Modulation of arachidonic acid metabolism in endotoxic horses: comparison of flunixin meglumine, phenylbutazone, and a selective thromboxane synthetase inhibitor

Two cyclooxygenase inhibitors (flunixin meglumine and phenylbutazone) and a selective thromboxane synthetase inhibitor were assessed in the management of experimental equine endotoxemia. Drugs or saline solution were administered to 16 horses 15 minutes before administration of a sublethal dose of endotoxin (Escherichia coli 055:B5). Plasma concentrations of thromboxane B2 (TxB2), prostacyclin (6-keto PGF1 alpha), plasma lactate, and hematologic values and clinical appearance were monitored for 3 hours after endotoxin administration. Pretreatment with flunixin meglumine (1 mg/kg of body weight) prevented most of the endotoxin-induced changes and correlated with a significant decrease in plasma TxB2 and 6-keto PGF1 alpha concentrations, compared with concentrations in nontreated horses (ie, pretreated with saline solution). Pretreatment with phenylbutazone (2 mg/kg) attenuated the effects of endotoxin and was associated with a brief, early, significant increase in plasma TxB2 concentrations, but not in plasma 6-keto PGF1 alpha concentrations. Pretreatment with the thromboxane synthetase inhibitor did not appear to clinically benefit the horses involved; however, arachidonic acid metabolism was redirected to prostacyclin production.     

Body weight,hematologic findings,and serum and plasma biochemical findings of horses competing in a 48-, 83-, or 159-km endurance ride under similar terrain and weather conditions

OBJECTIVE: To compare physiologic, hematologic, and selected serum and plasma biochemical variables obtained from horses competing in 48-, 83-, or 159-km endurance rides before competition and at the same cumulative distance points. ANIMALS: 83 horses. PROCEDURE: Weight and rectal temperature measurements and blood samples were obtained from horses before, during, and after 1 of 3 rides conducted on the same day. Plasma protein (PP), lactate, WBC, serum electrolyte, and calcium concentrations; PCV; and creatine kinase (CK) activity were determined. Assessments were made to determine whether any differences among groups, with respect to total distance competed, could be explained by differences in lap speed or conditioning and to investigate the effect of time in transit or on-site prior to competition on results of blood analyses or competition outcome. RESULTS: Horses in the 159-km distance group had the lowest preride serum sodium, chloride, bicarbonate, and calcium concentrations. As hours in transit increased, preride PP concentration was significantly greater; serum sodium, chloride, and bicarbonate concentrations were lower; CK activity at 159 km was greater; and horses were more likely to be eliminated. The preride sodium was significantly greater in horses that completed the ride, compared with those eliminated. CONCLUSIONS AND CLINICAL RELEVANCE: Among distance groups, distance ridden, speed, level of fitness, and years of experience of horses had little effect on the variables examined. Electrolyte and water supplementation and earlier arrival at the event may be beneficial for horses that are transported long distances to endurance competition.     

Effects of oral potassium supplementation on acid-base status and plasma ion concentrations of horses during endurance exercise

OBJECTIVE: To compare effects of oral supplementation with an experimental potassium-free sodium-abundant electrolyte mixture (EM-K) with that of oral supplementation with commercial potassium-rich mixtures (EM+K) on acid-base status and plasma ion concentrations in horses during an 80-km endurance ride. ANIMALS: 46 healthy horses. PROCEDURE: Blood samples were collected before the ride; at 21-, 37-, 56-, and 80-km inspection points; and during recovery (ie, 30-minute period after the ride). Consumed electrolytes were recorded. Blood was analyzed for pH, PvCO2, and Hct, and plasma was analyzed for Na+, K+, Cl-, Ca2+, Mg2+, lactate, albumin, phosphate, and total protein concentrations. Plasma concentrations of H+ and HCO3-, the strong ion difference (SID), and osmolarity were calculated. RESULTS: 34 (17 EM-K and 17 EM+K treated) horses finished the ride. Potassium intake was 33 g less and Na+ intake was 36 g greater for EM-K-treated horses, compared with EM+K-treated horses. With increasing distance, plasma osmolarity; H+, Na+, K+, Mg2+, phosphate, lactate, total protein, and albumin concentrations; and PvCO2 and Hct were increased in all horses. Plasma HCO3-, Ca2+, and Cl- concentrations were decreased. Plasma H+ concentration was significantly lower in EM-K-treated horses, compared with EM+K-treated horses. Plasma K+ concentrations at the 80-km inspection point and during recovery were significantly less in EM-K-treated horses, compared with EM+K-treated horses. CONCLUSIONS AND CLINICAL RELEVANCE: Increases in plasma H+ and K+ concentrations in this endurance ride were moderate and unlikely to contribute to signs of muscle fatigue and hyperexcitability in horses.     

Effect of administration of a phospholipid emulsion on the initial response of horses administered endotoxin

OBJECTIVE: To evaluate the effect of a phospholipid emulsion (PLE) on the initial response of horses to administration of endotoxin. ANIMALS: 12 healthy adult horses. PROCEDURES: Horses were assigned to 2 treatment groups (6 horses/group). The control group was administered 1 L of saline (0.9% NaCl) solution, and the treated group was administered PLE (200 mg/kg, IV); treatments were administered during a period of 120 minutes. An infusion of endotoxin was initiated in both groups starting 1 hour after initiation of the saline or PLE solutions. Physical examination and hemodynamic variables were recorded, and blood samples were analyzed for concentrations of tumor necrosis factor (TNF)-alpha, interleukin-6, thromboxane B2 (TxB2), 6 keto-prostaglandin F (PGF)1alpha, total leukocyte count, and PLE concentrations. An ANOVA was used to detect significant differences. RESULTS: Administration of PLE resulted in significantly lower rectal temperature, heart rate, cardiac output, right atrial pressure, and pulmonary artery pressure and higher total leukocyte counts in treated horses, compared with values for control horses. The TNF-alpha concentration was significantly less in treated horses than in control horses. The TxB2 and 6 keto-PGFF1alpha concentrations were significantly different between treated and control horses at 30 minutes (TxB2) and at 30 and 60 minutes (6 keto-PGF1alpha). CONCLUSIONS AND CLINICAL RELEVANCE: Prior infusion of PLE in horses administered a low dose of endotoxin decreased rectal temperature, heart rate, pulmonary artery pressure, and TNF-alpha concentrations. Results of this study support further evaluation of PLE for use in the treatment of horses with endotoxemia.     

Ibuprofen prevents Pasteurella hemolytica endotoxin-induced changes in plasma prostanoids and serotonin, and fever in sheep

Intravenous infusion of Pasteurella hemolytica endotoxin caused marked increases in the plasma levels of thromboxane B2 (TxB2), prostaglandins (PG) and serotonin in sheep. The control values for TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and serotonin before endotoxin infusion averaged 283 +/- 53 (standard error of mean), 281 +/- 14 and 199 +/- 27 pg/ml and 57 +/- 3 ng/ml, respectively. At 50 min during endotoxin infusion, these values were increased to their maximum of 376, 339, 325 and 202% of control, respectively. Body temperature increased from the control value of 39.5 +/- 0.1 degrees C to a maximum of 41.5 +/- 0.1 degrees C at 200-300 min of infusion. In the second part of this study, we have examined the effects of ibuprofen on endotoxin-induced increases in plasma PG, TxB2, and serotonin levels and body temperature. The control values for TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and temperature prior to ibuprofen and endotoxin infusion averaged 238 +/- 35, 335 +/- 44 and 248 +/- 28 pg/ml, 65 +/- 3 ng/ml and 40.1 +/- 0.2 degrees C, respectively. A loading dose (15 mg/kg) of ibuprofen was followed by infusion of endotoxin (12 micrograms/kg) and ibuprofen (43.3 mg/kg) over 500 min. Plasma levels of 6-keto-PGF1 alpha and serotonin increased only to 131 and 149% of control at 50 min of infusion, and levels of PGF2 alpha and TxB2 decreased to 50 and 80% of control at 100 and 150 min of infusion, respectively. Temperature remained unchanged. Ibuprofen effectively suppressed endotoxin-induced increases in the plasma levels of TxB2, 6-keto-PGF1 alpha, PGF2 alpha, and serotonin and body temperature. It was concluded from the present study that nonsteroidal anti-inflammatory drugs as an adjunct to antibiotic therapy might have a rational basis in treatment of endotoxin toxicity.     

Prostaglandin and thromboxane concentrations in plasma and lung lavage fluids during sequential infection of vaccinated and nonvaccinated calves with bovine respiratory syncytial virus

The potential action of immunologic reactions and mediators released during the course of bovine respiratory syncytial virus infection in pathogenesis of the ensuing disease process was examined in an experimental infection study. Prostaglandin (PG) E2, PGF2 alpha 6-keto-PGF1 alpha, and thromboxane B2 (TxB2) concentrations were quantitated in plasma and lung lavage fluid by radioimmunoassay at 3- to 4-day intervals during a primary and secondary virus infection of vaccinated, nonvaccinated, and control (mock-infected) calves. A significant increase in the plasma PGE2 concentration for the nonvaccinated calves was noticed on day 3 after primary infection and on day 7 after secondary infection. The PGF2 alpha plasma concentrations increased significantly for the nonvaccinated groups on day 10 after primary infection. Plasma 6-keto-PGF1 alpha concentrations increased for nonvaccinated and vaccinated calves 3 days after the secondary infection. Plasma TxB2 concentrations during the primary exposure did not vary significantly. However, 14 days after the secondary exposure, both experimental groups had concentrations significantly greater than did the control group. Lung lavage fluid concentrations of TxB2 had peaks of activity 7 days after primary and secondary viral infections for the nonvaccinated group. Increases in plasma PG concentrations corresponded variably with disease expression, whereas plasma TxB2 concentrations did not have any correlation with disease expression. However, there was a significant correlation between TxB2 concentration in lung lavage fluid of the nonvaccinated group with disease expression 7 days after primary and secondary virus infection.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of flunixin meglumine, phenylbutazone and a selective thromboxane synthetase inhibitor (UK-38,485) on thromboxane and prostacyclin production in healthy horses

The efficacy of three agents which alter the metabolism of arachidonic acid was investigated in normal, conscious horses. A dose response evaluation was made of flunixin meglumine and phenylbutazone, two cyclo-oxygenase inhibitors, and of a selective thromboxane synthetase inhibitor, UK-38,485. Radioimmunoassay of thromboxane B2 (TxB2) and 6-keto prostaglandin F1 alpha (PGF1 alpha) was used to assess the concentrations of thromboxane A2 (TxA2) and prostacyclin (PGI2) respectively, in serum. Flunixin was the most potent inhibitor of serum TxB2 and 6-keto PGF1 alpha production. UK-38,485 also decreased serum TxB2 generation while significantly increasing serum 6-keto PGF1 alpha levels, thus confirming its selectivity as a thromboxane synthetase inhibitor.     

Endotoxin-induced digital vasoconstriction in horses: associated changes in plasma concentrations of vasoconstrictor mediators

REASONS FOR PERFORMING STUDY: Lipopolysaccharide (LPS) infusion reduces digital perfusion, but the mediators responsible remain undetermined. OBJECTIVES: To identify vasoconstrictor mediators released following LPS infusion and relate their appearance in plasma to digital blood flow alterations. METHODS: Blood flow in the lateral digital vessels of 6 Thoroughbred horses, following a 30 min infusion of LPS (E. coli 055:B5; 30 ng/kg), was measured using Doppler ultrasonography. Concomitant measurements of hoof wall and coronary band surface temperatures (HWST and CBST) were made. Serial blood samples were collected and plasma LPS, tumour necrosis factor alpha (TNFalpha), 5-HT, thromboxane B2 (TxB2) and endothelin measured. RESULTS: Plasma LPS concentrations reached a maximum of 13.2 pg/ml during the infusion, followed by an increase in plasma TNFalpha concentration. Digital arterial and venous blood flow decreased by 43 and 63%, respectively; HWST and CBST similarly decreased. Systemic blood pressure remained unaltered. Plasma concentrations of TxB2 and 5-HT increased, coinciding with the onset of digital hypoperfusion. Plasma endothelin concentrations remained unchanged. CONCLUSIONS: The temporal relationship between the onset of digital hypoperfusion and increases in plasma 5-HT and TxB2 concentrations is consistent with these platelet-derived mediators being associated with LPS-induced laminitis. POTENTIAL RELEVANCE: These experimental data support the use of anti-platelet therapy in the prevention of laminitis associated with endotoxaemic conditions.     

Plasma ionized calcium and parathyroid hormone concentrations in horses after endurance rides

OBJECTIVE: To evaluate changes in plasma ionized calcium (Ca2+) and parathyroid hormone (PTH) concentrations in horses competing in endurance rides. DESIGN: Longitudinal clinical study. ANIMALS: 28 horses. PROCEDURE: Venous blood samples were obtained from horses before and after racing 80 km. Plasma pH and concentrations of Ca2+, PTH, inorganic phosphorus, albumin, lactate, and magnesium were measured. RESULTS: Overall, a significant decrease in mean (+/- SD) plasma Ca2+ concentration (from 6.44 +/- 0.42 to 5.64 +/- 0.42 mg/dl) and a significant increase in plasma PTH concentration (from 49.9 +/- 30.1 to 148.1 +/- 183.0 pg/ml) were found after exercise. Exercise also resulted in significant increases in plasma inorganic phosphorus, albumin, and lactate concentrations. No changes in plasma magnesium concentration or pH were detected after exercise. Plasma PTH concentration was not increased after exercise in 8 horses; in these horses, plasma PTH concentration decreased from 58.2 +/- 26.3 to 27.4 +/- 22.4 pg/ml, although plasma Ca2+ concentration was also decreased. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma Ca2+ concentration was decreased after racing for 80 km, compared with values obtained before racing. In most horses, an increase in plasma PTH concentration that was commensurate with the decrease in plasma Ca2+ was detected; however, some horses had decreased plasma PTH concentrations.     

Oxidant stress in sled dogs subjected to repetitive endurance exercise

OBJECTIVE: To determine whether repetitive endurance exercise in sled dogs was associated with substantial lipid peroxidation, decreases in antioxidant capacity of the serum, and skeletal muscle damage. ANIMALS: 24 lightly trained sled dogs. PROCEDURE: 16 dogs completed a 58-km run on each of 3 consecutive days; the other 8 dogs (control) did not exercise during the study. Blood samples were collected before the first exercise run and after the first and third exercise runs. Plasma isoprostane and serum vitamin E concentrations, total antioxidant status of plasma, and serum creatine kinase activity were measured. RESULTS: Plasma isoprostane concentrations in dogs in the exercise group were significantly increased after the first exercise run and further significantly increased after the third exercise run. Serum vitamin E concentration was significantly decreased after the first exercise run in dogs in the exercise group, and this change persisted after the third exercise run. There was a significant linear relationship between plasma isoprostane concentration and the logarithm of serum creatine kinase activity (adjusted ? = 0.84). CONCLUSIONS AND CLINICAL RELEVANCE: Results demonstrate that repetitive endurance exercise in dogs is associated with lipid peroxidation and a reduction in plasma antioxidant concentrations. We interpret these results as indicating that the antioxidant mechanisms of minimally trained dogs may, in some instances, be inadequate to meet the antioxidant requirements of repetitive endurance exercise.     

Endotoxin-induced bovine mastitis: arachidonic acid metabolites in milk and plasma and effect of flunixin meglumine

Arachidonic acid metabolites (AAM) were measured in milk and plasma during the course of acute endotoxin-induced mastitis in 12 lactating cows. Mastitis was induced by intramammary challenge exposure with 10 micrograms of Escherichia coli (026:B6) endotoxin. Endotoxin was injected into the teat cistern via the teat canal of a single randomly selected rear quarter of each cow. Concentrations of prostaglandin (PG) F2 alpha and thromboxane (Tx) B2 in fat-free unextracted milk and of 15-keto-13,14-dihydro-PGF2 alpha in plasma were measured by radioimmunoassay. Total production of AAM in milk was determined by measuring quarter milk production. The AAM were compared in 6 cows administered flunixin meglumine (1.1 mg/kg of body weight) and in 6 cows administered saline solution. Concentrations of TxB2 in milk were significantly (P less than 0.001) increased during the early course of acute mastitis in endotoxin-treated quarters of cows not administered flunixin meglumine. Peak concentrations of TxB2 in milk occurred at 8 hours after endotoxin inoculation. Flunixin meglumine treatment produced significant (P less than 0.05) reductions in milk TxB2 and plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations. Concentrations of PGF2 alpha in milk and total PGF2 alpha and TxB2 production per quarter per milking were not significantly influenced by endotoxin challenge or by flunixin meglumine treatment.     

Effect of ration and exercise on plasma creatine kinase activity and lactate concentration in Thoroughbred horses with recurrent exertional rhabdomyolysis

OBJECTIVE: To determine the effects of 3 rations (low grain, fat, high grain) on plasma creatine kinase (CK) activity and lactate concentration in Thoroughbred horses with recurrent exertional rhabdomyolysis (RER). ANIMALS: 5 Thoroughbreds with RER and 3 healthy Thoroughbreds (control horses). PROCEDURES: Rations were formulated to meet (low-grain and fat rations) or exceed (high-grain ration) daily energy requirements. Each ration was fed to horses in a crossover design for 3 weeks. Horses were exercised on a treadmill Monday through Friday; maximum speed on Monday and Friday was 11 m/s (6% slope), on Tuesday and Thursday was 9 m/s, and on Wednesday was 4.5 m/s. Plasma CK activity and lactate concentration were determined before and after exercise. RESULTS: Horses with RER fed the high-grain ration had significantly greater CK activity and change in CK activity 4 hours after exercise, compared with those fed the low-grain ration. Horses with RER exercised at the trot or canter had significantly greater increases in CK activity, compared with those exercised at the gallop. Plasma lactate concentrations after exercise were similar in control and affected horses. Lactate concentration and CK activity were not correlated in horses with RER. CONCLUSIONS AND CLINICAL RELEVANCE: Rations high in grain and formulated to exceed daily energy requirements may increase episodes of rhabdomyolysis in thoroughbred horses susceptible to RER.     

Low dose flunixin meglumine: effects on eicosanoid production and clinical signs induced by experimental endotoxaemia in horses

The efficacy of low doses of flunixin meglumine in reducing eicosanoid generation and clinical signs in response to experimentally induced endotoxaemia was investigated. Thromboxane B2 and 6-keto-prostaglandin F1 alpha were measured in serum and plasma by radioimmunoassay. Plasma flunixin concentrations were determined by high performance liquid chromatography and pharmacokinetic parameters derived non-compartmentally. In horses administered flunixin meglumine before endotoxin challenge, a significant suppression in plasma thromboxane B2 and 6-keto-prostaglandin F1 alpha generation was observed. Elevations in blood lactate were significantly suppressed in horses pretreated with 0.25 mg/kg bodyweight flunixin meglumine. Reduction of the clinical signs of endotoxaemia by flunixin meglumine was dose dependent. Low doses of flunixin inhibited eicosanoid production without masking all of the physical manifestations of endotoxaemia necessary for accurate clinical evaluation of the horse's status.     

Effects of exercise intensity and duration on plasma beta-endorphin concentrations in horses

OBJECTIVE: To determine the relationship between plasma beta-endorphin (EN) concentrations and exercise intensity and duration in horses. ANIMALS: 8 mares with a mean age of 6 years (range, 3 to 13 years) and mean body weight of 450 kg. PROCEDURE: Horses were exercised for 20 minutes at 60% of maximal oxygen consumption (VO2max) and to fatigue at 95% V02max. Plasma EN concentrations were determined before exercise, after a 10-minute warmup period, after 5, 10, 15, and 20 minutes at 60% VO2max or at the point of fatigue (95% VO2max), and at regular intervals after exercise. Glucose concentrations were determined at the same times EN concentrations were measured. Plasma lactate concentration was measured 5 minutes after exercise. RESULTS: Maximum EN values were recorded 0 to 45 minutes after horses completed each test. Significant time and intensity effects on EN concentrations were detected. Concentrations were significantly higher following exercise at 95% VO2max, compared with those after 20 minutes of exercise at 60% VO2max (605.2 +/- 140.6 vs 312.3 +/- 53.1 pg/ml). Plasma EN concentration was not related to lactate concentration and was significantly but weakly correlated with glucose concentration for exercise at both intensities (r = 0.21 and 0.30 for 60 and 95% VO2max, respectively). CONCLUSIONS AND CLINICAL RELEVANCE: A critical exercise threshold exists for EN concentration in horses, which is 60% VO2max or less and is related to exercise intensity and duration. Even under conditions of controlled exercise there may be considerable differences in EN concentrations between horses. This makes the value of comparing horses on the basis of their EN concentration questionable.     

Hyperkalemic periodic paralysis, plasma lactate and exercise tolerance

The purpose of this, trial was to determine the effect of hyperkalemic periodic paralysis (HYPP) on exercise tolerance in Quarter Horses. Five HYPP affected and five nonaffected horses were matched for age, size, gender and reproductive status. HYPP status was diagnosed by DNA analysis and potassium chloride challenge testing. Plasma lactate concentration and heart rate were used as indicators of work intensity. Serum potassium concentrations were also monitored. Two exercise experiments were conducted, the first being forty-five minutes of slow, aerobic exercise (hacking) and the other being moderate, partially anaerobic exercise (galloping). Post-exercise the horses were cooled out by randomly assigning them to either forty minutes, of standing still or forty minutes of walking. Heart rates of HYPP affected and unaffected horses were not significantly different during exercise or recovery. Plasma lactate concentrations changed slightly following slow exercise and were significantly higher for HYPP affected horses (P=0.01).At the end of exercise, values were 1.4±0.2 mmol/L and 1.0±0.1 mmol/L for HYPP affected and unaffected horses, respectively. Following moderate exercise, plasma lactate concentrations were much greater, and the difference (P<0.001) between affected and unaffected horses was more marked: immediately following exercise concentrations were 10.6±1.8 and 6.2±1.0 mmol/L in affected and unaffected horses, respectively. The higher post-exercise plasma lactate concentrations in affected horses indicates increased anaerobic muscle metabolism. Serum potassium concentrations rose following exercise and significantly higher values were seen in horses that were walked rather than stood still post-exercise.Hyperkalemic periodic paralysis (HYPP) is a dominant autosomal genetic defect occurring in American Quarter Horses and related breeds. ^1–5 The condition is widely geographically distributed and has been estimated to affect 0.4% of all Quarter Horses.⁶ Signs include sporadic attacks of muscle fasciculation, muscle spasm, sweating and weakness. Oral administration of potassium chloride produces a more severe hyperkalemia in HYPP affected horses and induces clinical attacks.¹ Electromyography reveals widespread continuous, spontaneous, muscle contraction.² Some people believe that HYPP affected horses are suitable for riding⁷; others have expressed doubts about the safety of this practice and the exercise tolerance of affected horses. HYPP affected horses have an unstable muscle membrane potential causing random muscle fiber contractions,^2,8 which could antagonize purposeful movement. This, in combination with increases in extracellular potassium concentration occurring during exercise,^9–11 may cause affected horses to stumble or collapse while being ridden, posing a danger to both horse and rider. In HYPP affected people, potassium concentration rises approximately one to two hours after exercise during which time HYPP attacks can occur.^9,10 For these reasons, the exercise tolerance of HYPP affected horses and the effects of exercise on spontaneous HYPP attacks deserves investigation.We standardized the exercise test and chose heart rate and plasma lactate concentrations as indicatoors, of exercise tolerance and energy metabolism.¹² Heart rate is the major determinant of oxygen delivery to muscle and the rate rises with exercise intensity until it reaches a plateau at high velocities.^13,14 Several lines of investigation indicate that plasma lactate concentrations reflect muscle work. Lactate release from resting muscle is minimal but large amounts are released during strenuous exercise.^15–17 Lactate release increases with increasing muscle work.^16,18 During exercise, muscle oxygen consumption increases until eventually a plateau is reached after which no further increase in oxygen consumption in response to increased work loads is possible.¹⁸ At this point the mitochondrial electron chain transport system is operating at its maximal possible rate, energy production can only be supplemented by the use of inefficient anerobic glycolytic metabolism and the muscle starts to release lactate. If the concentrations of plasma lactate are high, the muscles are depending on anaerobic metabolism and are working closer to exhaustion^16,18–21The objectives of this experiment were twofold. One was to determine if HYPP adversely affects exercise performance. The second was to study the effects of cooling out, by either standing still or walking, on serum potassium and plasma lactate concentrations.     

Evaluation of plasma catecholamine and serum cortisol concentrations in horses with colic

OBJECTIVE: To evaluate plasma epinephrine and norepinephrine concentrations and serum cortisol concentration in horses with colic and assess the relationship of these variables with clinical signs, routinely measured clinicopathologic variables, and outcome in affected horses. DESIGN: Prospective observational study. ANIMALS: 35 horses with colic. PROCEDURE: Blood samples were collected within 30 minutes of arrival at the veterinary hospital from horses referred because of colic. Plasma and serum samples were analyzed for cortisol, epinephrine, norepinephrine, lactate, and electrolyte concentrations and acid-base variables. Heart rate at admission and outcome (survival or nonsurvival) were recorded. Univariate logistic regression was used to calculate crude (unadjusted) odds ratios and 95% confidence intervals. RESULTS: Of the 35 horses with colic, 26 survived. Higher plasma epinephrine, plasma lactate, and serum cortisol concentrations were significantly associated with increased risk of nonsurvival, but plasma norepinephrine concentration was not associated with outcome. Plasma epinephrine concentration was significantly correlated with heart rate (r = 0.68), plasma lactate concentration (r = 0.87), blood pH (r = -0.83), anion gap (r = 0.74), and base excess (r = -0.81). CONCLUSIONS AND CLINICAL RELEVANCE: The risk of death appears to be greater in colic-affected horses with high circulating concentrations of epinephrine and cortisol. The correlation of epinephrine with other biochemical markers of illness severity and with heart rate indicates that the degree of sympathetic activation in horses with colic can be inferred from routinely measured variables.     

Plasma and urine nitric oxide concentrations in horses given below a low dose of endotoxin.

OBJECTIVE: To quantify plasma and urine nitric oxide (NO) concentrations before and after low-dose endotoxin infusion in horses. ANIMALS: 11 healthy adult female horses. Procedure-Eight horses were given endotoxin (35 ng/kg of body weight,i.v.) over 30 minutes. Three sentinel horses received an equivalent volume of saline (0.9% NaCl) solution over the same time. Clinical signs of disease and hemodynamic variables were recorded, and urine and plasma samples were obtained to measure NO concentrations prior to endotoxin infusion (t = 0) and every hour until postinfusion hour (PIH) 6, then every 2 hours until PIH 24. Blood for hematologic and metabolic analyses and for serum cytokine bioassays were collected at 0 hour, every hour until PIH 6, every 2 hours through PIH 12, and finally, every 6 hours until PIH 24. RESULTS: Differences in plasma NO concentrations across time were not apparent, but urine NO concentrations significantly decreased at 4 and 20 to 24 hours in endotoxin-treated horses. Also in endotoxin-treated horses, alterations in clinical signs of disease, and hemodynamic, metabolic, and hematologic variables were significant and characteristic of endotoxemia. Serum interleukin-6 (IL-6) activity and tumor necrosis factor (TNF) concentrations were increased above baseline values from 1 to 8 hours and 1 to 2 hours, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Plasma and urine NO concentrations did not increase in horses after administration of a low dose of endotoxin, despite induction of an inflammatory response, which was confirmed by increased TNF and IL-6 values characteristic alterations in clinical signs of disease, and hematologic, hemodynamic and metabolic variables.     

Comparison of the effects of fructose and glucose supplementation on metabolic responses in resting and exercising horses

The aim of this study was to compare the effects of two different carbohydrate sources (fructose and glucose) on the metabolic responses in resting and exercising horses. The following regimes were fed in randomized order to five trained horses at rest and immediately before or during exercise. The resting regime comprised 0.6 kg grass meal pellets (control) or 0.6 kg grass meal pellets supplemented with either 50% glucose or 50% fructose. The exercise regime comprised 0.3 kg grass meal (control) or 0.6 kg grass meal pellets supplemented with either 50% glucose or 50% fructose fed immediately before or during simulated endurance exercise on a treadmill (30 km, total running time 120 min; 15 min rest after 60 min running time). Blood samples were collected for the analysis of glucose, insulin, free fatty acids (FFA) and lactate. In resting horses, glucose supplementation resulted in a significantly higher glycaemic and insulinaemic response than the control or fructose feedings (treatment P < 0.05). Plasma glucose levels were significantly higher after glucose supplementation given before or during exercise. Similar plasma glucose concentrations were observed after fructose was fed before exercise, whereas fructose supplementation during exercise resulted in a lower glycaemic response than glucose feeding (P < 0.05). Plasma insulin, FFA and lactate levels showed exercise-related changes (time P < 0.05), but treatment did not effect these results. Plasma glucose concentrations were elevated during the simulated endurance exercise after glucose feeding, and no counter-regulation by insulin occurred. The higher glycaemic response might be beneficial as exogenous glucose can be used as an energetic substrate during prolonged exercise. Fructose exhibited no clear advantages in comparison with glucose as a carbohydrate source for exercising horses.     

Proglycogen, macroglycogen, glucose, and glucose-6-phosphate concentrations in skeletal muscles of horses with polysaccharide storage myopathy performing light exercise

OBJECTIVE: To determine concentrations of proglycogen (PG), macroglycogen (MG), glucose, and glucose-6-phosphate (G-6-P) in skeletal muscle of horses with polysaccharide storage myopathy (PSSM) before and after performing light submaximal exercise. ANIMALS: 6 horses with PSSM and 4 control horses. PROCEDURES: Horses with PSSM completed repeated intervals of 2 minutes of walking followed by 2 minutes of trotting on a treadmill until muscle cramping developed. Four untrained control horses performed a similar exercise test for up to 20 minutes. Serum creatine kinase (CK) activity was measured before and 4 hours after exercise. Concentrations of total glycogen (G(t)), PG, MG, G-6-P, free glucose, and lactate were measured in biopsy specimens of gluteal muscle obtained before and after exercise. RESULTS: Mean serum CK activity was 26 times higher in PSSM horses than in control horses after exercise. Before exercise, muscle glycogen concentrations were 1.5, 2.2, and 1.7 times higher for PG, MG, and G(t), respectively, in PSSM horses, compared with concentrations in control horses. No significant changes in G(t), PG, MG, G-6-P, and lactate concentrations were detected after exercise. However, free glucose concentrations in skeletal muscle increased significantly in PSSM horses after exercise. CONCLUSIONS AND CLINICAL RELEVANCE: Analysis of the results suggests that glucose uptake in skeletal muscle is augmented in horses with PSSM after light exercise. There is excessive storage of PG and MG in horses with PSSM, and high concentrations of the 2 glycogen fractions may affect functional interactions between glycogenolytic and glycogen synthetic enzymes and glycosomes.     

Evaluation of Indicators of Weight-Carrying Ability of Light Riding Horses

To answer the question of whether horse height, cannon bone circumference, and loin width can be used as indicators of weight-carrying ability in light horses, eight mature horses underwent a submaximal mounted standard exercise test under four conditions: carrying 15, 20, 25, or 30% of their body weight. Heart rate was monitored, plasma lactate concentration was determined in jugular blood samples pre-exercise, immediately post-exercise, and 10 minutes post-exercise, with serum creatine kinase activity determined at the same times as plasma lactate concentrations, with additional samples collected at 24 hours and 48 hours post-exercise. Muscle soreness and muscle tightness scores were determined using a subjective scoring system 24 hours before and 24 hours after exercise. Heart rates remained significantly higher when the horses carried 25 and 30% of their body weight. Plasma lactate concentrations immediately and 10 minutes after exercise differed when horses carried 30% of their body weight compared with 15, 20, and 25% weight carriage. Horses tended to have a greater change in muscle soreness and muscle tightness when carrying 25% of their body weight, and a significant change in soreness and tightness scores was found in horses carrying 30% of their body weight. Loin width and cannon bone circumference were found to be negatively correlated to the changes in muscle soreness and tightness scores. In conclusion, the data suggest that horses with wider loin and thicker cannon bone circumference became less sore when carrying heavier weight loads.