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P A Flecknell

Publications and source records attributed to P A Flecknell.

At least 19 recordsLinked to original sources
PubMed2006

Assessing the welfare of genetically altered mice.

In 2003, under the auspices of the main UK funders of biological and biomedical research, a working group was established with a remit to review potential welfare issues for genetically altered (GA) mice, to summarize current practice, and to recommend contemporary best practice for welfare assessments. The working group has produced a report which makes practical recommendations for GA mouse welfare assessment and dissemination of welfare information between establishments using a 'mouse passport'. The report can be found at www.nc3rs.org.uk/GAmice and www.lal.org.uk/gaa and includes templates for the recommended welfare assessment scheme and the mouse passport. An overview is provided below.

Animal Husbandry↗
PubMed2004

Behaviour-based assessment of the duration of laparotomy-induced abdominal pain and the analgesic effects of carprofen and buprenorphine in rats.

Prevention of unnecessary pain in laboratory animals requires reliable and practically useful tools for assessing pain severity and analgesic efficacy. We have used a behaviour-based pain scoring system to determine the duration of pain resulting from laparotomy, and the duration of analgesia afforded by orally administered (p.o.) buprenorphine and subcutaneously administered (s.c.) carprofen or buprenorphine in rats. One hour before laparotomy Fisher 344 rats received either saline as a control (0.2 ml/100 g s.c.), carprofen (5 mg/kg s.c.) or buprenorphine (0.05 mg/kg s.c. or 0.4 mg/kg p.o.). The rats were housed singly for 10-min periods of behaviour recording, beginning 30 min after completing surgery. Recording was repeated at three time points every 2 h. The behaviour of controls was distinct from that of the analgesic-treated animals throughout recording; however, the major signs of pain (back-arching, staggering and writhing) were prominent during only the first 270 min in the saline group. This was followed by a period of more subtle differences between the saline- and drug-treated groups. It was concluded that the most acutely painful effects of surgery in this model lasted for between 270 and 390 min, and that this was alleviated throughout its duration by subcutaneously administered carprofen or buprenorphine, and also buprenorphine administered orally. The study demonstrates a clinically relevant and practically useful approach to assessing the duration of post-surgical abdominal pain and analgesic effects in rats.

Abdominal Pain↗
PubMed2003

Excitatory effects of fentanyl upon the rat electroencephalogram and auditory-evoked potential responses during anaesthesia.

BACKGROUND AND OBJECTIVE: Previous studies have shown existence of inconsistent data concerning the use of auditory-evoked potential (AEP) and electroencephalogram (EEG) changes to measure the depth of anaesthesia in regimens involving the use of opioids. The present studies characterize the effects of fentanyl on those responses in rats. METHODS: The effects of a bolus of fentanyl (6-10 microg kg(-1) intravenously) alone or following naloxone (100 microg kg(-1) intravenously) were examined using brain responses in rats during light anaesthesia with either propofol (20-30 mg kg(-1) h(-1)) or isoflurane (0.8%). Electrophysiological data were recorded using silver ball electrodes. The rats' tracheas were intubated and a femoral artery cannula was inserted to monitor blood pressure. Body temperature, respiratory and pulse rate, and pedal withdrawal data were also collected. Parameters measured before and following administration of naloxone and fentanyl or of fentanyl alone were compared using repeated-measures ANOVA. RESULTS: Fentanyl significantly increased the latency of the major peak from the AEP during propofol and isoflurane anaesthesia (F = 13.2 and 13.5, respectively; P < 0.05) and the amplitude differential between two waveform complexes, and the second differential index (F = 28.3 and 57.2, respectively; P < 0.01). The spectral edge frequency and median frequency from the EEG tended to increase. These effects were abolished by the prior administration of naloxone. CONCLUSIONS: These excitatory effects were inconsistent with the classical concept of brain activity depression indicating a deepening of anaesthesia.

Analgesics, Opioid↗
PubMed2003

Effects of different propofol infusion rates on EEG activity and AEP responses in rats.

Parameters calculated from the auditory-evoked potential (AEP) recorded over the auditory cortex and from the electroencephalogram (EEG) recorded over the near vertex were compared in rats at three different infusion rates of propofol (62.5, 35 and 25 mg/kg/h). Depth of anaesthesia was assessed clinically using the strength of the pedal withdrawal reflex. Well-defined AEP responses were consistently obtained. As the propofol concentration was reduced, peak latencies decreased and peak to peak amplitudes increased. Amplitude and latency values were closely associated with the strength of the pedal withdrawal responses. Parameters calculated from the EEG showed no significant change as the propofol concentration was reduced. Periods of burst suppression became more frequent as the propofol infusion rate was increased. The study showed some of the difficulties that may be encountered when using EEG as a tool to assess depth of anaesthesia during propofol infusion. The AEP showed dose dependent changes in rats at different infusion rates of propofol. However, large variability between animals limits the use of this technique for monitoring depth of anaesthesia.

Anesthesia, General↗
PubMed2002

Buprenorphine: a reappraisal of its antinociceptive effects and therapeutic use in alleviating post-operative pain in animals.

Buprenorphine has been widely used for post-operative analgesia in laboratory animals. Clinical efficacy has been demonstrated in both subjective and objective pain assessment schemes, however doubts have been expressed as to its value as an analgesic. Initial dosage recommendations were based on analgesiometric studies. It is unlikely, however, that the pain elicited in analgesiometric tests is comparable to post-operative pain. This has resulted in recommendations of excessive dose rates and inappropriate clinical indications. Studies involving tests of the efficacy of buprenorphine for alleviating behavioural or other signs of tonic (post-surgical) pain provide a more appropriate estimation of the analgesic capabilities of the drug. However, buprenorphine also has major effects upon the behaviour of normal (unoperated) animals, and this makes assessments of efficacy difficult with some of the systems used for scoring clinical pain. Nevertheless, our most recent studies of the effects of buprenorphine upon pain-related behaviours in rats support the view that it is an effective post-operative analgesic. This short review critically reappraises the role of buprenorphine in this capacity and discusses a rational approach to the relief of pain in laboratory animals. We conclude that buprenorphine remains a valuable agent for pain relief in a wide range of animal species when used in an appropriate manner.

Analgesics, Opioid↗
PubMed2001

Behavioural effects of laparotomy and analgesic effects of ketoprofen and carprofen in rats.

Rat behaviour was studied to develop a reliable method of determining the severity and duration of post-laparotomy pain, and to assess analgesic effects of ketoprofen or carprofen. Behaviour was studied in groups of ten animals 1 h following subcutaneous (s/c) saline (0.2 ml/100 g), ketoprofen or carprofen (5, 10 or 15 mg/kg) given either alone, or prior to surgery. The frequency of over 150 individual behavioural acts was calculated during the first post-treatment hour, the hour immediately prior to darkness, and the first 15 min of each of 5 subsequent hours. Discriminant analysis and analysis of variance isolated several easily recognizable behaviours which were markedly altered in frequency by surgery. These were unaffected by drug administration alone and were mainly transient, easily quantifiable activities; 'cat-like' back arching, horizontal stretching followed by abdominal writhing and twitching while inactive. Reductions in the frequency of these behaviours following surgery with analgesic treatment supported the hypothesis that they reflected post-operative pain. Ketoprofen and carprofen were equipotent and no dose related effects were apparent. Analgesic activity lasted between 4 and 5 h with the 5 mg/kg dosage, this being estimated from the duration of overall and specific behaviour differences between saline and drug treated animals. The data provided substantial evidence as to the usefulness of behavioural criteria for estimating pain severity, and for the first time, the basis of a system for routine pain assessment and management in rats subjected to abdominal surgery.

Animals↗
PubMed2001

Functional assessment of non-heart-beating donor lungs: prediction of post-transplant function.

OBJECTIVES: To enable an increase in the numbers of donor lungs using organs from non-heart-beating donors (NHBD). To develop an isolated ventilation and perfusion technique to assess the degree of warm ischaemic organ injury suffered prior to retrieval, thereby enabling identification of lungs with predictably good post-transplant function. METHODS: Lungs from Landrace-Yorkshire White cross pigs were retrieved after 1 (NHBD(1)), 2 (NHBD(2)) or 4 h (NHBD(4)) post-hypoxic death induced by cessation of ventilation. Control organs were retrieved using standard techniques for each group from matched animals immediately following aortic cross-clamping (Control(1) and combined Control(2,4)). Modified Euro-Collins pulmoplegia was used in all groups, prior to ventilating a single lung with 100% oxygen and perfusion with neutrophil-depleted and deoxygenated blood. For all of the lungs in the NHBD(2) and combined Control(2,4) groups, and one of the successfully perfused NHBD(4), the contralateral lung was then transplanted with post-transplant function assessed for 12 h. All animals were anaesthetized throughout and euthanased without regaining consciousness. RESULTS: On assessment, oxygenation after 5 min of perfusion did not differ between NHBD(1) (n=4) vs. Control(1) (n=5; analysis of variance (ANOVA), P=0.152). However, oxygenation had deteriorated significantly in the NHBD(2) group (n=6) vs. Control(2,4) (n=8; ANOVA, P<0.0005) and was significantly poorer than initial values after 8 min (unpaired t-test with Bonferroni correction, P<0.03). In NHBD(4) (n=6), four lungs failed assessment due to the development of gross pulmonary oedema, although the remaining pair functioned as well as Control(2,4). Post-transplantation, NHBD(2) (n=6) contralateral lungs showed significantly poorer overall oxygenation, (mean+/-SD, 46+/-22 kPa) when compared with Control(2,4) (n=6; 59+/-16 kPa; ANOVA, P=0.001), although oxygenation was satisfactory. The contralateral organ from one successfully perfused NHBD(4) lung functioned well post-transplantation. CONCLUSIONS: The significant deterioration in oxygenating performance seen during assessment after 2 h warm ischaemia and the idiosyncratic function after 4 h warm ischaemia indicates the importance of functional testing of NHBD lungs. The similar deterioration in oxygenating performance seen post-transplantation in the contralateral lungs suggests that this method detects functional warm ischaemic lung injury.

Animals↗
PubMed2001

Analgesia of small mammals.

Small mammals receive analgesics much less frequently than more familiar species such as dogs and cats. This is probably related to the greater difficulty of recognizing pain in these species, and the uncertainty as to the most appropriate analgesic regimen to implement when the presence of pain is suspected. However, the same principles of pain assessment and analgesic use that are applied when dealing with other companion animals can be used to manage pain effectively in small mammals. All of the commonly used analgesic agents can be used safely and effectively in small mammals, although the size of many of these animals limits the use of techniques such as epidural administration or transdermal drug delivery systems. As with other species, it is important to integrate an analgesic regimen with the overall scheme of perioperative care, and to try to implement preemptive and multi-modal analgesic therapy.

Analgesia↗
PubMed2001

Induction of anaesthesia with desflurane and isoflurane in the rabbit.

The characteristics of two techniques of face-mask induction of desflurane anaesthesia (rapid or slow) were compared with the effects of slow isoflurane induction in five New Zealand White (NZW) rabbits. Slow induction used stepwise increments in vapour setting of 2% for desflurane and 0.5% for isoflurane at 30 s intervals. All animals were anaesthetized using each technique according to a randomized block design with one week between treatments. Observations were made of the quality of induction (any struggling or periods of apnoea) and the latency to, and the duration of loss of the righting and toe pinch reflexes recorded. Changes in respiratory rate, arterial blood gas and cardiovascular parameters were also recorded. Induction and recovery times were shorter with rapid desflurane induction in comparison to isoflurane (loss of righting reflex: 139+/-27 s cf. 205+/-48 s), but both techniques were associated with struggling and long periods of apnoea (> 1 min) during the first 4 min after administration. During this period a significant degree of bradycardia, hypercapnia and hypoxaemia occurred with both techniques, but these and the subsequent effects of rapid desflurane administration were less severe than with isoflurane. Slow induction with desflurane was tolerated best, with little or no deleterious behavioural or physiological effects, however excessively prolonged induction times (loss of righting reflex 337+/-160 s) limits the application of this method. Desflurane, administered rapidly, appears to be a more suitable agent than isoflurane. However, as with isoflurane, anaesthesia should only be induced following oxygen supplementation.

Anesthesia, Inhalation↗
PubMed2000

Effects of surgery and analgesic administration on spontaneous behaviour in singly housed rats.

The study examined the use of behaviour in assessing post-laparotomy pain in rats given subcutaneous injections of saline (0.2 ml 100 g(-1)) or the analgesics buprenorphine (0.05 mg kg(-1)) or ketoprofen (5 mg kg(-1)). Procedural control influences (handling/movement, anaesthesia, injections) were studied in a second group. Of 150 behaviours examined, discriminant analysis classified the main treatment effects, and class mean frequencies were compared between treatments within each group. With the exception of buprenorphine treatment, control procedures reduced the frequency of active, attentive and grooming behaviour, and increased sleeping during 24 hours following each treatment. Moving animals to the theatre was the main factor responsible for these changes. Surgery also reduced active and attentive behaviour. Animals given pre-operative saline were more frequently inactive than those given ketoprofen. These effects most likely resulted from post-surgery pain, but this was not significantly diminished with the ketoprofen dose used. In all cases, buprenorphine outweighed these effects, causing a sustained increase in active, inactive and attentive behaviour, such that determination of any analgesic effects was impossible. The study underlined a role for pain assessments based on rat behaviour. Drug-related effects emphasised a need for more comprehensive assessments encompassing procedural influences, before behaviour changes that are potentially pain related may be determined accurately.

Analgesics↗
PubMed2000

Sufentanil and medetomidine anaesthesia in the rat and its reversal with atipamezole and butorphanol.

Injectable anaesthetics are widely used to anaesthetize rats, but recovery times are often prolonged. Reversible anaesthetic regimens have the advantage that animals may be recovered quickly, thus reducing the incidence of postoperative complications such as hypothermia, and also providing a means of treating inadvertent anaesthetic overdose. This study assessed and compared the characteristics of anaesthesia induced with combinations of sufentanil and medetomidine administered as a single subcutaneous or intraperitoneal dose, and reversal with butorphanol and atipamezole. Combinations of sufentanil/medetomidine at 40 microg/150 microg and 50 microg/150 microg/kg administered subcutaneously, and 80 microg/300 microg/kg by intraperitoneal injection were found to produce surgical anaesthesia for 101+/-49, 124+/-45 and 76+/-23 min (means +/- SD) respectively. All three combinations produced marked respiratory depression 30 min after injection (< 50% of resting respiratory rate). Oxygen saturation, measured by pulse oximetry, was < 50% in all groups 30 min following drug administration. Subcutaneous administration is recommended since it resulted in a more reliable and more rapid induction of anaesthesia than intraperitoneal administration. The administration of butorphanol and atipamezole (0.2/0.5 mg/kg s.c.) resulted in a rapid (< 7 min) reversal of anaesthesia and an associated respiratory depression. The induction of anaesthesia with sufentanil/medetomidine and its reversal with a combination of atipamezole and butorphanol is an effective technique for anaesthetizing rats. However, due to the marked respiratory depression and the resulting hypoxia, we recommend that this regimen should only be used in animals which are free from respiratory disease and that oxygen should be provided during anaesthesia.

Anesthesia↗
PubMed2000

The successful use of fentanyl/fluanisone ('Hypnorm') as an anaesthetic for intracranial surgery in neonatal rats.

This study reports on the successful use of fentanyl citrate and fluanisone ('Hypnorm') anaesthesia for intracranial surgery in neonatal (7-day-old) rats. Provided the anaesthetic was administered subcutaneously, the animals showed a very high survival rate in the short term (81/85, 95%) and showed no ill effects in the long term. The depth of anaesthesia was sufficient to allow the operation to be carried out without the animal reacting to any painful stimuli. However, the animals did make random movements during the period of surgical anaesthesia which were not related to any painful stimuli. Although these movements did not interfere with the surgery performed here, such movements would interfere with operations requiring greater precision, such as the localized micro-injection of neural tracers.

Anesthesia↗
PubMed2000

Effects of repeated anaesthesia with ketamine/medetomidine and of pre-anaesthetic administration of buprenorphine in rats.

Two groups of rats were anaesthetized at weekly intervals for 6 weeks with either ketamine/medetomidine alone (60 mg/0.4 mg/kg i.p.) or ketamine/medetomidine (45 mg/0.3 mg/kg i.p.) one hour following buprenorphine (0.05 mg/kg s.c.). Animals that received buprenorphine had longer periods of surgical anaesthesia (P = 0.04) and a greater depression of both mean pedal withdrawal score (P < 0.01) and mean respiratory rate (P = 0.014). Mean total duration of anaesthesia was also greater in the buprenorphine group on day 1. Sleep times reduced with successive doses of anaesthetic in the buprenorphine group (P = 0.024). Two animals in the buprenorphine group died. Repeated anaesthesia with ketamine/medetomidine alone was not associated with anaesthetic mortality. These results indicate that although buprenorphine has a clear anaesthetic-sparing effect, its use with ketamine/medetomidine may be associated with an increased risk of anaesthetic-related mortality.

Anesthesia↗
PubMed1999

Comparison of the effects of oral or subcutaneous carprofen or ketoprofen in rats undergoing laparotomy.

Rats undergoing laparotomy received either carprofen (5 mg/kg) or ketoprofen (5 mg/kg) administered orally in flavoured gelatin, or by subcutaneous injection. A control group that received no analgesic showed a significant (3 per cent) fall in bodyweight (P = 0.009) after laparotomy. This decrease was greater than that seen in the groups receiving carprofen (P = 0.006) or ketoprofen (P = 0.012) administered subcutaneously, which continued to gain weight following surgery. All animals showed a significant fall in food consumption but this decrease was greater in the jelly alone group (47 per cent) than in the group receiving carprofen (17 per cent) (P = 0.015) administered subcutaneously. A significant fall in water consumption occurred in the control group (40 per cent) and in animals that received oral carprofen (13 per cent) or Ketoprofen (22 per cent). No significant decrease was seen in groups receiving either carprofen or ketoprofen administered subcutaneously (P > 0.1). This study shows that a relatively simple surgical procedure results in a major reduction in food and water consumption in rats. This reduction can be minimised by the administration of ketoprofen or carprofen (5 mg/kg subcutaneously), but higher dose rates are required if these drugs are to be administered by the oral route.

Administration, Oral↗
PubMed1999

Modulation of reperfusion injury after single lung transplantation by pentoxifylline, inositol polyanions, and sin-1.

OBJECTIVE: Previous studies have suggested reductions in lung reperfusion injury with pentoxifylline, inositol polyanions, and the nitric oxide donor, SIN-1, but these agents have never been directly compared to ascertain which is superior. We investigated these agents in a porcine model of left single lung transplantation. METHODS: Donor lungs were preserved with modified Euro-Collins solution for a mean ischemic time of 18.4 hours. Neutrophil trapping in the graft, pulmonary vascular resistance, free radical release (measured by malonaldehyde levels) and gas exchange were assessed over a 12-hour period. All groups were reperfused at an initial pulmonary artery pressure of 20 mm Hg. Group A (n = 5) was a control group with no interventions added; group B was reperfused with the addition of intravenous inositol polyanions (0.02 mg/kg/h), and group C was reperfused with intravenous SIN-1 (0.02 mg/kg/h). Group D was reperfused with the addition of intravenous pentoxifylline (2 mg/kg/h). RESULTS: Neutrophil sequestration was observed within 10 minutes of reperfusion in group A. This was attenuated significantly by interventions in groups B, C, and D. In group D, malonaldehyde levels were significantly lower than in other groups and was associated with superior oxygenation. Pulmonary vascular resistance was reduced in groups B, C, and D compared with group A. CONCLUSIONS: Pentoxifylline, when administered only to recipient animals was superior to the other interventions studied. Inositol polyanions are promising as a possible therapeutic intervention but were not as effective as the other agents studied.

Animals↗
PubMed1999

The influence of pre-anaesthetic administration of buprenorphine on the anaesthetic effects of ketamine/medetomidine and pentobarbitone in rats and the consequences of repeated anaesthesia.

Rats received pentobarbitone (60, 48 and 36 mg/kg i.p.) or ketamine/medetomidine (75/100, 60/80 and 45/60 mg/microg/kg i.p.) alone, or one hour following buprenorphine (0.5 mg/kg s.c.). Animals were anaesthetized once per week for 6 weeks with one of three anaesthetic doses according to a randomized block design. In the pentobarbitone group, animals which received buprenorphine had longer sleep times (236 +/- 22 cf. 204 +/- 21 min) and longer durations of surgical anaesthesia (83 +/- 14 cf. 27 +/- 8 min) (P<0.01), these effects being potentiated with increasing anaesthetic doses (P<0.01). A greater degree of respiratory depression was found in animals that received buprenorphine (P<0.01) although this was judged clinically acceptable in all cases. Unexpectedly high mortality and a high incidence of anaesthetic complications (nine of 16 animals) in the ketamine/medetomidine group made statistical analysis of these data impossible. We conclude that for pentobarbitone, pre-anaesthetic administration of buprenorphine reduces the dose of anaesthetic required to produce surgical anaesthesia, in addition to the presumed benefits of pre-emptive analgesia. In view of the high mortality encountered, we advise caution when considering pre-anaesthetic use of opioids in combination with ketamine/medetomidine in rats.

Analgesics, Opioid↗
PubMed1999

A new porcine model of reperfusion injury after lung transplantation.

Rodent models have been described to investigate lung preservation and reperfusion injury but have significant disadvantages. In large animals single lung transplant studies are probably optimal but problems remain over the ability to rigorously separate the lungs for assessment while promoting medium to long-term animal survival for meaningful investigation. Our aim was to develop a novel and refined large animal model to assess reperfusion injury in the transplanted lung, overcoming the difficulties associated with existing models. Specifically, small animal models of lung transplantation usually have short perfusion times (often one hour) and include extracorporeal circuits while larger animal models often require the contralateral lung to be excluded after transplantation-an unphysiological situation under which to evaluate the graft. A porcine model of left lung allotransplantation was developed in which native and donor lungs are individually ventilated. Sampling catheters placed within the graft lung allowed specimen withdrawal without mixing of blood from the contralateral lung after reimplantation. The model permits a variety of clinical scenarios to be simulated with the native lung supporting the animal irrespective of function in the graft. This model has been used in over 60 transplant procedures with a postoperative survival time of 12 h being readily achieved. The mean operating time was 2.6 h. The mortality rate is 4% in our series. We have found the model to be reliable, reproducible and flexible. We propose this model as an adaptable investigation for evaluating lung reperfusion injury and preservation.

Animals↗