The effect of premedication with phenylbutazone on systemic hemodynamic and diuretic effects of furosemide was examined in 6 healthy, conscious, mares. Mares were instrumented for measurement of systemic hemodynamics, including cardiac output and pulmonary arterial, systemic arterial, and intracardiac pressures, and urine flow. Each of 3 treatments was administered in a randomized, blinded study; furosemide (1 mg/kg of body weight, IV) only, phenylbutazone (8.8 mg/kg PO, at 24 hours and 4.4 mg/kg IV, 30 minutes before furosemide) and furosemide, or 0.9% NaCl. Phenylbutazone administration significantly attenuated, but did not abolish, the diuretic effect of furosemide. Phenylbutazone completely inhibited the immediate effect of furosemide on cardiac output, stroke volume, total peripheral resistance, and right ventricular peak pressure. Premedication with phenylbutazone did not inhibit equally the diuretic and hemodynamic effects of furosemide, indicating that some of furosemide's hemodynamic effects are mediated by an extrarenal activity of furosemide.

Effects of furosemide, exercise, and atropine on tracheal mucus transport rate (TMTR) in horses were investigated. Atropine (0.02 mg/kg of body weight) administered IV or by aerosolization significantly (P < 0.05) decreased TMTR at 60, but not at 30 minutes after its administration in standing horses. Furosemide (1.0 mg/kg, IV) did not have any significant effect on TMTR when measured at 2 or 4 hours after its administration in standing horses. Exercise alone or furosemide (1.0 mg/kg, IV) administration followed 4 hours later by exercise did not alter TMTR, compared with values for standing control or exercised horses administered saline solution. Atropine (0.02 mg/kg, IV) administered after exercise significantly (P < 0.05) decreased TMTR, compared with values for no exercise standing controls, for exercise after administration of saline solution, and for furosemide and exercise.

Four hours prior to exercise on a high-speed treadmill, 4 dosages of furosemide (0.25, 0.50, 1.0, and 2.0 mg/kg of body weight) and a control treatment (10 ml of 0.9% NaCl) were administered IV to 6 horses. Carotid arterial pressure (CAP), pulmonary arterial pressure (PAP), and heart rate were not different in resting horses before and 4 hours after furosemide administration. Furosemide at dosage of 2 mg/kg reduced resting right atrial pressure (RAP) 4 hours after furosemide injection. During exercise, increases in treadmill speed were associated with increases in RAP, CAP, PAP, and heart rate. Furosemide (0.25 to 2 mg/kg), administered 4 hours before exercise, reduced RAP and PAP during exercise in dose-dependent manner, but did not influence heart rate. Mean CAP was reduced by the 2-mg/kg furosemide dosage during exercise at 9 and 11 m/s, but not at 13 m/s. During recovery, only PAP was decreased by furosemide administration. Plasma lactate concentration was not significantly influenced by furosemide administration. Furosemide did not influence PCV or hemoglobin concentration at rest prior to exercise, but did increase both variables in dose-dependent manner during exercise and recovery. However, the magnitude of the changes in PCV and hemoglobin concentration were small in comparison with changes in RAP and PAP, and indicate that furosemide has other properties in addition to its diuretic activities. Furosemide may mediate some of its cardiopulmonary effects by vasodilatory activities that directly lower pulmonary arterial pressure, but also increase venous capacitance, thereby reducing venous return to the atria and cardiac filling.

A 6 year-old, spayed female, Maltese dog was presented with precordial thrill and mild coughing. Thoracic auscultation revealed a grade V/VI systolic murmur with maximal intensity over the left apex characterized by musical murmur. Echocardiography revealed mild myxomatous degeneration of mitral valve and ruptured chordae tendineae. Musical murmur was produced due to the vibration of ruptured piece of chordae tendineae along with regurgitant flow. After treatment with furosemide and ramipril, clinical signs resolved and precordial thrill reduced. This case report describes typical clinical signs and phonocardiogram of musical murmur in a dog with acute chordae tendineae rupture.

Objective: To determine the effects of carprofen and etodolac on renal function in euvolemic dogs and dogs with extracellular fluid volume depletion induced via administration of furosemide. Animals: 12 female Beagles. Procedures: Dogs received a placebo, furosemide, carprofen, etodolac, furosemide and carprofen, and furosemide and etodolac. The order in which dogs received treatments was determined via a randomization procedure. Values of urine specific gravity, various plasma biochemical variables, glomerular filtration rate (GFR [urinary clearance of creatinine]), and renal plasma flow (urinary clearance of para-aminohippuric acid) were determined before and after 8 days of drug administration. A washout time of approximately 12 days was allowed between treatment periods. Results: Administration of furosemide, furosemide and carprofen, and furosemide and etodolac caused changes in urine specific gravity and values of plasma biochemical variables. Administration of carprofen or etodolac alone did not have a significant effect on renal plasma flow or GFR. Concurrent administration of furosemide and carprofen or furosemide and etodolac caused a significant decrease in GFR. After 12-day washout periods, mean values of GFR were similar to values before drug administration for all treatments. Conclusions and Clinical Relevance: Results indicated GFR decreased after 8 days of concurrent administration of furosemide and carprofen or furosemide and etodolac to dogs. Administration of preferential cyclooxygenase-2 inhibitors to dogs with extracellular fluid volume depletion or to dogs treated with diuretics may transiently impair renal function.

Effects of echinocytosis on blood rheology and exercise performance were evaluated for 5 Thoroughbreds. Echinocytosis was induced by administration of furosemide (1 mg/kg of body weight, IM, q 12 h) for 4 days. Furosemide treatment resulted in decreases in serum sodium and serum chloride concentrations and in RBC chloride and potassium concentrations. Echinocytosis was associated with increased RBC density as determined by RBC density gradient centrifugation. However, samples containing echinocytes were more filterable than control samples, indicating that echinocytes were not rigid cells. Erythrocyte sedimentation rate was decreased in blood samples containing echinocytes, indicating that cell-to-cell interaction was reduced. Whole blood viscosity was not altered by presence of echinocytes. Echinocytes did not impair the capacity of horses to complete treadmill exercise tests, nor did they alter heart rate or blood gas variables. However, plasma lactate concentration was higher in samples obtained during exercise at a treadmill speed of 9 m/s. Echinocytosis was associated with higher postrace creatine kinase activity. These data indicate that echinocytes may be dense, but not rigid cells, which have decreased tendency to aggregate and do not increase whole blood viscosity. Therefore, echinocytes are unlikely to inhibit or obstruct microvascular blood flow.

High-intensity exercise results in a dramatic increase in mean pulmonary capillary blood pressure of horses, and administration of furosemide 4 hours before exertion significantly attenuates this exercise-induced increment. To test whether this effect of furosemide is mediated via release of prostaglandins, right atrial and pulmonary vascular pressures were measured in 8 healthy, sound, exercise-trained Thoroughbreds at rest and during incremental-step exercise on a treadmill. Horses were studied on 3 separate occasions: after IV administration of saline (0.9% NaCl) solution, after administration of furosemide (250 mg, iv, 4 hours before exercise) alone, and after administration of flunixin meglumine (1.1 mg/kg, IV, q 8 h for 3 days) and furosemide (250 mg, IV, 4 hours before exercise; last dose of flunixin meglumine was administered 90 seconds after furosemide injection). Experiments on each horse were separated by at least 7 days and were performed in random order. At rest and at the highest workload (14.5 m/s on a 5% uphill incline), mean pulmonary capillary blood pressure recorded after administration of furosemide alone was not significantly different from that recorded after administration of flunixin meglumine and furosemide. However, these values were significantly (P < 0.05) less than corresponding values of mean pulmonary capillary blood pressure recorded after administration of saline solution. Thus, it was concluded that furosemide-induced attenuation of the increment in pulmonary capillary blood pressure during strenuous exercise is probably not mediated via prostaglandin production.

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 suppressed the exertion-induced increase in plasma concentrations of atrial natriuretic peptide (mean [95% confidence interval] values of 63.9 [9.9 to 421] pg/ml vs 100 [15.4 to 652] pg/ml after furosemide or saline treatment, respectively), and enhanced the response of plasma renin activity to exertion (18.6 [5.7 to 60.4] ng/ml/h vs 6.0 [1.8 to 19.4] ng/ml/h, respectively). An effect of furosemide on the exertion-induced increase in plasma aldosterone concentration was not detected.

Nine horses with naturally acquired) congestive heart failure were treated with 2.2 Kg of digoxin/kg of body weight by the IV route, followed by 11 microgram/kg administered orally every 12 hours thereafter. Furosemide was administered IV concurrently with IV administered digoxin every 12 hours. Serum concentration of digoxin was measured after the first (IV) and seventh (orally administered) dose. After IV administration, digoxin disposition was described by a 2-compartment model, with a rapid distribution phase t1/2 alpha = 0.17 hour), followed by a slower elimination phase (beta = 0.096 +/- 0.055 h-1, t1/2 beta = 7.2 hours, where beta is the exponential term from the elimination phase of the concentration vs time curve). Bioavailability after oral administration was 21.2 10.8%. After the seventh orally administered dose, serum concentration of digoxin peaked 1 to 2 hours later, and was 1.9 +/- 0.7 ng/ml (mean +/- SD). In 4 horses, a second increase in serum digoxin concentration was observed 4 to 8 hours after the initial peak which possibly was evidence of enterohepatic recycling of the drug. Response to treatment included reduction in heart rate, peripheral edema, and pulmonary edema, but these could not be attributed to the digoxin alone because the horses were treated concurrently with furosemide.

Hematologic and rheologic changes were examined in 49 Thoroughbreds before and after competitive racing. Mean postrace values for RBC count, hemoglobin concentration, and PCV increased by 58 to 61%, whereas blood viscosity increased 2 to 3 times. Postrace echinocyte numbers were 162% greater than prerace values. Smaller, but statistically significant, changes were found for mean corpuscular hemoglobin concentration, red cell distribution width, plasma total protein concentration, total WBC count, neutrophil count, and lymphocyte count. Variables measured did not predict whether a horse was a bleeder not treated with furosemide, a bleeder treated with furosemide, or a nonbleeder.