Acute and long-term effects of isoflurane and sevoflurane anaesthesia in laboratory mice

Isoflurane is to date the most common volatile anaesthetic in laboratory rodents whereas the modern sevoflurane is usual for inhalation anaesthesia in human medicine. In this study it was aimed to characterize and compare the clinical properties and safety of both anaesthetics for anaesthetizing mice. In an approach that mirrors the laboratory routine (spontaneous breathing, gas supply via nose mask, preventing hypothermia by a warming mat) a 50-minutes anaesthesia was performed. Anaesthetics were administered at standardized dosages of 1.5 X minimum alveolar concentrations (1.85% for isoflurane, 3.25% for sevoflurane) in 100% oxygen. Induction and recovery from anaesthesia proceeded quickly, within 1 and 2 minutes respectively. During anaesthesia, all reflex testing were negative and no serious impairment of vital functions was found; all animals survived. Most prominent side effect during anaesthesia was the respiratory depression with marked decrease of respiration rate, hypercapnia and acidosis. Under anaesthesia, heart rate and core body temperature remained stable and within normal range, but were significantly increased for 12 hours after anaesthesia. Locomotor activity, food and water consumption and body weight progression showed no abnormalities after anaesthesia. No relevant differences between the two anaesthetics were found. In conclusion, both anaesthetics equally provide high safety margin with acceptable side effects and are therefore recommended for anaesthesia in laboratory mice

Establishing a pre-clinical growing animal model to test a tissue engineered valved pulmonary conduit

Background: Many valvular pathologies of the heart may be only sufficiently treated by replacement of the valve if a reconstruction is not feasible. However, structural deterioration, thrombosis with thromboembolic events and infective endocarditis are commonly encountered complications over time and often demand a re-operation. In congenital heart disease the lack of small diameter valves with the potential to grow poses additional challenges and limits treatment options to homo- or xenograft implants. Methods: In this study, a chronic sheep model (24 months follow-up), a self-constructed valved conduit was created out of a tissue engineered (TE) patch (CorMatrix® Cardiovascular, Inc, USA) and implanted in orthotopic right ventricular (RV)-pulmonary artery (PA) position. Thereafter, the sheep were regularly monitored by clinical, laboratory and echocardiographic examinations to evaluate cardiac function and the implanted RV-PA-conduit. Discussion: Here, we summarize the study protocol and our experiences during the perioperative phase and the follow up period and explain how we constructed a valved conduit out of a commercially available TE patch. Trial registration: License number: ZH 284/14

Variation in the viscoelastic properties of polydimethylsiloxane (PDMS) with the temperature at ultrasonic frequencies

Polydimethylsiloxane (PDMS) is an organic silicone with a viscoelastic behavior suitable for use in engineering. This material presents substantial changes in its properties depending on the temperature and the flow rate: at high temperatures or high flow rates, it behaves as a viscous liquid; whereas, at low temperatures or low flow rates, it behaves as an elastic solid. The lack of accurate information about the modifications in PDMS under thermal changes affects the design of transducers (both sensors and actuators) based on this material and also their calibration. In this study, 10:1 base-agent mixing ratio was analyzed in a 20 °C to 50 °C temperature range to assess the ultrasonic P-wave properties (velocity, attenuation, and variation of both with the frequency) and hence complex elastic modulii of this material under a temperature dependent environment. P-wave velocity and attenuation were extracted for every temperature step in a 3–7 MHz frequency range which is the typical range for medical applications. Acoustic dispersion of PDMS properties such as velocity and attenuation in a pulse-echo set up were analyzed to also compute attenuation coefficient, temperature and frequency dependent models and complex modulus

Ventricular Flow Field Visualization During Mechanical Circulatory Support in the Assisted Isolated Beating Heart

Investigations of ventricular flow patterns during mechanical circulatory support are limited to in vitro flow models or in silico simulations, which cannot fully replicate the complex anatomy and contraction of the heart. Therefore, the feasibility of using echocardiographic particle image velocimetry (Echo-PIV) was evaluated in an isolated working heart setup. Porcine hearts were connected to an isolated, working heart setup and a left ventricular assist device (LVAD) was implanted. During different levels of LVAD support (unsupported, partial support, full support), microbubbles were injected and echocardiographic images were acquired. Iterative PIV algorithms were applied to calculate flow fields. The isolated heart setup allowed different hemodynamic situations. In the unsupported heart, diastolic intra-ventricular blood flow was redirected at the heart's apex towards the left ventricular outflow tract (LVOT). With increasing pump speed, large vortex formation was suppressed, and blood flow from the mitral valve directly entered the pump cannula. The maximum velocities in the LVOT were significantly reduced with increasing support. For the first time, cardiac blood flow patterns during LVAD support were visualized and quantified in an ex vivo model using Echo-PIV. The results reveal potential regions of stagnation in the LVOT and, in future the methods might be also used in clinical routine to evaluate intraventricular flow fields during LVAD support

Burrowing is a sensitive behavioural assay for monitoring general wellbeing during dextran sulfate sodium colitis in laboratory mice

An impaired intestinal epithelial barrier is thought to be a major factor in the pathogenesis of human inflammatory bowel disease (IBD). IBD is frequently investigated by inducing a damaged barrier in murine models of colitis. This can be done by feeding mice with dextran sulfate sodium (DSS) polymers in their drinking water. Refinement measures should focus on alleviating unnecessary suffering during this probably painful condition. Appropriate parameters are needed to decide when to terminate the experiments. Our aim was to investigate whether a change in burrowing behaviour is a sensitive measure of animal welfare in murine models of colitis. Acute colitis was induced in C57BL/6 mice with 2.0% DSS over nine days. The burrowing test is based on the species-typical behaviour of mice to spontaneously displace items from tubes within their home cage. As a burrowing apparatus, a water bottle (250 mL, 150 mm length, 55 mm diameter) filled with 138-142 g of pellets of the animal's diet was used. The presence of intestinal inflammation as a result of acute DSS-induced colitis was confirmed by a decrease in body weight, colon length and an increase of murine endoscopic index of colitis severity, histological score and spleen weight in the group receiving DSS as compared with the control group. An onset of intestinal inflammation correlated with a significant decrease in burrowing behaviour (P < 0.05). Altered adrenal gland histology indicated stress as a result of acute colitis. Our findings provide evidence that changes of spontaneous burrowing behaviour correlate with the onset of inflammation in acute DSS-induced colitis