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International Journal of Bioelectromagnetism Vol. 4, No. 2, pp. 303-304, 2002. |
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www.ijbem.org |
DIURNAL variation of the Qt interval in miniature swine: RELATIONSHiP to autonomic nervous functionM. Kuwahara1, Y.
Noguchi1,
S. Nabeta1,
H. Tsubone1,
E. Kumagai2,
H. Tsutsumi2, Abstract: The purpose of this study was to investigate diurnal variation of QT interval and correlation with autonomic nervous function in miniature swine. Each animal was housed individually in an animal cage and was exposed to a 12/12–hour light/dark cycle. A 24-hour Holter ECG recording was obtained from each animal using the apex-base lead. All recordings were analyzed using an ECG processor (Softron, Tokyo). Heart rate variability, QT intervals, and RR intervals were calculated by the analyzer, and hourly and 24-hour mean values of each measurement were derived from each recording. There was a pronounced circadian variation in the QT interval in parallel with the trend in the RR interval. The QT interval was significantly longer in the dark phase than in the light phase. The QT interval showed a significant positive correlation with HF and a significant negative correlation with LF/HF. These results suggest that an increased parasympathetic nervous activity or a decreased sympathetic nervous activity increases QT interval in miniature swine. These data may be useful for biomedical research, because miniature swine have become increasingly popular as an animal model. INTRODUCTIONMiniature swine have become increasingly popular as an animal model for biomedical research. Cardiovascular physiologic and morphologic similarities to human beings make miniature swine better subjects than are most species. Recently, we showed diurnal variation of autonomic nervous activity in miniature swine [1]. Although it is generally thought that both the heart rate and the QT intervals are influenced by autonomic nervous system, assessment of the QT intervals including diurnal variations has not be done in miniature swine. Therefore, we investigated diurnal variation of QT intervals and correlation with autonomic nervous function in clinically normal miniature swine. METHODSSeven adult male Göttingen miniature swine (Sus Scrofa, body weight, 22.2 to 30.2 kg; age 8 to 12 mouths) obtained from a closed colony (Miniature Swine/CSK; CSK Research Park Inc. Nagano Japan) were studied. Each animal was housed individually in an animal cage and was exposed to a 12/12–hour light/dark cycle. Standard swine diet (‘NS’; Nisseiken Co, Ltd., Tokyo, Japan) and tap water were provided ad libitum. A 24-hour Holter ECG recording was made using a two-channel recorder (QUICK-CORDER QR-1200; Fukuda M-E Kogyo Co., Ltd., Tokyo, Japan), as described previously (Suzuki et al., 1998). All ECG records were analyzed using an ECG processor (Softron, Tokyo, Japan). The QT and preceding RR intervals were individually measured during the course of a 24-h period. Each ECG was magnified on the computer display, and the end of the T-wave was determined manually. Power spectral analysis of heart rate variability was performed as described previously [1]. Briefly, the ECG processor analyzing system (Softron, Tokyo, Japan) first detected R waves and calculated the RR interval tachogram as raw HR variability in sequence order. From this tachogram, data sets of 512 points were re-sampled at 3.5 Hz. We then applied each set of date to the Hamming window and the fast Fourier transform to obtain the power spectrum of the fluctuation. Squared magnitudes and the products of the computed discrete Fourier transforms were averaged to obtain spectral estimates. We used frequency bands of low frequency (LF) and high frequency (HF) according to the previous study [1]: LF (0.01-0.07 Hz) and HF (0.07-1.0 Hz). The ratio of LF and HF power (LF/HF) was also calculated. For assessment of diurnal variations, each hour’s spectral value was prepared from the average of 90 spectra computed over 2-min periods. RESULTSDiurnal variation of heart rate, QT and RR intervals Arrhythmias were not observed in the ECG of any of the miniature swine. Diurnal patterns, in which the values of HR during the light phase (07:00-19:00) were higher than those during the dark phase (19:00-07:00), were observed (Fig. 1). The change in 24-h plot of QT intervals had the same diurnal patterns, as did RR intervals (Fig. 2). The hourly QT and RR intervals during the dark phase were significantly longer than those during the light phase. Figure 1. Hourly heart rate for 24 h in miniature swine. Figure 2. Changes in 24-h plots of RR and QT intervals in miniature swine. Relation between QT and RR intervalsIn miniature swine, QT intervals strongly correlated with RR intervals. This correlation in the dark phase was higher than that in the light phase (r = 0.75 vs. r = 0.68). The slope of the QT/RR interval relation tended to be steeper in the dark phase than in the light phase (0.188 vs. 0.134). Moreover, we tried to pick up the same length of RR intervals from entire recordings and investigated the QT intervals in correspondence to these RR intervals. From this analysis, we found that a diurnal variation existed in the QT intervals derived from even same length of RR intervals. Diurnal variation of autonomic nervous activityLF and HF powers during the light phase were significantly lower than those during the dark phase. The LF/HF ratio also had a diurnal pattern. The value during the light phase was significantly higher than that during the dark phase. Relation between QT intervals and autonomic nervous activityThe correlations of the QT intervals with heart rate variability were assessed for mean hourly values of the 7 miniature swine by linear regression analysis. The QT intervals showed a significant positive correlation with HF and a significant negative correlation with LF/HF ratio (Fig. 3). DISCUSSION We have shown that the QT interval of normal miniature swine varies in a diurnal pattern along with variation in the RR interval. The QT intervals and the components of heart rate variability correlate closely. These results suggest that an increased parasympathetic nervous activity or a decreased sympathetic nervous activity increases QT interval in miniature swine, and consistent with observations in humans [2,3]. Figure 3. Correlation between QT and components of heart rate variability in miniature swine. Theoretically, the efferent sympatho-vagal valance at the myocardial level can be measured from the changes of the QT durations if the effects of heart rate can be eliminated. We have clearly shown a diurnal variation in the QT intervals derived from even same length of RR intervals. These results strongly suggest that autonomic nervous system may modulate ventricular depolarization and repolarization. In conclusion, the characteristics of diurnal variations of the QT intervals and autonomic nervous functions are almost the same as those of humans. Therefore, miniature swine may be a useful animal model for future pharmacotoxicologic studies. REFERENCES[1] M. Kuwahara, A. Suzuki, H. Tsutsumi, M. et al.. “Power spectral analysis of heart rate variability for assessment of diurnal variation of autonomic nervous activity in minature swine,” Lab Anim Sci, vol. 49, pp. 202-208, 1999. [2] M viitasalo, J. Karijalainen, M. Mäkijärvi, et al.. “Autonomic modulation of QT intervals in post-myocardial infarction patients with and without ventricular fibrillation,” Am J Cardiol,. Vol 82, pp. 154-159. 1998. [3] S. Ishida, M. Nakagawa, T. Fujino, et al.. “Circadian variation of QT interval dispersion,” J Electrocardiol, vol. 30, pp205-210. 1997.
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