The long term goal of the Principal Investigator (PI) is to examine autonomic responses in obstructive sleep apnea (OSA) and in other disease processes that affect the aged. The main objective of this project is to examine the effect of sympathetic blockade in OSA and to determine the effectiveness of nasal continuous positive airway pressure (nCPAP) therapy on sympathoexcitation. OSA is a syndrome that affects 4 percent of men and 2 percent of women. The prevalence may even be higher in the elderly. Morbidities associated with obstructive sleep apnea include hypertension (HTN), myocardial infarction (MI), cardiac arrhythmias, strokes and premature death. A key physiologic abnormality in OSA is heightened sympathetic tone which may underlie the cardiovascular morbidity. OSA is associated with arterial pressure oscillations. The increase in arterial pressure may be due to an increase in vasoconstrictor nerve traffic from heightened sympathetic activity. Preliminary data from our lab using time sequence analysis suggest that the MSNA and arterial pressure (AP) responses seen during apnea in OSA are accompanied by vasoconstriction. A recent study involving normal subjects investigated the effects of sympathetic blockade on neurocirculatory responses to breath-holds and the Mueller maneuver. This study demonstrated that sympathetic blockade essentially abolished MSNA and AP responses thus suggesting a causal relationship. To further explore whether surges in sympathetic discharge evokes vasoconstriction, we propose adrenergic blocking studies. Additionally, evidence suggests that treatment of OSA attenuates the sympathetic response to apneas, however, there are no prior studies that directly examined the effects of OSA therapy on sympathoexcitation - induced vasoconstriction. This project will further increase our knowledge of the pathophysiologic mechanisms responsible for the cardiovascular morbidity and mortality seen in OSA. The PI has been funded by a Minority Supplement to Dr. Sinoway's R01 proposal from the NIH. This proposal will give the PI the additional support and training necessary to become an independent funded investigator.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Mentored Patient-Oriented Research Career Development Award (K23)
Project #
5K23HL004190-05
Application #
6607600
Study Section
Special Emphasis Panel (ZHL1-CSR-F (M3))
Program Officer
Rothgeb, Ann E
Project Start
1999-08-01
Project End
2004-06-30
Budget Start
2003-07-01
Budget End
2004-06-30
Support Year
5
Fiscal Year
2003
Total Cost
$129,708
Indirect Cost
Name
Pennsylvania State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
129348186
City
Hershey
State
PA
Country
United States
Zip Code
17033
Imadojemu, Virginia A; Mawji, Zubina; Kunselman, Allen et al. (2007) Sympathetic chemoreflex responses in obstructive sleep apnea and effects of continuous positive airway pressure therapy. Chest 131:1406-13
Leuenberger, Urs A; Brubaker, Derick; Quraishi, Sadeq et al. (2005) Effects of intermittent hypoxia on sympathetic activity and blood pressure in humans. Auton Neurosci 121:87-93
Imadojemu, Virginia A; Mooney, Kenneth; Hogeman, Cindy et al. (2004) Extracellular calcium and vascular responses after forearm ischemia. Circulation 110:79-83
Imadojemu, Virginia A; Gleeson, Kevin; Quraishi, Sadeq A et al. (2002) Impaired vasodilator responses in obstructive sleep apnea are improved with continuous positive airway pressure therapy. Am J Respir Crit Care Med 165:950-3
Imadojemu, Virginia A; Gleeson, Kevin; Gray, Kristen S et al. (2002) Obstructive apnea during sleep is associated with peripheral vasoconstriction. Am J Respir Crit Care Med 165:61-6
Imadojemu, V A; Lott, M E; Gleeson, K et al. (2001) Contribution of perfusion pressure to vascular resistance response during head-up tilt. Am J Physiol Heart Circ Physiol 281:H371-5