Catecholamine and beta-adrenoceptor influences on airway reactivity to antigen in guinea pigs.

The aim of the present study was to analyze the increased airway reactivity to antigen induced by beta-adrenoceptor blockade, adrenalectomy or medullectomy and to assess the contribution of circulating catecholamines to the increased reactivity. In anesthetized guinea pigs sensitized to ovalbumin (OA), administration of OA produced a dose-related bronchoconstriction characterized by threshold increases in airway insufflation pressure at 0.1 mg/kg i.v. and a near-maximal increase by 0.3 mg/kg i.v. Pretreatment with R(+) propranolol (0.5 mg/kg i.v.) 5 min prior to antigen did not significantly alter airway responses to antigen when compared to vehicle-treated animals. However, pretreatment with 0.5 mg/kg i.v. S(-) propranolol, racemic propranolol or nadolol markedly enhanced (10- to 15-fold) the airway response to the low-dose antigen. In addition, in guinea pigs which had been adrenalectomized, the reactivity to low-dose antigen was enhanced to a similar extent as that of beta-antagonist-treated animals when compared to sham-operated animals. Baseline plasma concentrations of epinephrine were significantly higher in sham-operate guinea pigs (1,494 +/- 223 ng/ml) when compared to adrenalectomized animals (412 +/- 44 ng/ml). Upon antigen exposure, epinephrine levels rose 5-fold (6,859 +/- 1,308 ng/ml) from baseline in sham-operated guinea pigs and were not significantly changed in adrenalectomized animals (848 +/- 208 ng/ml). Specific airway conductance measurements in conscious guinea pigs revealed that animals which had been medullectomized 2 weeks previously responded to lower provocative concentrations of aerosol OA (0.05-0.5%) than corresponding sham-operated animals. Airway reactivity to inhaled acetylcholine (0.1-1%) was similar in medullectomized and sham guinea pigs. Plasma concentrations of epinephrine were significantly lower in medullectomized guinea pigs (327 +/- 88 ng/ml) when compared to sham-operated animals (832 +/- 162 ng/ml). The results of the present study indicate that beta-adrenoceptor antagonism or changes in circulating epinephrine levels markedly alter the response to antigen in sensitized guinea pigs.

A chronic Access Port model for direct delivery of drugs into the intestine of conscious dogs.

Gastric physiologic properties and emptying can significantly affect the stability and absorption of drugs given orally. A method to deliver drugs directly into the intestines and peritoneal cavity in conscious dogs by using a modified Vascular-Access Port (VAP) was developed and validated. Modified silastic VAP catheters size 7 or 9 French were placed in the duodenum, jejunum, colon, and/or peritoneal cavity in nine adult male dogs. Catheter placement was validated in six dogs by using contrast radiography and by monitoring the fecal excretion of blood after injection of blood via the VAP directly into the intestines. Three dogs were successfully used to evaluate the absorption of a peptide that inhibits platelet aggregation. Results showed this to be a feasible, easily validated model for delivering drugs directly into the intestines of conscious dogs.

Vascular access ports for chronic serial infusion and blood sampling in New Zealand white rabbits.

Although rabbit ear vessels are readily accessible, the veins can collapse and thrombose after multiple venipunctures, and the artery may undergo vasospasm when repeatedly catheterized. Twenty-two male and female New Zealand White rabbits were cannulated with the catheter tip located in the jugular vein. The mean life of the port was noted to be approximately 3.5 months, with ranges of 3 days to 10 months. With proper maintenance and care, vascular access ports are a useful alternative to multiple venipuncture for long-term studies, thereby sparing marginal and central vessels and minimizing stress to both animals and investigators.

Eosinophilic enteritis in a specific-pathogen-free cat.

Moderate to severe, chronic, segmental eosinophilic enteritis was diagnosed histopathologically in a 2-year-old, specific-pathogen-free cat. Peripheral eosinophilia was not observed, although eosinophilic infiltrates were found in mesenteric lymph nodes. Typical gastrointestinal signs characteristic of this disease (diarrhea, vomiting, and anorexia) were not seen; only weight loss was observed. Treatment was not instituted. Previously reported cases of feline eosinophilic enteritis have been associated with several domestic breeds having a diversity of backgrounds. The cat of this report had a known genealogy and disease-free history, was reared under barrier conditions, and was fed a restricted diet. The cause of the disease in this cat was not determined.

Use of danazol for treatment of corticosteroid-resistant immune-mediated thrombocytopenia in a dog.

A routine health screen of a 7 1/2-year-old female Beagle participating as a control in a long-term study revealed thrombocytopenia. Immune thrombocytopenia was diagnosed on the basis of regenerative bone marrow findings (high number of megakaryocytes) and evidence of antiplatelet antibodies. Treatment with prednisone at dosages up to 1 mg/kg of body weight every 12 hours resulted in limited improvement, with relapses of severe thrombocytopenia thwarting attempts to taper the corticosteroid, and was further complicated by side effects of the drug. Addition of danazol to the treatment regimen (5 mg/kg, q 12 h) resulted in remission of the thrombocytopenia within 2 weeks and permitted the dosage of prednisone to gradually be reduced and discontinued. Associated with this response was a decrease in platelet-associated IgG to values comparable with control samples.