Telemetry Aids Development of New Models for Hemodynamic Evaluation
Researchers at Roussel-Uclaf, a subsidiary of Hoechst in Romainville near Paris, France recently developed a conscious freely moving mini-pig model to evaluate drugs intended for treatment of heart failure. Veronique Stecyna, Yvon Fradin and Jean-Claude Vincent are seasoned cardiovascular researchers with more than 10 years experience. During their careers, they have developed numerous conscious animal models and have historically had to cope with the problems associated with traditional techniques such as laborious (and not always successful) maintenance of external catheters and skin buttons. They also have had to spend numerous hours in extensive training of animals that must remain stationary during monitoring. Given their experience with the limitations and drawbacks of traditional techniques, they were very enthusiastic when it became practical to use telemetry in their research lab about five years ago. Since its introduction at Roussel-Uclaf, they have come to rely on telemetry as an essential research tool in their laboratory.
Recently, Yvon Fradin, who is leading the experiments involving mini-pigs and primates, developed a model for the preclinical hemodynamic evaluation of new drugs for the improvement of exercise-tolerance, using Yucatan mini-pigs. With this model they want to study various aspects of moderate heart failure after gradual coronary artery occlusion, experimentally induced by an ameroid constrictor placed around the vessel. This causes functional deficiencies of the heart that do not appear when the animal is at rest, but are unveiled during exercise. For this development, the investigators employed telemetry in their research, using the Data Sciences D70-PCP transmitters to measure systemic pressure, LV pressure and ECG, all simultaneously, as a means of obtaining a more complete hemodynamic picture of the animals.
Animals are selected according to their willingness to run on a tread-mill. Under aseptic conditions and isoflurane anesthesia, the chest is opened via a left lateral thoracotomy at the fifth intercostal space. The systemic pressure catheter is inserted in the descending thoracic aorta, and the tip of the second pressure catheter is placed inside the left ventricle through a small hole in its apex. The pair of ECG leads are placed subcutaneously, the negative lead on the right shoulder, and the positive lead in the left groin area in order to obtain a lead II configuration. The incision is then closed in layers, and thoracic vacuum restored. After a two week recovery period, animals are trained on a treadmill according to the protocol used during the experiment.
The first results over a period of more than six months have been very encouraging. The mini-pigs have proven to be an outstanding model for this approach: they are good runners, and even during severe exercise (when speed and/or slope of the treadmill is increased), the telemetry receivers placed on either side of the animal provide good quality signals to the Dataquest LabPRO software, allowing reliable analysis. This technique promises to be an attractive and cost-effective model to evaluate the effectiveness of prospective drugs to treat heart failure, and their effect on exercise tolerance.