Patients with obstructive sleep apnea (OSA) experience repetitive nocturnal oscillations that occur in association with changes in respiration and changes in sleep state. The highest heart rate and arterial pressure of the apnea-recovery cycle occur at apnea termination, co-incident with both the nadir of oxygen saturation and arousal, an abrupt disruption of sleep. But the relative contributions of chemo- stimulation using a unique porcine model of airway occlusion during sleep, we have begun to isolate the hemodynamic consequences of chemo-stimulation from those of sleep disruption by defining regional changes in blood flow in response to arousal induced by respiratory and non-respiratory stimuli. Data gathered in this laboratory using porcine model lead us to propose a series of interrelated hypothesis: 1) airway obstruction during sleep, when associated with abrupt sleep disruption, typically causes a patterned cardiovascular responses, with regional blood flow changes consisting of hindlimb vasodilation and visceral vasoconstriction; 2) we further hypothesize that arousal, an abrupt disruption of sleep is necessary to initiate hindlimb vasodilation and renal vasoconstriction after respiratory and non-respiratory stimuli during sleep; 3) the patterned cardiovascular response to airway occlusion during sleep is, like the cardiovascular defense reaction, effected through sympathetic activation, and is independent of cardiovascular reflex responses (baroreflex, chemoreflex). We will make measurements of blood flow in iliac, renal, mesenteric, and coronary arteries in animals awake and sleep. In these animals we will use tracheal occlusion and acoustic and tactile stimuli to induce respiratory and non-respiratory arousals. We are interested in determining whether the hemodynamic response to airway occlusion has critical, defining features of the cardiovascular defense reaction, and further, in understanding what physiologic factors modify this response. We believe that these studies will importantly influence our understanding of the cardiovascular consequences of arousal and will promote greater understanding of the contribution of OSA to cardiovascular morbidity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL060292-02
Application #
6202616
Study Section
Project Start
1999-09-01
Project End
2000-08-31
Budget Start
1997-10-01
Budget End
1998-09-30
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Harvard University
Department
Type
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code
02115
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