Skeletal variation in Tennessee Walking Horses maps to the LCORL/NCAPG gene region.

Conformation has long been a driving force in horse selection and breed creation as a predictor for performance. The Tennessee Walking Horse (TWH) ranges in size from 1.5 to 1.7 m and is often used as a trail, show, and pleasure horse. To investigate the contribution of genetics to body conformation in the TWH, we collected DNA samples, body measurements, and gait/training information from 282 individuals. We analyzed the 32 body measures with a principal component analysis. Principal component (PC)1 captured 28.5% of the trait variance, while PC2 comprised just 9.5% and PC3 6.4% of trait variance. All 32 measures correlated positively with PC1, indicating that PC1 describes overall body size. We genotyped 109 horses using the EquineSNP70 bead chip and marker association assessed the data using PC1 scores as a phenotype. Mixed-model linear analysis (EMMAX) revealed a well-documented candidate locus on ECA3 (raw P = 3.86 × 10(-9)) near the LCORL gene. A custom genotyping panel enabled fine-mapping of the PC1 body-size trait to the 3'-end of the LCORL gene (P = 7.09 × 10(-10)). This position differs from other reports suggesting single nucleotide polymorphisms (SNPs) upstream of the LCORL coding sequence regulate expression of the gene and, therefore, body size in horses. Fluorescent in situ hybridization analysis defined the position of a highly homologous 5 kb retrogene copy of LCORL (assigned to unplaced contigs of the EquCab 2.0 assembly) at ECA9 q12-q13. This is the first study to identify putative causative SNPs within the LCORL transcript itself, which are associated with skeletal size variation in horses.

Adverse reactions in horses that underwent general anesthesia and cervical myelography.

BACKGROUND: The study was prompted by a perceived high prevalence of myelographic complications varying in severity and type, and attributed to the contrast material or the procedure. HYPOTHESES: 1. Any adverse reaction (AAR) is associated with a change in CSF volume induced either by removal of CSF or addition of contrast material. 2. AAR occurs more frequently in horses with higher premyelography neurologic grade. 3. Nonspecific hyperthermia is attenuated by anti-inflammatory and osmotic agents. ANIMALS: Horses (n = 278) that underwent myelography between 2000 and 2012 at 5 institutions: A (87), B (68), C (65), D (46), and E (12). METHODS: Multi-institutional, retrospective, observational cross-sectional study. RESULTS: AAR were observed in 95/278 (34%) horses, were associated with longer general anesthesia time (P = .04) and higher contrast-medium volume (P = .04); euthanasia because of AAR was performed in 5/278 (2%) horses. Adverse neurologic reactions were the most common type of complication observed occurring in 15/278 (5%) and 42/235 (18%) of horses in the intra- and postmyelography periods. A relationship between AAR and premyelography neurologic grade was not identified (P = .31). Nonspecific hyperthermia was observed in 25/235 (11%) horses; no relationship was observed with administration of anti-inflammatory drugs and osmotic agents (P = .30). CONCLUSIONS AND CLINICAL IMPORTANCE: The category of AAR occurred in one-third of the horses generally was mild and self-limiting. These reactions were associated with increased contrast-medium volume and longer anesthesia time; but, no specific procedural recommendations could be made because of small odds ratios (OR) of <2 for each 1 mL increase in contrast material and for each 1 minute of additional anesthesia time.

Analysis of soluble CD14 and its use as a biomarker in neonatal foals with septicemia and horses with recurrent airway obstruction.

Soluble CD14 (sCD14) binds bacterial lipopolysaccharide (LPS) and acts as an anti-inflammatory LPS-inhibitor in vivo. In humans, sCD14 is one of the soluble biomarkers used for various inflammatory diseases and conditions, however, sCD14 assays have not yet been evaluated in horses. Here, we developed and optimized a bead-based assay for the quantification of sCD14 in horses. The assay was then used to determine native sCD14 concentrations in serum from healthy and septic foals, in the colostrum of healthy mares and in plasma from adult horses with recurrent airway obstruction (RAO) and control horses. Healthy foals and adult horses had sCD14 concentrations in serum or plasma in the high ng/ml range. The concentration of sCD14 in colostrum samples from healthy mares was in the µg/ml range. Foals with septicemia and adult horses with RAO had significantly higher sCD14 concentrations in their circulation than the respective control groups. The findings suggest that sCD14 can become a valuable biomarker for neonatal septicemia, RAO and possibly also for other inflammatory diseases in horses. Further studies and larger samples numbers are required to determine normal sCD14 concentration ranges and those that are indicative of disease progression, severity or prognosis.

Serum interleukin-6 (IL-6) and IL-10 concentrations in normal and septic neonatal foals.

Previously it was reported that compared to surviving septic foals, non-surviving foals had a 35-fold increase in interleukin-10 (IL-10) and 15-fold increase in IL-6 gene expression in their peripheral blood mononuclear cells (PBMC). As gene expression profiles can be time-consuming, we sought to determine if serum IL-6 and IL-10 in foals would aid in the diagnosis and prognosis of septicemia. A prospective study of septic neonatal foals admitted to the Cornell University Equine Hospital during 2007 and 2008 was performed. Septicemia was confirmed in 15 foals using blood culture results and sepsis scores. Blood samples for measurement of serum IL-6 and IL-10 concentrations were collected at the time of admission (T0) and again 24 (T24) and 48 (T48) hours later. Blood samples from age-matched control foals (n=15) born at the Cornell Equine Park were obtained from foals 12-72h after birth (T0) and again 24 (T24) and 48 (T48) hours later. IL-6 and IL-10 concentrations were determined in the serum from dams of septic foals and serum and colostrum from dams of control foals. Serum IL-6 was also measured in healthy foals prior to ingestion of colostrum. Interleukin-6 was detected using an ELISA and IL-10 was detected using a bead-based fluorescent immunoassay. Group differences were detected using a Wilcoxon rank sum test with a Bonferroni correction applied to the p value. There were no significant differences in serum IL-10 concentration between the two groups of foals. Relative to control foals, septic foals had significantly lower serum IL-6 concentrations at all 3 time points. Relative to septic foals, control foals had significantly higher serum IL-6:IL-10 ratios. Serum IL-6 was undetectable in foals prior to ingestion of colostrum. However, colostral IL-6 concentration measured in the control mares was high (> or =215ng/mL) in all samples suggesting passive transfer of maternal IL-6 to the equine neonate. Colostral IL-10 was undetectable in 11/12 samples. Failure of passive transfer may directly influence the serum IL-6 concentration in septic foals. Neither serum IL-6 nor IL-10 alone, were useful diagnostic indices of sepsis in equine neonates. Although the number of animals involved in this study was too small for the identification of a concrete value, the serum IL-6:IL-10 ratio is likely to provide a valuable prognosticator for neonatal septicemia.

Histamine bronchoprovocation does not affect bronchoalveolar lavage fluid cytology, gene expression and protein concentrations of IL-4, IL-8 and IFN-gamma.

In diagnosing inflammatory airway disease (IAD) in performance horses, a histamine bronchoprovocation (HBP) test is often performed. In previously published studies, HBP is usually undertaken prior to cytological examination of the bronchoalveolar lavage (BAL) cells. The purpose of this study was to determine if HBP alters (1) the total nucleated cell numbers and distribution in BAL fluid (BALF) and (2) the mRNA and protein concentrations of selected cytokines in BAL cells and BALF, respectively. BALF was initially collected endoscopically from the right middle or diaphragmatic lung lobe in eight healthy young Standardbred horses. Five to six days later, HBP was performed by aerosolization of histamine (8mg) over a 2min period. BALF was again collected within 2-4h of the HBP from the left middle or diaphragmatic lung lobe. In both samples, total and differential WBC counts were obtained. The gene expressions of interleukin-4 (IL-4), IL-8, interferon-gamma (IFN-gamma) and beta-actin in BAL cells were measured using real-time RT-PCR. The cytokine protein concentrations were measured in the BALF using ELISA. HBP was not associated with either a change in the total BAL cell number or in the distribution of the BAL cells. BAL cell expression of IL-4, IL-8 and IFN-gamma, detected in all samples with the exception of IL-4 in one horse (post-HBP), was not altered as a result of HBP. HBP was not associated with a significant change in IL-8 or IFN-gamma concentrations in the BALF. IL-4 protein was undetectable in BALF either prior to or following HBP. We conclude that HBP can precede BALF collection performed within 2-4h of the former without affecting selected parameters analysed in the BAL cells or BALF.

The effect of adding oral dexamethasone to feed alterations on the airway cell inflammatory gene expression in stabled horses affected with recurrent airway obstruction.

BACKGROUND: Chemokine expression in airway epithelium and bronchoalveolar lavage fluid (BALF) cells of horses with recurrent airway obstruction (RAO) is increased. HYPOTHESIS: For RAO-affected horses that are stabled and fed a pelleted ration, the addition of oral dexamethasone further improves pulmonary function and reduces inflammatory gene expression in pulmonary cells. ANIMALS: Twelve RAO-affected horses. METHODS: In a randomized cross-over experiment, the effect of feeding pellets in lieu of hay to stabled, RAO-affected horses was compared with the effect of feeding pellets and administering a 21-day decreasing dose regimen of oral dexamethasone on the expression (by kinetic polymerase chain reaction) of interleukin-8 (IL-8), chemokine (C-X-C motif) ligand 2 (CXCL2), IL-1beta, IL-6, and beta-actin in the BALF cells and of IL-8, CXCL2, 2 IL-1 receptor (IL-1R2), Toll-like receptor 4 (TLR4), and glyceraldehyde 3-phosphate dehydrogenase in the bronchial epithelium 2 days after the final dose. RESULTS: Both treatments reduced airway neutrophilia and breathing efforts but the addition of dexamethasone was associated with fewer treatment failures. Compared with feed changes alone, dexamethasone administration further reduced the expression of IL-8, CXCL2, and IL-1beta in the BALF cells 3.3-, 2.5-, and 4.7-fold, respectively. In the airway epithelium, both treatments were equally efficacious in reducing the expression of IL-8 and CXCL2 expression relative to pretreatment values, but either treatment failed to alter the expression of IL-1R2 and TLR4. CONCLUSIONS AND CLINICAL IMPORTANCE: For a rapid and consistent improvement in pulmonary function and a reduction in inflammatory gene expression of the BALF cells, a decreasing dose of oral dexamethasone in combination with feed alterations is more efficacious for horses that must remain stabled.

Serum IgM concentrations in normal, fit horses and horses with lymphoma or other medical conditions.

The purposes of this study were to (1) prospectively establish serum IgM and IgG concentrations in normal, fit, adult horses over time and (2) determine the accuracy of serum IgM concentrations for diagnosing lymphoma. Serial IgM and IgG concentrations were measured with a radial immunodiffusion assay in 25 regularly exercised horses at 6-week intervals. Horses had serum IgM concentrations ranging from 50 to 242 mg/dL over 5 months, with 20% of horses having IgM < or = 60 mg/dL. The normal range for IgM in fit horses should be considered 103 +/- 40 mg/dL and a cut-point for an IgM deficiency, < or = 23 mg/dL. IgG concentrations ranged from 1,372 to 3,032 mg/dL. Retrospectively, medical records of adult horses (n = 103) admitted to the Cornell University Hospital for Animals for which serum IgM was measured were examined. Horses were categorized as "lymphoma negative" (n = 34) or "lymphoma positive" (n = 18). The sensitivity and specificity of a serum IgM concentration (< or = 60 mg/dL) for detecting equine lymphoma was 50 and 35%, respectively. At the new cut-point (< or = 23 mg/dL), the sensitivity was low at 28% and the specificity improved to 88%. The negative predictive values at various population prevalences indicate that a horse with a high serum IgM (> 23 mg/dL) is unlikely to have lymphoma, whereas the positive predictive value (70%) does not allow for reliable determination of lymphoma in a horse with serum IgM < or = 23 mg/dL. Therefore, serum IgM concentrations should not be used as a screening test for equine lymphoma.

Effects of pulmonary abscesses on racing performance of horses treated at referral veterinary medical teaching hospitals: 45 cases (1985-1997).

OBJECTIVE: To determine whether results of physical or radiographic examination or biochemical analyses in adult racehorses with primary lung abscesses were associated with ability to race following treatment. DESIGN: Multiple-center retrospective study. ANIMALS: 25 Standardbreds and 20 Thoroughbreds. PROCEDURE: Medical records of horses with a primary lung abscess that were admitted to any of 4 veterinary teaching hospitals were reviewed. Results of physical examination, laboratory testing, and thoracic radiography were reviewed. Racing performance after treatment was compared with performance before illness and with performance of the general population of racehorses of similar age, sex, and breed. RESULTS: 23 of 25 Standardbreds and 13 of 20 Thoroughbreds raced after diagnosis and treatment of a lung abscess. Most horses had a solitary abscess in the dorsal to caudodorsal lung fields. Results of initial physical examination, biochemical analyses, and culture and identification of the microbial isolate were not associated with whether a horse returned to racing. For horses that had raced prior to the illness, race performance after treatment of the lung abscess was not significantly different from performance before the illness. CONCLUSIONS AND CLINICAL RELEVANCE: On the basis of racing performance in those horses that resumed racing after treatment, long-term residual lung damage did not develop in horses with primary lung abscesses that were treated appropriately. It is not known whether horses that recovered would be more likely to bleed from the site of a prior infection when resuming strenuous exercise and whether lung abscesses contributed to a failure to resume racing.

Clinical, haematological and biochemical findings in foals with neonatal Equine herpesvirus-1 infection compared with septic and premature foals.

A retrospective multicentre study comparing historical, clinical, haematological, acid-base and biochemical findings of foals with Equine herpesvirus-1 (EHV-1) infection, septicaemia or prematurity was performed to determine if early diagnosis of EHV-1 foals was possible. Fifty-three foals were studied and were assigned to one of 2 groups: herpes positive (n = 14) or herpes negative (n = 39). The latter group included 20 septic, 11 premature, and 8 premature and septic foals. The presence of herpes antigen was confirmed by immunoperoxidase histochemical staining of tissues from necropsied foals. A nonparametric statistical analysis followed by a backwards elimination logistic regression was performed to establish a model at a P value of <0.05. All herpes positive foals died, while 47% (9/19) of the septic foals survived. Based upon our analysis, herpes positive foals were more likely to have total white blood cell counts less than 3 x 10(9)/l and to be icteric as compared to the septic and premature foals. Despite profound hepatic necrosis in the herpes positive foals, liver enzymes were not elevated and were not significantly different from the controls.

Hemothorax in 2 horses.

This report documents the successful conservative medical management of hemothorax in 2 horses. Hemothorax occurred after a lung biopsy procedure (horse 1) and strenuous exercise on a treadmill (horse 2). The horses had tachypnea, tachycardia, nostril flaring, hemoptysis, and pawing. Hemothorax was suspected based upon absence of auscultable ventral lung sounds; development of cool extremities and pale, tacky mucous membranes; the ultrasonographic appearance of moderate to severe amounts of pleural fluid; and a concurrent decrease in hematocrit and total plasma protein. Both horses were treated successfully by intranasal administration of oxygen, intravenous administration of balanced polyionic solutions, and treatment with antibiotics, nonsteroidal anti-inflammatory drugs, and analgesics. In neither case was pleural blood removed. The hemothorax resolved in both horses without lasting abnormalities. Hemothorax does not require drainage for successful resolution.

Effects of extrathoracic airway obstruction on intrathoracic pressure and pulmonary artery pressure in exercising horses.

OBJECTIVE: To determine whether dorsal displacement of the soft palate (DDSP) results in pulmonary artery hypertension and leads to increases in transmural pulmonary artery pressure (TPAP); to determine whether pulmonary hypertension can be prevented by prior administration of furosemide; and to determine whether tracheostomy reduces pulmonary hypertension. ANIMALS: 7 healthy horses. PROCEDURE: Horses were subjected to 3 conditions (control conditions, conditions after induction of DDSP, and conditions after tracheostomy). Horses were evaluated during exercise after being given saline (0.9% NaCl) solution or furosemide. RESULTS: Controlling for drug, horse, and speed of treadmill, DDSP-induced increase in intrathoracic pressure was associated with a significant increase in minimum (36 mm Hg), mean (82 mm Hg), and maximum (141 mm Hg) pulmonary artery pressure, compared with values for control horses (30, 75, and 132 mm Hg, respectively). Increases in pulmonary artery pressure did not induce concomitant increases in TPAP. Tracheostomy led to a significant reduction of minimum (53 mm Hg), and mean (79 mm Hg) TPAP pressure, compared with values for control horses (56 and 83 mm Hg, respectively). When adjusted for horse, speed of treadmill, and type of obstruction, all aspects of the pulmonary artery and TPAP curves were significantly decreased after administration of furosemide, compared with those for horses given saline (0.9% NaCl) solution. CONCLUSIONS: DDSP was associated with increases in pulmonary artery pressure but not with increases in TPAP. CLINICAL RELEVANCE: Expiratory obstructions such as DDSP are likely to result in pulmonary hypertension during strenuous exercise, but may not have a role in the pathogenesis of exercise-induced pulmonary hemorrhage.

Pulmonary capillary pressure in horses undergoing alteration of pleural pressure by imposition of various upper airway resistive loads.

We hypothesized that changes in pleural pressure induced by resistive breathing would affect transmural pulmonary artery, pulmonary capillary, and pulmonary wedge pressures. Seven horses were assigned to exercise with each of 4 upper respiratory resistive loads in random order at intervals of at least 2 days: 1) control--no added resistive loads; 2) inspiratory resistive load (Iobst)--left laryngeal hemiplegia; 3) expiratory resistive load (Eobst)--one-way valve in the right nostril; and 4) combined inspiratory and expiratory resistive loads (CIEobst)--left nostril occlusion. On each occasion, the horses performed an incremental exercise protocol consisting of exercise episodes of 3 min duration at 75, 90, and 100% of maximal heart rate (HRmax). Pulmonary artery and oesophageal pressures were recorded continuously. Subsequent analysis was carried out on the pulmonary arterial pressure signal with the oesophageal pressure signal subtracted, hence the pulmonary vascular pressures in this paper approximate transmural pressures. Pulmonary vascular pressures, heart rate, and arterial blood gas tensions were measured at each level of exercise. Pulmonary capillary and pulmonary wedge pressures were determined from the pulmonary artery waveform after dynamic occlusion of a branch of the pulmonary artery. During exercise, peak expiratory oesophageal pressure was more positive in horses with Eobst and CIEobst (adjusted means = 43, and 39 mmHg, respectively) compared with control (adjusted mean = 23 mmHg) (P = 0.0001). Peak inspiratory oesophageal pressure was more negative in horses at exercise with Iobst and CIEobst (adjusted means = -42 and -39 mmHg, respectively) compared with control (adjusted mean = -26 mmHg) (P = 0.0012). Eobst was associated with an increase in mean oesophageal pressure while Iobst was associated with a decrease in mean oesophageal pressure. There were significant increases in mean pulmonary artery pressure in horses with CIEobst (adjusted means = 82 mmHg) and in pulmonary wedge pressure in horses with CIEobst and Iobst (adjusted means = 51, and 55 mmHg, respectively) when compared to control (73 and 42 mmHg, respectively) (P = 0.0001). Pulmonary capillary pressure was significantly increased in horses with CIEobst or Iobst (adjusted means = 61 mmHg, 63 mmHg, respectively) when compared to control (adjusted mean = 50 mmHg)(P = 0.0001). At maximal exercise intensity with inspiratory obstruction, the mean oesophageal (pleural) pressure was -17 mmHg while the mean pulmonary capillary pressure was 77 mmHg. The latter exceeds the reported 75 mmHg threshold for capillary failure in horses. We conclude that inspiratory resistive breathing can lead to a significant increase in transmural pulmonary capillary pressure which may contribute to loss of capillary integrity and rupture.

Associations between physical examination, laboratory, and radiographic findings and outcome and subsequent racing performance of foals with Rhodococcus equi infection: 115 cases (1984-1992).

OBJECTIVE: To determine whether physical examination, laboratory, or radiographic abnormalities in foals with Rhodococcus equi infection were associated with survival, ability to race at least once after recovery, or, for foals that survived and went on to race, subsequent racing performance. DESIGN: Retrospective study. ANIMALS: 49 Thoroughbreds and 66 Standardbreds admitted to 1 of 6 veterinary teaching hospitals between 1984 and 1992 in which R equi infection was positively diagnosed. PROCEDURE: Results of physical examination, laboratory testing, and thoracic radiography were reviewed. Indices of racing performance were obtained for foals that recovered and eventually raced and compared with values for the US racing population. RESULTS: 83 (72%) foals survived. Foals that did not survive were more likely to have extreme tachycardia (heart rate > 100 beats/min), be in respiratory distress, and have severe radiographic abnormalities on thoracic radiographs at the time of initial examination than were foals that survived. Clinicopathologic abnormalities were not associated with whether foals did or did not survive. Forty-five of the 83 surviving foals (54%) eventually raced at least once, but none of the factors examined was associated with whether foals went on to race. Racing performance of foals that raced as adults was not significantly different from that of the US racing population. CLINICAL IMPLICATIONS: R equi infection in foals is associated with a decreased chance of racing as an adult; however, foals that eventually go on to race perform comparably to the US racing population.

Effects of airway obstruction on transmural pulmonary artery pressure in exercising horses.

OBJECTIVE: To determine whether laryngeal hemiplegia would increase transmural pulmonary artery pressure (TPAP). ANIMALS: 6 horses. DESIGN: Horses were studied under 5 conditions: control conditions, after induction of left laryngeal hemiplegia, during obstruction of the left nostril, after placement of an instrumented tracheostomy, and after placement of an open tracheostomy. Horses were evaluated after being given saline solution and after being given furosemide. PROCEDURES: Horses were exercised on a high speed treadmill, using a maximum speed of 13 m/s. During each exercise, airway pressures, airflow, esophageal and pulmonary artery pressures, and blood gas partial pressures were measured. RESULTS: When adjusted for horse, speed, and obstruction condition, mean TPAP (pulmonary artery pressure-esophageal pressure) and minimum TPAP were significantly lower after administration of furosemide than after administration of saline solution. In horses given saline solution, respiratory obstruction that increased intrapleural pressure significantly increased mean TPAP, and respiratory obstruction that decreased intrapleural pressure significantly decreased minimum TPAP. CONCLUSIONS: Changes in intrapleural pressure appear to play an important role in pulmonary artery pressure and TPAP. CLINICAL RELEVANCE: Because induction of laryngeal hemiplegia did not increase TPAP, laryngeal hemiplegia is unlikely to contribute to development of exercise-induced pulmonary hemorrhage.

Pulmonary-locomotory interactions in exercising dogs and horses.

In exercising quadrupeds, limb movement is often coupled with breathing frequency. This finding has lead some investigators to conclude that locomotory forces, associated with foot plant, abdominal visceral displacements or lumbo-sacral flexion, are the primary determinants of airflow generation. Analysis of respiratory muscle electrical activation (EMG) and contraction profiles in chronically instrumented dogs and horses, along with measurements of esophageal pressure (Pes) changes and limb movements, provide evidence that each breath during the exercise hyperpnea is determined by respiratory neuromuscular events. Specifically: (1) Phasic diaphragmatic EMG and tidal shortening are always synchronous with decreases in Pes; (2) decrements in Pes are always associated with inspiratory flow generation; and (3) strict phase coupling between breathing and stride frequency is not obligatory. Thus, although locomotory-associated forces may minimally assist with flow generation, they are not the primary determinants of breathing during exercise.

The effect of exercise on diaphragmatic activation in horses.

Horses chronically-instrumented with costal diaphragmatic electromyographic electrodes were studied during exercise while unencumbered by a breathing mask. Exercise-associated changes in esophageal (Pes), gastric (Pga) and transdiaphragmatic (Pdi) pressures were measured and related to diaphragmatic electromyographic activity (CS EMG) and to left forelimb impact. In all breaths examined, CS EMG always coincided with decrements in Pes. For all exercise trials, linear increases in CS EMG, Pga and Pdi and linear decreases in Pes, as a function of exercise intensity, always occurred. During all gaits, breathing frequency (fR) was entrained with stride frequency (fS) one for one. However, a constant phase-coupling relationship between fR and fS, observed when horses cantered and galloped, was absent when horses walked or trotted. We conclude that biomechanical forces contribute minimally to ventilation in exercising horses, that the diaphragm is always phasically active during each breath and its total electrical activity and mechanical output are proportional to the exercise hyperpnea.

Respiratory muscle perfusion and energetics during exercise.

The oxygen cost of breathing and blood flow requirements of the respiratory muscles during exercise are discussed along with the implications for limitation of locomotor muscle and exercise performance. Findings show that the oxygen cost of the hyperpnea achieved during very heavy exercise may approach 15% or more of VO2max under conditions that require extraordinary levels of ventilatory work. These conditions include those in the highly trained endurance athlete (at VE > 150 l.min-1), the older athlete at VE of 110-120 l.min-1), and athletic cursorial mammals at VO2max--all of whom experience significant expiratory flow limitation and sometimes even complete ventilatory limitation during heavy or maximum exercise. Rates of blood flow to the respiratory muscles under these peak exercise conditions may equal or exceed those to the limb locomotor muscles. The hypothesis is advanced that excessive requirements of ventilatory work (and therefore VO2 and blood flow) during heavy exercise may cause reflex vasoconstriction of locomotor muscles resulting in curtailment of endurance exercise performance.