Original ArticleCurrent options for obtaining glucose measurements in animal studies are limited in terms of the quality and quantity of data available. Glucometers and test strips are perhaps most commonly used. These require tail tip amputation or venipuncture, are stressful to the animal and handler, and often result in high measurement variability due to factors including measurement error, variability in the sampling process, and physiologic stress response. The use of arterial or venous cannulae can help facilitate sample collection and minimize subject and handler stress, but these require routine maintenance with blood loss and offer limited chronic patency. Options for continuous sampling for periods of a few days to 2 weeks include tethered automated blood sampling and some limited use of human continuous glucose monitors (CGMs), which have limited longevity and accuracy.Amperometric electrochemical sensors have been available for over 30 years and originated with the Clark electrode.2,3 The basic principle involves application of a reference voltage to an electrode (typically a noble metal such as platinum) to oxidize a target chemical and measure the current resulting from electron transfer to the electrode. The current is proportional to the availability of the target chemical.Many glucose sensors available today or under development are intended for use in humans with the sensor placed subcutaneously to measure glucose in interstitial fluid. These sensors are targeted at the management of diabetes where patient safety and minimal invasiveness are critical factors, thus precluding placement directly in the blood. These sensors are subject to notable biofouling due to foreign body immune response and are typically overgrown with a fibrous sheath in a matter of days. Background: Chronic continuous glucose monitoring options for animal research have been very limited due to various technical and biological challenges. We provide an evaluation of a novel telemetry device for continuous monitoring of temperature, activity, and plasma glucose levels in the arterial blood of rats for up to 2 months. Methods:In vivo testing in rats including oral glucose tolerance tests (OGTTs) and intraperitoneal glucose tolerance tests (IPGTTs) and ex vivo waterbath testing were performed to evaluate acute and chronic sensor performance. Animal studies were in accordance with the guidelines for the care and use of laboratory animals and approved by the corresponding animal care and use committees (Data Sciences International, Eli Lilly). Results:Results demonstrated the ability to record continuous measurements for 75 days or longer. Bench testing demonstrated a high degree of linearity over a range of 20-850 mg/dL with R 2 = .998 for linear fit and .999 for second order fit (n = 8 sensors). Evaluation of 6 rats over 28 days with 52 daily and OGTT test strip measurements each resulted in mean error of 3.8% and mean absolute relative difference of 16.6%. Conclusions:This device provides significant advantages in the qualit...

Euthanasia is a necessary component in research and must be conducted humanely. Currently, regulated CO2 exposure in conscious rats is acceptable, but data are divided on whether CO2 alone is more distressing than anesthesia prior to CO2. To evaluate distress in rats, we compared physiologic responses to CO2 euthanasia with and without isoflurane preanesthesia. Male Sprague–Dawley rats were implanted with telemetry devices to measure mean arterial pressure (MAP), heart rate (HR), and blood glucose. Animals recovered for 2 wk and were then exposed to either 5% isoflurane (n = 6) or 100% CO2(n = 7; calculated 30% chamber volume/min displacement) in their home cages to induce loss of consciousness. Euthanasia was then completed with CO2 in both groups. MAP and HR increased when the gas delivery lids were placed on the home cages of both groups. Both MAP and HR gradually decreased with isoflurane exposure. MAP increased and HR decreased with CO2 exposure. Glucose levels remained stable throughout the procedure, except for a small drop in conscious animals initially exposed to 100% CO2. These data suggest that both gases affect the measured parameters in a similar manner, andthat environmental factors, such as gas delivery lid placement, also change these measurements.

Continuous data recording, using telemetry, is the preferred way of collecting electrocardiographic (ECG) data in conscious freely moving animals. In small animals, however; the resulting recordings can have indistinguishable P, Q, R, S and T segments due to low signal to noise ratios. In large animals, this has been addressed using wireless telemetry devices with an intravascular negative electrode, or solid tip lead (STL). The purpose of this study was to determine if STLs could be implanted in rats and result in improved ECG signal quality and sensitivity to detect changes when compared to subcutaneous (SQ) leads. Three groups of Sprague Dawley rats (SQ lead placement, STL with shallow placement in the jugular vein, STLs with deep placement in the cranial vena cava) were dosed with verapamil to induce predictable interval changes in the ECG. The three types of ECG signals were compared for ease of automated analysis and signal quality through Q, R, S and T match and noise parameters. STLs resulted in improved signal quality and increased PR interval change following dose. Average number of waveform complexes identified as “bad” by the analysis software was substantially lower in the STL placements than the data collected with SQ electrodes. STLs were successfully implanted in rats and necropsy showed variable tip locations with no gross abnormalities. This application could be especially useful in other small animal models such as the guinea pig, to increase ECG quality and improve automated ECG analysis.

Continuous data recording, using telemetry systems, has proven to be the preferred way of collecting electrocardiogram (ECG) data in conscious freely moving animals. In small animals, however; the resulting recordings can have indistinguishable P, Q, R, S and T segments due to low signal to noise ratios. In large animals, similar challenges have been addressed by equipping wireless telemetry devices with an intravascular negative electrode, or solid tip lead (STL). The purpose of this study was to determine if STLs could be implanted in rats and result in improved ECG signal quality when compared to conventional subcutaneous leads. Two groups of Sprague Dawley rats, one with conventional lead placement (subcutaneous) and the other using the STL (vascular) were surgically implanted. ECG data were collected multiple times over a one year period. Signal quality was qualitatively and quantitatively evaluated between the STL and conventional lead groups, using a side by side visual comparison, and automated Q, R, S and T match percentage, by an experienced ECG analyst. ECG data collected with a STL was observably clearer when compared to the conventional lead group. At the completion of the study, the rats implanted with STLs were subjected to thorough necropsies. A histological examination of the tissue surrounding the STL was completed. In conclusion, STLs were successfully implanted in rats, resulting in improved signal quality with no detrimental evidence of inflammation noted at necropsy. The two ECG signals were compared for ease of automated analysis through comparison of Q, R, S and T match. This application could be especially useful in other small animal models such as the ferret or guinea pig, to increase ECG quality and improve automated ECG analysis.