY DESIGN: Prospective longitudinal study. METHODS: Data from tracheobronchoscopy and TW cytology were analysed using univariable and multivariable mixed-effects logistic regression. RESULTS: 1184 observations, from 177 horses, were analysed. The prevalence of tracheal blood was 7.2% (95%CI: 5.8, 8.8) and significant haemosiderophages in TW fluid was 36% (95%CI: 33.3, 38.8). Increased time in training was significantly associated with increased odds of EIPH. For each additional year spent in training the odds of tracheal blood and presence of significant proportions haemosiderophages increased approximately 1.5-fold (OR = 1.5; 95%CI: 1.1-2.0; P = .005; and OR = 1.5; 95%CI: 1.3, 1.8; P < .001, respectively). Current inflammation was associated with previous haemorrhage, but not current haemorrhage. MAIN LIMITATIONS: There are no standardised measures for quantification of TW cytological parameters for EIPH diagnosis. Few horses were examined following jumping. Recent racing dates were not included in analysis. CONCLUSIONS: Increasing time in training was a risk factor for both indicators of EIPH. Current inflammation was associated with previous haemorrhage, but not current or future haemorrhage, suggesting that haemorrhage leads to inflammation but not that inflammation leads to haemorrhage. Overall, our findings are consistent with the capillary stress failure theory of EIPH. The development of standardised measures for TW cytological diagnosis of EIPH is warranted.

Effect of one-time high load exercise on skeletal muscle injury in rats of different genders: oxidative stress and mitochondrial responses

Purpose: To evaluate the impact of one-time high load exercise on skeletal muscle injury and analysis its mechanism in different genders. Methods: Twenty-four male and 24 female rats were divided randomly into four groups respectively: control, 0 h, 6 h, and 24 h after exercise. The activities of creatine kinase (CK), lactate dehydrogenase (LDH), and myohemoglobin (MYO) in serum, the expression level of oxidative stress markers, mitochondrial respiratory chain complex enzyme, and the apoptosis related protein in quadriceps were detected. Results: The results showed that the activities of CK, LDH and MYO in serum increased immediately after exercise and restored faster in female rats. More obvious structural disorder and apoptosis in male rats were showed. Malondialdehyde (MDA) and superoxide dismutase (SOD) were increased while catalase (CAT) and glutathione (GSH) were decreased in male rats. SOD, CAT and GSH were increased in female rats. Mitochondrial complex enzyme activity was decreased in males and increased in females. Conclusions: The skeletal muscle injury in both genders of rat could be induced by one-time high load exercise due to the mitochondrial respiratory enzyme dysfunction and oxidative stress, which was relatively mild and recovered quicker in female rats.

Supplementation with Spirulina platensis Prevents Uterine Diseases Related to Muscle Reactivity and Oxidative Stress in Rats Undergoing Strength Training.

Strength training increases systemic oxygen consumption, causing the excessive generation of reactive oxygen species, which in turn, provokes oxidative stress reactions and cellular processes that induce uterine contraction. The aim of this study was to evaluate the possible protective effect of Spirulina platensis (SP), an antioxidant blue algae, on the contractile and relaxation reactivity of rat uterus and the balance of oxidative stress/antioxidant defenses. Female Wistar rats were divided into sedentary (CG), trained (TG), and T + supplemented (TG50, TG100) groups. Reactivity was analyzed by AQCAD, oxidative stress was evaluated by the malondialdehyde (MDA) formation, and the antioxidant capacity was measured by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method. Strength training increased contractile reactivity and decreased the pharmaco-mechanical component of relaxing reactivity in rat uterus. In addition, training decreased oxidation inhibition in the plasma and exercise increased oxidative stress in the uterine tissue; however, supplementation with algae prevented this effect and potentiated the increase in antioxidant capacity. Therefore, this study demonstrated that food supplementation prevents changes in reactivity and oxidative stress induced by strength training in a rat uterus, showing for the first time, that the uterus is a target for this exercise modality and antioxidant supplementation with S. platensis is an alternative means of preventing uterine dysfunction.

High Intensity Physical Exercise before the Brain Ischemia Promotes Increase in Brain Injury.

Studies have demonstrated the beneficial effects of light- and moderate-intensity physical exercise on the nervous system of animals with cerebral ischemia. To investigate the effects of two high-intensity physical exercise protocols, standardized for resistance and strength gain, in rats trained before cerebral ischemia induced by Bilateral Common Carotid Artery Occlusion (BCCAO). Forty-eight male Wistar rats were divided into two groups: with ischemia and without ischemia (sham). Both groups were subdivided into animals that performed high-intensity exercises in the muscle strength modality (I+Ex2; Sham+Ex2; n=16); animals submitted to high-intensity exercises in the aerobic modality (I+Ex1; Sham+Ex1; n=16), and animals that did not practice physical exercises - sedentary (I+Sed; Sham+Sed, n=16). Cerebral ischemia was induced using the BCCAO model. The physical training program used before the procedure was of high intensity, in the aerobic and muscular strength modalities, and was performed using a vertical ladder, for 4 weeks, 5 days per week. In order to process and stain the brain tissue, the Nissl method was used for neuron labeling and quantification in the cortex, striatum, and hippocampus. As for the animals' body weight and the heart weight differences were found between the groups I+Ex2 and Sham+Ex2 (p<0.05). Data on neuron quantification in the cerebral cortex, dentate gyrus, and right and left striatum revealed significant differences between groups. High-intensity physical training in the strength gain modality promotes significant damage to the animal's brain when performed prior to BCCAO-induced cerebral ischemia.

Intranasal administration of DHED protects against exhaustive exercise-induced brain injury in rats.

DHED (10ß,17ß-dihydroxyestra-1,4-dien-3-one) is a brain-selective prodrug of 17ß-estradiol and has been reported to have a strong neuroprotective effect. In this study, the exhaustive swimming rat model was used to investigate the therapeutic effects and mechanisms of intranasal DHED treatment. Male eight-week-old healthy Sprague Dawley rats were randomly divided into three groups: control group (Cont), exhaustive swimming (ES), and DHED + exhaustive swimming (DHED). The open-field test and beam-walking test were performed to measure exploratory behavior and general activity in rats. Immunofluorescence staining, western blotting, ELISA analysis and related assay kits were applied to measure brain damage, inflammatory cytokines, and apoptosis pathways. Behavioral data shows that DHED intranasal administration can prevent neurobehavioral impairment caused by exhaustive swimming. Using a series of bioanalytical assays, we demonstrated that DHED markedly abated neuronal injury compared to the exhaustive swimming group, as evidenced by the reduced expression of apoptosis-regulated proteins, the improvement of neural survival, and the prevention of myelin loss. In addition, mitochondrial fission was attenuated distinctly, and a dynamic equilibrium was restored. Intranasal administration of DHED likewise significantly suppressed reactive gliosis and the release of inflammatory cytokines in the rat cerebral motor cortex. Consistent with previous reports, DHED treatment ameliorated changes of excitatory neurotransmitters. These results provide strong support for the promising therapeutic effects of DHED on neuroprotection during exhaustive swimming. The underlying mechanisms may rely on mitochondrial dynamics, neuroinflammation, and the balance of neurotransmitters.

Fermented Deer Blood Ameliorates Intense Exercise-Induced Fatigue via Modulating Small Intestine Microbiota and Metabolites in Mice.

Intense and excessive exercise-induced fatigue has become an important health issue and can damage intestinal health. Deer blood, as a food byproduct with nutritional value, has been found to restore physical strength. However, little is known about the antifatigue effect of fermented deer blood (FDB) on intense exercise mice. The purpose of the present study is to investigate the antifatigue effect of FDB, and whether this effect is correlated with the altered small intestinal microbiota and metabolites in exercise mice. In this study, 5-week-old male C57BL/6J mice are given treadmill exercise with or without FDB supplementation (30 and 150 mg/kg/d) for 3 weeks. FDB significantly reduces metabolic byproduct accumulation, liver and intestinal damage, and enhances glycogen storage and antioxidant capacity in intense exercise mice. Moreover, FDB restructures the small intestinal microbiota by increasing the abundance of probiotics and butyric acid producing bacteria and decreasing the abundance of pathogenic bacteria. FDB also regulates the levels of metabolites involved in TCA cycle and amino acid metabolism in urine and small intestine content. Correlation analysis shows that FDB-modulated microbiota is highly associated with its antifatigue effect. FDB may ameliorate fatigue and intestinal injury through targeting small intestinal microbiota.

Developmental and lifelong dioxin exposure induces measurable changes in cardiac structure and function in adulthood.

Congenital heart disease (CHD) is the most common congenital abnormality. A precise etiology for CHD remains elusive, but likely results from interactions between genetic and environmental factors during development, when the heart adapts to physiological and pathophysiological conditions. Further, it has become clearer that early exposure to toxins that do not result in overt CHD may be associated with adverse cardiac outcomes that are not manifested until later life. Previously, interference with endogenous developmental functions of the aryl hydrocarbon receptor (AHR), either by gene ablation or by in utero exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent AHR ligand, was shown to cause structural, molecular and functional cardiac abnormalities and altered heart physiology in mouse embryos. Here, we show that continuous exposure to TCDD from fertilization throughout adulthood caused male mice to underperform at exercise tolerance tests compared to their control and female counterparts, confirming previous observations of a sexually dimorphic phenotype. Renin-angiotensin stimulation by angiotensin II (Ang II) caused measurable increases in blood pressure and left ventricle mass, along with decreased end diastolic volume and preserved ejection fraction. Interestingly, TCDD exposure caused measurable reductions in the myocardial hypertrophic effects of Ang II, suggesting that endogenous AHR signaling present in adulthood may play a role in the pathogenesis of hypertrophy. Overall, the findings reported in this pilot study highlight the complex systems underlying TCDD exposure in the development of cardiac dysfunction in later life.