非临床遥测心电图分析：记录速率和RR间期宽度对犬和食蟹猴的影响
Analysis of the nonclinical telemetered ECG: impact of logging rate and RR bin width in the dog and cynomolgus monkey.
作者信息
Holzgrefe Henry H, Cavero Icilio, Gleason Carol R
机构信息
Bristol-Myers Squibb Pharmaceutical Research Institute, United States.
出版信息
J Pharmacol Toxicol Methods. 2007 Jul-Aug;56(1):34-42. doi: 10.1016/j.vascn.2006.12.002. Epub 2006 Dec 20.
INTRODUCTION
Species-dependent ECG differences may affect QT interval analysis. Among these are the range of QT and RR values, heart rate variability, and respiratory sinus arrhythmia (SA). Importantly, the effects of data logging rates and RR bin width (BW) on QT analysis have not been characterized in dogs and nonhuman primates.
METHODS
Digital ECGs were collected for 18-21 h in telemetered dogs (n=7) and cynomolgus monkeys (n=7) employing epicardial ECG leads and analyzed by computerized algorithms. ECG intervals were determined employing beat-to-beat (1 ms BW) and 10 s logging rates (for 1, 10, 20, and 50 ms BW). Diurnal heart rate variability was defined as the beat-to-beat RR ratio (VR) where SA was defined as >+/-10% change in VR.
RESULTS
Canine beat-to-beat QT-RR data were curvilinear and plateaued, with multiple RR values associated to any given QT for RR>or=900 ms. Cynomolgus QT-RR data collected as beat-to-beat or at a 10 s logging rate were linear for all RR intervals. During the day, SA comprised 62.9+/-2.4% and 11.4+/-6.1% of total beats in the dog and cynomolgus, respectively, with no diurnal/nocturnal differences in either species. QT interval changes varied with BW such that 5 ms resolution was maintained for BW <or=11.5 and 41 ms in the dog and cynomolgus, respectively.
DISCUSSION
Differences in the QT interval, primarily due to SA, were responsible for skewed canine beat-to-beat QT-RR relationships. A 10 s logging rate eliminated this confounding factor, enabling the derivation of accurate QT rate-corrections. Thus, the uniform application of a 10 s logging rate in conjunction with a 10 ms RR BW ensured consistent and accurate QT analysis in both species. In conclusion, optimal BWs were defined which maintained beat-to-beat accuracy, while maximizing the number of QT-RR observations incorporated into QT-RR rate-correction models, a critical factor for robust probabilistic QT rate-corrections.
引言
物种特异性的心电图差异可能会影响QT间期分析。其中包括QT和RR值的范围、心率变异性以及呼吸性窦性心律失常（SA）。重要的是，数据记录速率和RR区间宽度（BW）对QT分析的影响在犬类和非人灵长类动物中尚未得到明确。
方法
使用心外膜心电图导联，对7只遥测犬和7只食蟹猴进行了18 - 21小时的数字心电图采集，并通过计算机算法进行分析。采用逐搏（1毫秒BW）和10秒记录速率（针对1、10、20和50毫秒BW）确定心电图间期。昼夜心率变异性定义为逐搏RR比值（VR），其中SA定义为VR变化>±10%。
结果
犬类逐搏QT - RR数据呈曲线且趋于平稳，对于RR≥900毫秒，任何给定的QT都有多个RR值与之相关。以逐搏或10秒记录速率收集的食蟹猴QT - RR数据在所有RR区间均呈线性。白天，SA分别占犬类和食蟹猴总心搏数的62.9±2.4%和11.4±6.1%，两种动物在昼夜均无差异。QT间期变化随BW而不同，犬类和食蟹猴分别在BW≤11.5毫秒和41毫秒时保持5毫秒分辨率。
讨论
QT间期的差异主要归因于SA，导致犬类逐搏QT - RR关系出现偏差。10秒记录速率消除了这一混杂因素，从而能够得出准确的QT心率校正值。因此，统一应用10秒记录速率并结合10毫秒RR BW可确保两种动物的QT分析一致且准确。总之，确定了最佳BW，其既能保持逐搏准确性，又能使纳入QT - RR心率校正模型的QT - RR观测值数量最大化，这是稳健概率性QT心率校正的关键因素。
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