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 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.     

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. 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.     

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. 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. 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.     

Aortic rupture and aorto‐pulmonary fistulation in the Friesian horse: Characterisation of the clinical and gross post mortem findings in 24 cases

Reasons for performing study: In horses, aortic sinus of Valsalva aneurysms or tears in the aortic root are well‐recognised conditions in breeding stallions, often leading to sudden death. A more uncommon form of aortic rupture, located proximal to the ligamentum arteriosum has been reported in 3 Friesian horses. Objectives: The purpose of this study was to phenotypically characterise aortic rupture and aorto‐pulmonary fistulation in Friesian horses in terms of clinical and post mortem data based on 24 cases. Methods: Friesian horses that were diagnosed with aortic rupture and aorto‐pulmonary fistulation over a period of 13 years (1997–2010) at the Department of Equine Sciences of Utrecht University (n = 15) and Wolvega Equine Hospital (n = 9), were included in this study. Case history, results of clinical examination and gross post mortem findings were screened and analysed. Results: Some cases were found dead without prior symptoms, but in several cases signs such as recurrent colic, peripheral oedema and sustained tachycardia were present for several weeks prior to cardiac failure. Clinical examination during hospitalisation revealed increased rectal temperature, peripheral oedema and increased jugular pulse with a bounding arterial pulse. In the majority of horses an aortic rupture of the aortic arch near the ligamentum arteriosum, concurrent with a circumferential cuff of perivascular haemorrhage and aorto‐pulmonary fistulation, was found at post mortem examination. Conclusions: Aorto‐pulmonary fistulation in conjunction with aortic rupture is more common in Friesians than previously estimated. In some cases findings demonstrate a progressive pathology rather than acute cardiac failure and sudden death. An appropriate approach is necessary during post mortem examination of the heart in order not to overlook the diagnosis. Potential relevance: Equine practitioners should realise that in Friesian horses presented with a history of recurrent false colic, coughing, sustained tachycardia and/or peripheral oedema, aortic rupture and aorto‐pulmonary fistulation should be included in the differential diagnosis.     

Sudden death in racing Thoroughbred horses: an international multicentre study of post mortem findings

Reasons for performing study: To improve the understanding of exercise related sudden death in Thoroughbred racehorses. Objectives: To describe the post mortem findings in cases of sudden death associated with exercise in 268 Thoroughbred racehorses. Methods: Gross and histological post mortem findings of 268 cases of sudden death were collated and reviewed. Cases originated from 6 racing jurisdictions around the world. Sudden death was defined as acute collapse and death in a closely observed and previously apparently healthy Thoroughbred racehorse, during, or within one hour after, exercise. Cause of death as determined by the attending pathologist was categorised as definitive, presumptive or unexplained and compared between the different populations. Cardiopulmonary lesions recorded at post mortem examination were compared between different populations. Results: Pathologists recorded a definitive cause of death in 53% (143/268) of cases. Major definitive causes of sudden death included cardiac failure, apparent pulmonary failure, pulmonary haemorrhage, haemorrhage associated with pelvic fractures or with idiopathic blood vessel rupture, and spinal cord injury. A presumptive cause of death was made in 25% (67/268) of cases and death remained unexplained in 22% (58/268) of cases. There were several statistically significant inter‐population differences in the cause of death and in reporting of cardiopulmonary lesions. Conclusions: Sudden death can be attributed to a variety of causes. Causes of sudden death and the lesions found in cases of exercise‐related sudden death are similar in different racing jurisdictions. However, the lesions are often not specific for the cause of death and determination of the cause of death is therefore affected by interpretation by the individual pathologist.     

The collateral ligaments of the distal interphalangeal joint: magnetic resonance imaging and post mortem observations in 25 lame and 12 control horses

Reasons for performing study: Magnetic resonance imaging (MRI) is used with increasing frequency to diagnose injuries of the collateral ligaments (CLs) of the distal interphalangeal (DIP) joint, but the results have not been verified by histology and the mechanism of injury is poorly understood. Hypothesis: Abnormal signal intensity and tissue contour represents change in tissue structure detected on histology. Objectives: To compare results in horses free from and those with chronic lameness and to describe possible progression of lesions. Methods: One or both feet of horses free from lameness (Group N: n = 12) and with foot‐related lameness (Group L: n = 25) were examined using MRI and by gross post mortem examination. The magnetic resonance (MR) images were graded. Sagittal sections from the proximal and distal aspect of each CL were examined histologically and each ligament assigned a score. Scintigraphic images from lame horses were also evaluated. Results: In Group N, 25 CLs were graded normal on both MR images and histology, 2 CLs were grade 1 on MR images, but were histologically normal, and 2 CLs had MR abnormalities verified histologically. However, 2 CLs appeared normal on MR images but were histologically abnormal. In Group L, 18 CLs were deemed normal on both MR images and histology, and 54 CLs had MR abnormalities verified histologically. However, 13 CLs appeared normal on MR images but were graded abnormal histologically. Lesions appeared to be degenerative, characterised by extensive fibrocartilaginous metaplasia and development of multiple, intercommunicating fissures within the degenerate collagen in severe lesions. There was an association between increased radiopharmaceutical uptake and a higher histological score. Conclusions: High‐field MRI is reasonably reliable for detection of lesions of the CLs of the DIP joint, but may underestimate their prevalence. Clinical relevance: Collateral ligament injury appears to be a primary degenerative process, which may explain the poor response to conservative treatment and a need for promotion of regeneration.     

Lesions of the deep digital flexor tendon in the digit: A correlative MRI and post mortem study in control and lame horses

Reasons for performing study: Lameness associated with lesions of the deep digital flexor tendon (DDFT) in the digit is now recognised as an important cause of lameness, but there is currently limited information about the pathological nature of the lesions. Objectives: To compare: signal intensity changes on magnetic resonance images with histopathology; and histopathological changes in the DDFT from horses with no history of foot‐related lameness (Group C) and horses with lesions of the DDFT confirmed using magnetic resonance imaging (MRI) (Group D). Methods: Transverse sections of the DDFT were harvested from 3 sites in all horses: 1) immediately proximal to the navicular bursa (E1); 2) at the level of the navicular bone (E2); and 3) close to the tendon's insertion (E3). If lesions were identified at E1 or had been identified further proximally using MRI, additional sections were obtained until, in most cases, the proximal limit of the lesion was identified. All DDFTs were graded histopathologically using predefined criteria. The MR images were reviewed to determine the location and sequences in which increased signal intensity was seen. Results: No haemorrhage or inflammatory cell infiltration was seen in any horse. At level E 1 , septal thickening, ghosting of blood vessels and blood vessel occlusion were common in Group D, but were not seen in Group C. Less commonly, there was core necrosis, only seen in Group D. At level E 2 , septal and vascular changes were most obvious in Group D. Core necrosis, dorsal splitting, crevicing and fibrillation were seen only in Group D. Septal and vascular changes were present in both Groups C and D at level E 3 , but fibrocartilaginous metaplasia, splitting, crevicing and fibrillation, or core necrosis or fibroplasia were seen only in Group D. Core lesions in Group D often extended proximal to E 1 , and ranged in length from 0.5–13 cm. Core necrosis was generally associated with increased signal intensity in fat suppressed images. Conclusions: Lesions of the DDFT in the digit appear to be primarily degenerative, and may be a sequel to vascular compromise. Increased signal intensity on fat suppressed MR images is not necessarily associated with frank fluid or evidence of inflammation, but may reflect major matrix changes in the tendon. Potential relevance: Further information about the causes of these lesions is required to develop preventative strategies.     

Effects of age, sex, and post mortem interval on intestinal lengths of horses during development

Lengths of small intestine, caecum, ascending colon and descending colon were measured in intestinal tracts from 103 foetuses, foals and adult horses. Intestinal tracts from 21 of the horses were measured at varying intervals after death. Total intestinal length increased markedly from mid-gestation to one year of age, then showed little increment up to 35 years. Small intestinal length increased most rapidly in the first month of life. Caecal length increased most rapidly from one to six months and length of ascending colon increased most rapidly between one week and one year. Descending colon length increased gradually after birth. Periods of rapid increase in length of various intestinal segments and alterations in the percentage of total intestinal length were associated with periods of rapid body growth and changes in dietary composition. Sex and post mortem interval did not affect intestinal length significantly.     

Analysis of post mortem aqueous humour chemistry in the horse, with particular reference to urea nitrogen and creatinine

The concentrations of several post mortem aqueous humour chemical constituents were compared with ante mortem serum chemical values in the horse. Urea nitrogen and creatinine values in post mortem aqueous humour were good predictors of ante mortem serum values. Aqueous humour urea nitrogen increased only slightly and creatinine did not change significantly for up to 24 h after death. Formulae were derived for calculating estimated ante mortem serum urea nitrogen and creatinine from aqueous humour values obtained after death. These results from normal horses identify analytes that are accurate predictors of ante mortem serum values. Determination of post mortem aqueous humour urea nitrogen of creatinine may assist in interpretation of the functional significance of equivocal histological lesions in the kidney.     

Studies on seminal vesiculitis in the bull. I. Semen examination methods and post mortem findings.

During the ten-year period 1968--1978, about 1500 bulls were examined yearly for possible inflammatory conditions in the genital organs. Thirty-one cases of vesiculitis with or without accompanying ampullitis, and one case of isolated, one-sided ampullitis were recorded. Twenty-three cases (72%) were found in young bulls aged 18 months or less. Diagnosis was based on clinical examination of the pelvic genital organs or examination of semen, or in most cases on both. In 17 (53%) of the cases the diagnosis was initially established in the laboratory. Of the laboratory methods, the most reliable was the demonstration of pus cells in Giemsa stained semen smears. Twenty-five cases (24 + one case of ampullitis) were examined post mortem. Fifteen showed interstitial vesiculitis, Group I (Galloway, 1964). The milder 'catarrhal' type (Group II) was found in 9 cases. The 'potential pathogenic' bacteria isolated from the inflamed vesicular glands were: Corynebact. pyogenes, 8 cases (33%), E. coli, 2 cases; Ureaplasma, 2 cases (one in combination with Corynebact. pyogenes). Four of the bulls were newly imported (stress ?), IN THREE BULLS THERE WAS A HISTORY OF NAVEL INFECTION DURING CALFHOOD, AND IN ONE CASE THE BULL HAD LARGE NUMBERS OF VESICAL CALCULI (ABOUT 300 G). In ten of the sets of pelvic organs examined (40%) rare congenital defects or anatomical variations were found in or around the colliculus seminalis (Blom, 1979b).     

Residue profile of phenylbutazone in the rabbit. A comparative evaluation by tissue kinetics prior to and post mortem

The disposition kinetics and residue levels of phenylbutazone (8 mg/kg) were studied in rabbit. The result suggested that distribution of phenylbutazone can be described by a two open compartment. Elimination half-time is short (2 h) and estimation of residue levels in muscle, liver and kidney did not differ significantly before and after bleeding. These results suggest that biopsy can be used to determine the phenylbutazone concentration in tissues of larger species. Moreover, using a pharmacokinetic approach based on drug concentrations in plasma, it appears that the mean resting quantity in the peripheral compartment was very close to the experimental data for the muscle.     

Penile and preputial tumours in the horse: a retrospective study of 114 affected horses

REASONS FOR PERFORMING STUDY: Preputial and penile tumours are more common in horses than in other domestic animals, but no large surveys of male horses with tumours of the external genitalia are available. OBJECTIVE: To present a retrospective analysis of male horses with neoplasms of the external genitalia. METHODS: The penile and preputial tumours of 114 horses were evaluated. Data recorded included age, gelding or stallion and breed; type and site of lesion; involvement of regional lymph nodes; histopathology (including grading of squamous cell carcinoma); and results of radiographic examination of the thorax. RESULTS: Mean age of horses was 19.5 years with no apparent breed predilection. Common presenting clinical signs were irregularities (e.g. the presence of a mass and/or ulceration) on the integument of the penis and prepuce, and purulent or sanguineous discharge from preputial orifice. Squamous cell carcinoma (SCC) was the most prevalent neoplasm followed by papillomas and melanomas. A basal cell carcinoma, neurofibrosarcoma, adenocarcinoma or fibrosarcoma were each found on single horses. Squamous cell carcinomas with poor differentiation had a higher tendency to metastasise than did more differentiated tumours. CONCLUSIONS: Squamous cell carcinoma is the most common urogenital tumour of the male horse and occurs primarily in old horses. Horses with poorly differentiated SCCs tend to have a higher incidence of regional metastases. Pathology of lymph nodes, even when not palpably enlarged, is a valuable diagnostic exercise. Radiology of the thorax to detect lung metastases is of little value.