Intravenous pentoxifylline does not enhance the pulmonary haemodynamic efficacy of frusemide in strenuously exercising thoroughbred horses.
The present study was carried out to examine whether pentoxifylline administration to horses premedicated with frusemide would attenuate the exercise-induced pulmonary arterial, capillary and venous hypertension to a greater extent than frusemide alone, thereby affecting the occurrence of exercise-induced pulmonary haemorrhage (EIPH). Using established techniques, we determined right heart and pulmonary vascular pressures in 6 healthy, sound Thoroughbred horses at rest and during exercise performed at maximal heart rate at a workload of 14 m/s on 3.5% uphill grade in the control (no medications), frusemide (250 mg i.v., 4 h pre-exercise)-control, and the frusemide (250 mg i.v., 4 h pre-exercise) + pentoxifylline (8.5 mg/kg bwt i.v., 15 min preexercise) treatments. Sequence of the 3 treatments was randomised for every horse and 7 days were allowed between them. In the control study, galloping at 14 m/s on 3.5% uphill grade elicited significant right atrial as well as pulmonary arterial, capillary and venous hypertension and all horses experienced EIPH as detected by the presence of fresh blood in the trachea on endoscopic examination. Frusemide administration was not attended by changes in heart rate at rest or during exercise. Although in the frusemide-control experiments, a significant reduction in mean pulmonary arterial, capillary and wedge pressures was observed both at rest and during galloping at 14 m/s on 3.5% uphill grade, all horses still experienced EIPH. Pentoxifylline administration to standing horses premedicated with frusemide caused nervousness, muscular fasciculations, sweating and tachycardia. Although these symptoms had largely abated within 15 min, there were no significant changes in the right atrial or pulmonary vascular pressures. Exercise in the frusemide + pentoxifylline experiments also caused significant right atrial as well as pulmonary arterial, capillary and venous hypertension, but these data were not found to be significantly different from the frusemide-control experiments. All horses in the frusemide + pentoxifylline experiments also experienced EIPH. In conclusion, our data indicate that pentoxifylline (8.5 mg/kg bwt i.v., 15 min pre-exercise) is ineffective in modifying the pulmonary haemodynamic effects of frusemide in exercising horses. It should be noted, however, that we did not examine whether erythrocyte plasticity was altered by the administration of pentoxifylline. Since the intravascular force exerted onto the blood-gas barrier of exercising horses premedicated with frusemide remained unaffected by pentoxifylline administration, it is concluded that concomitant pentoxifylline administration is unlikely to offer additional benefit to horses experiencing EIPH.
Manohar
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M
Department of Veterinary Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Illinois 61801, USA.
Goetz
T E
TE
Rothenbaum
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P
Humphrey
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D000818:Animals; D001947:Breeding; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004347:Drug Interactions; D005260:Female; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006734:Horse Diseases / Q000517:prevention & control*; D006736:Horses; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000517:prevention & control / Q000662:veterinary*; D007275:Injections, Intravenous / Q000662:veterinary; D008297:Male; D010431:Pentoxifylline / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D010805:Physical Conditioning, Animal / Q000009:adverse effects; D011652:Pulmonary Circulation / Q000187:drug effects / Q000502:physiology; D011897:Random Allocation; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use
D004232:Diuretics; D014665:Vasodilator Agents; D005665:Furosemide; D010431:Pentoxifylline