Search PubMed⌕ Search

Biomedical subjects

P Lees

Publications and source records attributed to P Lees.

At least 199 records · Page 11Linked to original sources
PubMed1970

Influence of halothane and catecholamines on heart rate and rhythm in the horse.

1. Ventricular ectopic beats were recorded in eight of thirteen conscious horses following the intravenous administration of adrenaline in doses of 3 mug/kg. Following pre-treatment with either atropine sulphate (0.1 mg/kg) or propranolol hydrochloride (0.1 mg/kg), the same dose level of adrenaline failed to produce ventricular ectopic beats.2. Halothane anaesthesia sensitized the equine heart to the arrhythmogenic actions of adrenaline; the incidence and duration of ventricular arrhythmias being greater than in conscious animals. In comparison with the findings in conscious horses, ether anaesthesia appeared to protect the heart against adrenaline-induced arrhythmias.3. From a comparison of the arrhythmogenic, chronotropic and pressor actions of adrenaline, noradrenaline and isoprenaline during halothane anaesthesia, it was concluded that sensitization to the arrhythmogenic actions of catecholamines resulted primarily from the action of halothane on the ventricle. The results also indicated that the pressor responses to catecholamines during halothane anaesthesia probably played some part in the genesis of arrhythmias.4. No "spontaneous" ventricular arrhythmias were recorded in twenty-four horses anaesthetized with halothane or in sixteen animals under ether anaesthesia.5. The available evidence indicates that a moderate to fairly severe degree of hypercapnia produced little increase in sympathetic control of the myocardium during halothane anaesthesia; the absence of irregularities in ventricular rhythm during halothane anaesthesia were attributed to this factor.

Anesthesia, Inhalation↗
PubMed1969

The influence of suxamethonium on cardiovascular and respiratory function in the anaesthetized horse.

1. In horses anaesthetized with halothane the intravenous administration of suxamethonium chloride, at a dose level of 0.2 mg/kg, produced a short-lived period of hypoventilation, which was associated with increases in arterial blood PCO(2) levels and in plasma concentrations of bicarbonate, sodium and potassium ions, and reductions in arterial blood pH and PO(2) values.2. The respiratory depressant action of suxamethonium chloride 0.2 mg/kg was accompanied by increases in blood pressure and heart rate. Doses of suxamethonium chloride 0.4 mg/kg produced similar but quantitatively greater changes in cardiovascular and respiratory function. These effects were not accompanied by cardiac arrhythmias, with the exception of one animal, in which an unusually prolonged period of apnoea occurred.3. The cardiovascular effects of suxamethonium during halothane anaesthesia were diminished but not abolished when the respiratory depressant action of suxamethonium was prevented by applying positive pressure ventilation.4. The cardiovascular effects of suxamethonium in horses anaesthetized with halothane were partially antagonized by propranolol and completely antagonized by hexamethonium. It is suggested that the cardiovascular effects of suxamethonium are mediated by two distinct mechanisms: reflexly mediated increases in heart rate and sympathetic vasoconstrictor tone due to the respiratory depression, and a direct stimulant action of suxamethonium on peripheral, autonomic ganglia.5. Much less pronounced changes in cardiovascular function, but not in respiratory function, were recorded when suxamethonium was administered to horses anaesthetized with ether.6. A slight degree of tachyphylaxis to the cardiovascular and respiratory effects of suxamethonium was recorded in horses anaesthetized with halothane.7. Some atypical effects of suxamethonium on respiration are described.

Anesthesia, Inhalation↗
PubMed1968

The influence of beta-adrenoceptive receptor blocking agents on urinary function in the rat.

1. Intramuscular or subcutaneous injections of isoprenaline and dichloroisoprenaline and subcutaneous injection of pronethalol reduced the rates of excretion of water, sodium, potassium and chloride in the urine of conscious, hydrated rats. Inulin excretion usually fell at high, but not at low, dose levels. These changes were attributed to direct stimulant actions on beta-adrenoceptors in the kidney.2. A reduction in perfusion pressure to the kidney may also have contributed to these urinary changes, because isoprenaline produced a transient fall in mean arterial blood pressure when given subcutaneously to anaesthetized rats.3. Intramuscular injection of pronethalol and subcutaneous injection of antidiuretic hormone both reduced the rate of urine flow without modifying other parameters of urinary function (excretion of inulin and electrolytes were not diminished).4. This latter action of pronethalol could not be ascribed to an increased secretion of antidiuretic hormone, for it also occurred in hypophysectomized rats.5. Propranolol increased the renal excretion of sodium and chloride. A small rise in urinary potassium levels also occurred but urine volume and inulin excretion were not modified. Some possible modes of action of propranolol are discussed.

Animals↗
PubMedDate not supplied

Pharmacodynamics and pharmacokinetics of flunixin in the cat.

The non-steroidal anti-inflammatory agent (NSAID) flunixin was administered as single doses both orally and intravenously to six cats at a dose rate of 1.0 mg/kg in a two-part cross-over study. After oral dosing rapid absorption to a mean peak concentration of 2.586 micrograms/ml occurred at a mean time of 1.33 h. Similar mean plasma concentration-time AUC values for oral and intravenous dosing indicated that absorption by the former route was virtually complete. The decline in plasma concentration occurred fairly rapidly with both routes, and elimination half-life was approximately 1.0-1.5 h. The time course of inhibition of serum TXB2 concentration was similar for the two routes of administration, suggesting that similar dosing schedules are likely to be appropriate for evaluation of flunixin in clinical trials.

Administration, Oral↗
PubMedDate not supplied

Pharmacodynamics and pharmacokinetics of miloxicam in the horse.

The novel non-steroidal anti-inflammatory drug (NSAID) miloxicam was administered intravenously to six New Forest ponies at a dosage rate of 0.6 mg/kg in a two-part cross-over study. In each part, three horses received miloxicam and three were given a placebo preparation. The actions of miloxicam, compared to placebo, were assessed in a carrageenan-sponge model of acute inflammation. The rise in skin temperature over the site of the acute inflammatory reaction was less in treated ponies, but differences were not statistically significant. Concentrations of the enzymes acid phosphatase (AP) and lysozyme in inflammatory exudates harvested at 4, 8, 12 and 24 h were not significantly different in drug-treated animals compared with those receiving placebo. Concentrations of protein and lactate dehydrogenase (LDH) in exudate and exudate leucocyte numbers were significantly reduced in drug-treated horses when data for all sampling times were pooled. The differences were not significant, however, at each sampling time. Exudate concentrations of the eicosanoids, bicyclic-PGE2, 6-keto-PGF1 alpha and TXB2, were reduced significantly by miloxicam at most sampling times, and serum TXB2 was also significantly reduced at 4 and 8 h but not at 12 and 24 h after drug administration. These pharmacodynamic findings correlated with the pharmacokinetic properties of miloxicam. The plasma concentration-time curve was defined by a three-compartment open model in one pony and by a two-compartment model in five ponies. Mean values for pharmacokinetic parameters for the five ponies were: t1/2 alpha 0.40 h; t1/2 beta 2.70 h; Vd area 0.158 l/kg; ClB 41.87 ml/kg/h. Exudate concentrations of miloxicam were initially similar to and eventually greater than concentrations in plasma, and this may explain the more prolonged inhibition of eicosanoid synthesis in exudate than in serum. These findings demonstrate the value of relating, in a single experimental study, drug action on a range of variables to drug fate in the body.

Animals↗
PubMedDate not supplied

Equine chondrocyte activation by a variety of stimuli.

There is increasing evidence that the chondrocyte is capable of considerable anabolic and catabolic activity. In the case of equine chondrocytes, this study demonstrates that a variety of factors involved in the pathogenesis of joint disease stimulate the production of prostaglandin E2. These include exposure to IL-1, bone fragments and LPS. In addition, an IL-1-like factor was shown to be produced by the chondrocyte itself, when stimulated by LPS, providing a possible mechanism for amplification of extra-cartilagenous signals and even autocrine control. Considered together with evidence of increased synthesis of proteoglycan molecules by chondrocytes in diseased cartilage, this offers the exciting possibility of development of therapeutic agents to assist cartilage repair.

Animals↗
PubMedDate not supplied

Flunixin in the cat: a pharmacodynamic, pharmacokinetic and toxicological study.

There are relatively few non-steroidal anti-inflammatory drugs (NSAIDs) for which basic pharmacokinetic and toxicological data are available in the cat. This paper describes some pharmacokinetics and pharmacodynamics of flunixin in this species. Six healthy adult female cats were given 1.0 mg kg-1 flunixin meglumine orally daily for 7 consecutive days. Indwelling catheters were placed on the day preceding the first and last flunixin doses and 2 ml blood samples were taken for flunixin and thromboxane B2 (TXB2) assay before dosing and at 1, 2, 3, 5, 7, and 24 h after the first and the last doses of flunixin. Blood samples for haematology were taken before any treatment had been given and on treatment days 4 and 7 as well as 7 days after the end of treatment. On the first day of dosing, Cmax ranged from 0.45-6.94 micrograms ml-1 flunixin and the mean plasma concentration was greatest at 1 h (2.46 micrograms ml-1). No flunixin was detected by 24 h. After 7 days dosing, Cmax ranged from 0.47-2.46 micrograms ml-1. The mean plasma concentration was again greatest at 1 h but was lower (1.68 micrograms ml-1) than on the first day of treatment. No flunixin was detected beyond 5 h after dosing. The area under the plasma concentration time curve 0-24 h on the first day was 6.82 +/- 1.85 micrograms ml-1h-1 and 3.32 +/- 0.73 micrograms ml-1h-1 on the seventh day. On the first treatment day, serum TXB2 was inhibited by at least 75% in all post-treatment samples up to 7 h but on the seventh day it was reduced only at 1 and 2 h after dosing. Serum TXB2 was significantly higher on the seventh treatment day compared with the first at 3, 5 and 7 h after dosing. No abnormal clinical signs were seen and appetite was unaffected throughout the study. Most biochemical and haematological values remained within normal limits although alanine aminotransferase increased from 11.4-21.3 iu l-1 on day 7 without any other evidence of abnormality. The data suggest that the cats developed tolerance to flunixin although it is not known whether this was due to liver enzyme induction or reduced drug absorption. It is interesting that the cat, despite its reputation for inability to eliminate NSAIDs, has a relatively short flunixin half life and appears to develop tolerance to the drug.

Administration, Oral↗