The partitioning of propofol within the blood, when administered in its usual emulsion carrier, has been determined in vitro in sheep. The blood:plasma ratio was found to be 1.13 and the blood-cell:plasma ratio 1.42. When oxalate was used as the anticoagulant, the plasma protein binding was calculated to be 92.6% - slightly lower than reported for dog, rat, rabbit and man. However, when heparin was the anticoagulant, the binding was significantly less, 83.0%. Differences from some results in the literature may be attributable to other workers using propofol without the lipid emulsion carrier. From the results of this study it is argued that anaemia and plasma levels of protein and lipid may affect propofol requirements.

Plasma triglyceride concentrations were measured in sheep given Intralipid or propofol, which is carried in a vehicle very similar to 10% Intralipid. A bolus dose was administered followed immediately by an infusion of the same agent for 2 h. In the animals that received propofol, the measured concentration increased by a mean amount of 3.39 mmol/l when the infusion rate was l ml/min (Group Pl) and by 7.13 mmol/l when it was 2 ml/min (Group P2). When 10% Intralipid was administered and infused at 1 ml/min (Group I10), the measured concentration increased only by 0.95 mmol/l. One hour after stopping the infusion, the excess of measured concentration over baseline had decreased in the Pl and I 10 groups to 0.52 and 0.13, respectively, of the corresponding maximum excess. The method adopted for measuring plasma triglycerides is widely used in hospitals; however, an incidental observation revealed that it is inappropriate in the presence of injections of propofol or Intralipid. Despite this, evidence and argument are presented to support the conclusion that, with propofol, plasma triglyceride concentrations increased more rapidly during the infusions and returned to baseline more slowly than with a corresponding amount of Intralipid.

alpha(2)-adrenoceptor agonist drugs can cause respiratory changes leading to a short period of hypoxaemia in sheep, It has been suggested that this is due to transient platelet aggregation and pulmonary microembolism. If platelet: aggregation were to follow platelet activation in response to the administration of alpha(2) agonists, plasma thromboxane levels would be expected to rise. This study was carried out to measure plasma thromboxane B-2 concentrations before and after the intravenous administration of the alpha(2)-agonist drug xylazine at a dose of 0.1 mg/kg. It. was found that the plasma thromboxane concentration rose by 320% and, furthermore, the rise was prevented by the prior administration of atipamezole hydrochloride(0.125 mg/kg), an alpha(2)-adrenoceptor antagonist.

In planning a study of the pharmacokinetics of propofol in sheep, contradictions were noted in the literature with regard to loss of propofol during storage of blood samples. This prompted a study of such loss from samples of sheep blood and plasma during storage at room temperature, +4 degrees C and -20 degrees C, for up to 17 days, over a range of concentrations from 1 to 20 micrograms/mL. Samples were drawn from 22 different sheep. Analysis was by the method of Adam et al. (1981). The best estimate of the overall mean loss rate was 0.7% per day with 95% confidence limits of 0.3% to 1.2% per day. The loss rate increased nonsignificantly with storage temperature. There were very small nonsignificant differences of loss rate between plasma and blood, between different concentrations, and between genders. There were significant differences of loss rate between sheep--up to about 2% per day in blood or plasma from any one sheep.

The pharmacokinetics of thiopentone sodium administered intravenously as a single dose (11 mg/kg) were studied in acepromazine pre-medicated horses and ponies in which anaesthesia was maintained with either halothane (Group 1) or isoflurane (Group 2). The results showed that the disposition kinetics of thiopentone in horses and ponies were best described by a three-compartment open model. In plasma, a very short initial distribution phase in both horses and ponies, half-life 1.4 +/- 1.2 min (mean +/- SD) and 1.3 +/- 0.7 min, respectively, was obtained, which was followed by a second comparatively slower redistribution phase, half-life 16 +/- 12 min and 11 +/- 5 min, respectively. The volume of distribution for the drug was large, especially in the ponies which received isoflurane (1127 +/- 86 ml/kg), compared to the horses which received halothane (742 +/- 89 ml/kg). The drug had a somewhat shorter elimination half-life in the horses (147 +/- 21 min) than in than ponies (222 +/- 44 min), but no obvious difference in clearance of the drug was observed between the horses (3.5 +/- 0.5 ml/min/kg) and ponies (3.6 +/- 0.8 ml/min/kg).

OBJECTIVE:To determine whether a small fixed perioperative dose of warfarin would prevent deep vein thrombosis after total hip replacement.DESIGN:Prospective, randomised, double blind placebo controlled trial.SETTING:Winford Orthopaedic Hospital, Bristol.SUBJECTS:148 patients having primary total hip replacement.INTERVENTION:Warfarin 1 mg given daily for one week before and three weeks after surgery.MAIN OUTCOME MEASURE:Deep vein thrombosis diagnosed by the iodine-125 labelled fibrinogen uptake method.RESULTS:Deep vein thrombosis occurred in 25 (34%) of the patients given warfarin and 19 (26%) of the controls (difference 8%; 95% confidence interval -6.8% to 22.8%).CONCLUSION:Fixed minidose warfarin does not prevent deep vein thrombosis after total hip replacement.

Radioiodinated monoclonal antibodies (MCA) were administered by the lumbar route into the cerebrospinal fluid (CSF) of four patients with malignant leptomeningeal disease. Evidence suggesting uptake of131I-MCA by tumour sites was seen in scintigrams. Dosimetry calculations were carried out, assuming that a proportion of the administered radionuclide was bound as a thin layer on the CSF surfaces of the meninges. The percentage injected dose and the clearance curves for the head and four spinal segments were obtained by scintigraphy after administration of tracer amounts of131I-MCA (7–18 MBq). Although radioisotope levels in the central nervous system (CNS) fell, as determined by both external scintillation counting and direct CSF sampling, a marked difference in the measurements developed with respect to time. The ratio of these two measurements reached a maximum of 49:1, 7 days after monoclonal antibody administration. Patients subsequently received therapeutic amounts (870–1600 MBq) of131I-MCAs, resulting in clinical remissions and prolonged survival. The mean absorbed radiation dose was estimated as 3.9 cGy·MBq−1 to the thoraco-lumbar region of the spine and 0.51 cGy·MBq−1 to the outer surface of the brain. The maximal dose delivered to the surface of the CNS in the region of the spine and brain was 5800 and 600 cGy, respectively.

1. Tissue perfusion was measured in seven sheep by the radioactive microsphere method. 2. The sheep were anaesthetised and ventilated to a near normal arterial carbon dioxide tension. 3. Cardiac output was measured utilizing the Fick principle as applied to thermodilution and at the end of the investigation the sheep were killed by an overdose of anaesthetic. 4. The results were compared with previously published values for conscious sheep and anaesthetised horses and found to be similar when known variations in body composition and physiology were considered.

In a single-centre prospective trial 200 consecutive patients undergoing thoracic surgery were randomised to receive one of two prophylactic regimes against deep vein thrombosis (DVT). These were 5000 units of subcutaneous heparin twice a day, alone or combined with the wearing of graded compression stockings. The diagnosis of DVT was made clinically and with 131I labelled fibrinogen. Six DVTs developed in the stocking group and 11 in the non-stocking group. The results suggest that the use of stockings reduces the incidence of DVT when added to herparin but the difference is not statistically significant. To obtain a predictive index for the development of DVT, discriminant analysis was applied to the control and stocking groups separately and combined. Five simple clinical variables gave a true positive prediction rate, for the combined group, of 94% and a false positive prediction rate of 26%.

Bone density of the radius was measured using both standard photon absorptiometry and X-ray computed tomography (CT) scanning, and of the femur using CT, in 21 young women with amenorrhea and estrogen deficiency due to hyperprolactinemia, 8 due to ovarian failure or weight loss, 17 postmenopausal women with bone fractures presumed to be due to osteoporosis, and 36 young normal controls. Bone density in the postmenopausal women was reduced by 18-20% in the radius and 11% in the femur (p less than 0.001). In the hyperprolactinemic group bone density was significantly reduced only in the femur (by 4%, p less than 0.01). Bone density appeared to be reduced in the other young amenorrheic women both in the radius (by 2-5%) and the femur (3%) but the difference was not significant, although the group was small. This and other studies of bone density suggest the need for prophylactic treatment to prevent osteoporosis in young women with amenorrhea and estrogen deficiency, whatever the cause.

Monoclonal antibody UJ13A, radiolabelled with 131I, was intravenously administered to patients with primary brain tumours. The antigen recognised by UJ13A is present on most neuroectodermally derived tissue. The ratio of uptake in tumour to normal brain, assessed by scintigraphy, improved with time. Maximal tumour uptake occurred between 4 and 48 h. Dynamic and static scintigrams indicated some early sequestration of radiolabelled antibody by the liver. Tumours were surgically resected in seven patients at various intervals after antibody administration showing tissue to blood ratios increasing with time in all parts of the lesion (viable and necrotic tumour, cyst fluid), and in normal brain. The highest tissue to blood ratio in viable tumour was 5.1 at 16 days after injection. In tissues resected 2–3 days after injection there was relatively greater uptake in the viable tumour compared to necrotic tumour and cyst fluid. In contrast, tissues resected later (6–16 days) showed greater uptake in ischaemic tissue than viable tumour, suggesting diffusion was an important factor influencing tumour uptake. The amount of radioactivity per gram of tumour tissue was less then 0.005% of the injected dose. Future studies are needed using different antibodies, antibody fragments and additional methods of optimising delivery.

The biodistribution of a radiolabelled monoclonal antibody (123I-NDOG2) was studied in patients with ovarian tumour. It was found that the uptake patterns in known tumour sites was variable and that the clearance of the agent from the vascular pool was due to renal excretion of the radionuclide and the redistribution of the radioactively labelled compound into other compartments. The mean (±SD) plasma clearance time was 20.8 (±2.3) h and the ratios of target (tumour) to background (thigh) ranged between 1.4 and 4.8. The ratio between the plasma radioactivity at either 3.5 or 20 h after administration was calculated relative to the initial plasma radioactivity. These values (0.79 and 0.48, respectively) were incorporated into an image-subtraction technique that allowed for redistribution outside the vascular pool. A whole-body dose equivalent to 16.3 μSv MBq-1 (60.4 mrem.mCi-1) was calculated.

A mathematical model of the cerebrospinal fluid (CSF) flow dynamics found in hydrocephalic infants with myelomeningocele lesions was constructed using criteria obtained from analogous clinical situations where 125I-labelled and 131I-labelled ortho-iodo-benzoyl-amino-acetic acid (hippuran) had been employed to measure CSF flow dynamics. The quantitative results from this study allowed clinical data to be assessed and the importance of various CSF transfer mechanisms to be discussed. The mathematical model indicates that the majority of radiopharmaceutical passes from the cerebral reservoir (the ventricles) into the blood. Experimental evidence indicates that the principal mechanism responsible for this movement is the bulk flow of CSF between its sites of production in the choroid plexus and absorption by the arachnoid villi.

Standard data for the horse which can be used in physiologically based mathematical computer modelling are presented. The data includes figures for tissue mass, density and perfusion, obtained by measurement mainly from horses weighing 200 to 300 kg. Other related parameters such as mean transit times and tissue blood volume have been calculated and included in the actual values listed for a 250 kg horse.

Equine Veterinary JournalVolume 16, Issue 3 p. 155-157 Mathematical modelling of the horse W. W. Mapleson, W. W. Mapleson University of Wales, Welsh National School of Medicine CardiffSearch for more papers by this authorG. E.Staddon, G. E.Staddon General Hospital, BristolSearch for more papers by this authorB. M. Q. Weaver, B. M. Q. Weaver Department of Veterinary Surgery, University of BristolSearch for more papers by this author W. W. Mapleson, W. W. Mapleson University of Wales, Welsh National School of Medicine CardiffSearch for more papers by this authorG. E.Staddon, G. E.Staddon General Hospital, BristolSearch for more papers by this authorB. M. Q. Weaver, B. M. Q. Weaver Department of Veterinary Surgery, University of BristolSearch for more papers by this author First published: May 1984 https://doi.org/10.1111/j.2042-3306.1984.tb01889.xCitations: 2AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat Citing Literature Volume16, Issue3May 1984Pages 155-157 RelatedInformation