First reported long-term two- and three-dimensional echocardiographic follow-up with histopathological analysis of a transcatheter pulmonary valve implantation in a pet dog.

Transcatheter pulmonary valve implantation (TPVI) is indicated for use in the management of failing pulmonary valves in humans. We report here the long-term follow-up of the first documented transcatheter pulmonary valve implanted in a client-owned dog. A one-year-old Beagle dog with severe congenital type A valvular pulmonic stenosis first underwent percutaneous balloon pulmonary valvuloplasty, leading two years later to severe pulmonary regurgitation. A TPVI using a Melody™ bioprosthetic valve was then successfully performed, with normalization of the right heart cavities. Repeated two- and three-dimensional transthoracic echocardiographic examinations combined with Doppler modes confirmed the appropriate position and function of the valve for four years. Mitral myxomatous valvular degeneration led to refractory left-sided congestive heart failure, and the dog was humanely euthanized. After postmortem examination, X-ray imaging and histopathological evaluation of the stent and the valve were performed. Ex-vivo imaging of the implanted valve using a Faxitron® Path radiography system and microscopic evaluation of the implanted stent and bioprosthetic leaflets did not show any relevant leaflet or stent alterations. This case provides a proof of concept in interventional veterinary cardiology, showing that TPVI can be performed in dogs with subsequent long-term maintaining normal pulmonary valve function.

The variety of phenotypes behind 'double outlet right ventricle': clinical and imaging presentations in four dogs and a cat.

This report describes five cases of double outlet right ventricle (DORV) in four dogs (aged 3-18 months, two males and two females) and a domestic shorthair cat (aged 6 months, female) who presented with various clinical signs including tachypnea (n = 5), exercise intolerance (n = 5), mucous cyanosis (n = 3), delayed growth (n = 2), and/or lethargy (n = 2). The represented canine breeds were poodle, Yorkshire terrier, Samoyed, and Shetland sheepdog. For all animals, echocardiography revealed marked aortic dextroposition with both arterial trunks totally arising from the right ventricle, associated with a ventricular septal defect and various other congenital abnormalities, including subvalvular aortic stenosis (n = 2), minor aortic insufficiency (n = 5), subvalvular pulmonic stenosis with pulmonary trunk hypoplasia (n = 1), patent ductus arteriosus (n = 1), minor mitral and/or tricuspid dysplasia (n = 3). Subsequent cardiac remodeling was characterized by marked right ventricular hypertrophy for all patients, associated with right ventricular and right atrial dilation for most of them (4/5). Two dogs died soon after the initial DORV diagnosis (i.e. after 24 h and two months). A surgical correction attempted for another dog confirmed the presence of a DORV associated with patent ductus arteriosus, but the animal died during the procedure from sudden cardiac arrest. The fourth dog underwent a contrast-enhanced retrospective electrocardiogram-gated multidetector computed tomography angiography under general anesthesia, which confirmed the conotruncal malformation. Despite episodes of exercise intolerance, this dog is still alive, at the age of 53 months, as is the cat at the age of 21 months.

Successful transcatheter pulmonary valve implantation in a dog: first clinical report.

Transcatheter pulmonary valve (TPV) implantation is a therapeutic approach approved by the United States Food and Drug Administration for human patients with failing pulmonary conduits in 2010 and for failing bioprosthetic surgical pulmonary valves in 2017. We report here the first successful transcatheter implantation of a stented valve in a pulmonary position in a dog with congenital pulmonary valve disease. A 3-year-old, 10.9 kg, client-owned Beagle dog was referred for a follow-up visit after a percutaneous balloon valvuloplasty performed 22 months before for treatment of a severe type A valvular pulmonary stenosis. The Doppler-derived peak pressure gradient was 348 mmHg before the procedure and 66 mmHg 24 h after. The dog was lethargic. Echocardiography revealed a mild pulmonary stenosis (pressure gradient-43 mmHg), severe pulmonary regurgitation, and secondary severe right ventricular and right atrial dilation. Worsening of right heart dilation was observed 2 months later despite medical therapy. A TPV implantation was performed using a prestented Melody bovine jugular bioprosthetic valve. The dog recovered uneventfully and was discharged 10 days after the procedure. Right heart dilation resolved within 15 days. The dog was doing well 7 months after valve implantation. This case demonstrates that TPV implantation with a stented valve is technically feasible in dogs with severe pulmonary valve disease. Stringent postoperative care, with particular attention to thrombosis and infectious endocarditis, and appropriate sizing and positioning of the valve stent are keys to the success of this procedure.

Successful transcatheter retrieval of embolized Amplatz Canine Duct Occluders in two dogs.

Transcatheter occlusion of patent ductus arteriosus (PDA) using an Amplatz® Canine Duct Occluder (ACDO) is routinely performed in dogs. Pulmonary embolization of the device is a rarely reported complication of this procedure. We report here the first two cases of successful transcatheter retrieval of an embolized ACDO. An 8-month-old, 21-kg, German shepherd (case 1) was referred for pulmonary edema secondary to a large PDA with left-to-right shunting. After medical stabilization, an emergency procedure for PDA closure was recommended. An 8-mm ACDO was deployed under general anesthesia. The device was released after confirming its stability with a gentle tug test but migrated into the pulmonary trunk. A 10-mm ACDO was subsequently successfully deployed and released. Vascular access was then obtained from the right jugular vein so that a vascular snare could be used to capture the ACDO waist and pull it back toward the right ventricle and then the right atrium. It was then removed through the jugular vein. The dog recovered uneventfully and was discharged after confirmation of complete ductal occlusion. The same complication occurred in a second case (case 2, asymptomatic 6-month-old, 7.9-kg, cocker spaniel), and a similar procedure was used to successfully retrieve the embolized device. Both dogs are still doing well 9 and 21 months, respectively, after the procedure. These cases illustrate that transcatheter retrieval of ACDO devices embolized in the pulmonary artery using vascular snares is technically feasible in the dog.

Comparative anatomy and angiography of the cardiac coronary venous system in four species: human, ovine, porcine, and canine.

INTRODUCTION: The coronary arterial system has been the subject of greater investigation than its venous system due to the importance of human coronary artery disease. With the advent of new percutaneous treatments, the anatomy of the coronary venous system has increasing relevancy. We compared the organization of the coronary venous circulation in three species commonly used in research and compared these to normal humans using both macroscopic anatomic and angiographic studies. ANIMALS: The anatomy of five explanted hearts from healthy dogs, pigs, and sheep were studied macroscopically, and 10 explanted hearts per animal species and 10 clinically normal human were examined by angiography. METHODS: Animal hearts were injected with latex and dissected macroscopically. The coronary venous system of humans was evaluated from clinical angiographic studies. In the animal hearts, a retrograde angiographic study was performed via a Foley catheter in the coronary sinus. RESULTS: The general organization of the coronary venous circulation was similar among humans, dogs, sheep, and pigs. Despite overall similarities to humans, animal hearts demonstrated the absence of the oblique vein of the left atrium and differences in position and organization of venous valves; venous diameters; number of tributary veins; and presence of an anastomosis between the left and right (human anterior and posterior) venous tree. The left azygos of the pig and sheep joined the coronary sinus. CONCLUSIONS: Anatomical differences must be considered when planning biomedical and veterinary studies incorporating cardiac veins. This study provides baseline data regarding structure and organization of the cardiac venous system.

Intracardiac echocardiography: use during transcatheter device closure of a patent ductus arteriosus in a dog.

Intracardiac echocardiography (ICE) is used in humans for percutaneous interventional procedures, such as transcatheter device closures. Intracardiac echocardiography provides high-resolution imaging of cardiac structures with two-dimensional, M-mode, Doppler, and also three-dimensional modalities. The present report describes application of ICE during transcatheter occlusion of patent ductus arteriosus using a canine ductal occluder in a dog for which transesophageal echocardiography could not provide an optimal acoustic window.

Hemodynamic exercise testing and hormonal status in a sheep model of congestive heart failure.

BACKGROUNDS: The aim of the present study was to investigate the hormonal status and hemodynamic performance of a sheep model of congestive heart failure at rest and during maximum exercise. METHODS: The current investigation was a prospective, experimental study and was carried out in an experimental laboratory. Animals were randomly assigned to a congestive heart failure or control group. In the congestive heart failure group, sequential intracoronary embolization with 90-micron polystyrene microspheres was performed until the left ventricle ejection fraction fell below 35%. All animals were chronically instrumented to continuously monitor the pulmonary artery flow, right ventricle pressure, and left ventricle pressure. Blood samples were collected for hormone assays (atrial natriuretic factor, endothelin, renin plasmatic activity, noradrenaline, and adrenaline), and hemodynamic variables, including expired gases, were measured at baseline and during exercise. RESULTS: Six animals in each group were studied. Compared to the controls, all of the studied plasma hormones were elevated in the model, and the most discriminative measurement was the atrial natriuretic factor (175±57 vs. 52±5 pg/mL, P<0.01). Exercise performance decreased by 30% to 40% in congestive heart failure animals compared to that of the controls (peak exercise VO2, 30±7 vs. 51±5 mL/min, P<0.01; anaerobic threshold, 21±7 vs. 37±2 mL/min, P<0.01; cardiac output, 201±33 vs. 350±45 mL/min.kg, P<0.01. CONCLUSION: Intracoronary embolization in sheep produces a stable and reproducible model that acceptably simulates congestive heart failure in humans. This model is suitable for the long-term assessment of therapeutic strategies and was designed to improve exercise capabilities.

Evaluation of the effect of autologous mesenchymal stem cell injection in a large-animal model of bilateral kidney ischaemia reperfusion injury.

OBJECTIVES: Adult mesenchymal stem cells (MSC) have been proven to be of benefit to the kidney in different experimental models of renal injuries. All studies have been performed in valuable rodent models, but the relevance of these results to large mammals and ultimately, to humans remains unknown. Therefore, the aim of this study was to investigate the effect of MSC transplantation in an alternative ovine large-animal model of bilateral kidney ischaemia reperfusion injury. MATERIAL AND METHODS: Sheep were divided into three groups: one sham-operated group and two groups submitted to renal bilateral ischaemia for 60 min. Animals with ischaemia reperfusion injury were treated with injection of autologous MSCs or with vehicle medium. RESULTS: The model sheep presented with renal histological manefestations that closely resembled lesions seen in patients. Transplanted MSCs were found in glomeruli but not in tubules and did not express glomerular cell markers (podocin, von Willebrand factor), but functional evaluation showed no beneficial effect of MSC infusion. Morphological and molecular analyses corroborated the functional results. MSCs did not repair kidney parenchyma and failed to modulate cell death and proliferation or cytokine release (tumour necrosis factor-alpha, vascular endothelial growth factor alpha (VEGF-alpha), Bcl-2, caspase). CONCLUSION: In this unique autologous large-animal model, MSCs did not exhibit reparative or paracrine protective properties.

Experimental study of urodynamic changes after ovariectomy in 10 dogs.

The urodynamic changes in 10 bitches up to 18 months after they had undergone ovariectomy were investigated. There were significant decreases in the maximum urethral closure pressure, the functional urethral length and the total integrated pressure profile 18 months after spaying, resulting in a caudal shift of the urethral profile, and a deterioration of urethral closure function. Each urethral pressure profile was divided into three equal sections; the mean cranial and middle integrated pressure decreased significantly and consistently over the 18-month observation period whereas the caudal integrated pressure increased.

Percutaneous implantation of an aortic valve prosthesis.

Recently, percutaneous aortic valve implantation has become an alternative technique to surgical valve replacement in patient at high risk for surgery. Our animal experimentation evaluated the technical feasibility of aortic valve replacement using a bovine pericardium valve sutured on a self-expandable stent in a sheep model. Precise implantation with satisfactory attachment on the adjacent tissues and absence of migration was obtain in 8 out of 14 animals. This study confirmed the feasibility of the endovascular implantation of a pericardium valve sutured on a self-expandable stent in a sheep model.

[Pacemaker implantation in dogs: results of the last 30 years]. / La pose de pacemaker chez le chien: le point sur les 30 dernières années.

Pacemaker implantation in veterinary practice is still not well known and remains uncommon. However, this technique is the only possible way to cure animals suffering from symptomatic bradycardia whose state does not improve with a medical treatment. In most cases, the use of pacemakers in veterinary medicine leads to the disappearance of the clinical and electrocardiographic signs. This retrospective study concerning the last 30 years draws up an evaluation of the improvements, advantages and drawbacks of this method. Moreover, this study allows the understanding of the evolution of pacemakers' use in veterinary cardiology.

[Exploration of a third degree atrioventricular block by standard echocardiography, tissue Doppler imaging, and treatment with a cardiac pacemaker in a German wire-haired pointer]. / Exploration d'un bloc atrio-ventriculaire du 3ème degré par échocardiographie conventionnelle, Doppler tissulaire, biopsie endomyocardique et traitement par pacemaker chez un Drathaar.

A nine-year-old intact male Drathaar was evaluated for syncope and extreme weakness, and was found to have a third degree atrioventricular (AV) block. As there were no biochemic, serologic, organic (thoracic radiographs, abdominal echography, standard and tissue Doppler echocardiographies) and histologic (interventricular septum biopsy) anomalies, the dog was treated with a permanently implanted cardiac pacemaker.

Successful surgical treatment of mitral valve stenosis in a dog.

OBJECTIVE: To report the successful surgical management (open mitral commissurotomy, OMC) of mitral stenosis (MS), incorporating heart-beating cardiopulmonary bypass (CPB), in a 1-year-old dog. STUDY DESIGN: Clinical case. ANIMALS: One-year-old Cairn Terrier with MS. MATERIALS AND METHODS: Diagnosis of MS was confirmed by means of 2-dimensional, continuous-wave and color-flow Doppler echocardiography. Surgery was performed through a left intercostal thoracotomy. CPB was initiated and the heart was kept beating. The fused commissures of the mitral valve were incised to free the cusps of the valve. RESULTS: Left intercostal thoracotomy allowed easy observation of the mitral orifice during heart-beating OMC. Persistent bleeding from the atriotomy site required a second surgical procedure after which the dog had an uneventful recovery. Echocardiography at 2 weeks and 1 year postoperatively indicated substantial improvement in left ventricular filling (pressure half-time=187 ms before surgery, 105 ms [2 weeks] and 110 ms [1 year] after surgery). Enlargement of the left atrium resolved; however, moderate mitral valve regurgitation was still present. CONCLUSIONS: MS can be successfully treated by OMC, facilitated by use of CPB. Substantial improvement in cardiac function was evident by ultrasound and Doppler examination postoperatively. CLINICAL RELEVANCE: OMC under heart-beating CPB should be considered for the treatment of MS in the dog.

[Percutaneous artificial heart valves: from animal experimentation to the first human implantation in a case of calcified aortic stenosis]. / Valves cardiaques artificielles percutanées: de l'expérimentation animale à la première implantation humaine dans un cas de rétrécissement aortique calcifié.

The development of artificial cardiac valves capable of being positioned by catheter has become an important subject for research, with the objective of treating valvular patients who are not operable or at very high surgical risk. We tested an artificial valve implantable by the percutaneous route, consisting of three leaflets of bovine pericardium sutured to the inside of a stainless steel stent, deployable by inflating a balloon. Following laboratory evaluation, this valve was implanted with success in animals, then for the first time in man, in a case of calcified aortic stenosis. The patient, a 57 year old male in cardiogenic shock, had associated multiple non-cardiac pathology and could not be operated on. Implantation was carried out by the trans-septal anterograde route, the only route available due to severe end stage arteritis. The artificial valve was deposited in the centre of the native aortic valve, without obstructing the coronaries nor reaching the mitral valve. The result was spectacular with instantaneous haemodynamic improvement and excellent valvular function confirmed by transoesophageal echocardiography every 15 days after implantation. Non-cardiac complications marred the progress, dominated by aggravation of pre-existing leg ischaemia, necessitating amputation for which the consequences were fatal at 4 months. This case demonstrates that implantation of a cardiac valve by the percutaneous route is possible in calcified aortic stenosis, and that it brings rapid clinical improvement. This technique could in future constitute an important alternative therapeutic approach for selected patients.

Development of an ultrasonically activated trocar system.

BACKGROUND: Although rare, visceral and vascular injuries related to the insertion of conventional laparoscopic trocars may have disastrous consequences. Most of these injuries are due to the high puncture force applied to the trocar. We present the results of an animal laboratory evaluation of a newly developed ultrasonically activated trocar. METHODS: A total of 40 punctures were made in four pigs with an average weight of 53 kg. An 11-mmHg pneumoperitoneum was created through a Veress needle. A 10-mm diameter trocar was inserted in the midline for a laparoscope. A series of five trocars were then inserted on each lateral wall under laparoscopic control. Twenty punctures were made with a conventional reusable 11-mm trocar (CT) whose tip was sharp and conical. Twenty punctures were made with an 11-mm ultrasonically activated trocar (UT), whose fequency was 23.5 KHz and amplitude 150 mm. The cutaneous incision was made large enough so that the skin did not interfere with the trocar insertion. The force applied to the trocar was measured with a push-pull gauge connected to a computer. The following data were recorded: maximal force applied to the trocar to obtain insertion of the tip through the abdominal wall, maximum abdominal pressure increase during trocar insertion, and time for abdominal penetration. RESULTS: The average time needed for trocar penetration was 12.8 s with CT and 4.5 s with UT (p < 0.001). The average maximal force was 6.8 kgF with CT and 0.4 kgF with UT (p < 0.001). The average abdominal pressure increase was 7.6 mmHg with CT and 0.8 mmHg with UT (p < 0.001). At 30 days, no necrosis was found. Pathological findings were similar in both groups. CONCLUSION: Ultrasonically activated trocars required less time and much less force to be inserted. This may be a breakthrough in the safety of trocar insertion.

Late oligodendrocyte progenitors coincide with the developmental window of vulnerability for human perinatal white matter injury.

Hypoxic-ischemic injury to the periventricular cerebral white matter [periventricular leukomalacia (PVL)] results in cerebral palsy and is the leading cause of brain injury in premature infants. The principal feature of PVL is a chronic disturbance of myelination and suggests that oligodendrocyte (OL) lineage progression is disrupted by ischemic injury. We determined the OL lineage stages at risk for injury during the developmental window of vulnerability for PVL (23-32 weeks, postconceptional age). In 26 normal control autopsy human brains, OL lineage progression was defined in parietal white matter, a region of predilection for PVL. Three successive OL stages, the late OL progenitor, the immature OL, and the mature OL, were characterized between 18 and 41 weeks with anti-NG2 proteoglycan, O4, O1, and anti-myelin basic protein (anti-MBP) antibodies. NG2+O4+ late OL progenitors were the predominant stage throughout the latter half of gestation. Between 18 and 27 weeks, O4+O1+ immature OLs were a minor population (9.9 +/- 2.1% of total OLs; n = 9). Between 28 and 41 weeks, an increase in immature OLs to 30.9 +/- 2.1% of total OLs (n = 9) was accompanied by a progressive increase in MBP+ myelin sheaths that were restricted to the periventricular white matter. The developmental window of high risk for PVL thus precedes the onset of myelination and identifies the late OL progenitor as the major potential target. Moreover, the decline in incidence of PVL at approximately 32 weeks coincides with the onset of myelination in the periventricular white matter and suggests that the risk for PVL is related to the presence of late OL progenitors in the periventricular white matter.

Minimization and management of wastes from biomedical research.

Several committees were established by the National Association of Physicians for the Environment to investigate and report on various topics at the National Leadership Conference on Biomedical Research and the Environment held at the 1--2 November 1999 at the National Institutes of Health in Bethesda, Maryland. This is the report of the Committee on Minimization and Management of Wastes from Biomedical Research. Biomedical research facilities contribute a small fraction of the total amount of wastes generated in the United States, and the rate of generation appears to be decreasing. Significant reductions in generation of hazardous, radioactive, and mixed wastes have recently been reported, even at facilities with rapidly expanding research programs. Changes in the focus of research, improvements in laboratory techniques, and greater emphasis on waste minimization (volume and toxicity reduction) explain the declining trend in generation. The potential for uncontrolled releases of wastes from biomedical research facilities and adverse impacts on the general environment from these wastes appears to be low. Wastes are subject to numerous regulatory requirements and are contained and managed in a manner protective of the environment. Most biohazardous agents, chemicals, and radionuclides that find significant use in research are not likely to be persistent, bioaccumulative, or toxic if they are released. Today, the primary motivations for the ongoing efforts by facilities to improve minimization and management of wastes are regulatory compliance and avoidance of the high disposal costs and liabilities associated with generation of regulated wastes. The committee concluded that there was no evidence suggesting that the anticipated increases in biomedical research will significantly increase generation of hazardous wastes or have adverse impacts on the general environment. This conclusion assumes the positive, countervailing trends of enhanced pollution prevention efforts by facilities and reductions in waste generation resulting from improvements in research methods will continue.

The Mom1AKR intestinal tumor resistance region consists of Pla2g2a and a locus distal to D4Mit64.

The Mom1 (Modifier of Min-1) region of distal chromosome 4 was identified during a screen for polymorphic modifiers of intestinal tumorigenesis in ApcMin/+ mice. Here, we demonstrate that the Mom1AKR allele consists of two genetic components. These include the secretory phospholipase Pla2g2a, whose candidacy as a Mom1 resistance modifier has now been tested with several transgenic lines. A second region, distal to Pla2g2a, has also been identified using fine structure recombinants. Pla2g2aAKR transgenic mice demonstrate a modest resistance to tumorigenesis in the small intestine and a very robust resistance in the large intestine. Moreover, the tumor resistance in the colon of Pla2g2aAKR animals is dosage-dependent, a finding that is consistent with our observation that Pla2g2a is expressed in goblet cells. By contrast, mice carrying the distal Mom1 modifier demonstrate a modest tumor resistance that is confined to the small intestine. Thus, the phenotypes of these two modifier loci are complementary, both in their quantitative and regional effects. The additive effects and tight linkage of these modifiers may have been necessary for the initial identification of the Mom1 region.