Pharmacokinetics of morphine, buprenorphine and pethidine were determined in 10 cats. Six cats received morphine (0.2 mg/kg) intravenously and four intramuscularly. Five received buprenorphine (0.01 mg/kg) intravenously and six intramuscularly. Six received pethidine (5 mg/kg) intramuscularly. Jugular venous blood samples were collected at time points to 24 h, and plasma morphine concentrations were measured by high performance liquid chromatograpy (HPLC), buprenorphine by radioimmunoassay (RIA) and pethidine by gas chromatography. Our data for morphine show elimination half-life (t1/2el) 76.3 min intravenous (i.v.) and 93.6 min intramuscular (i.m.); mean residence time (MRT) 105.0 and 120.5 min; clearance (Clp) 24.1 and 13.9 mL/kg/min; and volume of distribution (V(dss)) 2.6 and 1.7 L/kg, respectively. Comparable data for buprenorphine are t1/2el 416.8 and 380.2 min; MRT 417.6 and 409.8 min; Clp 16.7 and 23.7 mL/kg/min; and V(dss) 7.1 and 8.9 L/kg. For i.m. pethidine, t1/2el 216.4 min; MRT 307.5 min; Clp 20.8 mL/kg/min and V(dss) 5.2 L/kg. For i.m. dosing, the tmax for morphine, buprenorphine and pethidine were 15, 3 and 10 min, respectively. The pharmacokinetics of the three opioids in cats are broadly comparable with those of the dog, although there is a suggestion that the cat may clear morphine more slowly.
Although it is established that the fetus can successfully withstand a single, acute hypoxaemic challenge during gestation, little is known about what effects prevailing adverse intrauterine conditions might have on the fetal response to acute hypoxaemia. The aims of this study were therefore: (1) to characterise the effects of prevailing and sustained hypoxaemia, acidaemia or hypoglycaemia on the fetal cardiovascular responses to an episode of acute hypoxaemia; and (2) to determine the effects of these adverse intrauterine conditions on mechanisms mediating these cardiovascular responses. Thirty‐three Welsh Mountain sheep fetuses were chronically instrumented (1–2 % halothane) between 117 and 125 days of gestation (term is ca 145 days) with amniotic and vascular catheters and with a transit‐time flow probe around a femoral artery. The animals were divided retrospectively into four groups based upon post‐surgical, sustained, basal blood oxygen (chronically hypoxaemic; Pa,O2, 17.3 ± 0.5 mmHg; n= 8), glucose (chronically hypoglycaemic; blood glucose, 0.49 ± 0.03 mmol l−1; n= 6) and acid‐base (chronically acidaemic; pHa, 7.25 ± 0.01; n= 5) status. Values for compromised fetuses were −2 s.d. from a group of control (n= 14) fetuses. At 130 ± 4 days, a 1 h episode of acute, isocapnic hypoxaemia (9 % O2 in N2, to reduce carotid Pa,O2 to 12 ± 1 mmHg) was induced in all fetuses by reducing the maternal inspired O2 fraction (FI,O2). Fetal cardiovascular variables were recorded at 1 s intervals throughout the experimental protocol and arterial blood samples taken at appropriate intervals for biophysical (blood gases, glucose, lactate) and endocrine (catecholamines, vasopressin, cortisol, ACTH) measures. During acute hypoxaemia all fetuses elicited hypertension, bradycardia and femoral vasoconstriction. However, prevailing fetal compromise altered the cardiovascular and endocrine responses to a further episode of acute hypoxaemia, including: (1) enhanced pressor and femoral vasoconstriction; (2) greater increments in plasma noradrenaline and vasopressin during hypoxaemia; and (3) basal upward resetting of hypothalamic‐pituitary‐adrenal axis function. Only chronically hypoxaemic fetuses had significantly elevated basal concentrations of noradrenaline and enhanced chemoreflex function during acute hypoxaemia. These data show that prevailing adverse intrauterine conditions alter the capacity of the fetus to respond to a subsequent episode of acute hypoxaemia; however, the partial contributions of hypoxaemia, acidaemia or hypoglycaemia to mediating these responses can vary.
Six domestic shorthair cats, aged three to four years and weighing 5.1 to 7.4 kg, were used to assess the thermal antinociceptive effect of a transdermal buprenorphine patch, designed to supply 35 mug buprenorphine/hour, which was applied to the shaved thorax. The cats' thermal thresholds were tested before the patch was applied and two, four, six, eight, 10, 12, 14 and 16 hours after it had been applied, and then every six hours until it was removed after 72 hours, and for a further 24 hours afterwards. Blood was collected at each time to measure the plasma concentration of buprenorphine. The patches did not produce a significant change in the thermal thresholds of the cats throughout the testing period. The mean (sd) peak plasma buprenorphine concentration was 10 (0.81) ng/ml.
At birth, the endocrine pancreas must assume a glucoregulatory role if the neonate is to survive the transition from parenteral to enteral nutrition. In species like the horse, neonatal hypoglycaemia is common, which suggests that the glucoregulatory mechanisms are not always fully competent at birth. Hence, this study examined pancreatic cell function in newborn foals during nutritional adaptation over the first 10 days post partum. Over a 48 h period at three time intervals after birth (days 1-2, 5-6 and 9-10 post partum), the cell responses to suckling and to intravenous administration of glucose, arginine and saline were measured in seven normal pony foals. Basal plasma concentrations of proinsulin, but not insulin or glucose, increased significantly between days 1 and 10. Suckling caused a gradual increase in plasma glucose, which was accompanied by a significant increase in plasma insulin concentrations 15 min after the onset of suckling on days 5 and 9, but not day 1. There was no significant change in plasma proinsulin concentrations in response to suckling at any age. At all ages studied, glucose and arginine administration stimulated an increase in the plasma concentrations of insulin and proinsulin; these cell responses did not change significantly with postnatal age. The insulin responses to glucose were significantly greater than those of arginine at each time period. Glucose clearance was significantly slower on day 1 than subsequently. Proinsulin and glucose, but not insulin, concentrations decreased significantly after saline administration at all three ages. At each time period, there was a significant positive relationship between the plasma insulin and proinsulin concentrations, the slope of which was significantly shallower on days 1-2 than subsequently. These results show that equine cells are responsive to glucose and arginine and release both insulin and proinsulin during the immediate postnatal period. They also suggest that newborn foals may be insulin resistant on the first day after birth.
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