1008 AJVR, Vol 62, No. 7, July 2001 E xercise-induced pulmonary hemorrhage (EIPH) is 1 of the principal causes of poor performance in racing horses. The most plausible mechanism for EIPH is stress-induced failure of pulmonary capillaries attributable to high transmural pulmonary pressures and pulmonary capillary blood pressures produced during exercise. 1,2 Because of the hypothesized rela- tionship between stress-induced pulmonary capillary failure, high transmural pulmonary capillary pressures, and pulmonary capillary blood pressure during exer- cise and the high incidence of pulmonary hemorrhage in racing horses (approx 75% of racing horses), sever- al investigators have conducted studies to evaluate the effects of systemic and pulmonary vasodilators on pul- monary pressures and the incidence of EIPH. 3-6 Toward this end, the pulmonary hemodynamic effects of vari- ous drugs, including furosemide, clenbuterol, flunixin meglumine, nitroglycerin, and L-nitro arginine methyl ester (L-NAME), have been investigated but have not provided convincing evidence that the incidence of EIPH is reduced. 4-9 Angiotensin converting enzyme (ACE) inhibitors produce generalized vasodilatation in humans and dogs, thereby reducing cardiac preload and afterload and decreasing arterial and pulmonary vascular blood pressures. 10 They also inhibit the degradation of bradykinin and enhance bradykinin-mediated release of nitric oxide, decreasing peripheral and pulmonary vascular resistance. 10 Studies in humans and dogs pro- vide evidence that an ACE inhibitor (ie, enalaprilat) increases cardiac index, decreases pulmonary capillary wedge pressure (PCWP), and decreases afterload in resting animals. 10,11 Increases in PCWP and, in particu- lar, mean pulmonary capillary blood pressure are believed to be responsible for stress-induced failure in pulmonary capillaries. 2 Enalaprilat decreases pul- monary vascular pressure and PCWP, improves pul- monary function and pulmonary diffusion capacity, relieves pulmonary congestion, and increases exercise capacity in humans with chronic compensated heart failure. 12-15 Whether similar benefits would be exerted in clinically normal exercising horses is unknown. Enalapril, an inhibitor of ACE, is a prodrug that must be converted by hepatic esterase to its active moi- ety, enalaprilat. 10 This conversion can delay peak drug activity for several hours and is the reason that we elected to administer enalaprilat, the active metabolite. The objective of the study reported here was to deter- mine whether enalaprilat decreased exercise-induced increases in pulmonary and systemic vascular blood pressures and the extent to which enalaprilat inhibited serum ACE activity in horses during and immediately following an exercise test that simulated race condi- tions. Materials and Methods Horses—Six healthy horses (5 Thoroughbreds and 1 Standardbred; 4 geldings and 2 mares) ranging from 2 to 9 years old and weighing between 445 and 517 kg were used in Received May 16, 2000. Accepted Oct 16, 2000. From the Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, Columbus, OH 43210-1089. Supported in part by Merial. The authors thank Steve Schumacher, Judith Dutson, Cheri Edwards, and Shawn Rosensteel for technical assistance. Effects of enalaprilat on cardiorespiratory, hemodynamic, and hematologic variables in exercising horses William W. Muir III, DVM, PhD; Richard A. Sams, PhD; John A. E. Hubbell, DVM, MS; Kenneth W. Hinchcliff, BVSc, PhD; Jennifer Gadawski Objective—To determine the effects of IV adminis- tration of enalaprilat on cardiorespiratory and hemato- logic variables as well as inhibition of angiotensin con- verting enzyme (ACE) activity in exercising horses. Animals—6 adult horses. Procedure—Horses were trained by running on a treadmill for 5 weeks. Training was continued throughout the study period, and each horse also ran 2 simulated races at 120% of maximum oxygen con- sumption. Three horses were randomly selected to receive treatment 1 (saline [0.9% NaCl] solution), and the remaining 3 horses received treatment 2 (enalaprilat; 0.5 mg/kg of body weight, IV) before each simulated race. Treatment groups were reversed for the second simulated race. Cardiorespiratory and hematologic data were obtained before, during, and throughout the 1-hour period after each simulated race. Inhibition of ACE activity was determined during and after each race in each horse. Results—Exercise resulted in significant increases in all hemodynamic variables and respiratory rate. The pH and PO 2 of arterial blood decreased during simu- lated races, whereas PCO 2 remained unchanged. Systemic and pulmonary blood pressure measure- ments and arterial pH, PO 2 , and PCO 2 returned to baseline values by 60 minutes after simulated races. Enalaprilat inhibited ACE activity to < 25% of baseline activity without changing cardiorespiratory or blood gas values, compared with horses administered saline solution. Conclusions and Clinical Relevance—Enalaprilat administration almost completely inhibited ACE activ- ity in horses without changing the hemodynamic responses to intense exercise and is unlikely to be of value in preventing exercise-induced pulmonary hem- orrhage. (Am J Vet Res 2001;62:1008–1013) Unauthenticated | Downloaded 08/14/22 01:56 AM UTC