Evaluation of plasma time-activity curves of technetium-99m-mebrofenin for measurement of hepatic function in dogs.

In this study, plasma time-activity curves of 99mTc-mebrofenin were used to quantify hepatic function in dogs before and after induction of hepatic damage using a hepatotoxic agent. Nine dogs were determined to be healthy on the basis of physical examination, laboratory data and hepatic imaging. Plasma samples were collected 1, 3, 5, 7, 9, 15, 20, 30, 40, 50, and 60 minutes following a peripheral venous injection of 111-222 MBq (3-6 mCi) of 99mTc-mebrofenin. The area under the plasma time-activity curve (AUC) was calculated using two different methods and compared to direct measurement of the hepatic extraction efficiency. First pass hepatic extraction efficiency of 99mTc-mebrofenin was calculated from differential equation analysis of a two-compartment model following mesenteric venous injection of the radiopharmaceutical. In 7 of the original 9 dogs and 2 additional healthy dogs, plasma clearance and hepatic extraction efficiency determination were repeated following induction of hepatic injury by thiacetarsamide (3 mg/kg IV twice daily for 1 day). In one additional dog, hepatic injury was induced using carbon tetrachloride (0.3 ml/kg IP). Plasma time-activity curves of 99mTc-mebrofenin had kinetics of a two compartment model. Area under the curve was highly correlated with hepatic extraction efficiency. The AUC integrated from 1-60 minutes (AUC60) had the best correlation with hepatic extraction efficiency (r2 = 0.978, p < 0.001). A formula for calculation of hepatic extraction efficiency was derived using linear regression analysis: hepatic extraction efficiency = 105.583 - 3.099 x 10(5) x AUC60. Plasma clearance of a peripheral venous injection of 99mTc-mebrofenin is a simple, non-invasive, convenient method to quantify hepatic function which can be performed without a gamma camera.

Validation of deconvolutional analysis for the measurement of hepatic function in dogs with toxic-induced liver disease.

The extraction of the hepatobiliary radiopharmaceutical 99mTc-mebrofenin (Choletec) by the liver can be used to evaluate the severity of hepatocellular disease. The hepatic parenchymal cells extract mebrofenin from the blood by the same active transport mechanism as bilirubin. The ability of the liver to extract 99mTc-mebrofenin is a measure of hepatic parenchymal cell function. In this study, we induced hepatocellular disease by administration of a hepatotoxic drug and compared a direct method of determining the hepatic extraction of 99mTc-mebrofenin to hepatic extraction fraction derived from deconvolutional analysis. We also compared both methods of calculating the hepatic extraction of 99mTc-mebrofenin to liver histopathology. Hepatic extraction fraction derived from deconvolutional analysis correlated very well to the direct measurement technique (R=0.922, p < 0.001). Both methods of determining hepatic extraction correlated well to quantitative histopathology, having the same correlation coefficient and p values. (R=-0.833, p=0.003). As the hepatic extraction 99mTc-mebrofenin decreased, the severity of the histopathologic lesions of the liver increased in a linear fashion. There was a significant correlation of the hepatic excretion T1/2 to quantitative histopathology (R=0.949, p < 0.001). The hepatic excretion T1/2 increased as the severity of the histopathologic lesions of the liver increased. Hepatic extraction (HEF) and excretion of 99mTc-mebrofenin are good predictors of the severity of hepatocellular damage in toxic induced liver disease. This study helps validate the premise that HEF derived from deconvolutional analysis is a good predictor of the actual first pass hepatic extraction of 99mTc-mebrofenin.

Use of a modified surgical approach to the right atrium for retrieval of heartworms in a dog.

A 2-year-old 2-kg female Maltese dog was referred for treatment of dirofilariosis and mild caval syndrome characterized by hemolysis and lethargy. Ultrasonography revealed worms within the caudal vena cava, right auricle, right ventricle, and pulmonary artery. Because of the mild clinical signs and small size of the dog, jugular venotomy was not performed, and treatment with sodium caparsolate was instituted. A markedly adverse reaction was noticed on initial injection, characterized by cardiac and respiratory arrest. Further treatment with sodium caparsolate was discontinued. Because of progression of the dog's condition surgical removal of heartworms was elected. A modified surgical approach to the right atrium was performed, using a cannula introduced through a pursestring placed in the wall of the right auricle. This technique allowed almost complete removal of heartworms with minimal blood loss. Postoperative ultrasonography revealed a single heart-worm remaining in the distal portion of the left pulmonary artery, but it was subsequently absorbed.

Semiquantitative test for Dirofilaria immitis as a predictor of thromboembolic complications associated with heartworm treatment in dogs.

A semiquantitative heartworm test of antigen concentration was evaluated as a predictor of thromboembolism after adulticide treatment. Seventeen dogs with naturally acquired infections of Dirofilaria immitis (heartworms) were studied before and after thiacetarsamide treatment, using physical examinations, arterial blood gas analyses, thoracic radiography, and pulmonary hemodynamic and arteriographic tests. Eight dogs were considered to have a low burden of heartworms and 9 had a high burden. Dogs with a high worm burden had more severe pulmonary thromboembolism with pulmonary hypertension, dilated pulmonary arteries, flow obstruction of the caudal pulmonary arteries, and parenchymal lesions in the caudal lung lobes. Dogs with a low worm burden had minimal changes. Within each group of dogs, the severity of thromboembolism was less in some dogs in which all heartworms were not killed. Six of the 9 dogs with a high burden of heartworms had surviving heartworms, and 1 of these dogs had 38 live heartworms. Only 4 of the 8 dogs with a low worm burden had complete heartworm mortality, but only 1 dog had more than 3 surviving heartworms. We concluded that dogs with a high worm burden were more likely to have pulmonary thromboembolism after thiacetarsamide treatment and that dogs with a low worm burden were more likely to have minimal changes. A semiquantitative heartworm test of antigen concentration is recommended as part of the pretreatment evaluation of dogs infected with heartworms.

Pulmonary thromboembolism and hypertension after thiacetarsamide vs melarsomine dihydrochloride treatment of Dirofilaria immitis infection in dogs.

The severity of pulmonary thromboembolism and pulmonary hypertension induced by heartworms dying after administration of 2 adulticides was evaluated. Because melarsomine dihydrochloride (RM340) has been shown to be more effective in killing Dirofilaria immitis (heartworms) than the traditional approved adulticide, thiacetarsamide, an attempt was made to determine whether this new adulticide induced more severe lung disease. Before adulticide treatment, 32 dogs with naturally acquired heartworm infections received physical examinations, semiquantitative antigen concentration tests, CBC, platelet counts, serum biochemistry analyses, arterial blood gas determinations, thoracic radiography, pulmonary arteriography, and pulmonary hemodynamic tests. Eight dogs with a low burden and 9 dogs with a high burden of heartworms were treated with thiacetarsamide, and 7 dogs with a low burden and 8 dogs with a high burden were treated with RM340. Except for the heartworm-burden test, tests were repeated at regular intervals during the first 7 weeks after treatment. None of the dogs coughed or had dyspnea after treatment. Six of 9 dogs with high worm burdens and 4 of 8 dogs with low worm burdens had surviving heartworms after thiacetarsamide treatment, in contrast to only 3 of 15 RM340-treated dogs. Differences between the 2 adulticide treatments were minimal as determined by thoracic radiography, pulmonary hemodynamic tests, clinical laboratory analyses, pulmonary arteriography, or necropsy. The RM340 treatment was a more effective adulticide, but it did not increase the severity of hypertension and thromboembolism.

Complications following thiacetarsamide sodium therapy in Louisiana dogs with naturally-occurring heartworm disease.

Four hundred and sixteen dogs with naturally-occurring heartworm disease were evaluated for complications following thiacetarsamide sodium therapy. Of these, 109 dogs (26.2%) experienced complications. Increased lung sounds was the most commonly seen complication, followed by fever and coughing. In dogs with complications, 83.5% of them presented without clinical evidence of pulmonary thromboembolism or heart failure. There were no statistically significant differences between the age, sex, breed and body size of dogs that experienced complications following thiacetarsamide therapy and dogs that did not. Complications were most frequently seen 5 to 9 days following thiacetarsamide therapy although some dogs experienced initial complications as late as 28 days. Thirty-three of 109 dogs (33.0%) with complications responded to exercise restriction. The remaining 76 dogs with complications prior to or following thiacetarsamide required adjunct drug therapy. Of these, 35 dogs responded favorably to anti-inflammatory doses of prednisolone or prednisone. Five dogs died or were euthanatized because of the complications experienced. Eighteen of 416 dogs (4.3%) presented with clinical evidence of pulmonary thromboembolism or heart failure prior to the thiacetarsamide therapy. All 18 dogs experienced complications in spite of adjunct drug therapy and exercise restriction prior to, during, and following thiacetarsamide therapy. Survival rate following resolution of the thiacetarsamide-induced complications was greater than 98%.

Treatment of canine dirofilariasis: pulmonary thromboembolism caused by thiacetarsamide--microscopic changes.

Light and scanning electron microscopies were used to study the pulmonary embolism occurring in Dirofilaria immitis-infected dogs after treatment with thiacetarsamide. Lesions in control dogs (nontreated) which had been infected for 4 weeks with 9 Dirofilaria immitis adults were compared with lesions occurring in infected dogs at 2 weeks and at 4 weeks after they were treated with the adulticide. Extensive thromboembolism occurred in the caudal lobar pulmonary arteries of dogs at posttreatment weeks 2 and 4. Complicated villous proliferations were present at posttreatment week 2. The characteristic myointimal proliferation of dirofilariasis showed resolution in the large pulmonary arteries of the dogs at week 4. However, the caudal lobar pulmonary arterial and lung lesions were more severe in the later group. The pathophysiology of adulticide-induced thromboembolism and associated lung parenchymal changes were discussed.

Pulmonary thromboembolism during therapy of dirofilariasis with thiacetarsamide: modification with aspirin or prednisolone.

The effects that 4 weeks of treatment of dirofilaria-infected dogs with either aspirin or prednisolone had on the pulmonary thromboembolism which occurs after they are given thiacetarsamide were determined, using light and electron microscopies. Pulmonary lesions in control dogs at 4 weeks after thiacetarsamide was given were compared with lesions in dogs which were treated with either aspirin (22 mg/kg daily) or prednisolone (1 mg/kg daily) during the 4-week period after adulticide was given. Pulmonary vascular and perivascular lesions were most severe in the prednisolone-treated dogs and least severe in the aspirin-treated dogs. The aspirin-treated dogs had greater resolution of pulmonary arterial proliferative disease, and prednisolone-treated dogs had the lesser resolution.

Distal polyneuropathy after canine heartworm disease therapy complicated by disseminated intravascular coagulation.

A 3-year-old male Setter-type dog had a progressive distal sensorimotor polyneuropathy characterized by weakness, bilateral atrophy of distal appendicular musculature, and reduced response to tactile stimuli. The diagnosis of a distal axonopathy was supported by electromyographic findings of fibrillation potentials, positive sharp waves in distal limb muscles, and absence of evoked action potentials, myopathic changes of atrophic angular fibers, and myelinated nerve fiber depletion in distal parts of peripheral nerves. The neuropathy appeared 5 weeks after 38 days of heparin therapy for disseminated intravascular coagulation. The disseminated intravascular coagulation, a complication of thiacetarsamide therapy for heartworm disease, had resolved 40 days after the end of heparin therapy. The cause of the neuropathy was not determined.