目的 通過(guò)比較不同的校正公式來(lái)確定適合清醒Beagle犬QT間期校正的公式，以用于非臨床安全藥理學(xué)研究。方法 用12只已進(jìn)行遙測(cè)植入的Beagle犬（雌、雄各半）連續(xù)采集至少24 h的心電圖數(shù)據(jù)，測(cè)量并分析該期間內(nèi)動(dòng)物的RR和QT間期，采用8種校正公式（QTcF、QTcB、QTcHDG、QTcV、QTcFRM、QTcNAK、QTcI、QTca）計(jì)算QTc，然后對(duì)不同校正公式計(jì)算的QTc與RR進(jìn)行線性回歸分析，尋找R值最接近零和P值最大的校正公式，并進(jìn)行性別間的差異比較。結(jié)果 使用8種校正公式計(jì)算的QTc比較顯示，QTca個(gè)體校正公式校正的R值為-0.025，P值為0.679；QTcI校正的R值為-0.040，P值為0.501；QTcF校正的R值為0.044，P值為0.461。與其他公式相比QTca校正公式的R值最接近于零并且P值最高，表明QTca計(jì)算的QTc受RR的影響程度最小，且表明QTc與RR 2個(gè)變量之間無(wú)顯著相關(guān)性。在雄性Beagle犬中，通過(guò)QTcI個(gè)體校正公式校正的R值為0.070，P值為0.401；其次是QTca，R值為0.072，P值為0.391；再者為QTcF，R值為0.118，P值為0.159。在雌性Beagle犬中，通過(guò)QTcF通用校正公式校正的R值為-0.026，P值為0.755；其次是QTca，R值為-0.135，P值為0.108。雄性和雌性Beagle犬之間通過(guò)與其他公式的R值和P值的比較，表明QTca和QTcF校正公式計(jì)算的QTc都受RR影響程度較小且表明QTc與RR 2個(gè)變量之間無(wú)顯著相關(guān)性。結(jié)論 在本機(jī)構(gòu)試驗(yàn)條件下，使用個(gè)體校正公式QTca更適合校正清醒無(wú)束縛條件下Beagle犬的QT間期，可作為安全藥理學(xué)研究中的優(yōu)選方式。

Objectives The correction formulas suitable for QT interval correction in conscious Beagle dogs are determined by comparing different correction formulas in non-clinical safety pharmacology study. Methods 12 Beagle dogs (half male and half female) with existing telemetry implants are used to continuously collect ECG data for at least 24 hours, and the RR and QT intervals of the animals during the analysis period were measured and analyzed. QTc was calculated using eight correction formulas (QTcF, QTcB, QTcHDG, QTcV, QTcFRM, QTcNAK, QTcI, QTca), comand then linear regression analysis was performed on QTc calculated by different correction formulas and RR, searching for thecorrectionformulas with R value closest to zero and P value maximum, and comparing the differences between genders. Results The comparison of QTc calculated using eight correction formulas showed that R value corrected by QTca individual correction formula is -0.025 and P value is 0.679; R value corrected by QTcI is -0.040 and P value is 0.501; R value correctedby QTcF is 0.044 and P value is 0.461. The R value of the QTca-corrected formula is the closest to zero and the P value is the highest compared to the other formulas, indicating that QTca-calculated QTc was minimally affected by RR and indicating that there are no significant correlation between QTc and RR variables. In male Beagle dogs, R value by the individual correction formula for QTcI is 0.070, P value is 0.401; followed by QTca, R value is 0.072 and P value is 0.391; and furthermore, R value is 0.118 and P value is 0.159 for QTcF. In female Beagle dogs, R value by the universal correction formula for QTcF is -0.026, P value is 0.755; followed by QTca, R value is -0.135, P value is 0.108. Comparison of R and P values with other formulas between male and female Beagle dogs indicated that QTca and QTcF correction formula-calculated QTc were both less affected by RR and indicated no significant correlation between QTc and RR variables. Conclusion Under the experimental conditions in our institution, the effect on QT interval in conscious unrestrained Beagle dogs could be accurately corrected using the individual correction formula QTca which can be used as a preferred method in safety pharmacology study.

R965