Furosemide is a diuretic medication commonly administered to horses to prevent or reduce exercise-induced pulmonary hemorrhage (EIPH), a condition where blood enters the airways during intense physical activity. It functions by promoting the excretion of water and electrolytes through the kidneys, leading to a decrease in blood volume and pressure. This reduction is thought to alleviate the stress on pulmonary capillaries during exertion, thereby minimizing the occurrence of bleeding. Furosemide is frequently used in the context of horse racing and competitive equine sports. This page compiles peer-reviewed research studies and scholarly articles that investigate the effects, mechanisms, and regulatory aspects of furosemide use in equine athletes.
Freestone JF, Carlson GP, Harrold DR, Church G.Alterations in electrolyte and acid-base balance were studied in 6 horses for 8 hours after furosemide administration (1 mg/kg of body weight, IM), and the results were compared with those for 5 healthy untreated horses (controls) kept under identical environmental conditions. In the treated group, decreases in plasma potassium, chloride, and calcium concentrations and increases in total plasma protein content persisted for the 8-hour observation period, whereas there was no change in plasma sodium concentration, osmolality, or packed cell volume. Plasma bicarbonate concentration and PCO2 rema...
Woods WE, Wang CJ, Houtz PK, Tai HH, Wood T, Weckman TJ, Yang JM, Chang SL, Blake JW, Tobin T.A one step enzyme-linked immunosorbent assay (ELISA) and a particle concentration fluorescent immunoassay (PCFIA) test for furosemide were evaluated as part of a panel of pre- and post-race tests for illegal medication of racing horses. These tests are very sensitive to furosemide with an I-50 for furosemide of about 20 ng/ml. The test is also rapid; an average pre-race complement of 10 samples can be analyzed in 90 minutes or less. The ELISA test results can be read with an inexpensive spectrophotometer, or even by eye. Both the PCFIA test and the ELISA test readily detect the presence of fur...
Craig AM, Blythe LL, Appell LH, Slizeski ML.Dimethyl sulfoxide (DMSO) had been postulated to be a 'masking agent' when used concurrently with therapeutic or prohibited drugs in racing animals. Eight drugs (flunixin, furosemide, caffeine, apomorphine, phenylbutazone, lidocaine, cocaine, and acepromazine maleate) were administered to six horses singly and with concurrent intravenous DMSO. Urine samples were analyzed for the presence of the drugs and/or their metabolites by thin layer chromatography. Direct comparison of thin layer chromatograms of extracts of positive urine samples with and without DMSO verified that DMSO did not interfer...
Divers TJ, Whitlock RH, Byars TD, Leitch M, Crowell WA.Six horses had been admitted to the hospital because of illness other than renal failure; diarrhoea, myositis, abdominal pain and/or suspected bacterial sepsis. Hypotension and disseminated intravascular coagulopathy were frequent findings in the horses. Abnormally high serum creatinine concentration and urine specific gravity of less than 1.022 were found in the horses with acute renal failure. Hyponatraemia and hypochloraemia were the most common abnormal electrolyte findings. Pronounced hyperkalaemia was not found. Variable degrees of tubular necrosis were seen in three of the four horses t...
Muir WW, McGuirk S.Knowledge of the dosage, rate and route of administration, and potential side effects of drugs used to treat cardiac disease in horses has been refined. The judicious use of these drugs can increase exercise capacity, improve health, and potentially prolong life. Currently, antiarrhythmics (quinidine, lidocaine), positive inotropies (digoxin), and diuretics (furosemide) are the primary agents used to treat cardiovascular disease in horses. The development of newer drugs (verapamil, milrinone, bumetanide) and their usefulness in therapy for horses with cardiovascular disease require further inv...
Rose RJ, Gibson KT, Suann CJ.Five standardbred geldings were given 1 mg/kg bodyweight of frusemide by intramuscular injection to induce mild dehydration. After food and water deprivation overnight, the mean weight loss was 24.4 +/- 1.8 kg (5.5 per cent of bodyweight). The horses were then given an equivalent volume of an oral glucose-glycine-electrolyte solution by stomach tube. No more than 10 litres was given every 30 minutes until the calculated bodyweight loss had been replaced. Measurements made before, during and after the fluid administration included bodyweight, arterial blood haematocrit, PCO2, pH, standard bicar...
Manohar M.Systemic distribution of blood flow was studied in 11 healthy adult grade ponies, using radionuclide-labeled microspheres (15 micron diameter) that were injected into the left ventricle. Measurements were made at rest, during severe exercise (SE) without furosemide, as well as during SE at 10 minutes and 120 minutes after furosemide administration (1.0 mg/kg, IV). During SE, heart rate, cardiac output, mean aortic pressure, and whole body O2 consumption were 220 +/- 4 beats/min, 720 +/- 44 ml/min/kg, 169 +/- 4 mm of Hg, and 126 +/- 9 ml of O2/min/kg, respectively. With SE performed after furos...
Goetz TE, Manohar M.Pressures in the right side of the heart and esophagus (pleural) have not been determined in the exercising equine subjects. In the present study, 8 healthy ponies were examined to determine the changes in these variables caused by 2 degrees of exercise done on a treadmill (heart rate:183 +/- 5 beats/min [trot] and 220 +/- 6 beats/min [canter]). Measurements were also made during both degrees of exertion 10 minutes and 120 minutes after furosemide (1.0 mg/kg) administration. It was observed that both gaits resulted in significant increases in pulmonary artery, right ventricular, and right atri...
Pascoe JR, McCabe AE, Franti CE, Arthur RM.The repeatability of endoscopic observations of exercise-induced pulmonary hemorrhage (EIPH) and the efficacy of furosemide as a prophylactic treatment of horses with EIPH were studied in Thoroughbred race horses after consecutive breezes (at or near maximum speed, approx 16 m/s). Of 56 horses examined greater than or equal to 2 times, 21 (38%) had identical EIPH scores, whereas 26 (46%) and 9 (16%) had scores that differed by greater than or equal to 1 grade. In 56 nontreated horses, there was good agreement between 2 consecutive observations (K = 0.59, Z = 4.54, P less than 0.001). Similar c...
Muir WW, McGuirk SM.The rational therapy of cardiovascular disease in horses requires a thorough knowledge of the pharmacology and pharmacokinetics of several specific drugs (digitalis, digoxin). Calcium solutions, dopamine, and dobutamine are frequently used to treat congestive heart failure in horses. Quinidine, procainamide, lidocaine, and propranolol are used to treat a variety of supraventricular and ventricular arrhythmias. Furosemide, a highly potent loop diuretic, is used to eliminate edema and promote diuresis. A thorough understanding of the applied pharmacology, dosage recommendations, toxicity, and pr...
Gronwall R.Endogenous creatinine clearance and renal excretion of phenylbutazone, osmotically active material, and compounds contributing to the urinary refractive index were studied in 12 Thoroughbred mares after no treatment, after water administration, or after furosemide administration. Urine was quantitatively collected, using urinary bladder catheters. On average, urine flow of the mares was 9 microliters/min/kg without treatment and increased to about 50 microliters/min/kg after water administration and to about 70 microliters/min/kg after furosemide administration. Water administration increased ...
Soma LR, Laster L, Oppenlander F, Barr-Alderfer V.In 3 groups of horses with exercise-induced pulmonary hemorrhage (EIPH), comparisons of racing times and finishing positions were made between the 5 races before the horses were given furosemide and 5 races after furosemide administration. The horses were grouped according to 3 methods used to diagnose EIPH: group 1, observation of hemorrhage at the nostrils within 1 hour after a workout or race; group 2, observation of pulmonary hemorrhage only by endoscopic examination after a race or workout; and group 3, observation of hemorrhage at the nostrils during a race or immediately after a race. G...
Sufit E, Houpt KA, Sweeting M.The stimuli that elicit thirst were studied in four ponies. Nineteen hours of water deprivation produced an increase in plasma protein from 67 +/- 0.1 g/litre to 72 +/- 2 g/litre, a mean (+/- se) increase in plasma sodium from 139 +/- 3 to 145 +/- 2 mmol/litre and an increase in plasma osmolality from 297 +/- 1 to 306 +/- 2 mosmol/litre. Undeprived ponies drank 1.5 +/- 0.9 kg/30 mins; 19 h deprived ponies drank 10.2 +/- 2.5 kg/30 mins and corrected the deficits in plasma protein, plasma sodium and plasma osmolality as well as compensating for the water they would have drunk during the deprivat...
Kociba GJ, Bayly WM, Milne DW, Wigton DH, Gabel AA, Muir WW.Two groups of 6 Standardbred horses each were used to study hemostatic functions at rest and after exercise with furosemide or a placebo. One group which was trained was given maximum exercise on the racetrack, and the other, a less-fit group, was given submaximum exercise on the treadmill. There was no difference in furosemide compared to placebo trial results in either group in coagulation screening tests, platelet concentration, or retention of platelets in a glass bead column. Increased fibrinogen concentration and enhanced platelet retention were associated with maximum exercise. Aggregat...
Soma LR, Korber K, Anderson T, Hopkins J.The effects of furosemide (0.55 mg/kg IV) on the plasma and urinary fentanyl (PFE UFE) concentrations were studied during steady-state conditions. The PFE during the steady-state period was 0.31 +/- 0.027 ng/ml, with no significant changes occurring, even though the rate of excretion of fentanyl (EX) increased during the 1st hour from 112.0 +/- 21.6 to 534.5 +/- 82.9 ng/minute. The EX returned to control levels within 3 hours, as did the UFE. The injection of furosemide increased glomerular filtration rate from 1.97 +/- 0.21 to 3.81 +/- 0.75 ml/kg/min. The fractional reabsorption decreased fro...
Sweeney CR, Soma LR.Of 61 horses with a history of exercise-induced pulmonary hemorrhage and treated with furosemide 4 hours prior to racing, 34 (55.7%) continued to bleed. Of 24 horses with exercise-induced pulmonary hemorrhage that were not treated with furosemide prior to racing, 17 (70.8%) still bled. There was no statistically significant difference between the treated and the nontreated groups. Of 45 horses given hesperidin-citrus bioflavinoids, 38 (84.4%) bled when exercised 90 days later. There was no statistically significant difference between the results for hesperidin-citrus bioflavinoid-treated horse...
Broughton Pipkin F, Ousey JC, Wallace CP, Rossdale PD.Plasma renin substrate concentration was measured in 18, four-day-old pony foals after the administration of the natriuretic agent frusemide. Thirteen foals had been delivered spontaneously; labour had been induced in the remaining five mares. Plasma aldosterone concentration was measured in 12 of the spontaneously delivered foals. Renin substrate concentration had risen sharply within 15 mins (P less than 0.005) and peaked at 1 h. The response was consistently greater in the induced foals. Serum sodium concentration fell rapidly in the induced foals (P less than 0.002 by 60 mins) but was bett...
Sweeney CR, Soma LR, Bucan CA, Ray SG.Thoroughbreds with a confirmed history of exercise-induced pulmonary hemorrhage (EIPH) were treated pre-exercise with atropine sulfate, cromolyn, ipratropium or furosemide. Atropine prevented EIPH in 3 of 3 trials in 1 horse, while having no significant effect on bleeding status in the other 2 horses. Pre-exercise treatment with cromolyn had no significant effects in the 3 horses. Pre-exercise treatment of ipratropium was apparently responsible for preventing EIPH in 17 out of 18 trials in 2 horses. The pharmacologic properties of ipratropium in the horse have not been studied, but based on hu...
Chay S, Woods WE, Rowse K, Nugent TE, Blake JW, Tobin T.Studies were undertaken to determine blood levels of furosemide in horses after 0.5- and 1.0-mg/kg doses administered iv. Analyses indicated that the pharmacokinetic parameters were dose independent and best described by a three-compartment open model. The alpha-, beta-, and gamma-phase half-lives of 5.6, 22.3, and 158.5 min, respectively, were observed after the 0.5-mg/kg dose. Similarly, the respective half-lives after the 1.0-mg/kg dose were 5.8, 24.1, and 177.2 min. After a 0.5-mg/kg dose of furosemide, population frequency distributions were evaluated at 1 hr and 4 hr post-drug administra...
Alexander F.The effect of ethacrynic acid, bumetanide, frusemide, spironolactone and anti-diuretic hormone (ADH) on the urinary and faecal excretion of water and electrolytes by ponies was studied. Ethacrynic acid, bumetanide, and frusemide given intravenously, increased urinary sodium excretion, and, excepting frusemide, decreased faecal sodium excretion. Given by stomach tube ethacrynic acid reduced urinary and faecal sodium. Bumetanide, given intravenously, spironolactone, frusemide and ADH increased urinary sodium and all except frusemide intravenously decreased faecal sodium regardless of route of ad...
Brumbaugh GW, Thomas WP, Hodge TG.A 4-year-old Quarter Horse gelding with atrial fibrillation, mitral regurgitation, and signs of bilateral congestive heart failure was initially treated IV with digoxin and furosemide. After parenteral digitalization, a daily maintenance dose of digoxin was administered orally at a rate of 21.7 micrograms/kg of body weight. At this dosage, a steady-state serum digoxin concentration of 2.3 ng/ml was achieved without clinical signs of toxicosis. The furosemide dosage was decreased and eventually discontinued as clinical improvement occurred. Clinical signs of congestive heart failure were contro...
Combie J, Blake JW, Nugent TE, Tobin T.We have investigated the action of five sources of beta-glucuronidase enzymes on the hydrolysis of glucuronides of apomorphine, butorphanol, hydromorphone, nalbuphine, oxymorphone and pentazocine in equine urine. For all glucuronides tested, Patella vulgata beta-glucuronidase yielded the largest thin layer chromatographic (TLC) spots. For oxymorphone, P. vulgata was the only treatment to yield detectable TLC spots under test parameters. For these six drugs, TLC spot size and chromatographic quality were compared between control horses and horses pretreated with furosemide four hours earlier. F...
Pascoe JR, Ferraro GL, Cannon JH, Arthur RM, Wheat JD.Of 235 Thoroughbred racehorses examined with a flexible fiberoptic endoscope within 2 hours of racing to determine the frequency of exercise-induced pulmonary hemorrhage (EIPH), 103 (43.8%) had various degrees of hemorrhage in the tracheal lumen. Two of these horses (0.8%) subsequently had blood flow from the nostrils. Blood seemed to originate from the lung. Statistical analysis of frequency data for 191 horses which finished in 1st, 2nd, and 3rd places did not show any relationship between EIPH and horse's age, sex, or finishing position. However, a trend toward an increased frequency of EIP...
Combie J, Shults T, Nugent EC, Dougherty J, Tobin T.The locomotor responses of horses given morphine and fentanyl were blocked or lessened by administration of naloxone or acepromazine. Naloxone given at the dosage of 0.015 mg/kg completely blocked the locomotor activity induced in horses given fentanyl (0.020 mg/kg of body weight). The locomotor stimulation produced by morphine given at the dosage of 2.4 mg/kg was reduced by 75% of naloxone (0.020 mg/kg). Acepromazine partially blocked the locomotor responses to fentanyl and morphine. This blockade activity reached its peak about 30 minutes after acepromazine was given (IV) and lasted more tha...
Milne DW, Gabel AA, Muir WW, Skarda RT, Hamlin RL, Pipers FS.In a double-blind study under simulated racing conditions, six Standardbred horses, which had been trained for 12 weeks, were given 1 mg of furosemide/kg of body weight or saline solution IV 15 minutes before the first of two warm-up workouts (1.6 km at 60-minute intervals). Sixty minutes later, 135 minutes after drug or placebo injection, these horses were driven 1.6 km at maximum speed. Heart rate, respiratory rate, cardiac output, pulmonary trunk pressure, body temperature, PCV, arterial oxygen, and plasma lactic acid were recorded during and after the first warm-up workout and after a simu...
Hjortkjaer RK.In the first series of experiments enema containing a water soluble marker was given to two groups of horses fasted for 1 and 18 hours, respectively. The marker was only in 1 out of 14 experiments found orally of the pelvic flexure (Table II). Fasting seemed to facilitate the flow in oral direction. The results were discussed with the possible significance in the treatment of large intestinal impactions. In the second series the effect of enemas on water, electrolyte and acid-base status in the acute furosemide-dehydrated horse was studied. Moderate acidifying and hypokalemic effect was encoun...
Purohit RC, Nachreiner RF, Humburg JM, Norwood GL, Beckett SD.Circulating concentrations of angiotensin I and plasma renin activity (PRA) were determined in 45 Thoroughbreds before prerace medication (at rest), 1 to 1 1/2 hours before racing but after prerace medication (prerace), within 15 minutes after racing (immediately postrace), and between 1 to 2 hours after racing. Angiotensin I was measured by radioimmunoassay, and PRA was determined by the rate of generation of angiotensin I in plasma incubated at 37 C. Irrespective of prerace medication, there was a marked increase in angiotensin I (0.478 +/- 0.034 to 0.848 +/- 0.051 ng/ml) and PRA (0.191 +/- ...
Muir WW, Kohn CW, Sams R.The effects of IV administered furosemide upon plasma volume (PV) and extracellular fluid volume were determined in horses at rest and after exercise. Serum sodium, potassium, chloride, and osmolality determinations were made. Furosemide caused a significant (P less than 0.05) decrease in PV and serum potassium concentrations in resting horses only. Furosemide's effects upon PV and electrolytes were evident longer than its hemodynamic effects.
Araújo AC, Salvadori MC, Velletri ME, Camargo MM.The possibility of false negative results from TLC when a diuretic is administered concomitantly with flunixin was studied. Samples were subjected to solvent extraction from acidic aqueous solutions; duplicate samples were also subjected to alkaline hydrolysis at pH 12.5. The internal standard was flufenamic acid. The quantification of flunixin was performed by HPLC and the results confirmed by GC/MS. The data show that furosemide influences the urinary concentration of flunixin.
Dyke TM, Hubbell JA, Grosenbaugh DA, Beard W, Mitten L, Sams RA, Hinchcliff KW.The pharmacokinetics of furosemide were investigated in anaesthetized horses with bilateral ureteral ligation (BUL) with (n = 5) or without (n = 5) premedication with phenylbutazone. Horses were administered an intravenous (i.v.) bolus dose of furosemide (1 mg/kg) approximately 60-90 min after BUL. Plasma samples collected up to 3 h after drug administration were analysed by a validated high performance liquid chromatography method. Median plasma clearance (CLp) of furosemide in anaesthetized horses with BUL was 1.4 mL/min/kg. Apparent steady state volume of distribution (Vd(ss)) ranged from 1...
Freestone JF, Gossett K, Carlson GP, Church G.Six thoroughbreds were used in each of three trials to examine the effect of potassium depletion on exercise-associated muscle damage. Horses were exercised after a control period (Treatment 1), a 72-hour fast (Treatment 2), and furosemide and sodium bicarbonate (Treatment 3). During the preexercise period, feed withdrawal for 72 hours caused decreases in body weight, plasma sodium, chloride, and serum calcium. There were no changes in plasma potassium, erythrocyte potassium, or serum creatine phosphokinase (CK) activity. Furosemide and sodium bicarbonate administration resulted in a decrease ...
Greene S, Keegan R, Brown J, Kingston J, Bayly WM.This study evaluated the effects of pre-exercise frusemide administration and hypertonic saline (H) infusion during anaesthesia on arterial pH, blood gases and electrolytes in 6 Thoroughbred horses anaesthetised immediately post exercise. Horses received either frusemide (F) (0.5 mg/kg, i.v.) or a saline placebo (P) injection 4 h prior to treadmill exercise. Exercise consisted of a 3 min warm-up at 40% VO2max followed by exercise to fatigue. Detomidine (40 micrograms/kg, i.v.) was given within 5 min of stopping and followed 5 min later by zolazepam-tiletamine (1.25 mg/kg, i.v.) to induce anaes...
Singh AK, McArdle C, Ashraf M, Granley K, Mishra U, Gordon B.Equine plasma and urine samples were analyzed by using a high-performance liquid chromatography (HPLC), enzyme-linked immunosorbent assay (ELISA) and particle concentration fluorescence assay (PCFIA). Although ELISA and PCFIA were rapid, simple and sensitive for the screening of furosemide, they did not give reproducible quantitative results. The HPLC method, which required relatively longer analysis time, provided simple and reproducible quantitative analysis of furosemide in plasma and urine. The performance of the three methods was compared for the quantitation of furosemide in plasma obtai...
Knych HK, Wilson WD, Vale A, Kass PH, Steffey EP, Jones JH, Arthur RM.Although controversial, due to its reported effectiveness in attenuating bleeding associated with exercise-induced pulmonary hemorrhage (EIPH), furosemide is currently a permitted race day medication in most North American racing jurisdictions. The objective of this study was to assess the efficacy of furosemide in reducing the presence and severity of EIPH when administered 24 hr prior to strenuous treadmill exercise. Eight exercised Thoroughbred horses received saline or 250 mg of furosemide either 4 or 24 hr prior to high-speed treadmill exercise in a balanced 3-way cross-over design. Bl...
Chu KK, Cohen ND, Stanley SD, Wang N.To estimate the probability of concurrently exceeding thresholds for plasma concentration of furosemide and urine specific gravity after IV administration of furosemide in horses. Methods: 12 mature healthy Thoroughbred (n = 6) or Quarter Horse (6) mares. Methods: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after IV administration of 250 mg (first experiment) or 500 mg (second experiment) of furosemide. Urine was collected hourly between 1 and 6 hours after administration of furosemide at both doses. Concentrations of furosemide were...
Houpt KA, Northrup N, Wheatley T, Houpt TR.When a preliminary experiment in sodium-replete ponies revealed an increase, but not a significant increase, in salt consumption after furosemide treatment, the experiment was repeated using sodium-deficient horses in which aldosterone levels might be expected to be elevated to test the hypothesis that a background of aldosterone is necessary for salt appetite. Ten Standardbred mares were injected intravenously with furosemide or an equivalent volume of 0.9% sodium chloride as a control to test the effect of furosemide on their salt appetite and blood constituents. Sodium intake and sodium los...
Foreman JH.Differentiation of diseases of the equine respiratory tract is based on history, clinical signs, auscultation, endoscopy, imaging, and sampling of airway exudate. Upper respiratory therapies include surgical correction of airway obstructions; flushing of localized abscesses (strangles), guttural pouch disease, or sinusitis; and oral or parenteral antibiotic and anti-inflammatory therapy if deemed necessary. Pneumonia usually is treated with antimicrobials, anti-inflammatories, and bronchodilators. Pleural drainage is indicated if significant pleural effusion is present. The most commonly used ...
Harkins JD, Robinson NE, Woods WE, Lehner AF, Smith MD, Gates RS, Fisher M, Tobin T.Clenbuterol, a beta2 agonist/antagonist, is the only bronchodilator approved by the US Food and Drug Administration for use in horses. The Association of Racing Commissioners International classifies clenbuterol as a class 3 agent, and, as such, its identification in post-race samples may lead to sanctions. Anecdotal reports suggest that clenbuterol may have been administered by intratracheal (IT) injection to obtain beneficial effects and avoid post-race detection. The objectives of this study were (1) to measure the pharmacological efficacy of IT dose of clenbuterol and (2) to determine the ...
Alexander F.The effect of ethacrynic acid, bumetanide, frusemide, spironolactone and anti-diuretic hormone (ADH) on the urinary and faecal excretion of water and electrolytes by ponies was studied. Ethacrynic acid, bumetanide, and frusemide given intravenously, increased urinary sodium excretion, and, excepting frusemide, decreased faecal sodium excretion. Given by stomach tube ethacrynic acid reduced urinary and faecal sodium. Bumetanide, given intravenously, spironolactone, frusemide and ADH increased urinary sodium and all except frusemide intravenously decreased faecal sodium regardless of route of ad...
McKeever KH, Hinchcliff KW, Cooley JL, Lamb DR.The purpose of this study was to test the hypothesis that furosemide administration before exercise would cause greater increases in plasma arginine vasopressin (AVP) concentration in exercising horses than exercise alone. Six adult, clinically normal, unfit mares underwent three randomly ordered 60 minute standard exercise tests on an equine treadmill to examine the effect of furosemide administration on plasma AVP concentration. In one trial, furosemide (1 mg kg-1) was infused four hours before exercise (FUR-4) and a placebo (10 ml saline) was infused two minutes before exercise; in another ...
Langsetmo I, Weigle GE, Erickson HH, Fedde MR.Exercising horses have extremely high right and left atrial pressures. Limitation in ventricular function (i.e. relaxation) may play a role in these high pressures. We studied relaxation characteristics of the right ventricular myocardium and the impact of frusemide (2.0 mg/kg bwt i.v.) on these characteristics in horses exercising at 8, 10, 12 and 14 m/s. Exercise tests were performed 4 h after administration of frusemide. Right ventricular (RV) pressure was analysed using Fast Fourier Transform techniques to remove non cardiac components of the pressure signal. Mean right atrial (RA) pressur...
Chu KK, Wang N, Stanley S, Cohen ND.The pharmacokinetic behavior of furosemide concentrations in performance horses is of great interest to the equine industry and equine researchers. Specifically, such information is useful for the evaluation of the existing guidelines in several racing jurisdictions and for the possible development of new guidelines for varying time periods after administration. We studied several approaches within the framework of nonlinear mixed effects models to increase the accuracy of evaluating these guidelines. Theoretical properties of the proposed methods were examined and the variances of the resulti...
Olsen SC, Coyne CP, Lowe BS, Pelletier N, Raub EM, Erickson HH.Furosemide, which commonly is used as a prophylactic treatment for exercise-induced pulmonary hemorrhage in horses, may mediate hemodynamic changes during exercise by altering prostaglandin metabolism. To determine if furosemide's hemodynamic effects during exercise in horses could be reversed, cyclooxygenase inhibitors were administered with furosemide. Four treatments were administered 4 hours prior to treadmill exercise at 9 and 13 m/s. They included a control treatment (10 ml of 0.9% NaCl solution, IV), furosemide (1 mg/kg of body weight, IV) administered alone, and furosemide in combinati...
Uboh CE, Soma LR, Rudy JA, Morgan E, Mengeringhausen K, Sams R.This study was undertaken to determine the applicability of plasma concentration of furosemide and specific gravity (SG) of urine in regulating the use of furosemide administered 4 hours prior to race time in Exercise-Induced Pulmonary Hemorrhage (EIPH) race horses. Nonbleeders (CTL) and certified bleeders (FUR) actively racing in Illinois (IL) and Pennsylvania (PA) were used in the study. Various doses (less than 250, 250, 300, 350, 400 and 500 mg) were administered either as a single intravenous (IV) dose or as a combination (IV-IM) of IV and intramuscular (IM) administrations 4 hours before...
Cooley JL, Hinchcliff KW, McKeever KH, Lamb DR, Muir WW.Effects of furosemide administration on exertion-induced changes in plasma renin activity and plasma concentrations of atrial natriuretic peptide and aldosterone in horses during sustained submaximal exertion were examined. Furosemide (1 mg/kg of body weight) or heparinized saline solution was administered IV to each of 6 mares not conditioned to exercise, either 4 hours or 2 minutes before 60 minutes of sustained submaximal running on a treadmill. Horses ran at a speed that induced heart rate approximately 65% of maximal after saline treatment. After 15 minutes of running, furosemide suppress...
Rose RJ, Gibson KT, Suann CJ.Five standardbred geldings were given 1 mg/kg bodyweight of frusemide by intramuscular injection to induce mild dehydration. After food and water deprivation overnight, the mean weight loss was 24.4 +/- 1.8 kg (5.5 per cent of bodyweight). The horses were then given an equivalent volume of an oral glucose-glycine-electrolyte solution by stomach tube. No more than 10 litres was given every 30 minutes until the calculated bodyweight loss had been replaced. Measurements made before, during and after the fluid administration included bodyweight, arterial blood haematocrit, PCO2, pH, standard bicar...
Combie J, Blake JW, Nugent TE, Tobin T.We have investigated the action of five sources of beta-glucuronidase enzymes on the hydrolysis of glucuronides of apomorphine, butorphanol, hydromorphone, nalbuphine, oxymorphone and pentazocine in equine urine. For all glucuronides tested, Patella vulgata beta-glucuronidase yielded the largest thin layer chromatographic (TLC) spots. For oxymorphone, P. vulgata was the only treatment to yield detectable TLC spots under test parameters. For these six drugs, TLC spot size and chromatographic quality were compared between control horses and horses pretreated with furosemide four hours earlier. F...
Soma LR, Uboh CE, Nann L, Gerber AL.The administration of sodium bicarbonate (NaHCO3) or 'milk shakes' to Standardbred horses before racing is widespread. This study analysed nonrace day (CTL) and prerace venous acid-base values from Standardbred horses racing in Pennsylvania (PA) and New Jersey (NJ). Mean +/- s.d. CTL bicarbonate (HCO3) and base excess (BE) values, for a group of horses stabled during the 1993 racing season at Pocono Downs, Pennsylvania, were 28.6 +/- 1.9 and 2.6 +/- 1.7 mmol/l, respectively. In the same population of horses, mean +/- s.d. values for prerace HCO3- and BE values were 33.1 +/- 2.8 and 7.0 +/- 2.3...
Hubbell JA, Hinchcliff KW, Grosenbaugh DA, Beard WL, Beard LA.Frusemide reduces pulmonary vascular pressures in resting horses and attenuates exercise-induced increases in these pressures in exercising horses. The mechanism underlying these effects of frusemide is unclear. We tested the hypothesis that the haemodynamic effects of frusemide are dependent on diuresis by examining the effect of frusemide in anaesthetised horses in which diuresis was prevented by ligation of ureters. Twenty four horses were assigned randomly to one of 4 treatments: 1) frusemide (1 mg/kg bwt i.v.) and intact ureters; 2) frusemide and ligated ureters; 3) saline placebo and lig...
Craig AM, Blythe LL, Appell LH, Slizeski ML.Dimethyl sulfoxide (DMSO) had been postulated to be a 'masking agent' when used concurrently with therapeutic or prohibited drugs in racing animals. Eight drugs (flunixin, furosemide, caffeine, apomorphine, phenylbutazone, lidocaine, cocaine, and acepromazine maleate) were administered to six horses singly and with concurrent intravenous DMSO. Urine samples were analyzed for the presence of the drugs and/or their metabolites by thin layer chromatography. Direct comparison of thin layer chromatograms of extracts of positive urine samples with and without DMSO verified that DMSO did not interfer...
Hinchcliff KW, McKeever KH.The effect of blood volume repletion after frusemide administration on the right atrial and pulmonary artery pressure responses of horses to exercise has not been reported. We examined right atrial and pulmonary artery pressure and plasma atrial natriuretic peptide concentration (ANP) responses to an incremental exercise test in 6 Standardbred mares. Horses were treated, in a 3 way cross over design, with isotonic saline, frusemide (1 mg/kg bwt, i.v.), and frusemide followed 3 h later by lactated Ringer's solution (12 ml/kg bwt, i.v.). Three and a half hours after saline or frusemide administr...
Cohen ND, Chu KK, Stanley SD, Wang N.To estimate the probability for exceeding a threshold concentration of furosemide commonly used for regulatory purposes after IV administration of furosemide in horses. Methods: 12 mature healthy horses (6 Thoroughbreds and 6 Quarter Horses). Methods: Venous blood was collected from each horse prior to and 0.25, 0.5, 0.75, 1, 2, 3, 4, 4.5, 5, and 6 hours after administration of 250 or 500 mg of furosemide. Concentrations of furosemide were determined, using an ELISA. Concentration of furosemide was modeled as a function of time, accounting for inter- and intrahorse variabilities. On the basis ...
McCrae P, Guigand C, Jones KB, Thueson ES, Troudt TA, Warlick LM, Sides RH, Jones JH, Bayly WM, Léguillette R.High pulmonary blood pressure contributes to exercise-induced pulmonary hemorrhage. The objective of this study was to use bioimpedance spectroscopy to assess body fluid compartment volumes under 3 conditions in 6 racehorses: i) Pre- and post-supramaximal treadmill exercise (control); ii) Exercise 4 hours after furosemide (0.5 mg/kg body weight, IV); iii) Exercise, removal of ~14 L of blood and subsequent reinfusion of the blood. Statistical analysis used linear mixed effects models. Body compartment volumes did not change during the control runs. Total body water (TBW) ( = 0.007, = 0.007), e...
Soma LR, Korber K, Anderson T, Hopkins J.The effects of furosemide (0.55 mg/kg IV) on the plasma and urinary fentanyl (PFE UFE) concentrations were studied during steady-state conditions. The PFE during the steady-state period was 0.31 +/- 0.027 ng/ml, with no significant changes occurring, even though the rate of excretion of fentanyl (EX) increased during the 1st hour from 112.0 +/- 21.6 to 534.5 +/- 82.9 ng/minute. The EX returned to control levels within 3 hours, as did the UFE. The injection of furosemide increased glomerular filtration rate from 1.97 +/- 0.21 to 3.81 +/- 0.75 ml/kg/min. The fractional reabsorption decreased fro...
Brumbaugh GW, Thomas WP, Hodge TG.A 4-year-old Quarter Horse gelding with atrial fibrillation, mitral regurgitation, and signs of bilateral congestive heart failure was initially treated IV with digoxin and furosemide. After parenteral digitalization, a daily maintenance dose of digoxin was administered orally at a rate of 21.7 micrograms/kg of body weight. At this dosage, a steady-state serum digoxin concentration of 2.3 ng/ml was achieved without clinical signs of toxicosis. The furosemide dosage was decreased and eventually discontinued as clinical improvement occurred. Clinical signs of congestive heart failure were contro...
Mageed M, Wegert J, Dyab S, Gerlach K.This prospective, cross-sectional, pilot study aimed to investigate the effects of furosemide as a diuretic on the image quality of bone scintigraphy performed using Tc-HDP and to investigate the impact of furosemide on the radiation dose rate. Thirty-one horses undergoing bone scintigraphy were included. The horses were divided into the control (n = 14) and furosemide group (n = 17), which received 1 mg/kg furosemide intravenously 1 h post Tc-HDP administration. The image quality was assessed subjectively and semi-quantitatively. The bone-to-soft tissue (B:S) ratio was calculated from...
Manohar M, Goetz TE, Sullivan E, Griffin R.The present study was carried out to examine the effects of phenylbutazone treatment on the pulmonary haemodynamic effects of frusemide in strenuously exercising horses. Using catheter mounted manometers, whose in vivo signals were referenced at the point of the shoulder, heart rate, right atrial, right ventricular and pulmonary vascular pressures were measured in 3 different sets of experiments. Seven Thoroughbreds were subjected to 1) control (no medications), 2) frusemide control and 3) phenylbutazone + frusemide. The experiments were carried out in random order and were separated by 7 days...
