Brett Spitnale, Class of 2007
Urs A. Leuenberger, MD, Heart and Vascular Institute
Date of Project
June 1, 2004 â€“ August 6, 2004
To determine the effect of systemic hypoxemia on circulation blood pressure, blood flow, and resistance and sympathetic output in patients with Obstructive Sleep Apnea (OSA) and in control subjects.
OSA is characterized by intermittent pharyngeal obstructions, which lead to periodic episodes of hypoxemia during sleep. There has been shown to be a high prevalence of hypertension among patients with OSA. Conversely, many patients with hypertension also suffer from sleep disordered breathing, such as OSA. It is believed that the episodes of hypoxemia during sleep are responsible for the chronic increases in blood pressure. Although the mechanisms behind these complications are currently unknown, increases in sympathetic neural activity have been shown to be present in patients with OSA and are suspected to be responsible for the cardiovascular changes seen in these patients. These investigations will attempt to understand the link between OSA, the sympathetic nervous system, and systemic hypertension by observing the changes in vasculature (blood pressure, blood flow, and resistance) and sympathetic output seen with controlled episodes of hypoxemia in patients with OSA compared to age and BMI matched controls and normal healthy controls. Exposure to hypoxic gas normally stimulates vasodilation, a response that is thought to be attenuated in patients with OSA. This weakened vasodilator response may lead to an increase in blood pressure in OSA subjects during hypoxemia, which may or may not be seen in control subjects. We also expect to see an increase in blood flow in the control subjects but not in the patients with OSA, since they have a decreased vasodilator response. Thus, vascular resistance is expected to decrease in controls but not in patients with OSA. Finally, based on previous studies, we also expect to see a rise in sympathetic output during the episode of hypoxemia.
Patients with OSA, age and BMI matched controls, as well as normal healthy controls will be recruited. Before experimentation, all subjects will undergo a physical exam and have routine blood tests. Those subjects with illnesses that may affect sympathetic and/or vascular function, such as hypercholesterolemia and diabetes, will not be allowed to participate. All risks will be explained prior to implementation of experiment. All procedures will be performed in the General Clinical Research Center (GCRC) within the Hershey Medical Center.
Approximately 8 volunteers will be recruited for each group (age and BMI matched controls, normal healthy controls, and OSA patients).
Blood pressure will be monitored automatically and continuously with a non-invasive device (Dinamap or Finapres).
Muscle Sympathetic Nervous Activity (MSNA) will be determined by peroneal microneurography, a technique that measures sympathetic outflow via a microelectrode inserted into the peroneal nerve near the fibular head.
A pulse oximeter will be used to monitor oxygen concentration in the blood during the episodes of hypoxemia.
Blood flow will be measured using a Doppler Ultrasound probe at both the femoral and brachial arteries.
In order to determine how hypoxemia affects vasculature and sympathetic output, we will perform the following protocol in all three subject groups: after the initiation of the microelectrode into the peroneal nerve, baseline measurements (blood pressure, heart rate, blood flow, MSNA, and oxygen saturation) will be taken every thirty seconds for a minimum of five minutes. After a baseline is determined, the subjects will be exposed to hypoxic gas (FiO2 10.5%) for five minutes, during which the same measurements will be taken. A recovery period will also be recorded. We will use the Time Average Mean (TAM) value from the Doppler recording to determine blood flow, and will also use it in calculating resistance (Mean Arterial Pressure divided by Time Average Mean; MAP/TAM) in both the arm and the leg.
- Review current literature pertaining to Obstructive Sleep Apnea
- Recruit participants
- Assist in project protocols
- Perform data analysis
- Prepare final project report
- Oversee project
- Assist in data interpretation
- Leuenberger, Urs; Clifford W. Zwillich. “Blood Pressure Regulation and Sleep Apnea.” Respiratory-Circulatory Interactions in Health and Disease, 2001.
- Leuenberger, Urs, et.al. “Effects of Repetitive Hypoxic Apnea on Blood Pressure and Sympathetic Reflex Function.” IRB Protocol No. 2002-231 for Clinical Research Study. 2004.
- Carlson JT, Hedner J, Elam M, Ejnell H, Sellgren J, Wallin BG. “Augmented Resting Sympathetic Activity In Awake Patients With Obstructive Sleep Apnea.” Chest 1993; 103 (6): 1763-1768.
- Remsburg S, Launois SH, Weiss JW. “Patients with obstructive sleep apnea have an abnormal peripheral vascular response to hypoxia.” Journal of Applied Physiology 1999; 87 (3): 1148-1153.
- Somers VK, Dyken ME, Clary MP, Abboud FM. “Sympathetic Neural Mechanisms In Obstructive Sleep Apnea.” Journal of Clinical Investigation 1995; 96: 1897-1904.
- Imadojemu VA, Gleeson K, Quraishi SA, Kunselman AR, Sinoway LI, Leuenberger UA. “Impaired Vasodilator Responses in Obstructive Sleep Apnea Are Improved with Continuous Positive Airway Pressure Therapy.” American Journal of Respiratory Critical Care Medicine 2002; 165: 950-953.
I do give permission for my proposal to possibly be published on the College of Medicine Website.
Urs Leuenberger, MD Date
Brett Spitnale Date