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. 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. 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 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 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.     

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.     

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).     

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.     

Colic in the horse. A clinical and clinical chemical study of 42 cases

42 horses were examined. The physical signs with relation to circulatory insufficiency and the abdominal disease were registered following a two-phased examination procedure. Great prognostic value was found in the degree of circulatory insufficiency judged by pulse rate and character, filling of the jugular vein, skin temperature, colour of mucous membranes, capillary refill time, sweating, depression, skin turgor and degree of enophthalmus. In making a causal diagnosis the abdomen was examined for shape, tenderness, peristaltic sounds, gastric dilation by siphoning, abnormal rectal findings and macroscopic changes in peritoneal fluid. Greatest diagnostic difficulties were encountered in cases of intestinal atonia, acute enteritis and torsion of the colon. In selected (severe) cases laboratory tests were obtained. Blood samples were examined for packed cell volume, hemoglobin, red and white blood cell counts, differential white blood cell count, blood gases and acid-base status, lactate, serum total protein and albumin, plasma sodium, potassium, chloride, calcium, magnesium, inorganic phosphorus, glucose, creatinine, BUN, total bilirubin, ASAT, CK, BASP and GGT. Peritoneal fluid was examined for red blood and white cell counts, total protein, specific gravity, pH and lactate, and enzymes as in blood. Laboratory results generally confirmed the clinical signs of shock, and packed cell volume and blood lactate were regarded to be of greatest prognostic interest. Although the performed laboratory information, macroscopic evaluation was thought to reveal sufficient information in most cases. It was concluded that supervening shock is of decisive importance in severe forms of colic, and that a careful and repeated evaluation of the circulatory insufficiency often provides one with a tentative prognosis although the final diagnosis is not obtained. In spite of therapy fatal outcome was found in all seriously shocked horses.     

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.     

Toxicity of halogenated oxyquinolines in dogs. A clinical study. II. History, symptoms, laboratory findings, therapy, and follow-up

Intoxication due to short-term oxyquinoline therapy was studied in 100 dogs, which had been so treated because of diarrhoea (except in 2 cases). The latter condition was in itself mild and uncomplicated. The main symptoms of intoxication were listlessness or excitation and nervousness, aggressiveness, tremor, convulsions, and salivation. Clinical examination revealed myocarditis and liver injury. Mortality, i.e. the sum of spontaneous deaths and euthanasia, amounted to 30 %. The treatment considered to be most important was sedation and anticonvulsant measures. It was further essential to correct the dehydration, which was often present. A follow-up investigation showed that approx. 1/3 of the dogs which had recovered from the acute intoxication developed recurrent convulsions within the next 3 years.     

Studies on dioctyl sodium sulfosuccinate toxicity: clinical, gross and microscopic pathology in the horse and guinea pig.

Concentrations of dioctyl sodium sulfosuccinate (DSS) ranging from three to five times the recommended dosage produced severe diarrhea, rapid dehydration and death in seven horses and 66 guinea pigs when administered experimentally per os. Clinicopathological findings indicated hemoconcentration in both horses and guinea pigs. There was a leucocytosis in the guinea pigs given the highest dosages. In all cases the principal finding at necropsy was extreme fluid distention of the intestinal tract. There was histopathological evidence of epithelial denudation and vascular stasis. The LD50 in the guinea pig was approximately 0.65 g DSS/kg body weight.