Comparative efficacy of four commercially available heartworm preventive products against the MP3 laboratory strain of Dirofilaria immitis.

A controlled laboratory study was conducted to evaluate the efficacy of four commercial products administered as a single treatment for the prevention of heartworm disease caused by Dirofilaria immitis in dogs. Forty-four commercially sourced Beagle dogs, 6-7 months of age, were received at the test site (Auburn University, Department of Pathobiology) on Study Day (SD) -72 to begin acclimation. On SD -30, each dog was inoculated subcutaneously with 100 infective, third-stage D. immitis larvae (MP3 strain, TRS Laboratories, Inc., Athens, GA). On SD -1, 40 dogs weighing 18.2-25.3 lbs were ranked by decreasing body weight and randomized to five groups of eight dogs each. On SD 0, the dogs assigned to Group 1 were treated orally with ivermectin/pyrantel pamoate chewable tablets, Group 2 dogs were treated orally with milbemycin oxime flavored tablets, Group 3 dogs were treated with selamectin topical solution, and Group 4 dogs were treated with imidacloprid/moxidectin topical solution. Group 5 dogs remained nontreated. Dosages for dogs in Groups 1-4 were based on the individual body weight of each dog and current labeled dose banding for each commercial product. All dogs were fasted overnight prior to treatment. Food was returned four hours after treatment. Animals were observed for abnormal clinical signs involving eyes, feces, respiration, behavioral attitude, locomotion/musculature, or skin conditions at prescribed intervals immediately after treatment and at twice daily intervals thereafter. On SD 90, whole blood was collected and tested for adult heartworm antigen. On SDs 119/120, the dogs were euthanized and subjected to necropsy examination for recovery of adult D. immitis and/or worm fragments. At necropsy, all 8 dogs in the nontreated group were infected with adult D. immitis (34-70 worms/dog, geometric mean (GM)=51.6 worms/dog). One or more adult D. immitis and/or worm fragments were recovered from 7 of 8 of the dogs each in Groups 1-3 (87.5% were heartworm positive). The respective GM worm burdens/dog for Groups 1-3 was 2.3, 2.4, and 2.3 which resulted in 95.6, 95.4 and 95.5% efficacy, respectively. No worms were recovered from any of the 8 dogs in Group 4 resulting in 100% efficacy.

Surgical implantation of a cardiac resynchronization therapy device in a western lowland gorilla (Gorilla gorilla gorilla) with fibrosing cardiomyopathy.

A 24-yr-old, male western lowland gorilla (Gorilla gorilla gorilla) was diagnosed in March of 2003 with congestive heart failure (CHF). Transesophageal and transthoracic echocardiography demonstrated global left and right ventricular hypokinesia with a left ventricular ejection fraction of 0.20. At the time of diagnosis, the animal exhibited symptoms and signs of CHF with minimal exertion (New York Heart Association class III). Over a 16-mo period, the severity of CHF progressed to class IV (resting signs and symptoms) despite angiotensin-converting enzyme inhibition, beta-blockers, and diuretics. Because of intractable CHF and a QRS duration that was markedly prolonged compared with the normal range for this species, a cardiac resynchronization therapy (CRT) device was implanted using implantation techniques based on human surgical procedures. Placement of the right ventricular, right atrial, and left ventricular leads and pulse generator were accomplished in 5.5 hr. Telemetry of the device postoperatively via wand or remote radio frequency has allowed for noninvasive programming and interrogation. The clinical improvement in CHF with this therapy was immediate and dramatic for this animal. Six months after CRT device implantation, the device leads became dislodged during an altercation with another gorilla, with the rapid development of CHF upon cessation of biventricular pacing. A second procedure to replace the leads returned the gorilla to his previous level of activity. In 2007, the pulse generator was electively replaced for battery depletion with a device capable of remote radiofrequency programming and interrogation. CRT implantation, although requiring specialized equipment and surgical skill, appears to be a viable option for treatment of dilated cardiomyopathy in gorillas.

Activity of pulmonary intravascular macrophages in cats and dogs with and without adult Dirofilaria immitis.

Pulmonary intravascular macrophages (PIMs), large (20-80 microm diameter) monocytes are present in sheep, pigs, and horses, but not in dogs, rats, rabbits, or primates. The present study evaluated the phagocytic activity of various organs in cats and dogs and determined the influence of Dirofilaria immitis infections on PIM activity. Live or dead adult heartworm (HW) was transplanted via jugular venotomy into cats and dogs. Cats (four per group) were allocated to five groups: surgical controls--no HW, dead HW for 1 week, live HW for 1 week, dead HW for 3 weeks, or live HW for 3 weeks. Radioactive technetium (Tc-99m, 1.2mCi in 0.3ml) sulfa-colloid was injected intravenously. All cats with HW were clinically asymptomatic and developed radiographic pulmonary parenchymal changes. No gross changes were visible at necropsy for cats with HW; inflammatory changes were less severe in cats with live HW. In cats with dead HW for 3 weeks, worms were present but folded, flattened, and located in distal pulmonary arteries. Uninfected control dogs and those with dead HW did not demonstrate any PIM activity. In control cats, lungs were the primary phagocytic organ after systemic IV colloid injection (72.5% of the total recovered radioactive dose). The lung and liver together represented over 95% of the recovered Tc-99m colloid in all cats. In each group of cats with HW, phagocytic activity of the lung was significantly less (p < 0.001) than the PIM activity of controls. Cats with dead HW at 1 week (50.1%) had a significant (p < 0.019) decrease in PIM activity compared with cats with dead HW at 3 weeks (59.5%). The PIM activity in cats with live HW was significantly decreased (p < 0.001) from that in groups with dead HW, but there was no significant difference between the two groups infected with live worms. There were no significant differences in recovery between any groups in pairwise analysis of the spleen, heart, skeletal muscle, kidney, bone marrow, or blood. Significant increases (p < 0.001) in liver activity for each group inversely reflected the decreased lung activity; consistent with increased hepatic uptake of Tc colloid "escaping" a relatively suppressed lung macrophage system. Transmission electron microscopy confirmed PIM glycocalyx changes and vacuolization, moderate Type 1 cell damage and Type II cell hypertrophy in cats with dead HW. There was no evidence of PIM death. The significant decrease in PIM activity in groups with dead HW and a greater decrease in groups with live HW are consistent with a down-regulation of PIM function in cats with live HW.

Treatment of dogs infected with Hepatozoon americanum: 53 cases (1989-1998).

OBJECTIVE: To determine clinical and pathologic findings before and after short-term (group 1) and long-term (group 2) treatment in dogs with Hepatozoon americanum infection. DESIGN: Retrospective study. ANIMALS: 53 dogs with H. americanum infection. PROCEDURE: Medical records of dogs that were treated for hepatozoonosis diagnosed on the basis of meront or merozoite stages in skeletal muscle were reviewed. RESULTS: Circulating gametocytes of H. americanum were identified in 12 of 53 dogs. Dogs were treated with various drugs, including toltrazuril, trimethoprim-sulfadiazine, clindamycin, pyrimethamine, and decoquinate. Mean WBC counts prior to treatment were 85,700 and 75,200 cells/microl in groups 1 and 2, respectively, and 1 month after initiation of treatment were 12,600 and 14,600 cells/microl, respectively. Initial response to treatment was excellent in all dogs. Twenty-three of 26 dogs in group 1 relapsed at least once and died within 2 years; mean (+/- SD) survival time was 12.6+/-2.2 months. Twenty-two of 27 group-2 dogs survived; 11 dogs had no clinical signs and were still receiving decoquinate (mean duration of treatment, 21 months), 11 dogs had no clinical signs after treatment for 14 months (range, 3 to 33 months; mean survival time, 39 months [range, 26 to 53 months]), 2 dogs were lost to follow-up, and 3 dogs were euthanatized because of severe disease. CONCLUSIONS AND CLINICAL RELEVANCE: Although no treatment effectively eliminated the tissue stages of H. americanum, treatment with trimethoprim-sulfadiazine, clindamycin, and pyrimethamine followed by long-term administration of decoquinate resulted in extended survival times and excellent quality of life.

Left ventricular outflow tract to left atrial fistula associated with endocarditis in a dog.

A one-year-old, intact male, 28-kg, mixed-breed dog developed neurological episodes consistent with emboli. An acquired III/VI holosystolic heart murmur was ausculted in the mitral area, and valvular endocarditis with pulmonic and aortic insufficiency were noted at echocardiographic examination. An abnormal communication (i.e., fistula) between the left ventricular outflow tract (LVOT) and the left atrium adjacent to the mitral valve annulus was noted with Doppler imaging and confirmed with angiography. Infective valvular endocarditis was confirmed based on two of three blood cultures being positive for Staphylococcus intermedius. In humans, a sequela to infective endocarditis of the aortic or mitral valve, or both, is rupture of the mitral-aortic intervalvular fibrosa, resulting in a communication between the LVOT and the left atrium. This is the first report of this sequela in the dog.

Prevalence of feline heartworm infections among cats with respiratory and gastrointestinal signs: results of a multicenter study.

Although heartworm infection in cats was first described in 1921, the diagnosis of the infection remains elusive in many cases. This is due to nonspecific clinical signs of feline heartworm disease, typically low worm burdens, unique pathophysiology in the cat, and the limitations of currently available heartworm tests. Consequently, knowledge about this disease is still limited. An objective of this study was to survey the occurrence and clinical presentation of feline heartworm infection among cats presenting with clinical signs consistent with heartworm disease. Two-hundred fifteen cases were submitted from 15 private practices in Florida, South Carolina, Tennessee, and Texas. Cats entered in the study were at least 6 months of age and presented with one or more of the following clinical signs: respiratory signs, including tachypnea, dyspnea, or coughing; gastrointestinal signs, including a pattern of intermittent vomiting unrelated to eating; or sudden death of uncertain etiology, particularly associated with respiratory distress prior to death. Data collected included: history and indoor/ outdoor lifestyle; physical examination findings; thoracic radiography evaluations; Knott or DIFIL test results, DiroCHEK antigen test results, and antibody test results (Animal Diagnostics, Inc. and Heska Corporation); and CBC results. Recheck examinations were scheduled for any cat with positive heartworm serological test results and for cats with radiographic signs consistent with or suggestive of feline heartworm disease. Data from 215 cases were collected and analyzed: 94/215 (44%) tested antibody positive for one or both antibody tests that were performed; 18/94 (19%) of the antibody-positive cats were reported as living 100% indoors by their owners; (12%) of the antibody-positive cats spent less than or equal to 10% of their time outdoors. Eleven of 215 cats (5%) were DiroCHEK antigen positive on initial examination. One cat was both DiroCHEK and microfilariae positive, but negative for both antibody tests. Radiographs were obtained for 10 of these cats and 6/10 had radiographic signs consistent with or suggestive of feline heartworm infection. At necropsy, heartworms were found in one other cat from which blood was not obtained. Additionally, two cats that had positive radiographic signs of heartworm infection converted from antigen-negative to antigen-positive status at recheck examination for a total of 13/215 (6%) DiroCHEK antigen-positive cats. One case that was submitted after acute death was DiroCHEK antigen positive, but interestingly, had relatively low antibody levels for both antibody tests. Initial radiographs were available on 212 of the 215 cases. In 90/212 (42%) cases, initial thoracic radiographs showed signs consistent with or suggestive of heartworm disease. Follow-up radiographs showed varying progression with radiographic signs worsening, improving, or staying the same on individual cats. Feline heartworm disease should be among the primary differential diagnoses in cats with respiratory disease, vomiting, or acute death. Radiography, antibody testing, and antigen testing are all useful tools to aid in making the diagnosis. A confirmed diagnosis may require doing multiple tests and clinical reevaluation. Cats classified by their owners as indoor only cats were found to be heartworm infected, thus lifestyle of the cat cannot rule out the disease. Actual antibody levels (high or low) may not correspond to severity of disease.

Radiographic diagnosis of feline heartworm disease and correlation to other clinical criteria: results of a multicenter clinical case study.

Two-hundred fifteen cats with clinical signs consistent with feline heartworm disease (FHD) were entered into this clinical case study. In addition to physical examination, CBC, and heartworm antibody (Ab) and antigen (Ag) tests, thoracic radiographs were taken of 212 cats at initial examination. For cats that had a positive Ab or Ag test, or radiographic changes that could be associated with FHD, follow-up radiographs were taken at approximately 60 to 90 days after initial examination whenever possible. Each radiographic examination included VD, DV, and left lateral views, and each was read by the same board-certified radiologist who was blinded to heartworm serological results until after radiographic evaluation was completed. Criteria evaluated included heart size and shape, pulmonary artery enlargement, pulmonary parenchymal involvement, hyperinflation of lungs, tenting of the diaphragm, and pleural fluid accumulation. Summary interpretations and heartworm score were recorded. The heartworm score reflected the degree of suspicion of FHD based on radiographic signs: no radiographic signs of FHD; bronchointerstitial lung pattern only (consistent with but not specific for FHD); or pulmonary artery enlargement (with or without pulmonary or cardiac changes) mildly, moderately, or strongly indicative of FHD. Of 212 cats for which radiographs were taken at the initial examination, 38 (18%) had enlarged caudal lobar arteries indicative of FHD and 90 (42%) had bronchointerstitial pulmonary disease consistent with heartworms and/or enlarged caudal lobar arteries. Radiographic changes consistent with or indicative of FHD were evident in 9/22 cats (41%) presenting with gastrointestinal signs, 39/78 cats (50%) presenting with respiratory signs, and 41/80 cats (51%) presenting with both respiratory and gastrointestinal signs. Some cats presenting with only gastrointestinal signs had thoracic radiographic changes suggestive of FHD. Eleven cats tested DiroCHEK Ag positive, and radiographs were taken of 10. Of the 10 cats, 5 had radiographic changes indicative of FHD; one had changes consistent with FHD; and 4 cats showed no radiographic signs of FHD. Follow-up radiographs were taken of 6 of these 11 cats: 1/6 worsened in radiographic score, 3/6 improved in radiographic score, and 2/6 still demonstrated no radiographic signs of heartworm. Ninety-two cats tested Ab positive at initial examination, and radiographs were available for 91 of these cats. In 22/91 (24%), enlarged caudal lobar arteries indicated FHD. In 39/91 cats (43%) cats, radiographic signs consistent with or indicative of FHD were seen. Of the 38 cats that had radiographic signs indicative of FHD, 22 (58%) were Ab positive on one or both tests. Seven (32%) had positive DiroCHEK Ag tests at initial or recheck examination. At recheck examinations, 2 cats that initially had radiographic signs indicative of FHD converted from DiroCHEK Ag negative to positive, confirming their infection with at least 1 sexually mature female heartworm. While many affected cats show pulmonary arterial enlargement and/or a bronchointerstitial pattern typical of FHD, some cats with serologic evidence of heartworms do not demonstrate any thoracic radiographic changes. Conversely, some cats show radiographic signs suggesting heartworm disease when concurrent serology is negative. These discrepancies may be caused by time between infection and examination, by differences in individual cats' immune response to the presence of larval or adult stages of heartworm, or by aberrant migrations.

Feline heartworm disease: correlations of clinical signs, serology, and other diagnostics--results of a multicenter study.

In cooperation with 15 practices in Florida, South Carolina, Tennessee, and Texas, data were collected on 215 cats with signs consistent with feline heartworm disease (FHD). Cats included in the study were over 6 months of age and presented with primary complaints of coughing or dyspnea, vomiting unrelated to eating, or acute death. Detailed signalment, thoracic radiographs, CBC, Knott or DIFIL test, DiroCHEK antigen test (Ag), and antibody (Ab) tests performed by Animal Diagnostics (AD) and Heska Corp (HC) were collected on each cat. Any cat that had positive antibody or antigen tests, and any cat with radiographic signs suggestive of FHD was scheduled for recheck examinations at 30 to 45 days and/or 60 to 90 days after initial presentation. This study was designed to identify cats with concurrent or previous FHD, and to better characterize the presentation of this disease by following their progress. Of the 215 cats, 94 (44%) were Ab positive based on one or both tests. This indicated that the cat had been successfully infected with third-stage heartworm larvae and those larvae had developed to at least the fourth stage. Of the Ab-positive cats, 23/94 (24%) presented with vomiting; 39/94 (41%) presented with respiratory signs; and 27/94 (29%) had vomiting and respiratory signs. Discordant results between the AD and HC antibody tests occurred, with the AD test detecting a higher number of antibody-positive cats. When comparing results of these Ab tests, no correlation was seen between the intensity of Ab level measured by the two tests, suggesting that different Ab is detected. One cat that died acutely with signs associated with FHD had relatively low Ab detected on both tests but had a positive DiroCHEK antigen test. No correlation between the level of antibody and the severity of clinical signs or radiographic pattern was found. Eleven cars were DiroCHEK Ag positive on initial presentation. Of the Ag-positive cats, 2 were AD negative and 3 were HC negative. One cat was Ag positive and microfilaria positive but negative for Ab with both AD and HC tests. Although it has been presumed that most cats with FHD are Ag negative, it would appear that some individual cats with adult heartworms can also be Ab negative. Although eosinophilia and basophilia were more frequently associated with cats that were Ab positive, abnormal CBC values were observed in cats that were currently Ab negative. Radiographic lesions did not correlate with clinical signs or Ab levels. Some cats with no radiographic signs of FHD were Ag positive. Further, some cats with typical radiographic lesions of FHD were negative based on all serologic evaluations. These results demonstrate that successful transmission of heartworms to cats is more common than previously thought and is clinically associated with coughing, dyspnea, and vomiting. A cause and effect correlation cannot be proven between clinical signs and laboratory evaluation. Radiographic evidence of FHD in cats with repeated negative antibody results may be an indicator of residual damage from previous heartworm infections. Most experimental studies of FHD have been short-term (< 1 yr). However, in this study, many cats underwent repeated clinical evaluation over a relatively short time. This demonstrated that the clinical picture of spontaneous FHD is a constantly changing syndrome, highly dependent on the stage (immature L5, adult, adult death, residual damage) of the parasite in the cat and the individual cat's response. On evaluation of clinically affected cats, no one test proved to be definitive (without exceptions). The diagnosis of FHD continues to require a combination of clinical evaluation and a series of diagnostic tests, often requiring reevaluations over time.

ACE inhibitors in HF restore canine pulmonary endothelial function and ANG II vasoconstriction.

Chronic mitral regurgitation (MR) in dogs results in pulmonary congestion and increased cardiac angiotensin-converting enzyme (ACE) activity and angiotensin (ANG) II levels. ACE could contribute to altered pulmonary vasomotion in heart failure, and ACE inhibitor (ACEI) therapy may normalize pulmonary vasomotion. We evaluated pulmonary artery (PA) responses to ANG II and bradykinin (BK) in control dogs, in dogs with 4 mo of MR, in MR dogs treated with the ACEI ramipril (MR + R), and in control dogs treated with ramipril (C + R). Mean PA systolic pressure increased in MR dogs (21 +/- 4 mmHg) but was normal in MR + R dogs (13 +/- 1 mmHg). Constriction of PA rings to ANG II was depressed in MR dogs. ACEI treatment (MR + R) restored ANG II responsiveness, but peak ANG II response (3.6 +/- 0.2 g) in MR + R dogs remained lower than in C + R dogs (4.7 +/- 0.2 g). Endothelium-dependent relaxation to BK was decreased (-87 +/- 4% C, -65 +/- 4% MR; P < 0.05). Ramipril (MR + R) restored relaxation to BK. This demonstrates that pulmonary congestion results in impaired pulmonary vasomotion to ANG II and BK, which ACEIs could normalize, supporting the use of ACEIs in clinical management of chronic congestive heart failure.

Effect of alternate-day prednisolone administration on hypophyseal-adrenocortical activity in dogs.

OBJECTIVE: To evaluate effect of alternate-day oral administration of prednisolone on endogenous plasma ACTH concentration and adrenocortical response to exogenous ACTH in dogs. ANIMALS: 12 Beagles. PROCEDURE: Dogs were allotted to 2 groups (group 1, 8 dogs treated with 1 mg of prednisolone/kg of body weight; group 2, 4 dogs given excipient only). During a 30-day period, blood samples were collected for determination of plasma ACTH and cortisol concentrations before, during, and after treatment with prednisolone. From day 7 to 23, prednisolone or excipient was given on alternate days. Sample collection (48-hour period with 6-hour intervals) was performed on days 1, 7, 15, 21, and 28; on other days, sample collection was performed at 24-hour intervals. Pre- and post-ACTH plasma cortisol concentrations were determined on days 3, 9, 17, 23, and 30. RESULTS: A significant difference was detected between treatment and time for group 1. Plasma ACTH concentrations significantly decreased for 18 to 24 hours after prednisolone treatment in group-1 dogs. At 24 to 48 hours, ACTH concentrations were numerically higher but not significantly different in group-1 dogs. Post-ACTH plasma cortisol concentration significantly decreased after 1 dose of prednisolone and became more profound during the treatment period. However, post-ACTH cortisol concentration returned to the reference range 1 week after prednisolone administration was discontinued. CONCLUSIONS AND CLINICAL RELEVANCE: Single oral administration of 1 mg of prednisolone/kg significantly suppressed plasma ACTH concentration in dogs for 18 to 24 hours after treatment. Alternate-day treatment did not prevent suppression, as documented by the response to ACTH.

Hepatozoonosis in dogs: 22 cases (1989-1994).

OBJECTIVE: To document hepatozoonosis in dogs from Alabama and Georgia and to report associated clinical signs, method of diagnosis, response to treatment, and course of disease. DESIGN: Retrospective case series. ANIMALS: 22 dogs in which Hepatozoon canis was identified by microscopic examination of skeletal muscle. PROCEDURE: We reviewed medical records of all dogs with a definitive diagnosis of hepatozoonosis that were referred to the Auburn University Small Animal Clinic between 1989 and 1994. RESULTS: Diagnoses were confirmed by microscopic identification of H canis schizont or merozoite stages in skeletal muscle. The gametocyte stage was not detected in smears of blood obtained from a peripheral vein, buffy-coat smears, or bone marrow evaluation. Common clinical signs included fever, cachexia, ocular discharge, pain, stiffness, and paresis. Laboratory abnormalities included marked leukocytosis, hypoglycemia, hypoalbuminemia, mild anemia, hyperphosphatemia, and high alkaline phosphatase activity. Periosteal bone proliferation was evident radiographically in 18 of 22 dogs. Renal lesions included amyloidosis (1 dog), interstitial nephritis (3), and mesangioproliferative glomerulonephritis (4). Treatment with the anticoccidial drug toltrazuril, despite an initial favorable response, failed to prevent relapse in all but 3 of 21 treated dogs. Mean survival time was 12.6 +/- 2.2 months, with a mean time of remission before recurrence of clinical signs of 6 months. CLINICAL IMPLICATIONS: H canis infection in dogs can be associated with a distinct clinical syndrome that involves chronic myositis, debilitation, and death. The dogs of this report represent the first substantial number of domestic dogs naturally infected with H canis in the United States outside of the Texas Gulf Coast. Hepatozoon canis appears to be a serious pathogen in the United States that is becoming more widespread geographically.

Obstructive tracheal mass due to an inflammatory polyp in a cat.

A 13-year-old, male domestic shorthair was presented for a 1.5-year history of progressive dyspnea. Multiple intratracheal masses were seen on thoracic radiographs and during bronchoscopy. A diagnosis of an inflammatory polyp infiltrated with lymphocytes and plasma cells was made on histopathological examination of the largest mass following excisional biopsy.

Type I Glanzmann's thrombasthenia in a Great Pyrenees dog.

An 8-month-old female Great Pyrenees dog with chronic epistaxis and a history of gingival bleeding during shedding of deciduous teeth was evaluated for platelet function. Platelet morphology was normal at both the light and electron microscopic level. Platelet number and mean platelet volume were also normal. Platelet aggregation responses to adenosine diphosphate, collagen, platelet activating factor, and thrombin were markedly reduced, although shape change responses were normal. Clot retraction was markedly impaired. Monoclonal antibody (MoAb) Y2/51, a murine anti-human platelet beta 3 antibody that cross-reacts with canine platelet beta 3, and MoAb 5G11, a murine anti-dog platelet alpha IIb beta 3 antibody, bound minimally to affected dog platelets, as demonstrated by flow cytometry. Binding of MoAb Y2/51 was not detectable by immunoblot. MoAb CAP1, a murine anti-dog fibrinogen receptor-induced binding site antibody, failed to bind to affected dog platelets, as demonstrated by flow cytometry. A reduction in glycoproteins alpha IIb and beta 3 was demonstrated by two-dimensional protein electrophoresis. This is the first reported case of type I Glanzmann's thrombasthenia in the dog that closely resembles the clinical syndrome and the platelet morphology described in type I Glanzmann's thrombasthenia of human beings.

Adrenocorticotropic hormone and cortisol concentrations after corticotropin-releasing hormone stimulation testing in cats administered methylprednisolone.

The hypothalamic-pituitary-adrenocortical (HPA) axis was studied in 8 healthy cats after administration of supraphysiologic doses of methylprednisolone (MP). Ovine corticotropin-releasing hormone (oCRH) administration increased cortisol and adrenocorticotropic hormone (ACTH) concentrations. Significant (P < 0.05) suppression of cortisol and a trend toward suppression of ACTH was observed after 1 week of MP administration. The HPA axis quickly recovered from suppressive effects of MP 1 week after administration of the steroid was discontinued. Side effects of oCRH administration were minimal in 7 cats; however, 1 cat had a severe hypotensive reaction. Clinical abnormalities were not associated with MP administration. The HPA axis was suppressed by supraphysiologic doses of MP in all treated cats that lacked clinical signs consistent with iatrogenic HPA axis suppression. Despite the relatively active pars intermedia in cats, compared with human beings and dogs, feedback of MP on the HPA axis resulted in similar trends in oCRH-stimulated ACTH and cortisol concentrations as observed in human beings and dogs. Lack of consistent correlation between ACTH and cortisol concentrations was observed in 3 cats and possibly was related to the active pars intermedia in the cat.

Identification of an intrinsic platelet function defect in Spitz dogs.

A recently identified intrinsic platelet function defect in 2 Spitz dogs is described. Both affected dogs had a history of chronic intermittent bleeding primarily from the nasal, oral, and gastrointestinal mucosa. Platelet aggregation in response to adenosine diphosphate (ADP), collagen, and platelet activating factor (PAF) was absent; however, platelet shape change did occur. Platelets aggregated in response to gamma thrombin, although a delayed onset and a reduced velocity of aggregation were present. Platelet 14C-serotonin release was diminished in response to collagen and PAF. Glycoprotein IIIa was detected on the surface of platelets by flow cytometry. Platelets were morphologically normal under light and electron microscopy. Two male Spitz dogs, related to one of the affected dogs, did not have a bleeding diathesis. Collagen-induced platelet aggregation, however, was diminished in these 2 dogs. This platelet defect most closely resembles the defect described in Basset hounds.

Effects of lactated Ringer solution and prednisolone sodium succinate on dogs with induced hemorrhagic shock.

Hemorrhagic shock was induced in nonsplenectomized dogs by removing 41% of their blood volume over a 15-minute period. Hemodynamic and metabolic variables were determined prior to and for 3 hours after completion of hemorrhage. One group of 5 dogs was not treated. After the 30-minute sample was collected, a second group of 5 dogs was given lactated Ringer solution (LRS) at 88 ml/kg of body weight, IV. A third group of 5 dogs was given LRS (88 ml/kg, IV) and prednisolone sodium succinate (11 mg/kg, IV) 30 minutes after hemorrhage. The IV administration of LRS was completed within 15 minutes. The glucocorticoid was administered as an IV bolus after 500 ml of LRS had been given. The large volume and administration of LRS significantly (P = 0.05) improved many of the hemodynamic and metabolic effects of acute hemorrhage and hemorrhagic shock. At one time or another during the 2.5-hour observation period after the initiation of treatment, mean arterial pressure, cardiac index, systemic vascular resistance, heart rate, respiratory rate, lactate, glucose, and arterial and venous blood gas values were significantly (P = 0.05) improved, compared with baseline values. The addition of prednisolone sodium succinate to the treatment regimen improved the effectiveness of LRS alone only in some dogs at random sampling times. Significant trends were not observed except, possibly, the improvement of venous pH and A-V pH and PCO2 differences.

Platelet function, antithrombin-III activity, and fibrinogen concentration in heartworm-infected and heartworm-negative dogs treated with thiacetarsamide.

Platelet aggregation and release, platelet number, mean platelet volume, antithrombin-III activity, and fibrinogen concentration were evaluated in heartworm-negative and heartworm-infected dogs at baseline and on days 3, 10, and 21 after treatment with thiacetarsamide. Platelet reactivity was enhanced in a group of dogs naturally infected with Dirofilaria immitis, compared with 2 groups of heartworm-negative dogs, but platelet reactivity was not further enhanced after treatment with thiacetarsamide. A significant decrease in antithrombin-III activity was detected 21 days after treatment. The platelets from a group of laboratory Beagles implanted with 50 adult D immitis displayed enhanced reactivity 6 months after implantation, but by 18 months, platelet reactivity had returned to near, or less than, baseline. Platelet reactivity was enhanced after thiacetarsamide treatment in this group. Thiacetarsamide-associated changes were not observed in platelet number or size; antithrombin-III activity decreased, but the change was not significant. Fibrinogen concentration was increased significantly (P less than 0.05) on day 10. Enhanced adenosine diphosphate (ADP)-induced platelet aggregation was observed on days 3, 10, and 21 after treatment in heartworm-negative dogs. This change was not observed in 6 control Beagles not treated with thiacetarsamide. Although antithrombin-III activity was decreased on day 3 and fibrinogen concentration was increased on day 10, paralleling changes observed in the heartworm-infected dogs, the changes were not statistically significant. In this study, thiacetarsamide was procagulatory in heartworm-negative dogs and may be an important contributing factor to the thromboembolism observed with adulticidal therapy.

Effects of treatment with aspirin or aspirin/dipyridamole combination in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

To determine the drug dose required to inhibit platelet reactivity by at least 50%, 2 drug regimens were evaluated in heartworm-negative, heartworm-infected, and heartworm-infected dogs embolized with dead heartworms. Aspirin, or a combination of aspirin and dipyridamole, were administered to 2 groups of Beagles (n = 5 each) for 5 to 9 days; a third group of 5 Beagles served as nontreated controls. For heartworm-negative dogs, mean (+/- SD) aspirin dosage that inhibited collagen-induced platelet reactivity by at least 50% was 6 (+/- 2) mg/kg of body weight given once daily. The aspirin/diphridamole combination dosage was 1 mg of each drug/kg given every 12 hours. All dogs (n = 15) were implanted with 7 adult heartworms each and remedicated (or not treated) beginning at 21 days after heartworm implantation. In heartworm-infected dogs, mean aspirin dosage required to inhibit collagen-induced platelet reactivity greater than or equal to 50% was 10 (+/- 6) mg/kg. Mean dosage of aspirin/dipyridamole combination was 1.6 +/- (0.5) mg of each drug/kg given every 12 hours. When platelet reactivity in response to collagen was determined to be inhibited by at least 50% in all medicated dogs, each dog (n = 15) was embolized with 7 dead adult heartworms to mimic heartworm adulticidal treatment. Platelet reactivity was monitored for 21 days after treatment, and drug dose was adjusted to maintain platelet inhibition by at least 50%. In embolized dogs, mean aspirin dosage was 17 (+/- 14) mg/kg given once daily. Mean dosage of the aspirin/dipyridamole combination was 2.8 (+/- 1.3) mg of each drug/kg given every 12 hours. All dogs (n = 15) were euthanatized 21 days after heartworm embolization. Each lung lobe was evaluated for severity of lesions and presence of organized or fibrinous thrombi. Lesion severity in the aspirin- and aspirin/dipyridamole-treated dogs was not significantly different from that in control dogs.

Effects of treatment with ticlopidine in heartworm-negative, heartworm-infected, and embolized heartworm-infected dogs.

Ticlopidine hydrochloride was evaluated for its effectiveness in inhibiting platelet aggregation and serotonin release in 5 laboratory Beagles before and after heartworm implantation with 7 adult Dirofilaria immitis, and after embolization with 7 dead heartworms to mimic what happens after heartworm adulticide treatment. Five other laboratory Beagles, similarly implanted and embolized with heartworms, were used as nonmedicated controls. During the heartworm-negative stage, the dosage of ticlopidine that inhibited adenosine diphosphate (ADP)-induced platelet aggregation in 5 dogs by at least 50% after 5 days of treatment was 62 mg/kg of body weight once a day. In the same dogs implanted with 7 adult heartworms 21 days previously, mean (+/- SD) ticlopidine dosage required to obtain similar results was 71 (+/- 13) mg/kg given once daily. During the 21 days after dead heartworms were implanted in heartworm-infected dogs, mean ticlopidine dosage was 108 (+/- 35) mg/kg (range, 62 to 150 mg/kg). Ticlopidine treatment was associated with increased platelet numbers in all 5 dogs during the heartworm-negative stage and in 4 of 5 dogs during the heartworm implantation and heartworm embolization stages. Mean platelet volume tended to decrease as platelet numbers increased. At necropsy, gross and histologic pulmonary lesions were less severe in ticlopidine-treated dogs than in nonmedicated control dogs.

Multi-enzyme catalyzed rapid ethanol lowering in vitro.

Ethanol was oxidized to acetate by an enzyme system using yeast alcohol dehydrogenase (YADH), yeast aldehyde dehydrogenase (YALDH), and lactic dehydrogenase (LDH) recycling NAD in two model duodenal fluids and in canine duodenal aspirate in vitro. Sufficient enzyme activities were maintained to convert as much as 34% of the original ethanol to acetate with negligible acetaldehyde accumulation.