Long-term telemetric measurement of cardiovascular parameters in awake mice: a physiological genomics tool

摘要

The recent miniaturization of implantable radiotelemetric devices offers the possibility of an accurate, reliable, and simple phenotyping tool for long-term, hands-off measurement of blood pressure in unrestrained, untethered mice; however, use has been limited because of high morbidity and mortality in all but larger-than-average mice. Also, because the device was developed for abdominal aorta implantation at the renal artery level, its use has not been feasible in studies where infrarenal blood flow is critical, i.e., in pregnant mice. We provide details of a very successful alternative approach for implanting radio-telemeters in mice, whereby thoracic aortic implantation of the pressure-sensing catheter is combined with subcutaneous placement of the transmitter body along the right flank. We used female C57/BL6 (C57) or BPH/5 mice, a strain derived from the cross of inbred hypertensive and hypotensive mouse strains. We show that this is a reliable procedure for providing high-fidelity mean arterial pressure (MAP) and heart rate (HR) recordings for 50-60 days in mice weighing 22 g on average but as small as 17 g. No morbidity or mortality was observed in either strain using this procedure. Importantly, neither strain fully recovered from anesthesia and surgery, as indicated by a return of normal circadian rhythms, until 5-7 days postsurgery. This was also reflected in significantly elevated baseline MAP and HR levels in both strains during this recovery period. Moreover, strain-related differences in relative increases in MAP during the first 5 days of recovery masked the significant elevation in BPH/5 baseline MAP (vs. C57) observed in fully recovered mice. This suggests that methods must allow at least 5-7 days recovery from surgery to provide accurate cardiovascular (CV) phenotyping in mice. Finally, we show that CV parameters can be monitored continuously before, during, and after pregnancy in mice using this alternative implantation approach. The device did not interfere with conception, gestation, delivery, or postnatal care of pups. These results demonstrate the feasibility of stress-free, long-term monitoring of CV parameters in pregnant or nonpregnant mice of typical size and offer exciting possibilities for application in CV functional genomic research.