Comparison of one- and three-lead ECG to measure cardiac intervals and differentiate drug-induced multi-channel block.

INTRODUCTION: FDA has established initiatives to characterize clinical and non-clinical biomarkers to enable more precise prediction of proarrhythmia risk based upon knowledge of drug effect on multiple cardiac ion channels (Colatsky et al., 2016). The FDA has recently demonstrated superiority of early ventricular repolarization interval (JTp) in differentiating pure hERG block from multi-channel block in human subjects. Preclinical studies often acquire a single lead ECG, whereas FDA measurements of JTp were derived ​from a spatial vectorcardiogram computed using multiple leads. This study compares QT subintervals derived from single lead vs. spatial magnitude (SM) ECG and contrasts information obtained from multilead and single lead ECGs in the canine model. METHODS: Four beagle dogs were instrumented with 3-lead Holter monitors to acquire continuous surface ECG recordings for three consecutive days. A 24-h baseline recording was obtained on day 1 followed by administration of dofetilide on day 2 and atropine and dofetilide on day 3. Lead II and SM ECGs were automatically analyzed using the AE-1010 Rhythm Express™ (RE) software (VivaQuant, St. Paul, MN USA) without manual intervention or editing of the results (auto). Five-minute averages of beat-to-beat intervals measured on each lead were compared for agreement assessed by Bland-Altman (BA) statistics and consistency measured as the repeatability standard deviation (SD) from 5-min intervals. The fully automated results were screened by an operator (semi-automated) and compared to automated results. RESULTS: JTp and TpTe measured using SM lead are less sensitive to changes in posture and respiration related changes in T-wave morphology. The 24-h repeatability SD of 5-min subintervals for JTp and TpTe over the three days was improved by 15.4% and 15.5% respectively with the highest improvements of 23.3% for JTp on day 2 and 25.3% for TpTe on day 3. Drug induced changes in QTcV, QRS, RR, and PR intervals were qualitatively similar between the SM lead and Lead II and in close agreement based on BA statistics. Semi-automated and automated measurements from SM Lead were in close agreement based on BA statistics. DISCUSSION: Single lead ECG is adequate for PR, RR, QRS, and QT, but produces different and more variable results when assessing QT subintervals relative to the SM lead. Close agreement between automated and semi-automated measurements demonstrates Rhythm Express accuracy and the potential to streamline interval analysis.

Fully Implantable Arterial Blood Glucose Device for Metabolic Research Applications in Rats for Two Months.

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 quality and quantity of data that can be obtained relative to existing alternatives such as intermittent blood sampling. These devices provide the opportunity to expand the understanding of both glucose metabolism and homeostasis and to work toward improved therapies and cures for diabetes.