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Effects of conjugated oestrogens and aminocaproic acid upon exercise-induced pulmonary haemorrhage (EIPH)

Published online by Cambridge University Press:  01 May 2008

T S Epp ,
K L Edwards ,
D C Poole  and
H H Erickson
T S Epp*
Affiliation:
Department of Anatomy and Physiology, 228 Coles Hall, Kansas State University, Manhattan, KS66506, USA
K L Edwards
Affiliation:
Department of Anatomy and Physiology, 228 Coles Hall, Kansas State University, Manhattan, KS66506, USA
D C Poole
Affiliation:
Department of Anatomy and Physiology, 228 Coles Hall, Kansas State University, Manhattan, KS66506, USA
H H Erickson
Affiliation:
Department of Anatomy and Physiology, 228 Coles Hall, Kansas State University, Manhattan, KS66506, USA
*
*Corresponding author: tepp@vet.ksu.edu
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Abstract

Aminocaproic acid (ACA) and Premarin® (PRE) are used to treat exercise-induced pulmonary haemorrhage (EIPH) at the racetrack based upon their putative coagulation effects. We hypothesized that neither ACA nor PRE would reduce EIPH because the literature does not substantiate coagulation deficits being manifested in EIPH. Six Thoroughbreds were run from 4 m s− 1 until fatigue (1 m s− 1s × 1 min increments; 6° inclined treadmill) after being treated with placebo, PRE (25 mg) or ACA (5 g) at 2-week intervals in a randomized crossover design. Coagulation and exercise-related variables were measured at rest and maximal effort. EIPH and inflammation were quantified via bronchoalveolar lavage fluid (BALF) 30–60 min post-exercise. EIPH was not altered by either treatment (3.8 ± 1.7 (placebo), 4.6 ± 3.2 (ACA) and 2.4 ± 1.2 (PRE) × 106 RBC ml− 1 BALF; p = 0.12), nor was coagulation. However, inflammation was decreased (5.9 ± 0.9 (placebo), 4.4 ± 0.9 (ACA) and 4.2 ± 0.4 (PRE) × 105 WBC ml− 1 BALF; both p < 0.05). There was a trend for decreased time-to-fatigue (720 ± 27 (placebo), 709 ± 24 (ACA) and 726 ± 28 (PRE) s; p = 0.09 for placebo vs. ACA) and a reduction in plasma lactate (19.5 ± 3.0 (placebo), 14.7 ± 1.0 (ACA) and 17.6 ± 2.5 (PRE) mmol l− 1; p < 0.05 for placebo vs. ACA) following ACA administration. ACA and PRE were not effective in reducing EIPH, and ACA may be detrimental to performance. However, both may mitigate exercise-induced pulmonary inflammation.

Keywords

equineEIPHbronchoalveolar lavageaminocaproic acidconjugated oestrogen
Type
Research Paper
Information
Comparative Exercise Physiology , Volume 5 , Issue 2 , May 2008 , pp. 95 - 103
Copyright
Copyright © Cambridge University Press 2008

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References

1McKane, SA, Canfield, PJ and Rose, RJ (1993). Equine bronchoalveolar lavage cytology: survey of Thoroughbred racehorses in training. Australian Veterinary Journal 70: 401–404.CrossRefGoogle ScholarPubMed
2Meyer, TS, Fedde, MR, Gaughan, EM, Langsetmo, I and Erickson, HH (1998). Quantification of exercise-induced pulmonary haemorrhage with bronchoalveolar lavage. Equine Veterinary Journal 30: 284–288.Google Scholar
3Aguilera-Tejero, E, Pascoe, JR, Tyler, WS and Woliner, MJ (1995). Autologous blood installation alters respiratory mechanics in horses. Equine Veterinary Journal 27: 46–50.Google Scholar
4McKane, SA, Bayly, WM, Hines, MT and Sides, RH (1998). Autologous blood infusion into the lungs interferes with gas exchange and performance in exercising horses. World Equine Airways Symposium.Google Scholar
5Hinchcliff, KW (2005). Exercise-induced pulmonary hemorrhage. Proceedings of the American Association of Equine Practitioners 50: 342–347.Google Scholar
6Mason, DK, Collins, EA and Watkins, KL (1983). Respiratory system. In: Snow, DH, Persson, SGB and Rose, RJ (eds) Equine Exercise Physiology. Cambridge: Granta Editions, pp. 57–63.Google Scholar
7Macnamara, B, Bauer, S and Iafe, J (1990). Endoscopic evaluation of exercise-induced pulmonary hemorrhage and chronic obstructive pulmonary disease in association with poor performance in racing Standardbreds. Journal of the American Veterinary Medical Association 196: 443–445.Google Scholar
8Gunson, DE, Sweeney, CR and Soma, LR (1988). Sudden death attributable to exercise-induced pulmonary hemorrhage in racehorses: nine cases (1981–1983). Journal of the American Veterinary Medical Association 193: 102–106.Google Scholar
9Erickson, HH and Poole, DC (2007). Exercise-induced pulmonary hemorrhage. In: Lekeux, P (ed.) Equine Respiratory Diseases (available at:www.ivis.org).Google Scholar
10Geor, RJ, Ommundson, L, Fenton, G and Pagan, JD (2001). Effects of an external nasal strip and frusemide on pulmonary haemorrhage in Thoroughbreds following high-intensity exercise. Equine Veterinary Journal 33: 577–584.CrossRefGoogle ScholarPubMed
11Kindig, CA, McDonough, P, Fenton, G, Poole, DC and Erickson, HH (2001). Efficacy of nasal strip and furosemide in mitigating EIPH in thoroughbred horses. Journal of Applied Physiology 91: 1396–1400.Google Scholar
12McDonough, P, Kindig, CA, Hildreth, TS, Padilla, DJ, Behnke, BJ, Erickson, HH and Poole, DC (2004). Effect of furosemide and the equine nasal strip on EIPH and time to fatigue in running Thoroughbred horses. Equine and Comparative Exercise Physiology 1: 177–184.Google Scholar
13Poole, DC, Kindig, CA and Fenton, G (2000). Effects of external nasal support on pulmonary gas exchange and EIPH in the horse. Journal of Equine Veterinary Science 20: 578–585.Google Scholar
14Valdez, SC, Nieto, JE, Spier, SJ, Owens, SD, Beldomenico, P and Snyder, JR (2004). Effect of an external nasal dilator strip on cytologic characteristics of bronchoalveolar lavage fluid in Thoroughbred racehorses. Journal of the American Veterinary Medical Association 224: 558–561.Google Scholar
15Hildreth, TS, McDonough, P, Myers, DE, Padilla, DJ, Behnke, BJ, Poole, DC and Erickson, HH (2003). Is immunotherapy effective in reducing exercise-induced pulmonary hemorrhage (EIPH)? FASEB Journal 17: A939.Google Scholar
16Erickson, HH and Hildreth, TS (2004). Novel and emerging therapies for EIPH. Proceedings of the American College of Veterinary Internal Medicine 22: 734–736.Google Scholar
17Erickson, HH, Epp, TS and Poole, DC (2007). Review of alternative therapies for EIPH. Proceedings of the American Association of Equine Practitioners 53: 68–71.Google Scholar
18White, JG, Matlack, KL, Mundschenk, D and Rao, GHR (1976). Platelet studies in normal and a bleeder horse. Proceedings First International Symposium on Equine Hematology, Golden, Colorado, pp. 209–220.Google Scholar
19Bayly, WM, Meyers, KM, Keck, MT, Huston, LJ and Grant, BD (1983). Exercise-induced alterations in hemostasis in Thoroughbred horses. In: Snow, DH, Persson, SGB and Rose, RJ (eds) Equine Exercise Physiology. 1st edn.Cambridge, UK: Burlington Press/Granta Editions, pp. 336–343.Google Scholar
20Bayly, WM, Meyers, KM, Keck, MT, Huston, LJ and Grant, BD (1983). Effects of exercise on the hemostatic system of Thoroughbred horses displaying post-exercise epistaxis. Equine Veterinary Science 3: 191–193.Google Scholar
21Johnstone, IB, Viel, L, Crane, S and Whiting, T (1991). Haemostatic studies in racing Standardbred horses with exercise-induced pulmonary hemorrhage. Haemostatic parameters at rest and after moderate exercise. Canadian Journal of Veterinary Research 55: 101–106.Google Scholar
22Kociba, GJ, Bayly, WM, Milne, DW, Wigton, DH, Gabel, AA and Muir, WW (1984). Furosemide: effects on the hemostatic mechanism of resting and exercised Standardbred horses. American Journal of Veterinary Research 45: 2603–2606.Google Scholar
23McKeever, KH, Hinchcliff, KW, Kociba, GJ, Reed, SM and Muir, WW 3rd (1990). Changes in coagulation and fibrinolysis in horses during exercise. American Journal of Veterinary Research 51: 1335–1339.Google Scholar
24Kingston, JK, Bayly, WM, Meyers, KM, Sellon, DC and Wardrop, KJ (2002). Evaluation of binding of fibrin and annexin V to equine platelets in response to supramaximal treadmill exercise. Equine Veterinary Journal Supplement 34: 502–505.Google Scholar
25Epp, TS, McDonough, P, Padilla, DJ, Cox, JH, Poole, DC and Erickson, HH (2005). The effect of herbal supplementation on the severity of exercise-induced pulmonary haemorrhage. Equine and Comparative Exercise Physiology 2: 17–25.Google Scholar
26Verstraete, M (1985). Clinical application of inhibitors of fibrinolysis. Drugs 29: 236–261.CrossRefGoogle ScholarPubMed
27Heidmann, P, Tornquist, SJ, Qu, A and Cebra, CK (2005). Laboratory measures of hemostasis and fibrinolysis after intravenous administration of ɛ-aminocaproic acid in clinically normal horses and ponies. American Journal of Veterinary Research 66: 313–318.CrossRefGoogle Scholar
28Ross, J, Dallap, BL, Dolente, BA and Sweeney, RW (2007). Pharmacokinetics and pharmacodynamics of ɛ-aminocaproic acid in horses. American Journal of Veterinary Research 68: 1016–1021.Google Scholar
29Fedde, MR (1991). Blood gas analysis on equine blood: required correction factors. Equine Veterinary Journal 23: 410–412.Google Scholar
30Kopp, KJ, Moore, JN, Byars, TD and Brooks, P (1985). Template bleeding time and thromboxane generation in the horse: effects of three non-steroidal anti-inflammatory drugs. Equine Veterinary Journal 17: 322–324.Google Scholar
31Langsetmo, I and Poole, DC (1999). VO2 recovery kinetics in the horse following moderate, heavy, and severe exercise. Journal of Applied Physiology 86: 1070–1077.Google Scholar
32Weigle, GE, Langsetmo, I, Gallagher, RR, Dyer, RA, Erickson, HH and Fedde, MR (1998). Analysis of right ventricular function in the exercising horse: use of the Fourier Transform. Equine Veterinary Journal 32: 101–108.Google Scholar
33Epp, TS, McDonough, P, Padilla, DJ, Gentile, JM, Edwards, KL, Erickson, HH and Poole, DC (2006). Exercise-induced pulmonary haemorrhage during submaximal exercise. Equine Veterinary Journal Supplement 37: 502–507.Google Scholar
34McKane, SA and Rose, RJ (1993). Radiographic determination of the location of a blindly placed bronchoalveolar lavage catheter. Equine Veterinary Journal 5: 329–332.Google Scholar
35Chen, RH, Fazier, OH and Cooley, DA (1995). Antifibrinolytic therapy in cardiac surgery. Texas Heart Institute Journal 22: 211–215.Google Scholar
36Mannucci, PM (1998). Hemostatic drugs. New England Journal of Medicine 339: 245–253.Google Scholar
37Gaines, KK (2003). Aminocaproic acid (Amiar®): potent antifibrinolytic agent for treating hematuria. Urological Nursing 23: 156–158.Google Scholar
38King, C (1995). EIPH: rational approach to therapy. Journal of Equine Veterinary Science 15: 7–13.Google Scholar
39Marijunath, G, Fozailoff, A, Mitcheson, D and Sarnak, MJ (2002). Epsilon-aminocaproic acid and renal complications: case report and review of the literature. Clinical Nephrology 58: 63–67.Google Scholar
40Pascoe, JR (1981). Exercise-induced pulmonary hemorrhage in the racing horse. In: Proceedings of Symposium on Surgery and Diseases of the Oral Cavity and Respiratory Tract, Barossa Valley (Australian Equine Veterinary Association). pp. 83–88.Google Scholar
41DeVore, GR, Owens, O and Kase, N (1982). Use of intravenous Premarin® in the treatment of dysfunctional uterine bleeding – a double blind randomized control study. Obstetrics and Gynecology 59: 285–291.Google Scholar
42Liu, YK, Kosfeld, RE and Marcum, SG (1984). Treatment of uremic bleeding with conjugated oestrogen. Lancet 2: 887–889.Google Scholar
43Livivo, M, Mannucci, PM, Vigano, G, Mingardi, G, Lombardi, R, Mecca, G and Remuzzi, G (1986). Conjugated estrogens for the management of bleeding associated with renal failure. New England Journal of Medicine 315: 731–735.Google Scholar
44McCall, RE and Bilderback, KK (1997). Use of intravenous Premarin to decrease postoperative blood loss after pediatric scoliosis surgery. Spine 22: 1394–1397.Google Scholar
45Lewis, BS (1999). Medical and hormonal therapy in occult gastrointestinal bleeding. Seminars in Gastrointestinal Disease 10: 71–77.Google Scholar
46Menefee, MG, Flessa, HC, Glueck, HI and Hogg, SP (1975). Hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu Disease): an electron microscopic study of the vascular lesions before and after therapy with hormones. Archives of Otolaryngology 101: 246–251.Google Scholar
47Harrison, DFN (1982). Use of estrogen in treatment of familial hemorrhagic telangiectasia. Laryngoscope 92: 314–320.Google Scholar
48Marshall, JK and Hunt, RH (1997). Hormonal therapy for bleeding gastrointestinal mucosal vascular abnormalities: A promising alternative. European Journal of Gastroenterology and Hepatology 9: 521–525.Google Scholar
49McCarthy, ML and Stoukides, CA (1994). Estrogen therapy of uremic bleeding. Annals of Pharmacology 28: 60–62.Google Scholar
50Kingston, JK, Sampson, SN, Beard, LA, Meyers, KM, Sellon, DC and Bayly, WM (1999). The effect of supramaximal exercise on equine platelet function. Equine Veterinary Journal Supplement 30: 181–183.Google Scholar
51Kingston, JK, Bayly, WM, Sellon, DC, Meyers, KM and Wardrop, KJ (2001). Effects of sodium citrate, low molecular weight heparin, and prostaglandin E1 on aggregation, fibrinogen binding, and enumeration of equine platelets. American Journal of Veterinary Research 62: 547–554.Google Scholar
52Elliot, AR, Fu, Z, Tsukimoto, K, Prediletto, R, Mathieu-Costello, O and West, JB (1992). Short-term reversibility of ultrastructural changes in pulmonary capillaries caused by stress failure. Journal of Applied Physiology 73: 1150–1158.Google Scholar
53West, JB, Mathieu-Costello, O, Jones, JH, Birks, EK, Logemann, RB, Pascoe, JR and Tyler, WS (1993). Stress failure of pulmonary capillaries in racehorses with exercise-induced pulmonary hemorrhage. Journal of Applied Physiology 75: 1097–1109.Google Scholar
54Hinchcliff, KW (2000). Counting red cells – is it the answer? Equine Veterinary Journal 32: 363–363.Google Scholar
55Greilich, PE, Brouse, CF, Whitten, CW, Chi, L, DiMaio, JM and Jessen, ME (2003). Antifibrinolytic therapy during cardiopulmonary bypass reduces proinflammatory cytokine levels: A randomized, double-blind, placebo-controlled study of ɛ-aminocaproic acid and aprotinin. Journal of Thoracic and Cardiovascular Surgery 126: 1498–1503.Google Scholar
56Levy, JH (2007). Anti-inflammatory strategies and hemostatic agents: old drugs, new ideas. Hematology/Oncology Clinics of North America 21: 89–101.Google Scholar
57Speyer, CL, Rancilio, NJ, McClintock, SD, Crawford, JD, Gao, H, Sarma, JV and Ward, PA (2005). Regulatory effects of estrogen on acute lung inflammation in mice. American Journal of Physiology: Cell Physiology 288: C881–C890.Google Scholar
58Maia, H and Casoy, J (2007). Non-contraceptive benefits of oral contraceptives. European Journal of Contraceptive and Reproductive Health Care 1-8: i First Article.Google Scholar
59Straub, RH (2007). The complex role of estrogens in inflammation. Endocrine Reviews 28: 521–574.Google Scholar
60Robinson, NE and Derksen, FJ (1980). Small airway obstruction as a cause of exercise-associated pulmonary hemorrhage: a hypothesis. Proceedings of the American Association of Equine Practitioners 26: 421–430.Google Scholar
61O'Callaghan, MW, Pascoe, JR, Tyler, WS and Mason, DK (1987). Exercise-induced pulmonary hemorrhage in the horse: results of a detailed clinical, post mortem and imaging study V. Microscopic observations. Equine Veterinary Journal 19: 411–418.Google Scholar
62O'Callaghan, MW, Pascoe, JR and Tyler, WS (1987). Exercise-induced pulmonary hemorrhage in the horse: results of a detailed clinical, post mortem and imaging study VIII. Conclusions and implications. Equine Veterinary Journal 19: 428–434.Google Scholar
63McKane, SA and Slocombe, RF (1999). Sequential changes in bronchoalveolar cytology after autologous blood inoculation. Equine Veterinary Journal 30: 126–130.CrossRefGoogle Scholar
64McKane, SA and Slocombe, RF (2002). Alveolar fibrosis and changes in equine lung morphometry in response to intrapulmonary blood. Equine Veterinary Journal Supplement 34: 451–458.Google Scholar
65Newton, JR and Wood, JLN (2002). Evidence of an association between inflammatory airway disease and EIPH in young Thoroughbreds during training. Equine Veterinary Journal Supplement 34: 417–424.CrossRefGoogle Scholar
66Mahony, C, Rantanen, NW, DeMichael, JA and Kincaid, B (1992). Spontaneous echocardiographic contrast in the thoroughbred: high prevalence in racehorses and a characteristic abnormality in bleeders. Equine Veterinary Journal 24: 129–133.Google Scholar
67Weiss, DJ, Evanson, OA, McClenahan, D, Fagliari, J and Walcheck, B (1998). Shear-induced platelet activation and platelet-neutrophil aggregate formation by equine platelets. American Journal of Veterinary Research 59: 1243–1246.Google Scholar
68Weiss, DJ, Evanson, OA, Fagliari, JJ and Valberg, S (1998). Evaluation of platelet activation and platelet neutrophil aggregates in Thoroughbreds undergoing near-maximal treadmill exercise. American Journal of Veterinary Research 59: 393–396.CrossRefGoogle ScholarPubMed
69Weiss, DJ, McClay, CB, Smith, CM, Rao, GHR and White, JG (1990). Platelet function in the racing Thoroughbred: implication for exercise-induced pulmonary hemorrhage. Veterinary Clinical Pathology 19: 35–39.Google Scholar