Early morphological changes in cardiac mitochondria after subcutaneous administration of trastuzumab in rabbits: possible prevention with oral selenium supplementation.

Trastuzumab-mediated cardiotoxicity poses a significant challenge in the treatment of human epidermal growth factor receptor 2-positive breast cancer. To understand the underlying mechanisms, we conducted experiments to determine ultrastructural changes of rabbit cardiac tissue under different experimental conditions, including differing doses of trastuzumab and supplementation with oral sodium selenite, an antioxidant. Histopathology revealed lymphocyte and macrophage infiltration in myocardium of rabbits receiving four doses of trastuzumab. Transmission electron microscopy showed substantial changes with trastuzumab, including edema with separation of myofibril bundles and rupture of sarcomeres. Within mitochondria, edema resulted in disorganization of the cristae. Some mitochondria exhibited eccentric projections of their membranes with disruption of both inner and outer membranes. These changes were seen to a lesser extent in rabbits who received oral sodium selenite prior to trastuzumab. Selenium is integral to functioning of mitochondrial glutathione peroxidases, important antioxidants that also maintain membrane integrity. If mitochondria are disrupted as part of trastuzumab cardiac toxicity, selenium supplementation might be an important therapeutic or preventive consideration. Larger studies to explore this hypothesis are warranted.

Successful treatment of intracardiac and intraocular blastomycosis in a dog with combination azole therapy.

A 4 yr old spayed female Labrador retriever with clinical signs of blindness, cutaneous lesions, coughing, inappetence, and lethargy was diagnosed with disseminated blastomycosis based on cytologic (skin and lymph node aspirates) and histopathologic (skin biopsy) examinations of tissue samples. The dog deteriorated clinically during hospitalization and developed sustained ventricular tachycardia. Echocardiography revealed pericardial effusion, a nodule associated with the left ventricular papillary muscle, and a right atrial mural lesion. Therapy for myocardial performance and glaucoma was initiated. A combination of itraconazole and fluconazole successfully treated the dog. The dog regained vision in the left eye (oculus sinister [OS]) and had no residual cardiac disease detectable by either electrocardiography or echocardiography. This report is unique in documenting survival from intracardiac blastomycosis and in the use of combination azole therapy for treating disseminated disease with intraocular involvement.

Challenges of cardiopulmonary bypass-a review of the veterinary literature.

Cardiopulmonary bypass (CPB) has been used in veterinary medicine in experimental surgery and to address congenital and acquired diseases. We review the veterinary literature and expose common challenges of CPB in dogs and cats. Specifically, we describe the most specific elements of this technique in veterinary patients. The variety in animal size has made it difficult to standardize cannulation techniques, oxygenators, and priming volumes and solutions. The fact that one of the most common cardiovascular disorders, mitral valve disease, occurs predominantly in small dogs has limited the use of bypass in these patients because of the need for small, low prime oxygenators and pumps that have been unavailable until recently. Coagulation, hemostasis, and blood product availability have also represented important factors in the way CPB has developed over the years. The cost and the challenges in operating the bypass machine have represented substantial limitations in its broader use.

Congenital coronary-pulmonary arterial shunt in a German shepherd dog: diagnosis and surgical correction.

BACKGROUND: A 10 week-old intact female German shepherd dog was examined because of a heart murmur. METHODS: An echocardiogram revealed an extracardiac left-to-right shunt. An angiogram identified shunting between the aorta and the pulmonary artery in an unusual location. RESULTS: Thoracotomy was performed to better identify and correct the lesion; a tubular shunt between the left coronary artery and the pulmonary artery was found and ligated in a closed-heart procedure. The murmur resolved immediately upon ligation and the dog's heart size normalized over a period of several months after surgery. CONCLUSION: In the dog, surgical correction of a coronary artery-pulmonary artery shunt can be performed without complications and can be associated with reversal of cardiac remodeling.

Use of a jugular vein graft in a modified Blalock-Taussig procedure in dogs.

OBJECTIVE: To determine whether autologous jugular veins provide functional grafts with high 30-day patency rates in an experimental model of systemic-to-pulmonary shunting performed with a modified Blalock-Taussig procedure. ANIMALS: 15 healthy Beagles. PROCEDURE: A segment of the left jugular vein was implanted between the left subclavian and pulmonary arteries. Echocardiograms were obtained prior to surgery, at day 4 to 7, and at day 30 after surgery. Selective angiograms were performed immediately after surgery and on day 30. Oximetric shunt calculations were made via terminal angiography prior to euthanasia. Gross and histologic evaluations of the grafts were conducted. RESULTS: Grafts were patent in 12 of 15 dogs 30 days after surgery as assessed via auscultation, color Doppler ultrasonography, angiography, and histologic examination. Echocardiographic analysis revealed compensatory eccentric left ventricular hypertrophy. Mean pulmonary-to-systemic flow ratio was 1.5:1. Histologic evidence of endothelialization of the anastomotic sites and vein graft arterialization was detectable at 30 days. CONCLUSIONS AND CLINICAL RELEVANCE: Autologous jugular vein grafts were effectively used to create a systemic-to-pulmonary shunt by use of a modified Blalock-Taussig procedure. High patency, ready accessibility, low cost, and theoretical adaptative remodeling during patient growth make autologous jugular vein grafts a valuable alternative to synthetic materials.

Multiple endocrine neoplasia type I in a cat.

A 13-year-old 4.6-kg (10.2-lb) neutered male domestic long hair cat was evaluated because of a history of lethargy, exercise intolerance, and ventroflexion of the cervical portion of the vertebral column. After extensive assessment at the Veterinary Teaching Hospital at Michigan State University, the clinical signs were attributed to an aldosterone-secreting tumor of the adrenal gland. Subsequently, an insulin-secreting tumor of the pancreas as well as a functional parathyroid gland adenoma were diagnosed. All 3 masses were surgically removed, and the cat made a full recovery with complete resolution of clinical signs. The syndrome of multiple endocrine neoplasia is well described in humans, and the heritability of the condition has been confirmed. In cats and other species with 1 or more endocrine neoplasms, it is important to perform thorough clinical assessments of patients to identify other endocrine organs that may also be affected concurrently with neoplastic disease.