Evaluation of the PhysioTel™ Digital M11 cardiovascular telemetry implant in socially housed cynomolgus monkeys up to 16 weeks after surgery

Abstract Introduction The novel PhysioTel™ Digital M11 telemetry implant was evaluated in socially housed monkeys with respect to both safety pharmacological cardiovascular (arterial blood pressure (BP), heart rate (HR) and electrocardiogram (ECG)) and toxicological (clinical pathology and histopathology) endpoints. Methods Telemetry and clinical pathology data were obtained repeatedly up to 16 weeks after surgery in four female cynomolgus monkeys, followed by necropsy. Due to postsurgical complications, one spare animal was included and only toxicological endpoints from the affected (fifth animal) were reported. Continuous telemetry recordings were conducted at periods without dosing and after ascending doses of moxifloxacin (0, 10, 30, 100 mg/kg) and L-NAME (0, 0.1, 1, 10 mg/kg). Additionally, a retrospective power analysis was conducted based on baseline M11 implant data from 32 other animals. Results During periods without dosing, the cardiovascular endpoints were stable over time and within normal ranges. Moxifloxacin and L-NAME elicited the expected pharmacological responses with dose–dependent increase in QT ca (8, 17, 22 ms) and BP (mean BP: 12, 21, 34 mm Hg), respectively. Expected intravascular and tissue reactions were observed at the sites of the BP catheter and the transmitter. Signs of infection (localised to the transmitter implantation site with associated systemic effects) was noted in the fifth animal. No systemic pathologies were seen in any animals. Power analysis (80% power) indicated that the minimal differences which can be detected in a parallel group design (n = 6) are 7 mm Hg (mean BP), 16 bpm (HR), 12 ms (QT ca ). Discussion The M11 implant provided stable, high quality ECG and BP data for a duration covering the length of sub-chronic repeated dose toxicity studies without important impact on toxicological endpoints. Adequate power in order to elucidate major treatment-related cardiovascular effects was demonstrated. However to avoid post-surgical complications the implantation procedures should be carefully considered before using the method.