Repeated blood instillation into the airway of the horse does not cause pulmonary fibrosis.

REASONS FOR PERFORMING THE STUDY Exercise-induced pulmonary haemorrhage (EIPH) occurs in nearly all strenuously exercising horses. Recent studies have attempted to identify the role of free blood within the airspaces, in the lung fibrosis that develops within the lungs of EIPH horses. HYPOTHESIS Repeated exposure of the equine lung to autologous blood results in lung fibrosis similar to that observed in spontaneous EIPH. METHODS Forty ml of autologous blood from the jugular vein was instilled into preselected lung regions of 6 horses one, 2, 3, 4 or 5 times at 2 week intervals, with 40 ml of saline instilled into the contralateral lung serving as a control. The time interval between instillation of the first blood and euthanasia ranged from 2-10 weeks. The lung from each instillation site was harvested, and the histopathology was scored from each region based upon the presence and abundance of blood, haemosiderin and interstitial collagen. Consequently, at the time of euthanasia, the time since instillation of the first blood ranged from 2-10 weeks. RESULTS Beyond retention of blood, and the accumulation of haemosiderin, there was no visible increase in perivascular and interstitial collagen within the blood-instilled lung sites. In a small number of regions, there were foci of bronchiolitis obliterans organising pneumonia with collagen accumulation within these foci, but no collagen accumulation with the characteristic perivascular and interstitial histological distribution seen in EIPH. CONCLUSIONS Free blood within the airways of horses does not result in a qualitative increase in the amount of interstitial collagen within 8-10 weeks, and is therefore an unlikely aetiological factor in the lung collagen accumulation that occurs in EIPH. POTENTIAL RELEVANCE This study emphasises the efficiency of the equine lung in clearing blood from the airspaces. Further, it suggests that the aetiopathogenesis of EIPH is not driven by events within the airspace lumen, but rather emanates from within the vasculature and lung interstitium.

[1]  A. Nicholson,et al.  Increased local expression of coagulation factor X contributes to the fibrotic response in human and murine lung injury. , 2009, The Journal of clinical investigation.

[2]  L. Ruth-Sahd,et al.  Bronchiolitis obliterans organizing pneumonia. , 2007, Dimensions of critical care nursing : DCCN.

[3]  K. Williams,et al.  Regional Pulmonary Veno-occlusion: A Newly Identified Lesion of Equine Exercise-induced Pulmonary Hemorrhage , 2008, Veterinary pathology.

[4]  H. Al-Jahdali,et al.  Bronchiolitis obliterans organizing pneumonia: pathogenesis, clinical features, imaging and therapy review. , 2008, Annals of thoracic medicine.

[5]  Al-Jahdali Hamdan,et al.  Bronchiolitis obliterans organizing pneumonia: Pathogenesis, clinical features, imaging and therapy review , 2008, Annals of thoracic medicine.

[6]  N. Mackman,et al.  Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. , 2007, Arteriosclerosis, thrombosis, and vascular biology.

[7]  B. Uhal,et al.  Pulmonary response to airway instillation of autologous blood in horses. , 2007, Equine veterinary journal.

[8]  R. Slocombe,et al.  Alveolar fibrosis and changes in equine lung morphometry in response to intrapulmonary blood. , 2010, Equine veterinary journal. Supplement.

[9]  R. Chambers,et al.  Role of thrombin and its major cellular receptor, protease-activated receptor-1, in pulmonary fibrosis. , 2001, Biochemical Society transactions.

[10]  J. Cordier.  Organising pneumonia , 2000, Thorax.

[11]  M. Oikawa,et al.  Exercise-induced haemorrhagic lesions in the dorsocaudal extremities of the caudal lobes of the lungs of young thoroughbred horses. , 1999, Journal of comparative pathology.

[12]  N. Milman,et al.  Idiopathic pulmonary haemosiderosis. Epidemiology, pathogenic aspects and diagnosis. , 1998, Respiratory medicine.

[13]  M. Manohar,et al.  Pulmonary vascular pressures of exercising thoroughbred horses with and without endoscopic evidence of EIPH. , 1996, Journal of applied physiology.

[14]  S. Perry,et al.  "Alveolar septal structure in different species". , 1994, Journal of applied physiology.

[15]  M. Manohar,et al.  Pulmonary artery wedge pressure increases with high-intensity exercise in horses. , 1993, American journal of veterinary research.

[16]  M. Manohar,et al.  Pulmonary haemodynamics in the exercising horse and their relationship to exercise-induced pulmonary haemorrhage. , 1993, The British veterinary journal.

[17]  J. Pascoe,et al.  Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. IV. Changes in the bronchial circulation demonstrated by C.T. scanning and microradiography. , 1987, Equine veterinary journal.

[18]  W S Tyler,et al.  Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. V. Microscopic observations. , 1987, Equine veterinary journal.