title: Clenbuterol administration does not enhance the efficacy of furosemide in attenuating the exercise-induced pulmonary capillary hypertension in Thoroughbred horses.
abstract: The stimulation of pulmonary beta2-adrenergic receptors causes a decrease in vascular resistance. Thus, the present study was carried out to examine whether concomitant administration of clenbuterol-a beta2-adrenergic receptor agonist, to horses premedicated with furosemide would attenuate the exercise-induced pulmonary capillary hypertension to a greater extent than furosemide alone, and in turn, affect the occurrence of exercise-induced pulmonary hemorrhage (EIPH). Experiments were carried out on six healthy, sound, exercise-trained Thoroughbred horses. All horses were studied in the control (no medications), furosemide (250 mg i.v., 4 h pre-exercise)-control, and furosemide (250 mg i.v., 4 h pre-exercise)+clenbuterol (0.8 microg/kg i.v., 11 min pre-exercise) experiments. The sequence of these treatments was randomized for every horse, and 7 days were allowed between them. Using catheter-tip-transducers whose in-vivo signals were referenced at the point of the left shoulder, pulmonary vascular pressures were determined at rest, sub-maximal exercise, and during galloping at 14.2 m/s on a 3.5% uphill grade--a workload that elicited maximal heart rate. In the control study, incremental exercise resulted in progressive significant (P<0.05) increments in heart rate, right atrial as well as pulmonary arterial, capillary and venous (wedge) pressures, and all horses experienced EIPH. Furosemide administration caused a significant (P<0.05) reduction in mean right atrial as well as pulmonary capillary and venous pressures of standing horses. Although exercise in the furosemide-control experiments also caused right atrial and pulmonary vascular pressures to increase significantly (P<0.05), the increment in mean pulmonary capillary and wedge pressures was significantly (P<0.05) attenuated in comparison with the control study, but all horses experienced EIPH. Clenbuterol administration to standing horses premedicated with furosemide caused tachycardia, but significant changes in right atrial or pulmonary vascular pressures were not discerned at rest. During exercise in the furosemide+clenbuterol experiments, heart rate, mean right atrial as well as pulmonary arterial, capillary and wedge pressures increased significantly (P<0.05), but these data were not different from the furosemide-control experiments, and all horses experienced EIPH as well. Thus, it was concluded that clenbuterol administration is ineffective in modifying the pulmonary hemodynamic effects of furosemide in standing or exercising horses. Because the intravascular force exerted onto the blood-gas barrier of horses premedicated with furosemide remained unaffected by clenbuterol administration, it is believed that concomitant clenbuterol administration is unlikely to offer additional benefit to healthy horses experiencing EIPH.
authors.affiliation: University of Illinois at Urbana-Champaign, College of Veterinary Medicine, Departments of Veterinary Biosciences and Clinical Medicine, 212 Large Animal Clinic, 1102 W. Hazelwood Drive, Urbana, IL 61801, USA. mmanohar@uiuc.edu
authors.forename: M
authors.initials: M
authors.lastname: Manohar
authors.forename: T E
authors.initials: TE
authors.lastname: Goetz
authors.forename: P
authors.initials: P
authors.lastname: Rothenbaum
authors.forename: S
authors.initials: S
authors.lastname: Humphrey
mesh_terms: D000318:Adrenergic beta-Agonists / Q000627:therapeutic use*; D000818:Animals; D002976:Clenbuterol / Q000627:therapeutic use; D004232:Diuretics / Q000627:therapeutic use*; D004357:Drug Synergism; D005665:Furosemide / Q000627:therapeutic use*; D006736:Horses; D006976:Hypertension, Pulmonary / Q000188:drug therapy* / Q000209:etiology; D007275:Injections, Intravenous; D005082:Physical Exertion
chemical_list: D000318:Adrenergic beta-Agonists; D004232:Diuretics; D005665:Furosemide; D002976:Clenbuterol