2000 Fiscal Year Final Research Report Summary
The role of sympathetic nerve activity in sudden cardiac death in patients with heart failure
| Project/Area Number |
11670730
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | National Cardiovascular Center |
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Principal Investigator |
TAKAKI Hiroshi National Cardiovascula, Cente, Department of Cardiovascular Dynamics, Laboratory Chief, 循環動態機能部, 室長 (60216629)
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| Co-Investigator(Kenkyū-buntansha) |
KAWADA Toru National Cardiovascular Center, Department of Cardiovascular Dynamics, Research Stuff, 循環動態機能部, 室員 (30243752)
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| Project Period (FY) |
1999 – 2000
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| Keywords | sympathetic nerve system / Sudden Cardiac Death / Heart failure / muscle sympathetic nerve activity / electrocardiogram / QT interval / arterial baroreflex system |
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| Research Abstract |
(1) To characterize arterial baroreflex system taking account of feedback loop, we applied a nonparametric closed-loop system identification to the arterial baroreflex system by using a white-noise exogenous perturbation. Methods : In 8 healthy men, we recorded blood pressure (BP) and muscle sympathetic nerve activity (MSNA) while randomly applying lower body negative pressure (LBNP). Using LBNP as an exogenous perturbation, we estimated the central arc of arterial baroreflex system from BP to MSNA and the peripheral arc from MSNA to BP.Results : The central arc had a high-pass filter characteristics and the peripheral arc had a low-pass filter characteristics. The steady state total loop gain of ABR system was 1.25 ± 0.55.
(2) To characterize the ventricular repolarization abnormality in patients with heart failure, we applied coherence analysis to the relation between RR interval and QT interval. Methods : In 12 patients with dilated cardiomyopathy (DCM) and 8 normal control subjects,
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we recorded ECG under control respiration. We measured QT interval and RR interval in each beats and calculated the coherence of QT and RR intervals. Results : The coherence was larger in control subjects than DCM patients (control : 0.91±0.08 vs DCM : 0.63±0.30, p<0.05). Conclusion : In patients with heart failure, the ventricular repolarization variability was uncoupled from RR interval variability.
(3) To estimate the dynamic effects of sympathetic nerve activity on ventricular repolarization, the estimation of sympathetic nerve activity with sufficient tine resolution is essential. On the other hand, sympathetic nerve activity modulates ventricular repolarization both directly and through changes in RR intervals. The separation of those two effects is difficult in humans. To resolve these difficulties, we applied autoregressive(AR) model analysis on muscle sympathetic nerve activity(MSNA), RR arid OT intervals. Methods : In 8 healthy men, we recorded ECG (V_<5S>) and MSNA while irregularly changing SPA by lower body negative pressure. We measured RR and QT in each beat. By solving the multivariate(MSNA, RR, QT) AR model, we quantitatively characterized the direct effect of SNA on QT as well as the effect of RR on QT.Results : Sudden decreases in RR shortened QT rapidly in a few seconds and then more shortened gradually. Sudden increases in sympathetic nerve activity shortened QT with transient oscillatory response. Conclusion : AR model analysis of RR, QT and MSNA enables us to characterize the direct effect of sympathetic nerve activity on QT in human. Transient oscillatory QT response to sudden sympathetic nerve activation may contribute to the arrhythmogenesis when exposed to sudden stress. Less
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