Influence of cyclooxygenase inhibitors on furosemide- induced hemodynamic effects during exercise in horses

S. C. Olsen From the Departments of Anatomy and Physiology (Olsen, Lowe, Erickson) and Clinical Sciences (Coyne, Pelletier, Raub), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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C. P. Coyne From the Departments of Anatomy and Physiology (Olsen, Lowe, Erickson) and Clinical Sciences (Coyne, Pelletier, Raub), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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B. S. Lowe From the Departments of Anatomy and Physiology (Olsen, Lowe, Erickson) and Clinical Sciences (Coyne, Pelletier, Raub), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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N. Pelletier From the Departments of Anatomy and Physiology (Olsen, Lowe, Erickson) and Clinical Sciences (Coyne, Pelletier, Raub), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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E. M. Raub From the Departments of Anatomy and Physiology (Olsen, Lowe, Erickson) and Clinical Sciences (Coyne, Pelletier, Raub), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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H. H. Erickson From the Departments of Anatomy and Physiology (Olsen, Lowe, Erickson) and Clinical Sciences (Coyne, Pelletier, Raub), College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506.

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SUMMARY

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 combination with phenylbutazone (4 mg/kg, iv, q 12 h for 2 days) or with flunixin meglumine (1.1 mg/kg, iv, on the day of experiment). Five horses were randomly assigned to complete all treatments. Physiologic variables at rest prior to exercise were not influenced by treatments. Furosemide, administered alone, reduced mean right atrial pressure and mean pulmonary artery pressure during exercise. The combinations of furosemide and flunixin meglumine or furosemide and phenylbutazone, at both levels of exercise intensity, returned mean right atrial pressure and mean pulmonary artery pressure to the value of the control treatment. During rest and exercise, plasma lactate concentration, pcv, heart rate, mean carotid artery pressure, oxygen consumption, carbon dioxide elimination, and cardiac output were not altered by any of the treatments. At 5 minutes after exercise, the administration of furosemide, alone or with phenylbutazone, reduced mean right atrial pressure. Other measured variables were not significantly influenced by treatments during recovery from exercise. These results suggested that cyclooxygenase inhibition partially reverses the decrease in mean right atrial pressure or pulmonary artery pressure induced by furosemide during exercise. Furosemide may mediate some of its physiologic activities in exercising horses through the cyclooxygenase pathway.

SUMMARY

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 combination with phenylbutazone (4 mg/kg, iv, q 12 h for 2 days) or with flunixin meglumine (1.1 mg/kg, iv, on the day of experiment). Five horses were randomly assigned to complete all treatments. Physiologic variables at rest prior to exercise were not influenced by treatments. Furosemide, administered alone, reduced mean right atrial pressure and mean pulmonary artery pressure during exercise. The combinations of furosemide and flunixin meglumine or furosemide and phenylbutazone, at both levels of exercise intensity, returned mean right atrial pressure and mean pulmonary artery pressure to the value of the control treatment. During rest and exercise, plasma lactate concentration, pcv, heart rate, mean carotid artery pressure, oxygen consumption, carbon dioxide elimination, and cardiac output were not altered by any of the treatments. At 5 minutes after exercise, the administration of furosemide, alone or with phenylbutazone, reduced mean right atrial pressure. Other measured variables were not significantly influenced by treatments during recovery from exercise. These results suggested that cyclooxygenase inhibition partially reverses the decrease in mean right atrial pressure or pulmonary artery pressure induced by furosemide during exercise. Furosemide may mediate some of its physiologic activities in exercising horses through the cyclooxygenase pathway.

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