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.     

Salinity an Environmental “Filter” Selecting for Plant Invasiveness? Evidence from Indigenous Lepidium alyssoides on Chihuahuan Desert Shrublands

A better understanding of site-specific factors such as soil salinity that regulate plant invasions is needed. We conducted a 3-mo greenhouse study to evaluate the salinity responses of three local maternal sources of Lepidium alyssoides, which is an indigenous species shown to aggressively colonize disturbed shrubland sites in the southwestern United States, including those affected by high salinity and sodicity. Results indicated that there were little or no population effects on plant evapotranspiration (ET), growth, and tissue Na and Cl concentrations. Significant reductions in seedling growth and ET were largely independent of various isosmotic saline irrigation solutions that included NaCl, Na₂SO₄, and CaCl₂, each at ? 0.1 MPa and ? 0.2 MPa, suggesting that ET and growth were controlled by solution osmotic potential. The combined Na and Cl concentrations in leaves were 9–10% of dry weight with no visible sign of injury. However, increasing leaf mortality and abscission as a proportion of total leaf production was observed in the high-salt treatments (? 0.2 MPa), with a combined Na and Cl concentration reaching 16% with high NaCl. Under saline conditions, considerable foliage salt loads of this species could deposit high-salt litter to potentially alter a landscape to its own favor and to the detriment of other salt-sensitive species. Results of this study add to a limited quantitative database on site-specific salinity factors governing plant invasions by showing the potential for these populations to behave invasively under saline conditions and, thus, potential for soil salinity assessment to predict incipient populations. However, due to its halophytic traits and indigenous status, L. alyssoides may alternatively provide ecosystem services to salinized shrublands of the arid and semiarid southwestern United States.     

Extensive mast cell degranulation in bovine respiratory syncytial virus-associated paroxystic respiratory distress syndrome

Bovine respiratory syncytial virus (BRSV) infection is an important cause of outbreaks of respiratory disease among calves. This virus commonly induces mild to severe respiratory signs but, in a substantial proportion of cases, is also reported to be associated with paroxystic respiratory distress syndrome (PRDS). The pathogenesis of this 'malignant' clinical form has not been fully elucidated. The present study aimed at determining whether mast cell (MC) degranulation plays a role in the physiopathologic cascade leading to the PRDS. Paired serum samples were taken in herds during outbreaks of severe respiratory diseases (acute sera) and 3 weeks after (convalescent sera). Based on seroconversion to BRSV and clinical picture, 67 pairs of sera were selected from calves with a BRSV-associated PRDS for circulating MC tryptase determination. A MC metachromatic score was measured in post-mortem lungs from animals died from a BRSV-associated PRDS (principals) and compared with reference scores obtained from healthy lungs (controls). Levels of tryptase were significantly higher in acute sera (26.6 +/- 12.4 microg/l) compared to convalescent sera (8.4 +/- 7.8 microg/l; P<0.001). Metachromatic scores yielded significantly different results between controls and principals (P<0.01), demonstrating a significant disappearance of metachromatic granules from lung MCs in principals. Taken together, these data demonstrate the presence of an extensive MC degranulation in BRSV-associated PRDS.     

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.     

Demonstration of inflammatory cell population changes in rat lungs in response to intratracheal instillation of spring wheat dust using lung enzymatic digestion and centrifugal elutriation

The inhalation of grain dust by grain workers is responsible for a large number of pulmonary pathophysiologies. These problems may be acute or chronic and may be mediated by the chronic activation of the immune system. Constant inflammatory states in the lung may eventually lead to tissue damage and respiratory deficit. This study was designed to measure the changes in the relative number of inflammatory cells in peripheral blood, bronchoalveolar spaces, and lung interstitium that occur in response to intratracheally instilled airborne spring wheat dust in rats. It was found that 6h after instillation with dust, neutrophils were present in greater numbers in the blood and bronchoalveolar spaces than in lung interstitium. After 24h, there appeared to be a larger number of neutrophils in the lung interstitium in dust-instilled animals than in saline-instilled controls. These results indicate that intratracheal instillation of grain dust initiates an acute inflammatory reaction, and that there is an initial influx of neutrophils into the air spaces of the lung followed by transit of these cells into the lung interstitium.