Pulmonary passage of canine adipose tissue-derived mesenchymal stem cells through intravenous transplantation in mouse model.

IMPORTANCE: The intravenous administration of adipose tissue-derived mesenchymal stem cells (AdMSCs) in veterinary medicine is an attractive treatment option. On the other hand, it can result in severe complications, including pulmonary thromboembolism (PTE). OBJECTIVE: The present study assessed the occurrence of PTE after the intravenous infusion of canine AdMSCs (cAdMSCs) into experimental animals. METHODS: Five-week-old male BALB/c hairless mice were categorized into groups labeled A to G. In the control group (A), fluorescently stained 2 × 106 cAdMSCs were diluted in 200 µL of suspension and injected into the tail vein as a single bolus. The remaining groups included the following: group B with 5 × 106 cells, group C with 3 × 106 cells, group D with 1 × 106 cells, group E with 1 × 106 cells injected twice with a one-day interval, group F with 2 × 106 cells in 100 µL of suspension, and group G with 2 × 106 cells in 300 µL of suspension. RESULTS: Group D achieved a 100% survival rate, while none of the subjects in groups B and C survived (p = 0.002). Blood tests revealed a tendency for the D-dimer levels to increase as the cell dose increased (p = 0.006). The platelet count was higher in the low cell concentration groups and lower in the high cell concentration groups (p = 0.028). A histological examination revealed PTE in most deceased subjects (96.30%). CONCLUSIONS AND RELEVANCE: PTE was verified, and various variables were identified as potential contributing factors, including the cell dose, injection frequency, and suspension volume.

Obstructive cardiac myxosarcoma of the right ventricular outflow tract with pulmonary embolism and concurrent right atrial hemangiosarcoma in a dog.

A 13-year-old spayed female rottweiler crossbreed dog was presented with an 8-day history of abnormal gait and collapse associated with excitement or physical activity. A cardiac gallop was noticed on thoracic auscultation, and a 1st-degree atrioventricular block and sinus tachycardia were noted on an electrocardiogram. Echocardiography identified a hypoechoic, irregularly marginated luminal mass in the right ventricle at the level of the pulmonic valves. Postmortem gross examination confirmed the presence of a soft, polypoid, and botryoid mass (9 × 3 × 3 cm) with a smooth and glistening surface attached to the endocardium of the right ventricular outflow tract and extending to the pulmonary artery. The histological findings were consistent with the diagnosis of myxosarcoma with pulmonary embolism. In addition, the dog in this report had a right atrial hemangiosarcoma and a cutaneous hemangioma unrelated to her clinical findings. Key clinical message: Cardiac myxosarcomas are very rare neoplasms in dogs and concomitant primary heart tumors of different histogenesis are even rarer in dogs. To the authors' knowledge, this is the first report of coexistent myxosarcoma and hemangiosarcoma in the heart of a dog. Cardiac myxosarcomas should be considered in the differential diagnosis of intracavitary heart masses associated with signs of cardiac obstruction and failure.

Myxosarcome cardiaque obstructif de la voie d'éjection du ventricule droit avec embolie pulmonaire et hémangiosarcome auriculaire droit concomitant chez un chien. Une chienne croisée rottweiler stérilisée âgée de 13 ans a été présentée avec une histoire de démarche anormale et d'effondrement associés à l'excitation ou à l'activité physique depuis 8 jours. Un galop cardiaque a été noté à l'auscultation thoracique, un bloc auriculo-ventriculaire du 1er degré et une tachycardie sinusale ont été notés à l'électrocardiogramme. L'échocardiographie a permis d'identifier une masse luminale hypoéchogène et irrégulièrement marginalisée dans le ventricule droit au niveau des valvules pulmonaires. L'examen macroscopique post-mortem a confirmé la présence d'une masse molle, polypoïde et botryoïde (9 × 3 × 3 cm) avec une surface lisse et brillante attachée à l'endocarde de la voie d'éjection du ventricule droit et s'étendant jusqu'à l'artère pulmonaire. Les résultats histologiques concordaient avec le diagnostic de myxosarcome avec embolie pulmonaire. De plus, la chienne dans ce rapport présentait un hémangiosarcome auriculaire droit et un hémangiome cutané sans rapport avec ses résultats cliniques.Message clinique clé :Les myxosarcomes cardiaques sont des néoplasmes très rares chez le chien et les tumeurs cardiaques primaires concomitantes d'histogenèse différente sont encore plus rares chez le chien. À la connaissance des auteurs, il s'agit du premier rapport de myxosarcome et d'hémangiosarcome coexistant dans le cœur d'un chien. Les myxosarcomes cardiaques doivent être pris en compte dans le diagnostic différentiel des masses cardiaques intracavitaires associées à des signes d'obstruction et d'insuffisance cardiaque.(Traduit par Dr Serge Messier).

HEPATIC TO PULMONARY EMBOLISM OF ABSORBABLE GELATIN HEMOSTATIC SPONGE IN TWO EGYPTIAN FRUIT BATS (ROUSETTUS AEGYPTIACUS).

In a study on iron regulation, liver biopsies were collected at two time points from 34 adult Egyptian fruit bats (Rousettus aegyptiacus). An absorbable gelatin hemostatic sponge (GS) was inserted at biopsy sites for local hemostasis in 16 bats. In the subsequent 10 yr, 12 of these bats died or were euthanized, and 11 were examined histologically; in 2 bats, intravascular GS was identified in the lungs and in 1 bat, unabsorbed GS was also identified at the hepatic biopsy site. The remaining hepatic GS was associated with local abscessation and intralesional bacteria and fungi and remained at the hepatic biopsy site for a prolonged period after placement (1 yr). The findings of local hepatic abscessation and GS embolization in the lungs of these two bats highlights a potential adverse effect related to its use in zoologic species.

The wedge sign: A possible lung ultrasound sign for pulmonary thromboembolism.

OBJECTIVE: To describe the finding of the lung ultrasound (LUS) "wedge sign" in dogs with presumptive pulmonary thromboembolism (PTE). CASE SERIES SUMMARY: This case series describes 2 dogs with predisposing risk factors of (1) right transvenous pacemaker terminating in its right ventricle, severe protein-losing nephropathy, and glucocorticoid therapy, and (2) caval syndrome, each having the LUS "wedge sign" in upper lung regions, a sign consistent with pulmonary infarction and peripheral PTE. NEW OR UNIQUE INFORMATION PROVIDED: Historically, the diagnosis of canine PTE has been made through supportive findings because the gold standard test, computed tomography pulmonary angiography (CTPA), poses limitations. The use of LUS has shown promise in people for detecting PTE, with the advantages of availability, being radiation- and contrast medium-sparing, rapid (<90 s), point-of-care, real-time information. Our cases suggest a possible new first-line approach for suspecting canine PTE by using LUS and the finding of the "wedge sign" in nongravity-dependent caudodorsal and perihilar lung regions.

Non-thrombotic pulmonary embolism of brain, liver, or bone marrow tissues associated with traumatic injuries in free-ranging neotropical primates.

From 2016 to 2019, Southeastern Brazil faced an outbreak of yellow fever (YF) affecting both humans and New World primates (NWP). The outbreak was associated with a marked increase in traumatic lesions in NWP in the affected regions. Non-thrombotic pulmonary embolization (NTPE) can be a consequence of massive traumatic events, and it is rarely reported in human and veterinary medicine. Here, we describe NTPE of the brain, liver, and bone marrow in free-ranging NWP, highlighting the epidemiological aspects of these findings and the lesions associated with this condition, including data on traumatic injuries in wild NWP populations during the course of a recent YF outbreak. A total of 1078 NWP were necropsied from January 2017 to July 2019. Gross traumatic injuries were observed in 444 marmosets (44.3%), 10 howler monkeys (23.2%), 9 capuchins (31.0%), 1 titi-monkey (50.0%), and 1 golden lion tamarin (33.3%). NTPE was observed in 10 animals, including 9 marmosets (2.0%) and 1 howler monkey (10.0%). NTPE was identified in the lung and comprised hepatic tissue in 1 case, brain tissue in 1 case, and bone marrow tissue in 8 cases. Although uncommon, it is important to consider NTPE with pulmonary vascular occlusion during the critical care of traumatized NWP. In addition, this study highlights the importance of conservational strategies and environmental education focusing on One Health, not only to protect these free-ranging NWP populations but also to maintain the efficacy of epidemiological surveillance programs.

Cutaneous Vasculopathy and Pulmonary Thromboembolism in an Unstable Diabetic Cat.

A 6-year-old, male-neutered, domestic short-haired cat was referred for further management of a 3-month history of uncontrolled diabetes mellitus. The cat visited the hospital on 3 occasions during a 3-week time period. Hyperglycemia was documented at all visits. The cat initially presented with evidence of hypovolemia, cranial abdominal pain, and dehydration. Moderate hyperglycemia, mild ketonemia, and severe hypokalemia were documented. A 3 × 2 cm skin lesion with associated alopecia and erythema was first noticed at a routine follow-up examination (visit 2) 1 week later. A diagnosis of diabetic ketoacidosis was made 6 days later. The previously identified skin lesion now measured 6 × 2.5 cm. Two episodes of respiratory distress were identified at this visit, with no evidence of cardiac or pulmonary pathology. The cat developed a moderate anemia (packed cell volume 16 %, total solids 7.9 g/dL) on the fifth day of hospitalization. Fluid therapy, electrolyte supplementation, regular insulin, anti-emetic, and analgesia medications were administered during visits 1 and 3. Due to development of anemia, suspected pulmonary thromboembolism events and progression of skin lesions, euthanasia was elected. A diagnosis of cutaneous vasculopathy with secondary ischemic necrosis was made postmortem and pulmonary thromboembolism was confirmed. To the authors' knowledge, this is the first report of cutaneous vasculopathy and pulmonary thromboembolism in a cat with confirmed diabetes mellitus, warranting further research to assess if hypercoagulability is common in this patient population, as routine thromboprophylaxis and anticoagulation may be potentially indicated.

Lipids of lung and lung fat emboli of the toothed whales (Odontoceti).

Lipids are biomolecules present in all living organisms that, apart from their physiological functions, can be involved in different pathologies. One of these pathologies is fat embolism, which has been described histologically in the lung of cetaceans in association with ship strikes and with gas and fat embolic syndrome. To assess pathological lung lipid composition, previous knowledge of healthy lung tissue lipid composition is essential; however, these studies are extremely scarce in cetaceans. In the present study we aimed first, to characterize the lipids ordinarily present in the lung tissue of seven cetacean species; and second, to better understand the etiopathogenesis of fat embolism by comparing the lipid composition of lungs positive for fat emboli, and those negative for emboli in Physeter macrocephalus and Ziphius cavirostris (two species in which fat emboli have been described). Results showed that lipid content and lipid classes did not differ among species or diving profiles. In contrast, fatty acid composition was significantly different between species, with C16:0 and C18:1ω9 explaining most of the differences. This baseline knowledge of healthy lung tissue lipid composition will be extremely useful in future studies assessing lung pathologies involving lipids. Concerning fat embolism, non-significant differences could be established between lipid content, lipid classes, and fatty acid composition. However, an unidentified peak was only found in the chromatogram for the two struck whales and merits further investigation.

Comparison of Three Histological Techniques for Fat Emboli Detection in Lung Cetacean's Tissue.

Fat embolism is the mechanical blockage of blood vessels by circulating fat particles. It is frequently related to traumas involving soft tissues and fat-containing bones. Different techniques have been used for decades to demonstrate histologically fat emboli, being the extremely toxic post-fixation with osmium tetroxide one of the most used techniques in the last decades. In the present study, the osmium tetroxide technique was compared qualitatively and quantitatively, for the first time, with chromic acid and Oil Red O frozen techniques  for histological fat emboli detection in the lungs of eight sperm whales that died due to ship strikes. This was also the first time that chromic acid technique was tested in cetaceans. Results showed that the three techniques were valuable for the histological detection of fat embolism in cetaceans, even when tissues presented advanced autolysis and had been stored in formaldehyde for years. Although quantitative differences could not be established, the Oil Red O frozen technique showed the lowest quality for fat emboli staining. On the contrary, the chromic acid technique was proven to be a good alternative to osmium tetroxide due to its slightly lower toxicity, its equivalent or even superior capacity of fat emboli detection, and its significantly lower economic cost.

Brain Tissue Pulmonary Embolism Due to Severe Blunt Force Head Trauma in a Dog.

A 9-week-old male puppy was submitted for necropsy examination after a reported history of developing acute melaena and vomiting blood before death. Grossly, the animal had multiple skull fractures, mostly affecting the occipital region and cranial floor, associated with extensive regions of subcutaneous, periosteal and subdural haemorrhages, as well as petechial haemorrhages within the right middle and caudal lung lobes. Histopathology of the brain revealed multifocal acute meningeal and parenchymal haemorrhage with laceration of the cerebellar folia. In the lung, multiple small- and medium-calibre branches of pulmonary arteries were occluded by aggregates of brain tissue, which exhibited weak immunoreactivity for glial fibrillary acidic protein and strong labelling for neuron specific enolase on immunohistochemistry. These findings were consistent with brain tissue pulmonary embolism, an infrequent phenomenon following severe head trauma. To the best of the authors' knowledge, this is the first reported case of canine brain tissue pulmonary embolism.

Multimodality imaging of an azygous continuation of the caudal vena cava in a dog with pulmonary thromboembolic disease.

A 5-year-old spayed female English Bulldog was evaluated for acute anorexia, lethargy, respiratory distress, and syncope. Contrast-enhanced computed tomography revealed the vascular malformation of azygous continuation of the caudal vena cava with extensive thrombus formation and pulmonary arterial thromboembolic disease. The patient was hospitalized for supportive treatment and was prescribed long-term clopidogrel therapy. The patient survived to discharge and at last follow-up remained clinically stable. While this vascular malformation has been reported in canines, to the authors' knowledge, this is the first reported case of pulmonary thromboembolic disease in a canine concurrent with this condition.

Change in right ventricular function in an American cocker spaniel with acute pulmonary thromboembolism.

A 12-year-old neutered female American cocker spaniel weighing 9.9 kg was presented for evaluation with a 2-day history of dyspnea and anorexia. Echocardiography revealed severe pulmonary hypertension (estimated systolic pulmonary arterial pressure, 93.4 mmHg) with right heart enlargement, pulmonary arterial dilation, and right ventricular dysfunction. The dilation of left heart and congenital cardiac shunt were not observed. Pulmonary thromboembolism (PTE) was confirmed by computed tomographic angiography. After treatment with antiplatelet and anticoagulant, the clinical sign and the echocardiographic abnormality of right heart were improved. These echocardiographic findings are not specific for PTE, but it can be useful as a rule-in test for PTE when other causes of pulmonary hypertension are excluded and a monitor of therapeutic efficacy.

Multidetector computed tomographic pulmonary angiography in a cat with fatal heartworm disease.

A 17-month-old neutered male domestic shorthair cat was referred for a computed tomographic (CT) study of the thorax due to respiratory distress. Multidetector CT angiography showed a multifocal interstitial ground glass opacity, tortuous and blunted pulmonary arteries consistent with thromboembolism with perivascular lung infiltration and hypoventilation in multiple lung lobes. A blood antigen test was positive for Dirofilaria immitis. The cat's clinical condition rapidly declined and the owners elected euthanasia. The histopathologic examination confirmed heartworm disease with parasitic pulmonary thromboembolism.

Diagnosis of canine pulmonary thromboembolism by computed tomography and mathematical modelling using haemostatic and inflammatory variables.

There is no evidence-based diagnostic approach for diagnosis of pulmonary thromboembolism (PTE) in dogs. Many dogs with diseases that predispose to thrombosis are hypercoagulable when assessed with thromboelastography (TEG), but no direct link has been established. The aims of this study were: (1) to investigate if diseased dogs with PTE, diagnosed by computed tomography pulmonary angiography (CTPA), had evidence of hypercoagulability by TEG; (2) to characterise haemostatic and inflammatory changes in dogs with PTE; (3) to construct models for prediction of PTE based on combinations of haemostatic and inflammatory variables; and (4) to evaluate the performance of D-dimer measurement for prediction of PTE. Twenty-five dogs were included in this prospective observational study (PTE: n=6; non-PTE: n=19). Clot strength G values did not differ between the PTE and non-PTE groups in tissue factor (TF) or kaolin-activated TEG analyses. Haemostatic and inflammatory variables did not differ between the two groups. Linear discriminant analysis generated a model for prediction of PTE with a sensitivity and specificity of 100% when TF results were used as TEG data, and a model with sensitivity of 83% and specificity of 100% when kaolin results were used as TEG data. Receiver operating characteristic analysis of D-dimer levels showed that a value of >0.3mg/L yielded a sensitivity of 100% and a specificity of 71.4%. In conclusion, the study supports CTPA as method for diagnosing canine PTE, but shows that TEG alone cannot identify dogs with PTE. Models for prediction of PTE were generated, but require further validation.

Pulmonary vasculature in dogs assessed by three-dimensional fractal analysis and chemometrics.

Fractal analysis of canine pulmonary vessels could allow quantification of their space-filling properties. Aims of this prospective, analytical, cross-sectional study were to describe methods for reconstructing three dimensional pulmonary arterial vascular trees from computed tomographic pulmonary angiogram, applying fractal analyses of these vascular trees in dogs with and without diseases that are known to predispose to thromboembolism, and testing the hypothesis that diseased dogs would have a different fractal dimension than healthy dogs. A total of 34 dogs were sampled. Based on computed tomographic pulmonary angiograms findings, dogs were divided in three groups: diseased with pulmonary thromboembolism (n = 7), diseased but without pulmonary thromboembolism (n = 21), and healthy (n = 6). An observer who was aware of group status created three-dimensional pulmonary artery vascular trees for each dog using a semiautomated segmentation technique. Vascular three-dimensional reconstructions were then evaluated using fractal analysis. Fractal dimensions were analyzed, by group, using analysis of variance and principal component analysis. Fractal dimensions were significantly different among the three groups taken together (P = 0.001), but not between the diseased dogs alone (P = 0.203). The principal component analysis showed a tendency of separation between healthy control and diseased groups, but not between groups of dogs with and without pulmonary thromboembolism. Findings indicated that computed tomographic pulmonary angiogram images can be used to reconstruct three-dimensional pulmonary arterial vascular trees in dogs and that fractal analysis of these three-dimensional vascular trees is a feasible method for quantifying the spatial relationships of pulmonary arteries. These methods could be applied in further research studies on pulmonary and vascular diseases in dogs.

Pulmonary embolization of immature Fascioloides magna causing fatal hemothorax confirmed by molecular technique in a heifer in the United States.

The current report describes the use of a molecular technique to identify immature Fascioloides magna An 18-month-old Brangus heifer was found dead in the field without any prior clinical signs. The cause of death was exsanguination into the thoracic cavity associated with pulmonary embolization and infection by immature Fascioloides magna resulting in 2 large foci of pulmonary necrosis and focal arteriolar and lung rupture. The liver had a few random migratory tracts with typical iron and porphyrin fluke exhaust, but no identified fluke larvae. A single immature fluke was found in the lungs, and species level identification as F. magna was confirmed by DNA sequence analysis of the ribosomal internal transcribed spacer regions (ITS1 region, 5.8S rRNA gene, and ITS2) and of partial 28S rRNA gene sequence. This is one of only a few pulmonary fascioloidiasis cases associated with hemothorax in the veterinary literature.

Unusual caudal vena cava thrombosis in a cow, secondary to Trueperella (Arcanobacterium) pyogenes infection / Rara trombose da veia cava caudal em bovino, secundária à infecção por Trueperella (Arcanobacterium) pyogenes

The caudal vena cava thrombosis, or pulmonary thromboembolism, in cattle is correlated with lactic acidosis, caused by diets rich in grains and highly fermentable, associated or not to septic situations, used in feedlots of beef or high-producing dairy cattle. This paper reports an unusual caudal vena cava thrombosis in a cow, secondary to Trueperella (Arcanobacterium) pyogenes infection, resulting in reduced milk production, anorexia, pale mucous membranes, ruminal atony, sternal decubitus and autoauscultation position. The heart was enlarged at necropsy, presence of clots distributed along the thoracic cavity, adherence between lung and pleura, abscesses, emphysema, petechiae, suffusions and ecchymosis in lungs, thickening of the caudal vena cava wall, hepatomegaly with chronic passive congestion ("nutmeg" aspect), and rumenitis. In lab, the actinomycete Trueperella (Arcanobacterium) pyogenes was isolated from liver and lung samples, probably resulting through dissemination of the bacteria of the rumen content, what reaffirms the opportunistic behavior of this actinomycete.(AU)

A síndrome da veia cava caudal ou tromboembolismo pulmonar bovino está relacionada à acidose láctica causada por dietas ricas em grãos e altamente fermentáveis, associados ou não a quadros sépticos, usadas em confinamentos de bovinos de corte ou para vacas leiteiras de alta produção. O presente artigo reporta caso raro de trombose da veia cava caudal em uma vaca, secundária a infecção por Trueperella (Arcanobacterium) pyogenes, apresentando reduzida produção de leite, anorexia, palidez de mucosas, atonia ruminal, decúbito esternal e posição de autoauscultação. À necrópsia observou-se coração aumentado de tamanho, coágulos distribuídos por toda cavidade torácica, aderência entre os pulmões e pleura, abscessos, enfisema, petéquias, sufusões, equimoses nos pulmões, espessamento da parede da veia cava caudal com trombo, hepatomegalia com congestão passiva crônica (aspecto de "noz moscada"), e ruminite. Em laboratório isolou-se o actinomiceto Trueperella (Arcanobacterium) pyogenes a partir de amostras de fígado e pulmão, provavelmente resultando da disseminação da bactéria proveniente do conteúdo ruminal, e reafirma o comportamento oportunista deste actinomiceto.(AU)