Date of Award

5-1-2004

Degree Type

Restricted Access Dissertation

Degree Name

Doctor of Philosophy

Field of Study

Integrative Physiology

Department

Graduate School of Biomedical Sciences

First Advisor

Michael L. Smith

Second Advisor

Peter V. Raven

Third Advisor

Fred Downey

Abstract

Cutler, Michael J., The Effects of Short-Term Intermittent Hypoxic Apneas on Sympathetic Nerve Activity and the Chemorelex Control of Sympathetic Nerve Activity in Humans. Doctor of Philosophy (Integrative Physiology), May 2004. Obstructive sleep apnea is associated with sustained elevation of muscle sympathetic nerve activity (MSNA) and altered chemoreflex control of MSNA both of which likely play an important role in the development of hypertension in these patients. Hypoxia is postulated to be primary stimulus for elevated daytime MSNA and altered chemoreflex control of MSNA both of which likely play an important role in the development of hypertension in these patients. Hypoxia is postulated to be the primary stimulus for elevated daytime MSNA and altered chemoreflex control of MSNA in OSA patients. Recently, short-term exposure to hypoxia was shown to produce sustained elevation of MSNA. Therefore, we studied the effects of 20 min of intermittent voluntary hypoxic apneas (to mimic OSA) on MSNA and the chemoreflex control of MSNA during 180 min post exposure. Also, we compared MSNA and chemoreflex control of MSNA for 180 min following either 20 min of intermittent voluntary hypoxic apneas, hypercapnic hypoxia, or isocapnic hypoxia. Consistent with our hypotheses, both total MSNA and MSNA burst frequency were elevated following 20 min of intermittent hypoxic apnea compared to baseline (p<0.05). Both total MSNA and MSNA burst frequency remained elevated throughout the 180 min recovery period and were statistically different from time control subjects throughout this period (p<0.05). Additionally, a significant main effect for chemoreflex control of SNA was observed following 20 min of intermittent hypoxic apneas (p<0.001). Specifically, the MSNA response to a single hypoxic apnea was attenuated 1 min post exposure compared to baseline (p<0.001), became augmented within 30 min of recovery, and remained augmented through 165 min of recovery (p<0.05). Finally, comparison of treatment groups (hypoxic apnea, hypercapnic hypoxia, and isocapnic hypoxia) revealed no differences in resting MSNA (p=0.50) and the chemoreflex control of MSNA (p=0.69) during recovery. Therefore, these data support the hypothesis that short-term exposure to intermittent hypoxic apneas resulted in sustained elevation of MSNA and altered chemoreflex control of MSNA. Furthermore, these responses appear to be mediated by hypoxia.

Comments

Cutler, Michael J., The Effects of Short-Term Intermittent Hypoxic Apneas on Sympathetic Nerve Activity and the Chemorelex Control of Sympathetic Nerve Activity in Humans. Doctor of Philosophy (Integrative Physiology), May 2004. W 4 C989e 2004

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