Pharmacokinetics of detomidine administered to horses at rest and after maximal exercise.

REASON FOR PERFORMING STUDY: Increased doses of detomidine are required to produce sedation in horses after maximal exercise compared to calm or resting horses. OBJECTIVES: To determine if the pharmacokinetics of detomidine in Thoroughbred horses are different when the drug is given during recuperation from a brief period of maximal exercise compared to administration at rest. METHODS: Six Thoroughbred horses were preconditioned by exercising them on a treadmill. Each horse ran a simulated race at a treadmill speed that caused it to exercise at 120% of its maximal oxygen consumption. One minute after the end of exercise, horses were treated with detomidine. Each horse was treated with the same dose of detomidine on a second occasion a minimum of 14 days later while standing in a stocks. Samples of heparinised blood were obtained at various time points on both occasions. Plasma detomidine concentrations were determined by liquid chromatography-mass spectrometry. The plasma concentration vs. time data were analysed by nonlinear regression analysis. RESULTS: Median back-extrapolated time zero plasma concentration was significantly lower and median plasma half-life and median mean residence time were significantly longer when detomidine was administered after exercise compared to administration at rest. Median volume of distribution was significantly higher after exercise but median plasma clearance was not different between the 2 administrations. CONCLUSIONS AND POTENTIAL RELEVANCE: Detomidine i.v. is more widely distributed when administered to horses immediately after exercise compared to administration at rest resulting in lower peak plasma concentrations and a slower rate of elimination. The dose requirement to produce an equivalent effect may be higher in horses after exercise than in resting horses and less frequent subsequent doses may be required to produce a sustained effect.

Vagal innervation influences the whole body oxygen consumption-delivery relationship in the dog.

Vagotomy alters regional blood flow distribution by interrupting the tonic central inhibitory effect of cardiopulmonary vagal afferent nerves on sympathetic outflow predominantly to the renal, splanchnic, and cutaneous circulations. We hypothesized that the alteration of blood flow distribution by vagotomy would lead to disruption of the oxygen consumption-oxygen delivery relationship (VO2/DO2), increase critical DO2 (DO2Crit), and decrease whole-body oxygen extraction ratio (O2ER). Nineteen chloralose-anesthetized, paralyzed, splenectomized dogs were submitted to either bilateral vagosympathectomy (n = 7), bilateral vagotomy (n = 6), or sham denervation (n = 6) following baseline cardiorespiratory parameter measurement. VO2 was measured by indirect calorimetry and carotid blood flow by ultrasonic flow probe. Incremental hemorrhages (1-5 mL/kg) were performed to determine the VO2/DO2 relationship. Cardiorespiratory parameters were measured after each hemorrhage at steady-state VO2. DO2Crit was derived from the VO2/DO2 relationship using a best-fit regression analysis technique. The average DO2Crit values of the vagotomy (9.1 +/- .54) and vagosympathectomy (11.5 +/- 1.2 mL/min/kg) groups were significantly greater than the control group (7.72 +/- .43). After hemorrhage had been performed to a point that decreased mean arterial pressure to approximately 70 mmHg from baseline values, carotid blood flow in the vagosympathectomy group was significantly greater than the control group. We conclude that vagotomy disrupts the VO2/DO2 relationship. Vagosympathectomy causes a severe disruption of the VO2/DO2 relationship, probably by the combined effect of vagotomy and interruption of sympathetic nervous system control of blood flow to the head and neck.

Epidemiology of Sarcocystis neurona infections in domestic cats (Felis domesticus) and its association with equine protozoal myeloencephalitis (EPM) case farms and feral cats from a mobile spay and neuter clinic.

Equine protozoal myeloencephalitis (EPM) is a serious neurologic disease in the horse most commonly caused by Sarcocystis neurona. The domestic cat (Felis domesticus) is an intermediate host for S. neurona. In the present study, nine farms, known to have prior clinically diagnosed cases of EPM and a resident cat population were identified and sampled accordingly. In addition to the farm cats sampled, samples were also collected from a mobile spay and neuter clinic. Overall, serum samples were collected in 2001 from 310 cats, with samples including barn, feral and inside/outside cats. Of these 310 samples, 35 were from nine horse farms. Horse serum samples were also collected and traps were set for opossums at each of the farms. The S. neurona direct agglutination test (SAT) was used for both the horse and cat serum samples (1:25 dilution). Fourteen of 35 (40%) cats sampled from horse farms had circulating S. neurona agglutinating antibodies. Twenty-seven of the 275 (10%) cats from the spay/neuter clinic also had detectable S. neurona antibodies. Overall, 115 of 123 (93%) horses tested positive for anti-S. neurona antibodies, with each farm having greater than a 75% exposure rate among sampled horses. Twenty-one opossums were trapped on seven of the nine farms. Eleven opossums had Sarcocystis sp. sporocysts, six of them were identified as S. neurona sporocysts based on bioassays in gamma-interferon gene knockout mice with each opossum representing a different farm. Demonstration of S. neurona agglutinating antibodies in domestic and feral cats corroborates previous research demonstrating feral cats to be naturally infected, and also suggests that cats can be frequently infected with S. neurona and serve as one of several natural intermediate hosts for S. neurona.

Haemodynamic effects of small volume hypertonic saline in experimentally induced haemorrhagic shock.

A comparison of the haemodynamic benefits of small volume hypertonic saline (2,400 mOsm/litre) versus isotonic saline (300 mOsm/litre) was conducted in 12 adult horses using a haemorrhagic shock model. The horses were anaesthetised and intravascular catheters placed for the measurement of haemodynamic data. Mean systemic arterial pressure was then reduced to 50 to 60 mmHg by controlled haemorrhage and maintained at that level for 40 mins. Cardiac output, stroke volume, mean systemic arterial pressure, plasma volume and urine production decreased significantly following blood loss. Hypertonic or isotonic saline was administered randomly by intravenous infusion and haemodynamic data recorded for a 2 h period. Treatment with hypertonic saline produced rapid elevations in cardiac output, stroke volume, mean systemic and pulmonary arterial pressures, cardiac contractility and urine output, and was accompanied by expansion of the plasma volume. The changes in cardiac output and stroke volume were maintained for the duration of the recording period, whereas increases in mean systemic arterial pressure were not as remarkable. Infusion of isotonic saline caused only transient increases in cardiac output and mean systemic and pulmonary arterial pressure, and cardiac output; urine output and plasma volume did not change. This study indicates that hypertonic saline produces haemodynamic improvements in experimentally induced haemorrhagic shock in horses.

Haematological, serum electrolyte and blood gas effects of small volume hypertonic saline in experimentally induced haemorrhagic shock.

The effects of treatment with small volume hypertonic (2400 mOsm/litre) and isotonic (300 mOsm/litre) saline on serum electrolyte and biochemical concentrations, haemograms and blood gases were evaluated in 12 horses using a haemorrhagic shock model. Intravascular catheters were placed surgically for sample collection prior to anaesthesia. Controlled haemorrhage was initiated and continued until mean systemic pressure reached 50 to 60 mmHg. Hypertonic or isotonic saline (2 litres) was administered by intravenous infusion and data collected for 2 h. Following haemorrhage, packed cell volume (PCV), haemoglobin, blood glucose concentrations and erythrocyte numbers increased whereas plasma total protein and albumin concentrations decreased. Infusion of hypertonic saline resulted in a further decrease in total protein and albumin concentrations. Glucose concentrations and other haematological variables were unaffected. Isotonic saline administration did not affect electrolyte, total protein or albumin concentrations. Concentrations of sodium and chloride were unaffected by hypotension but increased significantly following hypertonic saline treatment, exceeding normal values during the immediate post treatment period. Serum osmolality increased concurrently. No significant changes in arterial and venous blood gas values were observed with haemorrhage or isotonic saline treatment. A transient decrease in arterial and venous blood pH and a sustained decrease in venous bicarbonate and base excess concentrations occurred following hypertonic saline administration. No significant increases in any serum biochemical concentrations occurred during hypotension or following infusion of either isotonic or hypertonic saline. These results demonstrate that small volume hypertonic saline can be administered safely to horses without producing extreme changes in electrolyte concentrations, blood gases or haematological parameters.

The effects of copper supplementation on the prevalence of cartilage lesions in foals.

The potential role of dietary copper in the development of cartilage defects in foals was investigated. Twenty-one mares were fed rations containing 13 ppm copper (CuC, control) or 32 ppm copper (CuS, supplemented) during the last three to six months of gestation and first three months of lactation. Their foals were fed pelleted concentrate containing 15 or 55 ppm Cu and were destroyed at 90 (5 CuC and 5 CuS foals) or 180 (6 CuC and 5 CuS foals) days. Focal cartilage lesions were found at multiple sites on necropsy. In foals killed at 90 days, there were over twice (9 versus 4) as many lesions of osteochondrosis and more than four times (9 versus 2) as many articular lesions of osteophyte formation or thinning in CuC foals compared with CuS foals. These differences were due predominantly to a higher number of lesions in one CuC foal. Two 90-day CuC foals had osteochondrosis of articular-epiphyseal (A-E) complex, one with thickenings and separation from subchondral bone and one with subchondral fibrosis. One 90-day CuS foal had a cartilage thickening of the A-E complex in the tibiotarsal joint with separation from subchondral bone. In foals killed at 180 days, there were seven times more articular lesions (21 versus 3) of osteophyte formation or thinning, nearly twice as many lesions of osteochondrosis (13 versus 8) [corrected] in the physis and over five times as many involving the A-E complex (11 versus 2) in six CuC foals compared with five CuS foals.(ABSTRACT TRUNCATED AT 250 WORDS)

Jejunal mucosal lactase activity from birth to three weeks in conventionally raised calves fed an electrolyte solution on days 5, 6 and 7 instead of milk.

The purpose of this study was to evaluate the effect of withdrawal of lactose from the diet for 72 hours on lactase activity in the jejunal mucosa of conventionally raised calves. The descending portion of the duodenum of six Holstein calves less than 24 hours old was cannulated. The calves were fed milk except on days 5, 6 and 7 when they were given the same volume of an electrolyte solution. Sequential biopsy specimens of the proximal jejunal mucosa were obtained for three weeks and the lactase activity determined. Lactase activity was highest on day 1 and a trend toward decreased lactase activity from birth until three weeks was observed. Mean lactase activity was significantly (p less than 0.05) higher for days 1, and 3 compared to days 9, 13 and 17. The withdrawal of milk and replacement by an electrolyte solution during three days had no significant effect on jejunal mucosal lactase activity in neonatal calves.

Pathophysiologic features of swine dysentery: cyclic nucleotide-independent production of diarrhea.

Net electrolyte and water transport and unidirectional Na+ fluxes were examined in ligated colonic loops of clinically normal pigs and in pigs with swine dysentery (etiologic agent Treponema hyodysenteriae) in the presence or absence of theophylline. In normal pigs, theophylline abolished net Na+ absorption via a reduction in the lumen-to-blood flux, decreased Cl- absorption, and increased HCO3- accumulation in the lumen. In infected pigs, all net ion transport was abolished, with the addition of theophylline producing little effect. The absence of net Na+ absorption in infected pigs was also the result of a decreased lumen-to-blood flux. Seemingly, colonic malabsorption may be the primary transport alteration in swine dysentery. Concentrations of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) were measured in samples of colonic mucosa from normal and infected pigs after in vitro exposure to a Ringer's solution containing 0 or 20 mM theophylline. Basal values of cAMP or cGMP did not increase in infected colonic mucosa. There was a diminished capacity of the infected mucosa to respond to theophylline. Alterations in ion transport in conjunction with measurements of cAMP and cGMP indicated that the pathogenic mechanism(s) in swine dysentery were not similar to those of Salmonella, Shigella, Vibrio cholerae, or Escherichia coli diarrhea.

Hemodynamic response of endotoxemic calves to treatment with small-volume hypertonic saline solution.

The hemodynamic effects of hypertonic saline solution (HSS) resuscitation on endotoxic shock were examined in pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli (055:B5) endotoxin was infused IV at dosage of 0.1 microgram/kg of body weight for 30 minutes. Endotoxin induced large decreases in cardiac index, stroke volume, maximal rate of change of left ventricular pressure (+dP/dtmax), femoral and mesenteric arterial blood flow, glomerular filtration rate, urine production, and mean aortic pressure. Severe pulmonary arterial hypertension and increased pulmonary vascular resistance were evident at the end of endotoxin infusion. Treatment with HSS (2,400 mosm of NaCl/L, 4 ml/kg) or an equivalent sodium load of isotonic saline solution (ISS: 300 mosm of NaCl/L, 32 ml/kg) was administered 90 minutes after the end of endotoxin administration. Both solutions were infused IV over a 4- to 6-minute period. Administration of HSS induced immediate and significant (P less than 0.05) increase in stroke volume and central venous pressure, as well as significant decrease in pulmonary vascular resistance. These effects were sustained for 60 minutes, after which all variables returned toward preinfusion values. The hemodynamic response to HSS administration was suggestive of rapid plasma volume expansion and redistribution of cardiac output toward splanchnic circulation. Plasma volume expansion by HSS was minimal 60 minutes after resuscitation. Administration of ISS induced significant increase in cardiac index, stroke volume, femoral arterial blood flow, and urine production. These effects were sustained for 120 minutes, at which time, calves were euthanatized. Compared with HSS, ISS induced sustained increase in mean pulmonary arterial pressure and only a small increase in mesenteric arterial blood flow.(ABSTRACT TRUNCATED AT 250 WORDS)

Respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution in endotoxemic calves.

The respiratory, renal, hematologic, and serum biochemical effects of hypertonic saline solution (HSS) treatment were examined in 12 endotoxic, pentobarbital-anesthetized calves (8 to 20 days old). Escherichia coli endotoxin (055:B5) was infused IV at a rate of 0.1 microgram/kg of body weight over 30 minutes. Endotoxin induced severe respiratory effects, with marked hypoxemia and increases in arterial-alveolar O2 gradient (P[A-a]O2), physiologic shunt fraction (Qs/Qt), and physiologic dead space to tidal volume ratio (Vd/Vt). Oxygen consumption was decreased, despite an increase in the systemic O2 extraction ratio. Peak effects were observed at the end of endotoxin infusion. The renal response to endotoxemia was characterized by a decrease in free-water reabsorption and osmotic clearance, as well as a decrease in sodium and phosphorus excretion. Endotoxemia induced leukopenia, thrombocytopenia, hyperphosphatemia, hypoglycemia, acidemia, and increased serum alkaline phosphatase concentrations. Calves were treated with HSS (2,400 mosm/L of NaCl, 4 ml/kg, n = 4) or an equivalent sodium load of isotonic saline solution (ISS; 300 mosm/L of NaCl, 32 ml/kg, n = 4 90 minutes after the end of endotoxin administration. Both solutions were infused over a 4- to 6-minute period. A control group (n = 4) was not treated. Infusion of HSS or ISS failed to induce a significant change in Pao2, P(A-a)O2, (Qs/Qt), (Vd/Vt), or oxygen consumption. Both solutions increased systemic oxygen delivery to above pre-endotoxin values. Hypertonic saline infusion induced significant (P less than 0.05) increases in serum Na and Cl concentrations and osmolality, whereas ISS induced a significant increase in serum Cl concentration and a significant decrease in serum phosphorus concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Jejunal mucosal lactase activity from birth to 3 weeks in conventionally raised calves.

The descending portion of the duodenum of 6 Holstein calves less than 24 hours old was cannulated. Sequential biopsy specimens of the proximal jejunal mucosa were obtained every other day for 3 weeks. Lactase activity in the mucosal specimens was determined and was highest at day 1, but decreased with age. Mean lactase activity was significantly (P less than 0.05) higher for days 1, 3, 5, and 7, compared with days 19 and 21.

Plasma, urine, and synovial fluid disposition of methylprednisolone acetate and isoflupredone acetate after intra-articular administration in horses.

OBJECTIVE--To document plasma, urine, and synovial fluid disposition of 2 common intra-articularly administered steroid preparations, methylprednisolone acetate (MPA) and isoflupredone acetate (IPA). DESIGN--Descriptive investigation. SAMPLE POPULATION--100 mg of MPA or 4 mg of IPA was administered to 2 groups of 4 healthy sound radiographically normal female horses. PROCEDURE--Blood samples were collected at time 0 (before) and 2, 4, 6, 8, 10, 12, 24, 36, 48, 72, and 96 hours after administration of the designated steroid. Complete urine collection for measurement of designated steroid was accomplished by use of occluding 28-F balloon catheters. Synovial fluid samples were aseptically aspirated from the injected and contralateral uninjected tarsocrural joint at time 0 and 8, 24, 48, 240, and 672 hours after administration of the designated steroid. All samples were screened by ELISA to detect parent drug or metabolite equivalent, with a sensitivity of 2.5 ng/ml for MPA and 0.1 ng/ml for IPA. If drug was detected by ELISA in the plasma or synovial fluid, the samples were further quantified and specified, using HPLC with a lower limit of quantification (10 ng/ml). RESULTS--Between 2 and 12 hours after administration, plasma contained < 10 ng of MPA or IPA/ml (parent drug or metabolite equivalent), as intermittently detected by ELISA. Parent drug or metabolite equivalent was detected in the urine for 24 and 72 hours after injection of IPA and MPA, respectively. Synovial fluid from the contralateral joint contained no detectable MPA or IPA at any sample collection time. Median half-life for MPA, as detected by HPLC, was 10.3 hours (range, 6.1 to 10.6) in the synovial space. Median half-life for methylprednisolone, as detected by HPLC, was 10.4 (range, 9.9 to 32.1) hours. CONCLUSIONS--Both steroids appeared to be rapidly hydrolyzed to their respective ester forms, as detected by HPLC. The ELISA appeared to be a useful screening tool for detection of corticosteroids in this variety of body fluids.

Anesthetic, cardiorespiratory, and metabolic effects of four intravenous anesthetic regimens induced in horses immediately after maximal exercise.

OBJECTIVE: To determine the anesthetic, cardiorespiratory, and metabolic effects of 4 IV anesthetic regimens in Thoroughbred horses recuperating from a brief period of maximal exercise. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were preconditioned by exercising them on a treadmill. Each horse ran 4 simulated races, with a minimum of 14 days between races. Races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until fatigued or for a maximum of 2 minutes. Two minutes after exercise, horses received a combination of xylazine hydrochloride (2.2 mg/kg of body weight) and acepromazine maleate (0.04 mg/kg) IV. Five minutes after exercise, horses received 1 of the following 4 IV anesthetic regimens: ketamine hydrochloride (2.2 mg/kg); ketamine (2.2 mg/kg) and diazepam (0.1 mg/kg); tiletamine hydrochloride-zolazepam hydrochloride (1 mg/kg); and guaifenesin (50 mg/kg) and thiopental sodium (5 mg/kg). Treatments were randomized. Cardiopulmonary indices were measured, and samples of blood were collected before and at specific times for 90 minutes after each race. RESULTS: Each regimen induced lateral recumbency. The quality of induction and anesthesia after ketamine administration was significantly worse than after other regimens, and the duration of anesthesia was significantly shorter. Time to lateral recumbency was significantly longer after ketamine or guaifenesin-thiopental administration than after ketaminediazepam or tilet-amine-zolazepam administration. Arterial blood pressures after guaifenesin-thiopental administration were significantly lower than after the other regimens. CONCLUSIONS AND CLINICAL RELEVANCE: Anesthesia can be safely induced in sedated horses immediately after maximal exercise. Ketamine-diazepam and tilet-amine-zolazepam induced good quality anesthesia with acceptable perturbations in cardiopulmonary and metabolic indices. Ketamine alone and guaifenesin-thiopental regimens are not recommended.

Plasma renin activity and aldosterone and vasopressin concentrations during incremental treadmill exercise in horses.

Six untrained mares were subjected to incremental treadmill exercise to examine exercise-induced changes in plasma renin activity (PRA) and plasma aldosterone (ALDO) and plasma arginine vasopressin (AVP) concentrations. Plasma renin activity, ALDO and AVP concentrations, and heart rate (HR) were measured at each step of an incremental maximal exercise test. Mares ran up a 6 degree slope on a treadmill set at an initial speed of 4 m/s. Speed was increased 1 m/s each minute until HR reached a plateau. Plasma obtained was stored at -80 C and later was thawed, extracted, and assayed for PRA and ALDO and AVP values by use of radioimmunoassay. Exercise caused significant increase in HR from 40 +/- 2 beats/min (mean +/- SEM) at rest to 206 +/- 4 beats/min (HRmax) at speed of 9 m/s. Plasma renin activity increased from 1.9 +/- 1.0 ng/ml/h at rest to a peak of 5.2 +/- 1.0 ng/ml/h at 9 m/s, paralleling changes in HR. Up to treadmill speed of 9 m/s, strong linear correlations were obtained between exercise intensity (and duration) and HR (r = 0.87, P less than 0.05) and PRA (r = 0.93, P less than 0.05). Heart rate and PRA reached a plateau and did not increase when speed was increased from 9 to 10 m/s. Plasma ALDO concentration increased from 48 +/- 16 pg/ml at rest to 191 +/- 72 pg/ml at speed of 10 m/s. Linear relation was found between exercise intensity (and duration) and ALDO concentration (r = 0.97, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiorespiratory and metabolic effects of walking, standing, and standing with a splint during the recuperative period from maximal exercise in horses.

OBJECTIVE: To determine the effects of walking, standing, or standing with a splint on 1 forelimb on rate of recuperation of horses after a brief, intense bout of exercise. ANIMALS: 6 adult Thoroughbreds (435 to 542 kg). PROCEDURE: Horses were preconditioned by exercise on a treadmill to establish a uniform level of fitness. Once fit, the treadmill speed causing each horse to exercise at 120% of its maximal oxygen consumption was determined and was used in simulated races at 14-day intervals. Horses were instrumented for collection of arterial and mixed venous blood samples for measurement of acid-base status, concentrations of metabolites, and cardiopulmonary indices. The horses were exercised at a speed inducing 120% of their maximal oxygen consumption until fatigued or for a maximum of 2 minutes. Three recuperative interventions were evaluated: walking at 1.8 m/s for 30 minutes, then standing for the remainder of the 90-minute trial; standing stationary for 90 minutes; and standing stationary for 90 minutes with a splint on the right forelimb. RESULTS: Walking significantly increased cardiac output during the recuperative phase and hastened recovery of normal acid-base status and return of blood lactate concentration to baseline values. CONCLUSION: Limiting movement of horses during the recuperative period delays recovery from maximal exercise. Most measured indices returned to baseline by 60 minutes after exercise. All measured cardiopulmonary indices returned to baseline values by 90 minutes after exercise. CLINICAL RELEVANCE: Horses that are not allowed to walk during recuperation from exercise may have a prolonged recovery period.

Cardiorespiratory and metabolic effects of xylazine, detomidine, and a combination of xylazine and acepromazine administered after exercise in horses.

OBJECTIVE: To determine sedative, cardiorespiratory and metabolic effects of xylazine hydrochloride, detomidine hydrochloride, and a combination of xylazine and acepromazine administered i.v. at twice the standard doses in Thoroughbred horses recuperating from a brief period of maximal exercise. ANIMALS: 6 adult Thoroughbreds. PROCEDURE: Horses were preconditioned by exercising them on a treadmill to establish a uniform level of fitness. Each horse ran 4 simulated races, with a minimum of 14 days between races. Simulated races were run at a treadmill speed that caused horses to exercise at 120% of their maximal oxygen consumption. Horses ran until they were fatigued or for a maximum of 2 minutes. One minute after the end of exercise, horses were treated i.v. with xylazine (2.2 mg/kg of body weight), detomidine (0.04 mg/kg), a combination of xylazine (2.2 mg/kg) and acepromazine (0.04 mg/kg), or saline (0.9% NaCl) solution. Treatments were randomized so that each horse received each treatment once, in random order. Cardiopulmonary indices were measured, and samples of arterial and venous blood were collected immediately before and at specific times for 90 minutes after the end of each race. RESULTS: All sedatives produced effective sedation. The cardiopulmonary depression that was induced was qualitatively similar to that induced by administration of these sedatives to resting horses and was not severe. Sedative administration after exercise prolonged the exercise-induced increase in body temperature. CONCLUSIONS AND CLINICAL RELEVANCE: Administration of xylazine, detomidine, or a combination of xylazine-acepromazine at twice the standard doses produced safe and effective sedation in horses that had just undergone a brief, intense bout of exercise.

Effects of topical administration of 0.005% latanoprost solution on eyes of clinically normal horses.

OBJECTIVE: To determine the effect of 0.005% latanoprost solution on intraocular pressure (IOP) of eyes of clinically normal horses and establish the frequency of adverse effects of drug administration. ANIMALS: 20 adult clinically normal horses. PROCEDURE: IOP was recorded (7, 9, and 11 AM; 3, 5, and 7 PM) on days 1 and 2 (baseline), days 3 to 7 (treatment), and days 8 to 9 (follow-up). Latanoprost was administered to 1 randomly assigned eye of each horse every 24 hours during the treatment period, following the 7 AM IOP recording. Pupil size and the presence or absence of conjunctival hyperemia, epiphora, blepharospasm, blepharedema, and aqueous flare were recorded prior to IOP measurement. RESULTS: IOP was reduced from baseline by a mean value of 1.03 mm Hg (5%) in males and 3.01 mm Hg (17%) in females during the treatment period. Miosis developed in all treated eyes and was moderate to marked in 77% of horses, with the peak effect observed 4 to 8 hours after drug administration. Conjunctival hyperemia, epiphora, blepharospasm, and blepharedema were present in 100, 57, 42, and 12% of treated eyes, respectively, 2 to 24 hours following drug administration. Aqueous flare was not observed at any time point. CONCLUSIONS AND CLINICAL RELEVANCE: Although IOP was reduced with every 24-hour dosing of latanoprost, the frequency of prostaglandin-induced adverse events was high. Because recurrent uveitis appears to be a risk factor for glaucoma in horses, topical administration of latanoprost may potentiate prostaglandin-mediated inflammatory disease in affected horses.

Renal tubular function in horses during submaximal exercise.

Exercise-induced changes in renal function were examined during steady-state submaximal treadmill exercise in six unfit mares. Horses were randomly assigned to either an exercise or parallel control (no exercise) trial on day 1 and the alternate trial 1 wk later. The mares ran on a treadmill, set at a 6 degrees incline, for 1 h at 55-60% of maximal heart rate. Exercise significantly (P less than 0.05) increased plasma osmolality, plasma [K+], urine flow (+ 45%), Na+ excretion (+ 371%), K+ excretion (+ 57%), osmotic clearance (+ 32%), Na+ clearance (+ 391%), K+ clearance (+ 33%), and fractional Na+ excretion (+ 320%) and significantly decreased plasma [Cl-], Cl- excretion (-46%), Cl- clearance (-41%), and fractional Cl- excretion (-47%). Glomerular filtration rate, fractional K+ excretion, and free water clearance did not change during exercise. Atrial natriuretic peptide increased during exercise from 11 +/- 1 pg/ml at rest to a peak of 40 +/- 9 pg/ml (264%, P less than 0.05) at 40 min. Increases in plasma renin activity (66%, P less than 0.05) were accompanied by increases in plasma aldosterone concentration (760%, P less than 0.05). Vasopressin concentration increased (P less than 0.05) steadily over the 60-min period of exercise. It was concluded that, in horses, submaximal exercise-induced increases in urine flow and sodium excretion are associated with a concurrent increase in the plasma concentration of atrial natriuretic peptide.

Lung innervation and the hemodynamic response to 7% sodium chloride in hypovolemic dogs.

A pulmonary vagal reflex triggered by passage of hypertonic saline through the pulmonary circulation has been proposed as one of the mechanisms by which hypertonic saline resuscitates dogs in hemorrhagic shock. Thirteen anesthetized dogs with denervated left lung lobes were subjected to a standard hemorrhage model to evaluate this purported reflex. We then infused 7% NaCl (4 ml/kg) into either the innervated (six dogs) or the denervated (seven dogs) pulmonary circulation. There were no differences in cardiac output, mean arterial pressure, right atrial pressure, heart rate, or peripheral vascular resistance between groups during a 1 hr period after 7% NaCl infusion. Changes in hematocrit, total plasma protein, and osmolality after 7% NaCl administration suggested that plasma volume expansion had occurred and was similar between groups. We conclude that a pulmonary reflex elicited by hypertonic saline does not contribute to the beneficial hemodynamic effects associated with administration of 7% NaCl during hemorrhagic shock.

Comparative effects of 7.5% NaCl in 6% Dextran 70 and 0.9% NaCl on cardiorespiratory parameters after cardiac output-controlled resuscitation from canine hemorrhagic shock.

We resuscitated severely hemorrhaged (mean arterial pressure at 40 mm Hg for 30 min) pentobarbital-anesthetized dogs to 120% of control cardiac output with 7.5% NaCl in 6% Dextran 70 (HSD) or 0.9% NaCl (IS) to compare the effects on hemodynamic and oxygen transport parameters. Hemodynamic parameters and oxygen delivery did not differ between groups. Oxygen consumption and oxygen extraction ratio tended to be higher, and mixed venous oxygen tension lower (P < 0.05) for HSD during the first hour of the postresuscitation period. Resuscitation of the HSD group required significantly less time (10.4 +/- 2.0 vs. 23.6 +/- 1.7 min; P < 0.01) and fluid volume (8.0 +/- 1.1 vs. 47.0 +/- 3.3 ml.kg-1; P < 0.01). We conclude that the resuscitation of hypovolemic dogs with HSD and IS to equivalent cardiac output results in identical improvements in hemodynamics and oxygen delivery but that HSD may provide a better oxygen supply/demand balance during the first hour postresuscitation.