Stress failure of pulmonary capillaries in racehorses with exercise-induced pulmonary hemorrhage.

Bleeding into the lungs in thoroughbreds is extremely common; there is evidence that it occurs in essentially all horses in training. However, the mechanism is unknown. We tested the hypothesis that exercise-induced pulmonary hemorrhage (EIPH) is caused by stress failure of pulmonary capillaries. Three thoroughbreds with known EIPH were galloped on a treadmill, and after the horses were killed with intravenous barbiturate the lungs were removed, inflated, and fixed for electron microscopy. Ultrastructural studies showed evidence of stress failure of pulmonary capillaries, including disruptions of the capillary endothelial and alveolar epithelial layers, extensive collections of red blood cells in the alveolar wall interstitium, proteinaceous fluid and red blood cells in the alveolar spaces, interstitial edema, and fluid-filled protrusions of the endothelium into the capillary lumen. The appearances were consistent with the ultrastructural changes we have previously described in rabbit lungs at high capillary transmural pressures. Actual breaks in the endothelium and epithelium were rather difficult to find, and they were frequently associated with platelets and leukocytes that appeared to be plugging the breaks. The paucity of breaks was ascribed to their reversibility when the pressure was lowered and to the fact that 60-70 min elapsed between the gallop and the beginning of lung fixation. Capillary wall stress was calculated from pulmonary vascular pressures measured in a companion study (Jones et al. FASEB J. 6: A2020, 1992) and from measurements of the thickness of the blood-gas barrier and the radius of curvature of the capillaries. The value was as high as 8 x 10(5) dyn/cm2 (8 x 10(4) N/m2), which exceeds the breaking stress of most soft tissues. We conclude that stress failure of pulmonary capillaries is the mechanism of EIPH.

Hepatic sarcocystosis in a horse.

Hepatic sarcocystosis was diagnosed in a horse in association with refractory bacterial osteomyelitis and plasma cell tumor of the maxilla and hepatic salmonellosis. Gross lesions included pleural, pericardial, and peritoneal effusions, hepatomegaly, gastric ulceration, colonic edema, and proliferative tissues filling 2 maxillary dental alveoli. Histologically, liver was characterized by severe suppurative, necrotizing, periportal hepatitis, and severe periacinar necrosis. Hepatocytes frequently contained protozoal schizonts in various stages of development. In mature schizonts, merozoites were often arranged radially around a central residual body, consistent with asexual division by endopolygeny. Ultrastructural features of merozoites included an apical conoid and polar ring, anterior micronemes, central nuclei, and absence of rhoptries. These protozoa did not react to antisera raised against Neospora caninum, Sarcocystis neurona, Toxoplasma gondii, or Hammondia hammondi. The microscopic and ultrastructural characteristics and immunoreactivity of this organism are consistent with a Sarcocystis sp. other than S. neurona. This is the first report of Sarcocystis-associated hepatitis in a horse. The life cycle of this organism and source of infection are unknown.

The effect of doxapram-induced hyperventilation on respiratory mechanics in horses.

To investigate the influence of increased respiratory frequency on respiratory mechanics in the horse, measurements were made in two groups of seven tracheostomized horses before and after the administration of doxapram. The horses in group I had normal base line values for respiratory mechanics, whereas the horses in group II had significantly lower values of dynamic compliance (Cdyn), higher respiratory resistance (R), and a higher total change in pleural pressure (delta P). The administration of 0.3 mg kg-1 doxapram intravenously resulted in a significant increase in respiratory frequency (fR), R, delta P, tidal volume (VT), and peak to peak respiratory flow (V), and a decrease in Cdyn in both groups of horses. The group II horses had significantly greater increases in R and delta P than the horses in group I.

Iridium-192 interstitial brachytherapy for equine periocular tumours: treatment results and prognostic factors in 115 horses.

One hundred and fifteen horses with periocular tumours were treated with iridium-192 interstitial brachytherapy. Tumours included squamous cell carcinomas (n = 52) and sarcoids (n = 63). All horses were scheduled to receive 60 Gy (minimal tumour dose) given at a low dose rate (0.034 +/- 0.010 Gy/h). The mean and median follow-up times to last contact or death were 24 and 16 months, respectively. Chronic radiation reactions included palpebral fibrosis (10.4%), cataract (7.8%), keratitis and corneal ulceration (6.9%). Cosmetic changes included permanent epilation (21.7%) and hair dyspigmentation (78.3%). The one year progression-free survival (PFS) rates for sarcoids and carcinomas were 86.6% and 81.8% and the 5 year PFS rates were 74.0% and 63.5%, respectively. The horse age and sex, histopathological type, anatomical subsite and classification (WHO T1-3) were included in the analysis of prognostic factors. The only significant prognostic factor that independently affected PFS time was the WHO T-classification (P = 0.009, relative risk = 0.85). When compared to horses with T1 lesions, horses with T2 and T3 lesions had 1.8-fold and 3.4-fold increased risks, respectively, for tumour recurrence (relative excess risk). The one year PFS rates for T1, T2 and T3 lesions were 95.2%, 89.5% and 66.2%, respectively. The 5 year PFS rates were 72.2%, 74.0% and 53.1%, respectively. The results of this study indicate that irradiation is an effective treatment option for horses with T1-2 lesions and should be part of a combined treatment modality for horses with T3 lesions.

Body position and direction preferences in horses during road transport.

It has been hypothesised that horses have a preference for facing backward in a trailer during road transport in order to minimise shifts of body weight due to accelerations and decelerations. To determine if horses have preferences for facing forward vs. backward in a horse trailer, the authors analysed the percentages of time horses spent in different body positions and directions while standing in a moving or parked horse trailer. Body positions and directions of 8 Thoroughbred geldings were videotaped while horses were transported singly and untethered in a 4-horse stock trailer over a 32 km route of country roads; or while the same horses were untethered in the same trailer stationary in a parking lot. Analysis of the logit-transformed percentages of time horses spent in different directions indicated that they spent significantly more time facing backward when the trailer was in motion, but not when it was parked. Several horses displayed strong individual preferences for the directions they faced during road transport.

Autologous blood instillation alters respiratory mechanics in horses.

To investigate physiological consequences of autologous blood instillation in the lungs of healthy horses, respiratory mechanics and bronchial response to histamine were studied in 8 Thoroughbreds before and after introducing autologous blood (n = 5) and sterile saline solution (n = 3) into their lungs. Blood instillation resulted in a decrease in dynamic compliance (Cdyn) and increased respiratory resistance (R). Bronchial sensitivity and reactivity were unchanged after blood introduction. There were no significant changes in pulmonary mechanics or bronchial response after saline instillation.

Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. I. Clinical profile of horses.

Detailed physical and clinical examinations were performed on 26 Thoroughbred racehorses which were used subsequently in a series of studies to investigate the contribution of the pulmonary and bronchial arterial circulations to the pathophysiology of exercise-induced pulmonary haemorrhage (EIPH). Twenty-five of the horses had been retired from race training in Hong Kong during the 1984-85 season, all but four raced that season; one horse had been retired the previous season. The average number of races for the group that season was 4.1 +/- 2 with an average distance of 1502 +/- 216 metres, mean racing speed 15.5 +/- 0.5 metres/sec. Time from last race to necropsy was 177 +/- 155 days, range 12 to 572 days. All but one horse had a known history of either EIPH or epistaxis. Time from last recorded incident of expistaxis (17 horses) to necropsy was 156 +/- 141 days, range 12 to 513 days, with a longer interval since last recorded endoscopic observation of EIPH. Focal abnormal lung sounds were detected in the dorsocaudal lungfields on auscultation during rebreathing in three horses and six had tracheobronchial cytology consistent with previous episodes of pulmonary haemorrhage (haemosiderophages). No other characteristics which might have allowed separation of this group of horses from other Thoroughbred horses recently in race training were identified.

Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. II. Gross lung pathology.

Gross post mortem examinations were performed on the lungs of 26 Thoroughbred horses of known exercise-induced pulmonary haemorrhage (EIPH) status. The most consistent finding was a variable degree of bilaterally symmetrical, dark discolouration of the dorsocaudal regions of the caudal lung lobes. In more severely affected lungs, the stained areas extended cranially along the dorsal surfaces of the lungs, and in some cases affected approximately one third of the lung surface. Discoloured areas of lung were denser than normal, collapsed less readily, often contained trapped air and were slow to inflate. The subpleural bronchial arteries were more prominent in the discoloured regions. Pleural adhesions were noted in two horses but were not related to the discoloured lung regions. It was concluded that the discoloured lesions have a complex pathogenesis and were related directly to previous bouts of EIPH. Associated with them were signs indicating probable partial small airway obstruction, decreased tissue compliance and direct involvement of the bronchial arterial circulation.

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.

The purpose of this study was to use radiographic contrast techniques and special imaging methods to identify and high-light bronchial arterial involvement in lung lesions associated with exercise-induced pulmonary haemorrhage (EIPH) in horses. The lungs from four horses with histories of EIPH were prepared for computerised tomographic scanning and microradiography by perfusing the broncho-oesophageal artery with a mixture of red latex and either barium or iodine contrast materials while the pulmonary supply received only blue latex. Computerised tomographic scan slices of the prepared inflated lungs were obtained from the caudal tip of the lung to the hilus. Microradiography of selected lung slices was also performed on a Faxitron. Diffuse areas of increased density, with preferential bronchial arterial supply noted on the computerised tomographic scans were confirmed by microradiography. Dense focal and diffuse plexuses of markedly hypertrophied and highly branched bronchial arterial networks were identified, centred around certain small airways. The vascular supply to these plexuses was recruited predominantly from neighbouring bronchial vessels, and in some cases, from the enlarged vasa vasorum of pulmonary arteries sending anastomoses to the affected areas. The authors conclude that bronchial vascular lesions in EIPH cases are the likely origin of haemorrhage; that small airway disease is the probable initiating stimulus for bronchial vascular proliferation in these lesions; and that the morphology and nature of the neovascular tissue in these lesions provides the conditions leading to haemorrhage in the lungs of horses with EIPH.

Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. III. Subgross findings in lungs subjected to latex perfusions of the bronchial and pulmonary arteries.

Latex was injected under pressure into bronchial and pulmonary arteries of the inflated lungs of Thoroughbreds and transverse sections taken to calculate the area of lesions resulting from exercise-induced pulmonary haemorrhage. Extensive areas of dense brown haemosiderin varying from 0 to 45 per cent of total lung volume were identified, predominantly in the dorsocaudal lungfields. Bronchial arterial proliferation appeared to have replaced the pulmonary supply in affected areas of the lung. Closely associated with the staining and bronchial arterialisation, there was widespread small airway disease. The most severely affected bronchioles contained thick gelatinous or mucous exudate or mucoid plugs and had grossly thickened walls. These lesions suggest that the source of haemorrhage in exercise-induced pulmonary haemorrhage is from alveolar capillaries anomalously supplied by the bronchial arterial circulation through the development of pathological shunts. Small airway disease is suggested as being of major importance in the pathogenesis of the disease and may have led to the initial proliferation of the bronchial circulation.

Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. V. Microscopic observations.

Lungs from 19 Thoroughbred racehorses with a history of exercise-induced pulmonary haemorrhage (EIPH) were studied using several forms of microscopy. Light microscopy of paraffin sections revealed three lesions in the caudodorsal region of the lungs from each horse. These correspond with the location of blue to brown stains seen at necropsy. These lesions include sequelae of bronchiolitis, hemosiderophages and increased connective tissue. Much of each of the lungs appeared normal, especially the more cranial or ventral portions. Foci of eosinophil infiltration were found in seven of the 19 lungs examined. With two exceptions, these eosinophilic foci had a different distribution to the three lesions. In areas of severe bronchiolar changes and fibrosis, vascular lesions typical of hypertension were found occasionally. Transmission electron microscopy was used to confirm cell types seen by light microscopy and to examine arterioles for changes characteristic of neovascularisation. Areas of enlarged airspaces from the vascular injected right lungs were examined by scanning electron microscopy. The balance of fibrosis and destruction varied in these areas, but none were as extensive as those seen in chronic obstructive pulmonary disease. The authors hypothesise that bronchiolitis and related neovascularisation are essential components of the aetiology of EIPH.

Exercise-induced pulmonary haemorrhage in the horses: results of a detailed clinical, post mortem and imaging study. VII. Ventilation/perfusion scintigraphy in horses with EIPH.

Detailed post mortem examination of the lungs of horses with exercise-induced pulmonary haemorrhage (EIPH) has demonstrated significant small airway disease and intense bronchial arterial proliferation in the dorsocaudal lungfields. The purpose of this study was to investigate ventilation and perfusion distribution in the lungs of a similar group of horses to compare changes in the live animal with the previously reported post mortem findings. Thoracic radiography and ventilation/perfusion (V/Q) scintigraphy were performed on five racing Thoroughbreds with recent histories of EIPH. Parametric images of V/Q ratios for left and right lungfields were also generated from the scan images. In all horses, ventilation and perfusion deficits were demonstrated in the dorsocaudal areas of the lung corresponding closely to the observed radiographic lesions. In particular, the perfusion images and V/Q ratio displays indicated that, in affected areas of lung, pulmonary arterial perfusion was the more seriously impaired. This finding appears to confirm the post mortem evidence of reduced pulmonary arterial perfusion and bronchial arterial dominance in these areas. Ventilation deficits in the same areas also confirmed the likelihood of partial airway obstruction consistent with the small airway disease noted in previous post mortem observations. These results suggest that the vascular and airway lesions demonstrated in detailed post mortems of horses with EIPH are also functionally important in affected horses, even at rest. As a consequence of the apparent persistent, insidious and progressive nature of the lesions associated with EIPH there are serious long term implications for management of the condition.

Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. VIII. Conclusions and implications.

This paper reviews a series of clinical, post mortem and imaging studies on exercise-induced pulmonary haemorrhage (EIPH) performed on 26 Thoroughbred racehorses. Post mortem techniques included routine gross, subgross and histological examination; coloured latex perfusions of pulmonary and bronchial circulations; and microradiography and computerised tomography scans of lungs with contrast injected vasculature. The major lesions were multiple, separate and coalescing foci of moderately proliferative small airway disease accompanied by intense neovascularisation of the bronchial circulation. As a result of bronchial artery angiogenesis, the systemic circulation dominated the vascular supply of the air exchange structures in affected areas, producing an apparent left to right shunt. Extensive areas of sequestered haemosiderophages indicated previous haemorrhage from vessels apparently supplied by the bronchial arteries. Diffuse and focal parenchymal destruction and connective tissue reactions in affected areas were considered to be secondary to localised haemorrhage and macrophage-induced damage. The aetiology of EIPH was not determined, but the multifocal, small airway-centred lesions indicated that low grade bronchiolitis, possibly of viral origin, was a factor. Gravitational effects also appear to contribute to dorsal distribution of the lesions. The mild focal and subclinical lesions confined to secondary lobules are thought to evolve into the serious lung pathology observed in EIPH cases through the effects of localised hypoxia induced by maximal exercise and partial airway obstruction. Once initiated, a vicious cycle of increasing inflammatory damage and further local bleeding is set in motion.

Radiographic and microscopic correlation of diffuse interstitial and bronchointerstitial pulmonary patterns in the caudodorsal lung of adult thoroughbred horses in race training.

Complete thoracic radiographic examinations were performed on 7 horses ranging in age from 24 to 60 months, followed by in-situ lung fixation. Radiographs were examined by 3 radiologists for the presence, degree and distribution of generalised pulmonary patterns within a region of interest in the caudodorsal lung. Pulmonary tissue was obtained from 12 sites within a designated volume of interest in the caudodorsal lung, corresponding to the area of interest evaluated radiographically, and examined for the presence, character and severity of microscopic lesions. Radiographic findings within the volume of interest consisted of mild to moderate bronchial, bronchointerstitial, or interstitial pulmonary patterns. Interstitial and bronchointerstitial radiographic findings were related to severity of peribronchiolar mononuclear cell infiltrates, the degree of bronchiolar mucosal plication, and alveolar capillary and peribronchial blood vessel erythrocyte content. The severity of the interstitial radiographic pattern was inversely associated with the perceived diagnostic quality of the radiographic examinations. There was no evidence of spatial variation in the severity of the microscopic changes examined in this limited pulmonary region. Inter-rater reliability between radiologists was good in the assessment of diagnostic quality of the radiographic examinations but poor in assessing severity of the primary generalised pulmonary patterns within the radiographic region of interest.

Endoscopic anatomy and map of the equine bronchial tree.

To develop a bronchoscopic map of the equine respiratory tree, the major airways of the lungs of 6 healthy Thoroughbred horses were systematically explored with a flexible fibreoptic endoscope through a tracheostomy while the horses were sedated in stocks. With the carina as the reference point, measurements were made of distances to the branches of the major airways using markers on the shaft of the endoscope. All branches were explored until the narrowing of their diameters prevented further advancement of the endoscope. Positions of origins of branches from the parent bronchus were recorded in relation to a 12 h clock. Branching patterns of the right and left lungs were similar. Seventeen branches of the principal and caudal lobar bronchi of the left lung, and 18 branches of the principal and caudal lobar bronchi of the right lung were identified. Mean explorable distances from the carina to the ends of the right and left caudal lobar bronchi were 34.0 +/- 3.5 (sd) and 34.5 +/- 3.0 cm, respectively. Generally, smaller horses had shorter explorable bronchial lengths. Branching patterns of the parent bronchi were fairly consistent among horses, particularly the branches closest to the carina. After endoscopy and euthanasia, the lungs were removed, and dried with pressurised air flowing through them for 7-10 days. Attempts to explore the airways of the dried lungs endoscopically were relatively unsuccessful, because airways were much smaller in the dried lungs, and many of the branches were distorted when compared with their antemortem appearances. However, having a dried lung specimen as a reference during the bronchoscopic procedure was useful for maintaining orientation in the lungs. Radiographs were used to estimate the location of the origin and destination of each airway branch in relation to the nearest intercostal space. This makes the airway map useful when lesions identified radiographically are to be lavaged.

Radiographic, high detail radiographic, microangiographic and histological findings of the distal portion of the tarsus in weanling, young and adult horses.

Clinical radiographic (LM and D35L-P1MO views), high detail radiographic, microangiographic and histological findings of the distal portion of the tarsus of 16 horses (five weanling, four young and six adult), without known clinical histories, were evaluated to determine the sensitivity of clinical radiographs for the detection of abnormalities in the distal tarsus and the prevalence of abnormalities in this population. Clinical radiographic and high detail radiographic abnormalities were observed in at least 30 per cent of the tarsi examined. Statistical agreement between observations from clinical radiographs and corresponding post mortem high detail radiographs was not good for subchondral bone plate irregularities and joint margin changes. Three patterns of sclerosis of the medullary spongiosa were visualised on high detail radiographs: thickening of the subchondral bone plate was seen commonly in the weanling group, whereas arching and bridging patterns were more prevalent in the young and adult groups. Bone production on the dorsal cortex of the central and third tarsal bones did not increase with age. Abnormalities in vascular perfusion and articular cartilage histology were observed in association with subchondral bone plate irregularities and focal regions of osteopenia observed on high detail radiographs.

Osteomyelitis of the axial border of the proximal sesamoid bones in seven horses.

Destructive lesions of the axial region of the proximal sesamoid bones were identified by radiography in eight fetlocks and seven lame adult horses. Lameness ranged from 2 to 5 (mean 4; scale 1 to 5) at the time of examination, with a duration of 10 days to two years (mean 5.6 months). Destructive lesions involved both proximal sesamoid bones when examined radiographically and were situated primarily at the level of the mid-body and apical region of the axial borders. Some lesions were cystic, whereas others eroded the axial border more diffusely. Scintigraphy revealed markedly increased activity within the proximal sesamoid bones of the clinically lame limb of four of the five horses examined. In four horses, post mortem computed tomography revealed axial border bone destruction and cavitary lesions within cancellous bone of affected proximal sesamoid bones. Lesions seen by computed tomography were larger than those identified on radiographic examination. Cavitary lesions not seen radiographically were identified in the proximal sesamoid bones of two clinically unaffected fetlocks examined for comparison in two of the seven horses. Evidence of acute, subacute or chronic/reparative osteomyelitis of the axial region of the proximal sesamoid bones was seen in the 10 fetlocks identified as abnormal from radiography or computed tomography. Also, three horses had septic synovitis of the flexor sheath of the clinically affected limb; of these, two had septic arthritis of the fetlock joint.

Exercise-induced pulmonary haemorrhage in the horse: results of a detailed clinical, post mortem and imaging study. VI. Radiological/pathological correlations.

This study was initiated to determine if the extent and intensity of lung lesions associated with exercise-induced pulmonary haemorrhage (EIPH) in horses could be predicted from thoracic radiographs. Sets of thoracic radiographs from 24 horses with varied histories of EIPH were subjectively coded for radiographic quality, and perceived extent and intensity of diffuse interstitial opacity by three radiologists who had no knowledge of the corresponding autopsy results. Codes assigned from radiographs for the chosen parameters were compared with coded estimates of lung surface staining assigned at post mortem and volume measurements of haemosiderin deposits and bronchial arterial neovascularisation recorded from lung slices in separate studies. The non-parametric Spearman rank correlation test was used to test for statistical significance. All radiographically coded estimates of lesion severity were positively correlated with post mortem measurements of actual lesion involvement, but only the correlation between coded estimates of lesion opacity versus haemosiderin deposits and bronchial artery neovascularisation were statistically significant (P less than 0.05). Correlations between radiographic codes for lesion extent versus haemosiderin deposits and neovascularisation were just beyond the level of significance (P greater than 0.05 less than 0.1). These findings indicate that there are graded, radiographically discernible increases in interstitial opacity related to actual lesion severity. However, under the conditions of the study, accurate prediction of lung pathology in individual cases based on radiographic criteria was precluded by the wide variance of the coded values. The authors believe that with good radiographic technique and careful criteria selection, satisfactory prediction of lesion severity in EIPH cases could be achieved.

Resolution of a left ureteral stone using electrohydraulic lithotripsy in a thoroughbred colt.

A 3-year-old Thoroughbred colt was presented for evaluation of azotemia and anorexia. Physical examination revealed a ureterolith in the left ureter, approximately 10 cm from the bladder, which was thought to obstruct urine flow by approximately 90% when viewed cystoscopically. Ultrasonographic examination of both kidneys revealed indistinct corticomedullary junctions, and the right kidney was more hyperechoic. A percutaneous biopsy of the right kidney revealed chronic interstitial nephritis with marked interstitial medullary fibrosis. Medical therapy consisting of IV fluids, sodium chloride PO, and ammonium chloride PO was initiated. Ureteroscopic electrohydraulic lithotripsy via a perineal urethrostomy was used to successfully remove the stone. Klebsiella oxytoca, which responded to oral enrofloxacin therapy, was cultured from the urine after surgery. Azotemia resolved and the horse resumed training.

Topographic distribution of pulmonary ventilation and perfusion in the horse.

The regional distribution of ventilation to perfusion ratios (VA/Q) in the lungs of 8 healthy standing Thoroughbred geldings (4.4 +/- 1.5 years, 465.7 +/- 46.6 kg) was studied, using steady-state inhalation and IV infusion of the radioactive gas krypton-81m. The VA/Q was uniformly distributed within a vertical lung strip centered over the 9th rib on the right side. Ventilation per unit of alveolar volume (V/VA) assessed from the clearance of inhaled radioactive gas in 5 horses increased from 0.49 +/- 0.13 (arbitrary units) in nondependent lung zones to 1.45 +/- 0.16 in dependent lung zones. Seemingly, a vertical gradient of pulmonary ventilation exists in the horse that is matched by a similar gradient of perfusion.