Evaluation of respiratory function in freely moving Beagle dogs using implanted impedance technology
| Autor: | Teresa Gleason, Philip Atterson, Timothy Edwards, Kenneth Kearney, Monica Metea |
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| Rok vydání: | 2010 |
| Předmět: |
Population
Respiratory System Agents Toxicology Electrocardiography Dogs Heart Rate medicine Electric Impedance Tidal Volume Plethysmograph Animals Telemetry Respiratory function Respiratory system education Tidal volume Pharmacology education.field_of_study business.industry Safety pharmacology Respiration Reproducibility of Results Doxapram Plethysmography Anesthesia Ambulatory Calibration Models Animal Respiratory Physiological Phenomena business medicine.drug |
| Zdroj: | Journal of pharmacological and toxicological methods. 62(2) |
| ISSN: | 1873-488X |
| Popis: | Introduction The Safety Pharmacology ICH S7A guidelines mandate the preclinical evaluation of drug effects on respiratory function. Chronic measurements of potential drug effects are commonly performed in rodents due to lack of a viable alternative in large animals. Presently, although the value and validity of these standard methods cannot be refuted, each method presents inherent limitations; such as the introduction of restraint stress (e.g. head-out rodent plethysmography and the pneumotachograph-equipped dog face mask), or sensitivity issues (e.g. whole body plethysmography). Since these approaches may limit the number of time points tested or affect respiratory parameters, new and accurate methods are needed for assessing respiratory function in conscious, freely moving animals. Methods We evaluated a new surgically implanted telemetry device, which adds an impedance sensor for the chronic measurement of respiratory parameters to the standard device used for safety pharmacology cardiovascular studies. The feasibility of the implantable device was assessed based on concordance of respiratory data with pneumotachograph-recorded parameters in conscious Beagle dogs following intravenous administration of a positive control (4 mg/kg doxapram). Results Linear regression analysis of data collected under restrained conditions showed a high correlation (R 2 0.95) between impedance-derived respiratory parameters (tidal volume and respiratory frequency) and direct measurements of respiration via pneumotachograph. The correlation was reproduced when animals were challenged under the same dosing regimen. Volume changes similar to those obtained during the restrained collection were observed during the ambulatory collection following doxapram administration. Calibration of impedance-based values was adequate using both individual and population-based baseline conversion factors, both approximating actual mean respiratory variables collected with the pneumotachograph. Discussion The benefit of this model is the accurate, continuous measurement of respiratory endpoints in restrained, as well as ambulatory settings. Assessment of multiple physiological parameters collected concurrently and the use of population-based calibrations may enable the maximization of resources and shortened timelines in drug development. |
| Databáze: | OpenAIRE |
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