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EIPH: Rational approach to therapy
Aminocaproic acid (ACA) and Premarin w (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 Thor-oughbreds were run from 4 m s 21 until fatigue (1 m s 21 s £ 1 min increments; 68 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) £ 10 6 RBC ml 21 BALF; p ¼ 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) £ 10 5 WBC ml 21 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 ¼ 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 21 ; 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 perform-ance. However, both may mitigate exercise-induced pulmonary inflammation.
To determine whether epsilon-aminocaproic acid (EACA) administered IV affects hemostasis and fibrinolysis in clinically normal horses and ponies.
20 clinically normal adult horses and ponies.
Blood samples were collected 24 hours before (baseline) and 1 and 5 hours after i.v. administration of a low dose (30 mg/kg) or high dose (100 mg/kg) of EACA. Platelet count, fibrinogen concentration, prothrombin time, partial thromboplastin time (PTT), D-dimer concentration, alpha2-antiplasmin activity, and thrombin-antithrombin complex concentration were measured. Values at 1 and 5 hours were compared with baseline values.
hour after administration of a low dose of EACA, mean fibrinogen concentration was significantly lower than baseline concentration. Mean PTT was significantly shorter than the baseline value 5 hours after administration of a low dose of EACA. One hour after administration of 100 mg of EACA/kg, mean alpha2-antiplasmin activity was significantly higher than baseline activity. Mean fibrinogen concentration was significantly lower than baseline concentration 1 and 5 hours after administration of a high dose of EACA. Mean PTT was significantly shorter than the baseline value 5 hours after administration of a high dose of EACA.
i.v. administration of 30 and 100mg of EACA/kg to clinically normal horses significantly modified some laboratory measures of hemostasis, consistent with its known antifibrinolytic effects. Although enhanced clot maintenance and diminished bleeding were not directly assessed, the clinical use of EACA may benefit some patients.
High-intensity exercise results in a dramatic increase in mean pulmonary capillary blood pressure of horses, and administration of furosemide 4 hours before exertion significantly attenuates this exercise-induced increment. To test whether this effect of furosemide is mediated via release of prostaglandins, right atrial and pulmonary vascular pressures were measured in 8 healthy, sound, exercise-trained Thoroughbreds at rest and during incremental-step exercise on a treadmill. Horses were studied on 3 separate occasions: after IV administration of saline (0.9% NaCl) solution, after administration of furosemide (250 mg, IV, 4 hours before exercise) alone, and after administration of flunixin meglumine (1.1 mg/kg, IV, q 8 h for 3 days) and furosemide (250 mg, IV, 4 hours before exercise; last dose of flunixin meglumine was administered 90 seconds after furosemide injection). Experiments on each horse were separated by at least 7 days and were performed in random order. At rest and at the highest workload (14.5 m/s on a 5% uphill incline), mean pulmonary capillary blood pressure recorded after administration of furosemide alone was not significantly different from that recorded after administration of flunixin meglumine and furosemide. However, these values were significantly ( P < 0.05) less than corresponding values of mean pulmonary capillary blood pressure recorded after administration of saline solution. Thus, it was concluded that furosemide-induced attenuation of the increment in pulmonary capillary blood pressure during strenuous exercise is probably not mediated via prostaglandin production.
This article addresses many aspects of exercise-induced pulmonary hemorrhage (EIPH). Reports of the prevalence, effect on performance, and the clinical signs and means of diagnosis of EIPH are included. Radiologic and scintigraphic findings in horses with EIPH are reported. Pathogenesis and treatment are discussed.
Exercise induced pulmonary haemorrhage (EIPH) is a serious problem in the Thoroughbred industry. The condition apparently occurs essentially in all Thoroughbreds in training but the mechanism has proved elusive. There is now strong evidence that the condition is caused by mechanical failure of the walls of the pulmonary capillaries when the pressure inside them rises to very high levels. It is well known that pulmonary capillaries have extremely thin walls to allow rapid exchange of respiratory gases across them. Recently we have shown that the wall stresses are very large when the capillary transmural pressure is raised, and in anesthetised rabbits, ultrastructural damage to the walls is seen at pressures of 40 mmHg and above. The incidence of stress failure is greatly increased at high lung volumes; and many of the ultrastructural changes are rapidly reversible when the capillary pressure is reduced. The principal forces acting on the capillary have been analysed. The strength of the thin part of the capillary wall can be attributed to the Type IV collagen in the extracellular matrix. The pulmonary vascular pressures of galloping Thoroughbreds reach very high levels. Mean pulmonary artery and left atrial pressures of up to 120 and 70 mmHg respectively have been directly measured with indwelling catheters. The reason for the high pulmonary vascular pressures is that these animals have been selectively bred over hundreds of years to run at great speeds over short distances and their maximal oxygen consumptions are very high. As a consequence, cardiac outputs are substantial, and the left ventricle needs very high filling pressures.(ABSTRACT TRUNCATED AT 250 WORDS)