Thrombolytic Therapy in Dogs and Cats

Objective: To review the thrombolytic agents most commonly used in humans, their mechanisms of action, potential uses, adverse effects, and reports of their use in dogs and cats.
Human data synthesis: Thrombolytic agents avaliable in human medicine include streptokinase, urokinase, tissueplasminogen activator (t-PA), single-chain urokinase plasma activator (scu-PA) and anisoylated plasminogen-strep-tokinase activator complex (APSAC). These agents were originally used for the management of proximal deep vein thrombosis and severe pulmonary embolism but more recently, use of these drugs has been extended to include the treatment of acute peripheral arterial disease, cerebrovascular disease (stroke) and acute coronary thrombosis. The most predictable side effect associated with the use of thrombolytic therapy is hemorrhage.
Veterinary data synthesis: Clinical experience with thrombolytic agents in small animals is limited to streptokinase and t-PA. It is possible, that as in humans, canine and feline patients with PTE and right ventricular dysfunction may benefit from thrombolytic therapy but there are no veterinary studies to support this theory to date. Successful use of streptokinase has been documented in a small number of canine patients with systemic thromboembolism. ⁶³ Thrombolytic therapy is relatively efficacious in cats with aortic thromboemboli but is associated with a high mortality rate. ^59,60,64 With regard to use of t-PA in veterinary medicine, the small number of animals treated with varying protocols makes it impossible to provide safe and effective dose recommendations at this time.
Conclusions: Future goals for thrombolytic therapy in veterinary medicine include determination of more specific clinical indications, as well as design of effective protocols that minimize mortality and morbidity.     

Effect of administration of a phospholipid emulsion on the initial response of horses administered endotoxin

OBJECTIVE: To evaluate the effect of a phospholipid emulsion (PLE) on the initial response of horses to administration of endotoxin. ANIMALS: 12 healthy adult horses. PROCEDURES: Horses were assigned to 2 treatment groups (6 horses/group). The control group was administered 1 L of saline (0.9% NaCl) solution, and the treated group was administered PLE (200 mg/kg, IV); treatments were administered during a period of 120 minutes. An infusion of endotoxin was initiated in both groups starting 1 hour after initiation of the saline or PLE solutions. Physical examination and hemodynamic variables were recorded, and blood samples were analyzed for concentrations of tumor necrosis factor (TNF)-alpha, interleukin-6, thromboxane B2 (TxB2), 6 keto-prostaglandin F (PGF)1alpha, total leukocyte count, and PLE concentrations. An ANOVA was used to detect significant differences. RESULTS: Administration of PLE resulted in significantly lower rectal temperature, heart rate, cardiac output, right atrial pressure, and pulmonary artery pressure and higher total leukocyte counts in treated horses, compared with values for control horses. The TNF-alpha concentration was significantly less in treated horses than in control horses. The TxB2 and 6 keto-PGFF1alpha concentrations were significantly different between treated and control horses at 30 minutes (TxB2) and at 30 and 60 minutes (6 keto-PGF1alpha). CONCLUSIONS AND CLINICAL RELEVANCE: Prior infusion of PLE in horses administered a low dose of endotoxin decreased rectal temperature, heart rate, pulmonary artery pressure, and TNF-alpha concentrations. Results of this study support further evaluation of PLE for use in the treatment of horses with endotoxemia.     

Rough vaccines in animal brucellosis: structural and genetic basis and present status

Brucellosis control and eradication requires serological tests and vaccines. Effective classical vaccines (S19 in cattle and Rev 1 in small ruminants), however, induce antibodies to the O-polysaccharide of the lipopolysaccharide which may be difficult to distinguish from those resulting from infection and may thus complicate diagnosis. Rough attenuated mutants lack the O-polysaccharide and would solve this problem if eliciting protective immunity; the empirically obtained rough mutants 45/20 and RB51 have been used as vaccines. Strain 45/20 is reportedly unstable and it is not presently used. RB51 is increasingly used instead of S19 in some countries but it is rifampicin resistant and its effectiveness is controversial. Some controlled experiments have found good or absolute protection in adult cattle vaccinated orally (full dose) or subcutaneously (reduced dose) and in one field experiment, RB51 was reported to afford absolute protection to calves and to perform better than S19. Controlled experiments in calves, however, have shown reduced doses of RB51 to be ineffective, full doses only partially effective, and RB51 less effective than S19 against severe challenges. Moreover, other observations suggest that RB51 is ineffective when prevalence is high. RB51 is not useful in sheep and evidence in goats is preliminary and contradictory. Rough mutants obtained by molecular biology methods on the knowledge of the genetics and structure of Brucella lipopolysaccharide may offer alternatives. The B. abortus manBcore (rfbK) mutant seems promising in cattle, and analyses in mice suggest that mutations affecting only the O-polysaccharide result in better vaccines than those affecting both core and O-polysaccharide. Possible uses of rough vaccines also include boosting immunity by revaccination but solid evidence on its effectiveness, safety and practicality is not available.     

Ventricular pneumocephalus and septic meningoencephalitis secondary to dorsal rhinotomy and nasal polypectomy in a dog

CASE DESCRIPTION: A 4-year-old sexually intact female French Bulldog was evaluated because of lethargy, anorexia, and chronic rhinitis-sinusitis. The dog had nasal discharge of 18 months' duration; dorsal rhinotomies were performed 3 months and 2 weeks prior to referral. CLINICAL FINDINGS: On initial evaluation, intraventricular pneumocephalus and sinusitis were diagnosed; CSF analysis revealed high total protein concentration and mononuclear pleocytosis. The dog's condition improved with treatment. Two weeks after discharge, it was treated by a local veterinarian because of upper airway obstruction; 3 days later, the dog was referred because of seizures. Computed tomography revealed a large fluid-filled, left lateral ventricle and a soft tissue mass protruding through a cribriform plate defect. The mass was histologically consistent with brain tissue. Findings of clinicopathologic analyses were unremarkable. Results of cytologic examination of a CSF sample were indicative of septic, suppurative inflammation, and bacteriologic culture of CSF yielded Escherichia coli. TREATMENT AND OUTCOME: Amputation of the herniated olfactory bulb and antimicrobial treatment resolved the septic meningoencephalitis, but neurologic deficits recurred 6 weeks later. Definitive correction of the cribriform plate defect with bone and fascial grafts was attempted. Postoperative rotation of the bone graft resulted in cerebral laceration and hemorrhage, and the dog was euthanized. CLINICAL RELEVANCE: Findings suggest that following dorsal rhinotomy and nasal polypectomy surgery, the dog developed herniation of the left olfactory bulb, intra-ventricular pneumocephalus, and septic meningo-encephalitis because of a cribriform plate defect. Care must be taken to prevent rotation of bone grafts used in cribriform defect repair.     

The effects of two analgesic regimes on behavior after abdominal surgery in Steller sea lions

This study examined the effects of two non-steroidal anti-inflammatory drug (NSAID) treatment protocols on the behavioral responses of juvenile Steller sea lions after abdominal surgery. Sea lions were randomly assigned to one of two treatments designed to control post-operative pain. The flunixin group (n=6) received flunixin meglumine (1mg/kg) administered as a single intramuscular (IM) injection before extubation from surgery. The carprofen group (n=5) received carprofen (4.4 mg/kg) as an IM injection before extubation, then orally at 24, 48 and 72 h after surgery. Seven behaviors related to post-operative pain were monitored by observers, blinded to treatment, for a total of 10 days (3 days pre-, day of surgery, and 6 days post-surgery). All seven behaviors changed after surgery regardless of NSAID treatment, two of which returned to baseline within 6 days of surgery. Only one behavior was mildly affected by analgesic treatment: sea lions in the carprofen group tended to spend less time lying down in Days 1-3 following surgery (i.e., the days which they received oral carprofen). These results suggested that neither treatment, at the dose administered, was effective in controlling pain in the days following this surgery.     

Ultrasonographic assessment of maternal cardiac function and peripheral circulation during normal gestation in dogs

The aim of this study was to describe changes in cardiac morphology, systolic function and some peripheral hemodynamic parameters during normal pregnancy in dogs. Twenty healthy bitches, 10 pregnant (PG) and 10 non-pregnant controls (CG), were evaluated every 10 days using echocardiography from day 0 of the estrus cycle to parturition or to day 65 for the PG and CG groups, respectively. Systolic blood pressure (SBP) and uterine artery resistance index (RI) were also assessed. Throughout the study, the shortening fraction and cardiac output increased up to 30% vs. 5% (P<0.01) and 45% vs. 2% (P<0.01) in the PG and CG groups, respectively. In contrast, SBP and RI diminished up to 20% vs. 1% (P<0.01) and 29% vs. 0% (P<0.01) in the PG and CG groups, respectively. In conclusion, a decrease in afterload, an increase in cardiac output and cardiac hypertrophy appear to be the result of the hemodynamic modifications occurring during pregnancy in dogs.     

Use of a sustained release preparation of clotrimazole to treat dermatophytosis in a siamang (Hylobates syndactylus).

In November 2004, an adult male siamang (Hylobates syndactylus) from The Tisch Family Zoological Gardens-Jerusalem Biblical Zoo (Israel) presented with skin lesions on various body parts. Lesions consisted of alopecia and dry, crusty areas of hyperkeratosis. A diagnosis of dermatophytosis due to Microsporum canis was determined by fungal culture of skin scraping taken from the edge of several lesions. Treatment with various oral and topical antifungal agents such as griseofluvin, itraconozole, and lufenuron resulted in the resolution of most lesions and a decrease in size of the single remaining lesion, which continued to be culture positive for M. canis. The animal was anesthetized and an experimental sustained-release clotrimazole varnish was painted directly on the lesion. Initially there was no change in the lesion, and 2 months later a slightly altered formula was applied under anesthesia. One month later, the lesion began to reduce in size; 3 months after the start of treatment, although 2 years after the onset of clinical signs, the lesion resolved. Minimizing the number of treatments is always an advantage when dealing with exotic animals or zoological collections.     

Retrospective Study: Incidence of ionized hypocalcemia in septic dogs and its association with morbidity and mortality: 58 cases (2006–2007)

Objective – To determine the incidence rate and prognostic significance of ionized hypocalcemia (iHCa) among septic dogs. Design – Retrospective study Setting – Veterinary teaching hospital Animals – Fifty‐eight septic dogs that were presented to Cornell University Hospital for Animals between January 2006 and December 2007. Procedure – Cases were diagnosed with sepsis if they exhibited 2 or more criteria of the systemic inflammatory response syndrome with a concurrent documented infectious focus. Cases were excluded if diagnosed with a concurrent illness reportedly associated with calcium derangements. Lowest, mean, and highest blood ionized calcium concentrations were recorded and statistically analyzed for an association with morbidity, as measured by duration of hospitalization and number of blood product transfusions, and outcome. In addition, the incidence rate of iHCa was recorded. Results – Of the 58 cases included in this study, iHCa was documented in 4 of 6 (67%) patients that died, 5 of 19 (26%) euthanized patients and 5 of 33 (15%) patients that survived to discharge, with an overall incidence of 24%. Dogs that died during hospitalization had more severe iHCa than patients that were discharged or euthanized as well as significantly lower mean ionized calcium concentrations than patients who were discharged. Severity of iHCa was also associated with a longer duration of hospitalization. The highest ionized calcium concentration was not associated with outcome. Conclusion and Clinical Relevance – This study is the first to document the incidence of iHCa among septic dogs. Because both low mean ionized calcium and the lowest documented ionized calcium concentration are associated with poor outcome, it is likely that both the severity and duration of hypocalcemia are important in these patients. Further prospective studies investigating the prognostic significance, etiology and treatment of iHCa among septic veterinary patients are needed to better understand its role in sepsis.