Association between circulating angiotensin-converting enzyme and exercise-induced pulmonary haemorrhage in Thoroughbred racehorses

doi:10.1016/j.rvsc.2011.10.011

Research in Veterinary Science

Volume 93, Issue 2, October 2012, Pages 993-994

https://doi.org/10.1016/j.rvsc.2011.10.011 Get rights and content

Abstract

Exercise-induced pulmonary haemorrhage has an impact on racehorse performance. Although endoscopic diagnosis (with or without the aid of bronchoalveolar lavage) is considered to be the standard diagnostic method for this condition, the use of biomarkers that could aid in quantifying risk and severity of the condition would represent an advance in equine sport medicine. This preliminary research investigated the use of angiotensin-converting enzyme (ACE) activity in plasma of racehorses and demonstrated that ACE activity is increased in horses with higher degrees of haemorrhage and is a promising biomarker for EIPH in racehorses.

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Cited by (3)

Pharmacokinetic/pharmacodynamic modeling of benazepril and benazeprilat after administration of intravenous and oral doses of benazepril in healthy horses
2017, Research in Veterinary Science
Citation Excerpt :
Furthermore, heart valve regurgitation is associated with an activation of the renin angiotensin aldosterone axis (Gehlen et al., 2002). In a preliminary report, Costa et al. (2012) also found greater serum ACE activity in horses with exercise-induced pulmonary hemorrhage; therefore, it might be a promising marker of this condition. However, this together with the vasodilatory effects might lead to fraudulent administration of these pro-drugs despite the fact that they are a prohibited (benazepril) or controlled (enalapril) medication according to the FEI (Fédération Equestre Internationalle).
Pharmacokinetic and pharmacodynamic (PK/PD) properties of the angiotensin-converting enzyme inhibitor (ACEI) benazeprilat have not been evaluated in horses. This study was designed to establish PK profiles for benazepril and benazeprilat after intravenous (IV) and oral (PO) administration of benazepril using a PK/PD model. This study also aims to determine the effects of benazeprilat on serum angiotensin converting enzyme (ACE), selecting the most appropriate dose that suppresses ACE activity. Six healthy horses in a crossover design received IV benazepril at 0.50 mg/kg and PO at doses 0 (placebo), 0.25, 0.50 and 1.00 mg/kg. Blood pressures (BP) were measured and blood samples were obtained at different times in order to measure serum drug concentrations and serum ACE activity, using liquid chromatography-tandem mass spectrometry (LC-MS/MS) and spectrophotometry, respectively. Systemic bioavailability of benazeprilat after PO benazepril was 3–4%. Maximum ACE inhibitions from baseline were 99.63% (IV benazepril), 6.77% (placebo) and 78.91%, 85.74% and 89.51% (for the three PO benazepril doses). Significant differences in BP were not found. Although oral availability was low, benazeprilat 1.00 mg/kg, reached sufficient serum concentrations to induce long lasting serum ACE inhibitions (between 88 and 50%) for the first 48 h. Additional research on benazepril administration in equine patients is indicated.
Bronchoalveolar lavage fluid in Standardbred racehorses: Influence of unilateral/bilateral profiles and cut-off values on lower airway disease diagnosis
2014, Veterinary Journal
Citation Excerpt :
Firstly described by the presence of post-exertional epistaxis in severe cases (Cook, 1974), different diagnostic methods for EIPH have been used. These include post-exercise tracheobronchoscopic evaluation of blood (Pascoe et al., 1981; MacNamara et al., 1990; Lapointe et al., 1994; Birks et al., 2002; Hinchcliff et al., 2005a; Costa et al., 2012), or detection/quantification of erythrocytes (Langsetmo et al., 2000; Epp et al., 2006; McKane and Slocombe, 2010) and/or haemosiderophages (Fogarty and Buckley, 1991; McKane et al., 1993; Langsetmo et al., 2000; Doucet and Viel, 2002; Newton and Wood, 2002; Sanchez et al., 2005) in respiratory fluids. Recommendations still differ regarding the method of choice for diagnosing EIPH, and no methods reported so far allow for an accurate evaluation of the severity of bleeding (Derksen et al., 2011).
The aim of this study was to determine whether the lung side being sampled would significantly influence bronchoalveolar lavage (BAL) cytological profiles and subsequent diagnosis in Standardbred racehorses. One hundred and thirty-eight French Trotters in active training and racing were included in a prospective observational study. BAL was performed using videoendoscopy in both right and left lungs during summer meetings in 2011 (64 horses) and 2012 (74 horses). Cytological data performed 24 h later from right and left lungs were compared and specifically used to classify horses as affected with exercise-induced pulmonary haemorrhage (EIPH), inflammatory airway disease (IAD), or were ‘controls’. For IAD, cytological definition was based on two different cut off values.
Neutrophil percentages, haemosiderophage percentages and the haemosiderophage/macrophage (H/M) ratios were significantly higher in the right compared to the left lung. Measures of intra-class correlation coefficients revealed a fair agreement between left and right lungs for percentages of mast cells, eosinophils, and for the H/M ratio, and a moderate agreement for neutrophil percentages. Fair to moderate agreements were observed between left and right lungs for the diagnosis of IAD and/or EIPH based on kappa coefficients. When sampling one lung only, the risk of incorrectly classifying a horse as a ‘control’ increased with the use of the restraint cut-off values for IAD. As BAL from one lung is not representative of the other lung in the same horse, both lungs should be sampled for a better assessment of lung cellularity and for a precise diagnosis of lower airway diseases.
Exercise-induced pulmonary haemorrhage in horses -review
2013, Acta Veterinaria Brno

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Association between circulating angiotensin-converting enzyme and exercise-induced pulmonary haemorrhage in Thoroughbred racehorses

Abstract

Clinics in Chest Medicine

Trends in Pharmacological Sciences

Distribution of plasma angiotensin I-converting enzyme levels in healthy men: relationship to environmental and hormonal parameters

Journal of Laboratory and Clinical Medicine

Normoxic lung ischemia/reperfusion accelerates shedding of angiotensin converting enzyme from the pulmonary endothelium

American Journal of Respiratory Critical Care Medicine

Evaluation of race distance, track surface, and season of the year on exercise-induced pulmonary haemorrhage in flat racing Thoroughbreds in Brazil

Equine Veterinary Journal Supplement

Pulmonary capillary endothelial metabolic dysfunction: severity in pulmonary arterial hypertension related to connective tissue disease versus idiopathic pulmonary arterial hypertension

Arthritis and Rheumatism

Pulmonary response to airway instillation of autologous blood in horses

Equine Veterinary Journal

Advances in mechanisms of repair and remodelling in acute lung injury

Intensive Care Medicine

A sensitive fluorimetric assay for serum angiotensin-converting enzyme

American Journal of Clinical Pathology