Influence of general anaesthesia on the pharmacokinetics of intravenous fentanyl and its primary metabolite in horses

REASONS FOR PERFORMING STUDY: In order to evaluate its potential as an adjunct to inhalant anaesthesia in horses, the pharmacokinetics of fentanyl must first be determined. OBJECTIVES: To describe the pharmacokinetics of fentanyl and its metabolite, N-[1-(2-phenethyl-4-piperidinyl)maloanilinic acid (PMA), after i.v. administration of a single dose to horses that were awake in Treatment 1 and anaesthetised with isoflurane in Treatment 2. METHODS: A balanced crossover design was used (n = 4/group). During Treatment 1, horses received a single dose of fentanyl (4 microg/kg bwt, i.v.) and during Treatment 2, they were anaesthetised with isoflurane and maintained at 1.2 x minimum alveolar anaesthetic concentration. After a 30 min equilibration period, a single dose of fentanyl (4 microg/kg bwt, i.v.) was administered to each horse. Plasma fentanyl and PMA concentrations were measured at various time points using liquid chromatography-mass spectrometry. RESULTS: Anaesthesia with isoflurane significantly decreased mean fentanyl clearance (P < 0.05). The fentanyl elimination half-life, in awake and anaesthetised horses, was 1 h and volume of distribution at steady state was 0.37 and 0.26 l/kg bwt, respectively. Anaesthesia with isoflurane also significantly decreased PMA apparent clearance and volume of distribution. The elimination half-life of PMA was 2 and 1.5 h in awake and anaesthetised horses, respectively. CONCLUSIONS AND POTENTIAL RELEVANCE: Pharmacokinetics of fentanyl and PMA in horses were substantially altered in horses anaesthetised with isoflurane. These pharmacokinetic parameters provide information necessary for determination of suitable fentanyl loading and infusion doses in awake and isoflurane-anaesthetised horses.     

Involvement of PAPP‐A and IGFR1 in Cystic Ovarian Disease in Cattle

Cystic ovarian disease (COD) is one of the main causes of infertility in dairy cattle. It has been shown that intra‐ovarian factors, such as members of the insulin‐like growth factor (IGF) system, may contribute to follicular persistence. The bioavailability of IGF to initiate its response by binding to specific receptors (IGFRs) depends on interactions with related compounds, such as pregnancy‐associated plasma protein A (PAPP‐A). The aim of this study was to determine IGFR1 and PAPP‐A expression both in follicles at different stages of development and in cysts, to evaluate the roles in the etiopathogenesis of COD in cattle. The mRNA expression of PAPP‐A was higher in granulosa cells of large tertiary follicles than in cysts, whereas the protein PAPP‐A present in the follicular fluid from these follicles showed no differences. Although no PAPP‐A mRNA expression was detected in smaller tertiary follicles, in their follicular fluid, this protease was detected in lesser concentration than in cysts. The mRNA expression of IGFR1 was lower in granulosa cells from cystic follicles than in those from tertiary ones. However, the protein expression of this receptor presented the highest levels in cystic structures, probably to increase the possibility of IGF response. The data obtained would indicate that animals with COD have an altered regulation of the IGF system in the ovary, which could be involved in the pathogenesis of this disease in cattle.     

Acute small intestinal obstruction associated with Parascaris equorum infection in young horses: 25 cases (1985–2004)

AIMS: To retrospectively evaluate the medical and surgical records of horses with acute small intestinal obstructions associated with Parascaris equorum infection; to describe the gastrointestinal lesions; and to determine the outcome of cases with such lesions.

METHODS: Records of 25 horses with acute small intestinal obstruction associated with P. equorum between 1985 and 2004 were reviewed to determine signalment, history, physical examination, surgical or post-mortem findings, and outcome.

RESULTS: All horses except one were less than 12 months old. Standardbreds were over-represented in the population studied. Sixteen horses (72%) had been administered anthelmintics, including pyrantel (n=8), ivermectin (n=7), and trichlorphon (n=1), within 24 h prior to the onset of colic. Of the 25 cases reviewed, 16 had simple obstructive ascarid impactions (SOAIs), and nine had complicated obstructive ascarid impaction (COAI) including volvulus (n=6) or intussusception (n=3), both concurrent with ascarid impaction of the small intestine. Short-term survival (discharge from hospital) occurred in 79% of horses treated for SOAI, and was 64% for all horses. Long-term survival (>1 year) occurred in 33% of horses with SOAI, and the overall long-term survival was 27% for all horses. Formation of adhesions was the most frequent finding associated with death for horses that did not survive long-term.

CONCLUSIONS AND CLINICAL RELEVANCE: The incidence of anthelmintic treatment within 24 h of the onset of colic in this study population (72%) was higher than that previously reported. Resistance of P. equorum to ivermectin recently reported in Ontario may be associated with increased ascarid burdens, predisposing horses to ascarid impaction. The long-term survival of these horses was better than that reported previously.     

Acute myelogenous leukaemia in a mare

SUMMARY: A 5-year-old Thoroughbred mare presented with a 4 week history of weight loss, fever and leukopenia. Rectally, a large active foetus, thickened spleen and an abdominal mass were palpated. Leukopenia, mild anaemia, marked thrombocytopenia and hyperfibrinogenaemia were found. Cytology and cytochemical staining of a bone marrow aspirate supported a diagnosis of acute myelogenous leukaemia. The mare deteriorated despite medical therapy and was humanely euthanased.     

Cerebral and conjunctival haemorrhages associated with von Willebrand factor deficiency and canine angiostrongylosis

A case of angiostrongylosis is described in a 14-month-old golden retriever bitch. Conjunctival haemorrhage and neurological signs, referable to a space-occupying cerebral lesion, were associated with defective primary haemostasis caused by low levels of von Willebrand factor. Full clinical recovery followed treatment with desmopressin, fresh whole blood transfusion, fenbendazole and supportive care. The magnetic resonance image of the suspected organising haematoma is described. Similarities to the human condition, acquired von Willebrand syndrome, and a possible role for aberrant larval migration in haematoma formation are suggested.