Bienta’s Laboratory Animal Research Centre was built in the end of 2018, in order to address rapidly growing demand in in vivo pharmacokinetic and toxicology studies in rodents. Our in vivo facilities currently occupy approximately 700 square meters (7000 square feet) of lab space, equipped and maintained according to current industrial quality standards. Animal housing conditions are constantly monitored according to AAALAC recommendations.
Our in-house core breeding unit is currently able to produce approximately 1200 animals per month. A stock of 10 various mice and rat strains were imported and maintained, in particular:
- two outbred (CD-1; NMRI (Han)) mice strains;
- four inbred (Balb/cAnN; C57BL/6N; C57BL/6J; C3H) mice strains;
- two immunodeficient (CD1-Foxnlnu/nu; CB17.Cg-PrkdcscidLystbj-J) mice strains;
- three rat strains (maintained separately): Wistar, SD (Sprague-Dawley) and SHR.
Other strains can be imported on customer’s demand, maintained and prepared for special experimental designs.
Our animals are usually housed by pairs or groups in suitable cages with small coverings to minimize stress and ensure most comfortable living conditions. Temperature, humidity and light/darkness cycle are constantly monitored and controlled. Bienta Animal Facility has adequate protection to maintain safe environment for the animals and to prevent contamination. Air ventilation barriers are designed to protect and secure Animal Facility staff as well as animals from any risk. Food and bedding is purchased from certified suppliers.
All our studies are designed and conducted under Bienta’s Institutional Animal Care and Use Committee (IACUC) review in accordance to the 3Rs rules (replacement, reduction, refinement). Our Animal Facility team is committed to comply with the International Guiding Principles for Biomedical Research Involving Animals.
Animal care at Bienta’s Laboratory Animal Research Centre is provided by trained personnel. Our Animal Facility professional team consists of biologists, geneticists, veterinarians and animal technicians. They support general maintenance of animals, breeding program, acclimatization and adaptation of new arrivals, hosting inspections, experimental performance and project coordination.
Perfused Isolated Langendorff Heart for the Assessment of the Electrophysiologic and Hemodynamic Effects of Drug Candidates
Background: Predicting cardiac toxicity is one of the most important challenges in drug discovery. Over the past 25 years, several non-cardiac drugs got under investigation due to increased morbidity and mortality associated with adverse cardiac events, such as life-threatening arrhythmias. More than 100 clinically used drugs belonging to a variety of unrelated classes were marked as possibly proarrhythmic, leading to removal of drugs from the market in some cases. The International Conference on Harmonization (ICH) firmly advocates that preclinical and clinical tests for hemodynamic effects and proarrhythmic potential be performed for all drug candidates prior to approval by government regulatory agencies, regardless of the intended therapeutic application.
The Langendorff heart is the only comprehensive assay capable of evaluating both electrophysiological parameters and the hemodynamic effects of a compound. This model is a physiologically relevant bridge between in vitro assays and in vivo studies. The Langendorff heart has proven to be highly correlated to in vivo approaches and highly predictive of in vivo effects.
The isolated heart perfused with increasing concentrations of test articles is also useful for measuring spontaneously-beating or stimulated hearts RR, PR, QRS, QT, QTc intervals of ECG, left ventricle contraction, heart rate, blood pressure. We also employ this tool as an ischemia reperfusion model in drug discovery investigations.
Service details: The isolated Langendorff heart is employed in our cardiovascular studies for: prolonged QT Interval, Heart Rate, Blood Pressure, ECG, as well as lead compounds screening for cardiovascular effects.
- Source: rat, guinea pig, rabbit.
- Number of hearts exposed to the test article: 6 hearts;
- Number of concentrations of test article tested: 4 or more;
- The model can be surgically altered to reproduce disease characteristics of interest;
- Stimulation: variable frequencies of stimulation or spontaneously beating hearts;
- A study includes positive, negative, and vehicle controls.
Deliverable: The main parameters estimated are: mean EC 50(MFF) – average of effective concentration of the drug reducing MFF by 50% in the atrial preparations tested; mean TC50(IR) – average of the toxic concentration of the drug reducing inotropic response (contraction) by 50% in the right atrial preparations tested; mean TC 50(CR) – average of the toxic concentrations of the drug reducing chronotropic response (atrial rate) by 50% in the right atrial preparations tested. Final report includes methodology, raw data, graphs (if necessary) and interpretation.