Effects of isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl on physiological variables continuously measured by telemetry in Wistar rats.

BACKGROUND: This study investigated effects on cardiovascular parameters during anaesthesia with isoflurane (ISO, 2-3 Vol%), ketamine-xylazine (KX, 100 mg•kg(-1) + 5 mg•kg(-1)) or a combination of medetomidine-midazolam-fentanyl (MMF, 0.15 mg•kg(-1) + 2.0 mg•kg(-1) + 0.005 mg•kg(-1)) in rats throughout induction, maintenance and recovery from anaesthesia. Rats were instrumented with a telemetric system for the measurement of systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), pulse pressure (PP), heart rate (HR) and core body temperature (BT). The parameters were continuously measured before, during and after each type of anaesthesia. Forty minutes after induction, ISO delivery was terminated and MMF was antagonized with atipamezole-flumazenil-naloxone (AFN, 0.75 mg•kg(-1) + 0.2 mg•kg(-1) + 0.12 mg•kg(-1)) whereas KX was not antagonized. RESULTS: Differences were observed between anaesthesias with KX (301 min) lasting much longer than MMF (45 min) and ISO (43 min). HR in ISO ([Formula: see text] = 404 ± 25 bpm) increased during the time of surgical tolerance whereas a HR decrease was observed in KX ([Formula: see text] = 255 ± 26 bpm) and MMF ([Formula: see text] = 209 ± 24 bpm). In ISO (MAP during time of surgical tolerance: [Formula: see text] = 89 ± 12.3 mmHg) and KX (MAP during wake-up period: [Formula: see text] = 84 ± 8.5 mmHg) mild hypotensive values were observed, whereas blood pressure (BP) in MMF (MAP during time of surgical tolerance: [Formula: see text] = 138 ± 9.9 mmHg) increased. Despite keeping animals on a warming pad, a loss of BT of about 1°C was seen in all groups. Additionally, we observed a peaked increase of HR ([Formula: see text] = 445 ± 20 bpm) during the wake-up period with ISO and an increase of PP ([Formula: see text] = 59 ± 8.5 mmHg) in MMF during the time of surgical tolerance. CONCLUSION: The anaesthesias influenced very differently the cardiovascular parameters measured in Wistar rats. ISO caused mild hypotension and increased HR whereas MMF produced a marked hypertension and a significant decrease of HR. The slightest alterations of BP, HR and BT were observed using KX, but the long wake-up and recovery period suggest the need for prolonged monitoring.

Influence of repeated anaesthesia on physiological parameters in male Wistar rats: a telemetric study about isoflurane, ketamine-xylazine and a combination of medetomidine, midazolam and fentanyl.

BACKGROUND: This study evaluated the influence of repeated anaesthesia using isoflurane (ISO, 2-3 Vol%), ketamine-xylazine (KX, 100 mg·kg(-1) + 5 mg·kg(-1), i.m.) or a combination of medetomidine-midazolam-fentanyl (MMF, 0.15 mg·kg(-1) + 2.0 mg·kg(-1) + 0.005 mg·kg(-1), i.m.) on heart rate (HR), arterial blood pressure (BP), body temperature (BT), duration of anaesthetic intervals and body weight (BW) in Wistar rats. Rats were instrumented with a telemetric system for the measurement of systolic, diastolic and mean arterial pressure (SAP, DAP, MAP), pulse pressure (PP), HR and BT during induction, maintenance and recovery of anaesthesia. Each anaesthesia was performed six times within three weeks. KX was not antagonized, but ISO delivery was terminated 40 minutes after induction and MMF was reversed with atipamezole-flumazenil-naloxone (AFN, 0.75 mg·kg(-1) + 0.2 mg·kg(-1) + 0.12 mg·kg(-1), s.c.). RESULTS: With repeated anaesthesia, ISO showed a decrease of HR and BP. A significant decrease of PP could be observed with repeated anaesthesia using MMF. HR and BP were not affected by repeated KX anaesthesia, but we noted a reduction of sleeping time and BW. Neither MMF nor ISO showed significant differences in the duration of anaesthetic intervals and BW. With KX we observed tissue necrosis at the injection site and surgical tolerance was not achieved in 25% of the anaesthesias performed. CONCLUSION: HR, BP values, BT, duration of anaesthetic intervals and BW were affected differently by repeated anaesthesia performed with ISO, KX or MMF. ISO produced a reproducible anaesthesia, thereby being suitable for repeated use, but with a decrease of HR and BP throughout the six anaesthesias. The use of ISO in cases where these parameters should be unaffected is therefore not advised. The inability to produce a surgical tolerance, the reduction of sleeping time and BW, as well as the tissue necrosis are significant contraindications for a repeated use of KX. Only mild changes of BP were found with repeated MMF anaesthesia, so it seems suitable for serial use, unless the high BP and the low HR during the surgical plane of anaesthesia are undesirable for a special procedure.

Development of an implantable trapezium carpal bone replacement for measuring in vivo loads at the base of the thumb.

Understanding the loads that occur across musculoskeletal joints is critical to advancing our understanding of joint function and pathology, implant design and testing, as well as model verification. Substantial work in these areas has occurred in the hip and knee but has not yet been undertaken in smaller joints, such as those in the wrist. The thumb carpometacarpal (CMC) joint is a uniquely human articulation that is also a common site of osteoarthritis with unknown etiology. We present two potential designs for an instrumented trapezium implant and compare approaches to load calibration. Two instrumented trapezia designs were prototyped using strain gauge technology: Tube and Diaphragm. The Tube design is a well-established structure for sensing loads while the Diaphragm is novel. Each design was affixed to a 6-DOF load cell that was used as the reference. Loads were applied manually, and two calibration methods, supervised neural network (DEEP) and matrix algebra (MAT), were implemented. Bland-Altman 95% confidence interval for the limits of agreement (95% CI LOA) was used to assess accuracy. Overall, the DEEP calibration decreased 95% CI LOA compared with the MAT approach for both designs. The Diaphragm design outperformed the Tube design in measuring the primary load vector (joint compression). Importantly, the Diaphragm design permits the hermetic encapsulation of all electronics, which is not possible with the Tube design, given the small size of the trapezium. Substantial work remains before this device can be approved for implantation, but this work lays the foundation for further device development that will be required.

Effect of HBV polymerase inhibitors on renal function in patients with chronic hepatitis B.

BACKGROUND & AIMS: Therapy of chronic hepatitis B with HBV-polymerase inhibitors, in particular tenofovir or adefovir, may affect renal function. To assess renal function more accurately in the normal range, we used the recently validated, Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula to calculate the estimated glomerular filtration rate (eGFR). METHODS: Patient subgroups included: patients with HBV-monoinfection treated with lamivudine (n=36), adefovir (n=32), entecavir (n=32), or tenofovir (n=37). HBsAg-positive untreated patients (n=60) served as control. For comparison HIV-monoinfected patients treated with tenofovir (n=120) or zidovudine (n=52) based antiretroviral therapy and antiretroviral naive patients (n=109) were assessed. CKD-EPI equation was used to calculate eGFR. In a more sensitive approach, we modeled the individual change in eGFR over time with linear mixed effects models (LME). RESULTS: Yearly predicted median changes in individual eGFR according to the LME model were: HBV untreated -2.05 ml/min, HBV lamivudine -0.92 ml/min, HBV adefovir -1.02 ml/min, HBV entecavir -1.00 ml/min, and HBV tenofovir -0.92 ml/min (p<0.01 for HBV untreated vs. HBV treated). In HIV-monoinfected patients: HIV untreated -0.62 ml/min, HIV treated with tenofovir -2.64 ml/min, HIV treated with zidovudine -1.0 ml/min (p=0.017 for tenofovir vs. no treatment, p<0.001 for tenofovir vs. zidovudine). CONCLUSIONS: Therapy of HBV infection irrespective of medication seems to result in a milder decrease of renal function. In contrast tenofovir as part of HIV combination therapy seems to impair renal function in this Caucasian population.

Medetomidine/midazolam/ketamine anaesthesia in ferrets: effects on cardiorespiratory parameters and evaluation of plasma drug concentrations.

OBJECTIVE: To evaluate the cardiorespiratory effects and plasma concentrations of medetomidine-midazolam-ketamine (MMK) combinations administered by intramuscular (IM) or subcutaneous (SC) injection in sable ferrets (Mustela putorius furo). STUDY DESIGN: Prospective randomized experimental study. ANIMALS: Eighteen adult ferrets: weight median 1.19 (range 0.81-1.60) kg. METHODS: Animals were allocated to one of three groups: group IM07 received 20 µg kg(-1) medetomidine, 0.5 mg kg(-1) midazolam and 7 mg kg(-1) ketamine IM; group IM10 20 µg kg(-1) medetomidine, 0.5 mg kg(-1) midazolam and 10 mg kg(-1) ketamine IM; and group SC10 20 µg kg(-1) medetomidine, 0.5 mg kg(-1) midazolam and 10 mg kg(-1) ketamine SC. Following instrumentation, cardiorespiratory parameters and plasma drug concentrations were measured every 5 minutes (T5-T30) for 30 minutes Ferrets were then euthanased. Data were analysed using anova for repeated measures. p<0.05 was considered significant. RESULTS: Results are mean ± SD. Induction of anaesthesia (minutes) in IM07 and IM10 [2 (1)] was significantly faster than in SC10 [5 (2)]. All groups demonstrated the following: results given as groups IM07, IM10 and SC10 respectively. Mean arterial blood pressures (mmHg) were initially high [186 (13); 174 (33) and 174 (9) at T5] but decreased steadily. Pulse rates were initially 202 (20), 213 (17) and 207 (33) beats minute(-1) , decreasing with time. PaO(2) (mmHg) was low [54.0 (8), 47.7 (10) and 38.5 (1)] at T5, although in groups IM07 and IM10 it increased over time. Plasma concentrations of all drugs were highest at T5 (36, 794 and 8264 nmol L(-1) for medetomidine, midazolam and ketamine, respectively) and decreased thereafter: for both midazolam and ketamine, concentrations in IM07 and IM10 were higher than SC10. CONCLUSIONS AND CLINICAL RELEVANCE: MMK combinations containing either 7 or 10 mg kg(-1) ketamine and given IM are suitable combinations for anaesthetising ferrets, although the observed degree of hypoxaemia indicates that oxygen administration is vital.

Cardiovascular effects of fentanyl and propofol on hemodynamic function in rabbits.

OBJECTIVE: To evaluate short-term cardiovascular effects after IV administration of boluses of fentanyl in rabbits. ANIMALS: 6 healthy New Zealand White rabbits. PROCEDURES: Each rabbit was anesthetized with propofol (4.0 to 8.0 mg/kg, IV); anesthesia was maintained by administration of propofol (1.2 to 1.3 mg/kg/min, IV). Subsequently, 3 injections of fentanyl (0.0053 mg/kg) were administered. Before and for 10 minutes after injections, the following variables were measured: vessel diameter, peak systolic blood flow velocity, minimum diastolic blood flow velocity, end-diastolic blood flow velocity, time-average blood flow velocity, mean volumetric flow (VFmean), resistance index (RI), and pulsatility index for the left common carotid artery after the first injection and abdominal aorta after the third injection; mean arterial pressure (MAP); heart rate (HR); arterial oxygen saturation; end-tidal partial pressure of carbon dioxide; and body temperature. Echocardiography was performed after the second injection. RESULTS: Fentanyl injections caused a transient and significant decrease in diameter and VFmean of the abdominal aorta and end-diastolic blood flow velocity of the left common carotid artery and an increase in peak systolic blood flow velocity and RI of the left common carotid artery. Also, MAP, HR, and body temperature decreased significantly after injections. CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl injections induced a short-term decrease of vessel diameter in the abdominal aorta and increased resistance in the distal distribution area of the left common carotid artery. Results revealed decreases in MAP, HR, and body temperature, with an increasing effect after the third bolus injection, which indicated a cumulative drug effect.

Cardiovascular effects of dipyrone and propofol on hemodynamic function in rabbits.

OBJECTIVE: To evaluate the short-term cardiovascular effects of IV administration of dipyrone (metamizole) as an intraoperative analgesic during total IV anesthesia with propofol. ANIMALS: 6 healthy female New Zealand White rabbits. PROCEDURES: Anesthesia was induced with propofol (4.0 to 8.0 mg/kg, IV) and maintained with the same drug (1.2 to 1.3 mg/kg/min, IV). After induction, 3 doses of dipyrone (65 mg/kg each) were administered IV at 25-minute intervals. Before and for 10 minutes after each dipyrone injection, the following vascular and hemodynamic variables were recorded at the left common carotid artery every minute after the first injection: vessel diameter; peak systolic, minimum diastolic, end-diastolic, and mean blood flow velocities; mean volumetric flow; resistance and pulsatility indices; mean arterial blood pressure (MAP); heart rate; arterial oxygen saturation (SpO(2)); and end-tidal partial pressure of CO(2) (PETCO(2)). Echocardiography was performed after the second injection. The same variables were measured at the abdominal aorta (AA) after the third injection. RESULTS: Dipyrone injections caused a significant, transient decrease in the resistance index at the AA. Also detected were a minor decrease in pulsatility index at the left common carotid artery and a minor increase in end-diastolic blood flow velocity at the AA. The MAP, heart rate, SpO(2), and PETCO(2) did not significantly change after injections. A comparison of HR and MAP after the first and third bolus injections revealed only minor changes. CONCLUSIONS AND CLINICAL RELEVANCE: Dipyrone used with propofol anesthesia in rabbits appeared not to significantly impair cardiovascular and hemodynamic function.

Cystatin C as a marker of renal function is affected by HIV replication leading to an underestimation of kidney function in HIV patients.

BACKGROUND: Broad use of tenofovir and an ageing HIV- infected population have created an interest in renal function in HIV patients. Serum cystatin C is a newer marker of renal function and might be more sensitive than creatinine. METHODS: Patients were enrolled consecutively in an observational study. HIV-seropositive patients naive to antiretroviral therapy (n = 261) were compared with healthy volunteers undergoing check-up procedures (n = 193). Estimated glomerular filtration rate (eGFR) was derived using creatinine-based Modification of Diet in Renal Disease (MDRD) and Cockcroft-Gault formulas or cystatin C-based calculations. HIV-seropositive patients starting antiretroviral therapy (n = 92) were followed prospectively after enrolment. RESULTS: MDRD showed a higher median eGFR in antiretroviral-naive HIV-seropositive patients compared with controls (104 versus 93 ml/min; P < 0.001). Cockcroft-Gault gave similar results (118 versus 106 ml/min; P < 0.001). By contrast, cystatin C levels in HIV-seropositive individuals were higher, resulting in a lower median eGFR compared with controls (99 versus 120 ml/min; P < 0.001). Cystatin C was positively correlated with HIV RNA (r = 0.33, P < 0.01) and inversely correlated with CD4+ T-cell count (r = -0.29, P < 0.01). Initiating antiretroviral therapy (n = 92) decreased cystatin C levels and led to an increased cystatin C-based eGFR from median 84 to 103 ml/min at week 24 (P < 0.001). Serum creatinine was not substantially altered. CONCLUSIONS: Correlation of cystatin C with HIV RNA and CD4+ T-cell count, plus decrease of cystatin C after suppression of HIV replication, suggest an increase of cystatin C levels by active HIV infection. This might result in overestimation of renal impairment, particularly in treatment-naive patients. Therefore, use of cystatin C to calculate GFR in HIV-seropositive individuals should not be recommended without further validation.

Evaluation of cardiovascular and ECG parameters in the normal, freely moving Göttingen Minipig.

INTRODUCTION: The objective of this study was to evaluate the normal cardiovascular and ECG parameters in freely moving minipigs and to use these data as the basis of pharmacological drug safety evaluation. METHODS: 7 Göttingen Minipigs were equipped with radiotelemetry transmitters (ITS). Aortic pressure (AP), left ventricular pressure (LVP), lead II of the ECG and body temperature were continuously monitored. Notocord HEM 4.2 software was used for data acquisition. Power calculations for the various parameters were done to assess appropriate sample sizes. RESULTS: We obtained excellent signal quality and found stable hemodynamic parameters with a low intrinsic heart rate in the Göttingen Minipig. After oral dosing of vehicle, the hemodynamic parameters returned quickly to baseline values indicating that the procedure was well tolerated. The heart rate dependency of the QT interval had to be corrected individually. A sufficient power could be achieved with a sample size of 4 due to the low variability of the parameters measured. DISCUSSION: These are, to our knowledge, the first data documenting the course of systemic arterial and ventricular hemodynamic parameters in the freely moving Göttingen Minipig over 24 h. As such, they may serve as a basis for future studies in which drug effects are studied in these animals.

Protection against transplacental transmission of moderately virulent classical swine fever virus using live marker vaccine "CP7_E2alf".

Classical swine fever (CSF) remains as one of the most important infectious diseases of swine. While prophylactic vaccination is usually prohibited in free countries with industrialized pig production, emergency vaccination is still foreseen. In this context, marker vaccines are preferred as they can reduce the impact on trade. The live-attenuated Suvaxyn® CSF Marker vaccine by Zoetis (based on pestivirus chimera "CP7_E2alf"), was recently licensed by the European Medicines Agency. Its efficacy for the individual animal had been shown in prior studies, but questions remained regarding protection against transplacental transmission. To answer this question, a trial with eight pregnant sows and their offspring was performed as prescribed by the OIE Manual of Diagnostic Tests and Vaccines for Terrestrial Animals. Six of the sows were intramuscularly vaccinated on day 44 of gestation, while the other two remained as unvaccinated controls. All sows were challenged with the moderately virulent CSFV strain "Roesrath" and euthanized shortly before the calculated farrowing date. Sows and piglets were grossly examined and necropsied. Organs (spleen, tonsil, lymph node, and kidney), EDTA-blood and serum were collected from all animals. All samples were tested for antibodies against CSFV glycoproteins E2 and Erns as well as CSFV (virus, antigen and genome). It could be demonstrated that the vaccine complies with all requirements, i.e. no virus was found in the blood of vaccinated sows and their fetuses, and no antibodies were found in the serum of the fetuses from the vaccinated sows. All controls were valid. Thus, it was demonstrated that a single dose vaccination in the sows efficiently protected the offspring against transplacental infection with a moderately virulent CSFV strain.

Deletion at the 5'-end of Estonian ASFV strains associated with an attenuated phenotype.

African swine fever (ASF) was introduced into the Eastern European Union in 2014 and led to considerable mortality among wild boar. In contrast, unexpected high antibody prevalence was reported in hunted wild boar in north-eastern Estonia. One of the causative virus strains was recently characterized. While it still showed rather high virulence in the majority of experimentally infected animals, one animal survived and recovered completely. Here, we report on the follow-up characterization of the isolate obtained from the survivor in the acute phase of infection. As a first step, three in vivo experiments were performed with different types of pigs: twelve minipigs (trial A), five domestic pigs (trial B), and five wild boar (trial C) were inoculated. 75% of the minipigs and all domestic pigs recovered after an acute course of disease. However, all wild boar succumbed to infection within 17 days. Representative samples were sequenced using NGS-technologies, and whole-genomes were compared to ASFV "Georgia 2007/1". The alignments indicated a deletion of 14560 base pairs at the 5' end, and genome reorganization by duplication. The characteristic deletion was confirmed in all trial samples and local field samples. In conclusion, an ASFV variant was found in Estonia that showed reduced virulence.

Fetoscopic closure of punctured fetal membranes with acellular human amnion plugs in a rabbit model.

OBJECTIVE: To explore a surgical plug formed from decellularized term human amnion membrane for fetoscopic closure of iatrogenic defects in fetal membranes in a rabbit model. METHODS: The study was performed in eight rabbit does. Punctures were created at midgestational day 23 by 14-gauge needle fetoscopy on surgically exposed rabbit amniotic sacs. The entry sites were fetoscopically plugged either with decellularized term human amnion membrane (n=10) or previously successful commercial collagen matrix foil (n=10), followed by their primary fixation with fibrin glue and myometrial suturing. Seven punctured sacs without any plugging and 31 sacs without any manipulation served as two reference groups. Amniotic integrity and fetal parameters were assessed at gestational day 30. RESULTS: We established a facile method to prepare sheets of decellularized term human amnion membrane and verified its nontoxicity and cell compatibility in vitro. Decellularized term human amnion membrane sheets could be delivered precisely and controlled by fetoscopy as compact plugs into amniotic defects. The surgical handling characteristics of decellularized term human amnion membrane were better than the commercial collagen matrix foil. Treatment with human decellularized term human amnion membrane was comparable to treatment with the collagen matrix with regard to efficiency in restoring amniotic integrity. Seventy-five percent and 71.4% of amniotic sacs treated with decellularized term human amnion membrane or the commercial collagen matrix foil, respectively, showed amniotic integrity, compared with 25% in the left-open study group. Histology at the 1 week experimental endpoint showed no evidence for inflammation or beginning of anatomic healing of grafted, decellularized term human amnion membrane. CONCLUSION: Fetoscopic delivery of plugs made of decellularized term human amnion membrane presents a potentially practical surgical method to restore amniotic integrity of punctured fetal membranes. LEVEL OF EVIDENCE: III.

Enteral exsorption of acetaminophen after intravenous injection in rats: influence of activated charcoal on this clearance path.

The fate of acetaminophen after intravenous injection in whole bowel-irrigated rats (n = 40) and the influence of activated charcoal on the kinetics were investigated. After randomization to four groups (n = 10, each group), plasma concentration and the quantities of acetaminophen and metabolites excreted into bile, urine and intestine were determined using an in vivo model with or without orally administered activated charcoal and with or without bile duct cannulation. The cumulative amount of acetaminiphen and metabolites exsorbed into the small intestine within 3.5 hr after intravenous injection was about 20% of dose in the animals with bile duct cannulation and about 7% of dose in the animals without. Correspondingly, about 13% of dose was detected in the externalized bile. Activated charcoal did not influence the amount exsorbed into the small intestine. Terminal half-life in plasma ranged from 35 to 51 min. within the four treatment groups without statistically significant difference (P = 0.152). Correspondingly, the area under the curve did not vary much and ranged between 2.6 and 3.3 g/min./l (P = 0.392). Deposition of acetaminophen and metabolites in liver and kidney after 3.5 hr was marginal and ranged between 0.02% and 0.6% of the dose within all groups. The excretion of acetaminophen and metabolites into urine varied strikingly between 31% and 56% of the dose within all groups and correlated with diuresis. The lack of effect of activated charcoal on the elimination of acetaminophen and metabolites may be due to the small amount of the drug being exsorbed into the intestine or the reduced adsorbent capacity of activated charcoal to acetaminophen and metabolites, which also could be influenced by inadequate luminal stirring.

[Pain therapy in small pets]. / Schmerztherapie bei kleinen Heimtieren.

Although many advances in pain therapy have been made in recent years, pain therapy is more difficult in the small domestic animal than in cats and dogs. However, there is the ethical obligation that these animals also receive adequate pain therapy. An analgesic is rarely authorized for use in small pets, with pharmacological investigations often lacking and dosages frequently only determined empirically. The small size of the animals often requires a higher dose per kilogram bodyweight compared to cats and dogs. The dosage itself is also difficult to apply in small animals, because many analgesics must be diluted before their use. In addition, frequent manipulation of small animals for analgesic administration induces stress in the patient, which can intensify the pain. In the present article, those analgesics suitable for use in the small domestic animal are described and the indications for the use of the various types of analgesics are explained. A specialized section concentrates on pain detection and algesimetry in the small domestic animal. The detection of pain is much more difficult in small domestic animals. In the last few years so-called "grimace scales" have been developed which are used to assess the facial expression of the animals.

Effect of a change in housing conditions on body weight, behavior and brain neurotransmitters in male C57BL/6J mice.

The development of modern housing regimes such as individually ventilated cage (IVC) systems has become very popular and attractive in order to reduce spreading of pathogenic organisms and to lower the risk to develop a laboratory animal allergy for staff members. Additionally, optimal housing of laboratory animals contributes to improve animal health status and ensures high and comparable experimental and animal welfare standards. However, it has not been clearly elucidated whether 1) a change to IVC systems have an impact on various physiological phenotypic parameters of mice when compared to conventional, standard cages and 2) if this is further affected by changing from social to single housing. Therefore, we investigated the influence of a change in housing conditions (standard cages with social housing changed to standard or IVC cages combined with social or single housing) on body weight, behavior and a neurochemical fingerprint of male C57BL/6J mice. Body weight progression was significantly reduced when changing mice to single or social IVC cages as well as in single standard cages when compared to social standard housing. Automated motor activity measurement in the open field showed that mice maintained in social husbandry with standard cages displayed the lowest exploratory behavior but the highest activity difference upon amphetamine treatment. Elevated plus maze test revealed that a change to IVC single and social housing as well as single standard housing produced anxiety-related behavior when compared to maintenance in social standard housing. Additionally, postmortem neurochemical analysis of the striatum using high-performance liquid chromatography coupled to electrochemical detection showed significant differences in striatal dopamine and serotonin turnover levels. In summary, our data indicate a crucial influence of a change in housing conditions on several mouse phenotype parameters. We propose that the maintenance of well-defined housing conditions is mandatory to ensure reproducible and comparable results and contributes to the application of the 3R refinement principle in animal studies by contributing to welfare and hygienical standards.

Repeated anaesthesia with isoflurane and medetomidine-midazolam-fentanyl in guinea pigs and its influence on physiological parameters.

Repeated anaesthesia may be required in experimental protocols and in daily veterinary practice, but anaesthesia is known to alter physiological parameters in GPs (Cavia porcellus, GPs). This study investigated the effects of repeated anaesthesia with either medetomidine-midazolam-fentanyl (MMF) or isoflurane (Iso) on physiological parameters in the GP. Twelve GPs were repeatedly administered with MMF or Iso in two anaesthesia sets. One set consisted of six 40-min anaesthesias, performed over 3 weeks (2 per week); the anaesthetic used first was randomized. Prior to Iso anaesthesia, atropine was injected. MMF anaesthesia was antagonized with AFN (atipamezole-flumazenil-naloxone). Abdominally implanted radio-telemetry devices recorded the mean arterial blood pressure (MAP), heart rate (HR) and core body temperature continuously. Additionally, respiratory rate, blood glucose and body weight were assessed. An operable state could be achieved and maintained for 40 min in all GPs. During the surgical tolerance with MMF, the GPs showed a large MAP range between the individuals. In the MMF wake- up phase, the time was shortened until the righting reflex (RR) returned and that occurred at lower MAP and HR values. Repeated Iso anaesthesia led to an increasing HR during induction (anaesthesias 2-6), non-surgical tolerance (anaesthesias 3-6) and surgical tolerance (anaesthesias 4, 6). Both anaesthetics may be used repeatedly, as repeating the anaesthesias resulted in only slightly different physiological parameters, compared to those seen with single anaesthesias. The regular atropine premedication induced HR increases and repeated MMF anaesthesia resulted in a metabolism increase which led to the faster return of RR. Nevertheless, Iso's anaesthesia effects of strong respiratory depression and severe hypotension remained. Based on this increased anaesthesia risk with Iso, MMF anaesthesia is preferable for repeated use in GPs.

Classical Swine Fever-An Updated Review.

Classical swine fever (CSF) remains one of the most important transboundary viral diseases of swine worldwide. The causative agent is CSF virus, a small, enveloped RNA virus of the genus Pestivirus. Based on partial sequences, three genotypes can be distinguished that do not, however, directly correlate with virulence. Depending on both virus and host factors, a wide range of clinical syndromes can be observed and thus, laboratory confirmation is mandatory. To this means, both direct and indirect methods are utilized with an increasing degree of commercialization. Both infections in domestic pigs and wild boar are of great relevance; and wild boars are a reservoir host transmitting the virus sporadically also to pig farms. Control strategies for epidemic outbreaks in free countries are mainly based on classical intervention measures; i.e., quarantine and strict culling of affected herds. In these countries, vaccination is only an emergency option. However, live vaccines are used for controlling the disease in endemically infected regions in Asia, Eastern Europe, the Americas, and some African countries. Here, we will provide a concise, updated review on virus properties, clinical signs and pathology, epidemiology, pathogenesis and immune responses, diagnosis and vaccination possibilities.

Successful implantation of an abdominal aortic blood pressure transducer and radio-telemetry transmitter in guinea pigs - Anaesthesia, analgesic management and surgical methods, and their influence on hemodynamic parameters and body temperature.

INTRODUCTION: Guinea pigs (GPs) are a valuable cardiovascular pharmacology model. Implantation of a radio-telemetry system into GPs is, however, challenging and has been associated with a high failure rate in the past. We provide information on a novel procedure for implanting telemetry devices into GPs and we have measured the hemodynamics (arterial blood pressure, BP and heart rate, HR) and core body temperature (BT) in the 24h after surgery. METHODS: Male Hartley GPs (Crl:HA, 350-400g, 6.5weeks, n=16) were implanted with a radio transmitter abdominally and were then monitored continuously (HR, BP and BT) for 24h after surgery. RESULTS: 13 of 16 GPs (81%) survived the surgery. Surgery duration was 94min (min) (range: 76-112min) and anaesthesia duration was 131min (range: 107-158min). GPs lost body weight until 2days after surgery and then regained weight. Mean arterial BP increased from 33.7mmHg directly after surgery to 59.1mmHg after 24h. HR increased from 206bpm directly after surgery to 286bpm at 8h and fell to 251bpm at 24h after implantation. BT was 36°C directly after surgery, fell to 35.4°C until regaining of the righting reflex and then stabilized at 38.5°C after 24h. DISCUSSION: A high survival rate in telemetered GPs is possible. We achieved this through a procedure with minimal stress through habituation and planning, continuous warming during anaesthesia, an optimal anaesthetic and analgesic management, efficient surgical techniques and vitamin C supplementation.

Comparison of Physiological Parameters and Anaesthesia Specific Observations during Isoflurane, Ketamine-Xylazine or Medetomidine-Midazolam-Fentanyl Anaesthesia in Male Guinea Pigs.

Guinea pigs (GPs) are difficult to anaesthetize successfully, the choices for anaesthesia are limited and physiological parameters are likely to be influenced substantially under anaesthesia. We implanted blood pressure radio-telemetry devices into 16 male GPs and subjected them to anaesthesia with ketamine-xylazine (KX), medetomidine-midazolam-fentanyl (MMF) or isoflurane (Iso, plus atropine premedication) in a randomized order with a 7 day interval between anaesthesias. Each anaesthesia lasted 40min, after which Iso was discontinued, MMF was fully antagonized with atipamezole-flumazenil-naloxone and KX was partially antagonized with atipamezole. Hemodynamics were recorded continuously for at least 240min after induction and the GPs were monitored for respiratory rate, reflex responses and specific observations until regaining of their righting reflex (RR). Blood for glucose testing was taken from the ear at 7.5, 20 and 40min during anaesthesia. Recovery time was short with MMF and Iso but long for KX. MMF induced only a transient blood pressure drop after antagonization, whereas Iso caused a marked hypotension during maintenance and KX led to moderate hypotension after antagonization. MMF and Iso produced tolerable heart rate changes, but KX led to long term post-anaesthetic bradycardia. Hypothermia occurred with all anaesthesias, but the GPs returned to normothermia the fastest under MMF, followed shortly by Iso. KX, however, caused a profound and prolonged hypothermia. The respiration was depressed with all anaesthesias, substantially with MMF (-41%) and KX (-52%) and severe during Iso maintenance (-71%). Blood glucose with MMF and KX increased throughout the anaesthesia, but the values remained within reference values with all anaesthetics. The reflex responses character and strength varied between the anaesthetics. In conclusion, MMF is the anaesthetic of choice and Iso may be used for short, non-painful procedures. We advise against the use of KX in GPs.

Injection anaesthesia with fentanyl-midazolam-medetomidine in adult female mice: importance of antagonization and perioperative care.

Injection anaesthesia is commonly used in laboratory mice; however, a disadvantage is that post-anaesthesia recovery phases are long. Here, we investigated the potential for shortening the recovery phase after injection anaesthesia with fentanyl-midazolam-medetomidine by antagonization with naloxone-flumazenil-atipamezole. In order to monitor side-effects, the depth of anaesthesia, heart rate (HR), core body temperature (BT) and concentration of blood gases, as well as reflex responses, were assessed during a 50 min anaesthesia. Mice were allowed to recover from the anaesthesia in their home cages either with or without antagonization, while HR, core BT and spontaneous home cage behaviours were recorded for 24 h. Mice lost righting reflex at 330 ± 47 s after intraperitoneal injection of fentanyl-midazolam-medetomidine. During anaesthesia, HR averaged 225 ± 23 beats/min, respiratory rate and core BT reached steady state at 131 ± 15 breaths/min and 34.3 ± 0.25℃, respectively. Positive pedal withdrawal reflex, movement triggered by tail pinch and by toe pinch, still occurred in 25%, 31.2% and 100% of animals, respectively. Arterial blood gas analysis revealed acidosis, hypoxia, hypercapnia and a marked increase in glucose concentration. After anaesthesia reversal by injection with naloxone-flumazenil-atipamezole, animals regained consciousness after 110 ± 18 s and swiftly returned to physiological baseline values, yet they displayed diminished levels of locomotion and disrupted circadian rhythm. Without antagonization, mice showed marked hypothermia (22 ± 1.9℃) and bradycardia (119 ± 69 beats/min) for several hours. Fentanyl-midazolam-medetomidine provided reliable anaesthesia in mice with reasonable intra-anaesthetic side-effects. Post-anaesthetic period and related adverse effects were both reduced substantially by antagonization with naloxone-flumazenil-atipamezole.