1999 Fiscal Year Final Research Report Summary
Role of central nervous system in sympathetic circulatory regulation in chronic heart failure.
| Project/Area Number |
09670706
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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 | TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY |
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Principal Investigator |
ASANIOI Hidetsugu Toyama Medical and Pharmaceutical University, Hospital, Assistant Professor, 附属病院, 講師 (00150128)
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| Co-Investigator(Kenkyū-buntansha) |
TAKASHIMA Shutaro Toyama Medical and Pharmaceutical University, Faculty of Medicine, Research Associate, 医学部, 助手 (50146586)
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| Project Period (FY) |
1997 – 1999
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| Keywords | Heart failure / Sympathetic nerve activity / Central nervous system / Sleep apnea / Lung stretch reflex / Alpha 2 agonist |
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| Research Abstract |
To elucidate the role of central nervous system in sympathoexcitation in heart failure, we examined l) modulation of sympathetic tone by lung stretch reflex, 2) sleep rhythm and autonomic function, and 3) effects of central sympathoinhibition for heart failure treatment. Close coupling between the brain stem respiratory oscillator and the central sympathetic network was examined by dynamic nature of reflex sympathoinhibition by lung inflation in patients with heart failure. Patients with a higher sympathetic drive had a spontaneous shallow respiration, I.e., a decreased input to lung inflation reflex and a greater tidal volume required to suppress muscle sympathetic nerve activity, I.e., an increased sympathoinhibitory threshold. One of the mechanisms for the increased sympathoinhibitory threshold could involve an increased baseline sympathetic tone. An overnight sleep study revealed that central sleep apnea and resultant oxyhemoglobin desaturation occurred frequently during shallow sl
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eep. The grade of desaturation correlated well with the level of plasma norepinephrine concentration (r = 0.84, p<0.01). Thus, in patients with heart failure, the abnormal breathing patterns in awake and sleeping states could contribute to the sympathoexcitation through attenuated inhibitory and enhanced excitatory mechanisms. To evaluate the effects of central sympathoinhibition on clinical status of heart failure, we gave a central alpha-2-adrenergic agohist, guanfacine, to patients with various severity of heart failure. Low dose (0.25mg/day) of guanfacine dramatically suppressed muscle sympathetic nerve activity and plasma norepinephrine level and augmented parasympathetic nerve activity assessed by heart rate variability. Naturesis was exaggerated despite of a significant fall in blood pressure. These beneficial actions were observed only in patients with severe heart failure and higher sympathetic tone. These findings suggest that the central nervous system plays an causative role in sympathoexcitation in heart failure and that the central sympathoinhibition could provide a new therapeutic option in this disorder. Less
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