To apply newer electromyographic techniques to upper airway muscles with a view towards identifying important therapeutic targets in obstructive sleep apnea. Career development goals: To provide sufficient time for mentoring of trainees and research activities. Research project: Obstructive sleep apnea is an important disease due to its high prevalence and well established neurocognitive and cardiovascular sequelae. Treatment of this disease remains problematic since the existing therapies are either poorly tolerated or have variable efficacy, leading many to advocate for further research into underlying mechanisms. Prior research has established in the importance of the upper airway muscles (such as the genioglossus and tensor palatini) in the pathogenesis of sleep apnea. However, multi-unit electromyographic recordings provide an average representation of innumerable motor units yielding fairly incomplete information about the behavior of individual motor units. We have current R01 funding to perform high frequency sampling of the electromyogram to define the various motor units within the genioglossus muscle. These newer studies have revealed marked complexity in the behavior of the genioglossus muscle, with 6 distinct firing patterns being identifiable. A rise or fall in the genioglossal multiunit EMG is therefore difficult to interpret since these changes could be mediated by any of a number of individual motor unit firing changes. We have observed specific units which may be most critical for the maintenance of pharyngeal patency. Such units would thus we logical therapeutic targets which we can address with our neuroanatomy collaborators. We have also begun studies using single fiber EMGs and MacroEMGs which a view towards performing more quantitative assessments of various upper airway muscles. We will use the K24 funding to focus on clinically relevant findings from the R01 such that ultimately clinicians will be able to define upper airway motor function without the need for complex or invasive physiology testing. This K24 award would allow us to pursue interesting hypotheses which may ultimately lead to new easily applicable treatments for sleep apnea. This award will also allow the PI to dedicate more time to training young investigators in the field of sleep and respiratory physiology by reducing his clinical responsibilities. The need for an investigator pipeline has been termed a crisis (Sleep. 2006 29:1260) which the PI would like to continue to address through his research and his dedication to his trainees.

Public Health Relevance

Obstructive sleep apnea is a common problem in which people stop breathing when they are asleep and this breathing pattern can lead to health problems. Some people with sleep apnea may have weak muscles in the back of the throat. We will test whether special tests are helpful in diagnosing the problem and whether specific exercises can help some people who are suffering from sleep apnea.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Midcareer Investigator Award in Patient-Oriented Research (K24)
Project #
5K24HL132105-04
Application #
9654770
Study Section
NHLBI Mentored Patient-Oriented Research Review Committee (MPOR)
Program Officer
Laposky, Aaron D
Project Start
2016-06-01
Project End
2021-02-28
Budget Start
2019-03-01
Budget End
2020-02-29
Support Year
4
Fiscal Year
2019
Total Cost
Indirect Cost
Name
University of California, San Diego
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
804355790
City
La Jolla
State
CA
Country
United States
Zip Code
92093
Girard, Timothy D; Exline, Matthew C; Carson, Shannon S et al. (2018) Haloperidol and Ziprasidone for Treatment of Delirium in Critical Illness. N Engl J Med :
Light, Matthew; Orr, Jeremy E; Malhotra, Atul et al. (2018) Continuous positive airway pressure device detects atrial fibrillation induced central sleep apnoea. Lancet 392:160
Deacon-Diaz, Naomi; Malhotra, Atul (2018) Inherent vs. Induced Loop Gain Abnormalities in Obstructive Sleep Apnea. Front Neurol 9:896
Mahajan, Sanjiv; Gupta, Kartik; Sinha, Sanjeev et al. (2018) Effect of kidney transplantation on sleep-disordered breathing in patients with End Stage Renal Disease: a polysomnographic study. Sleep Med 45:140-145
Light, Matthew; McCowen, Karen; Malhotra, Atul et al. (2018) Sleep apnea, metabolic disease, and the cutting edge of therapy. Metabolism 84:94-98
Hepokoski, Mark L; Bellinghausen, Amy L; Bojanowski, Christine M et al. (2018) Can We DAMPen the Cross-Talk between the Lung and Kidney in the ICU? Am J Respir Crit Care Med 198:1220-1222
Gupta, Ankit; Quan, Stuart F; Oldenburg, Olaf et al. (2018) Sleep-disordered breathing in hospitalized patients with congestive heart failure: a concise review and proposed algorithm. Heart Fail Rev 23:701-709
Hepokoski, Mark L; Malhotra, Atul; Singh, Prabhleen et al. (2018) Ventilator-Induced Kidney Injury: Are Novel Biomarkers the Key to Prevention? Nephron 140:90-93
Hepokoski, Mark L; Odish, Mazen; Malhotra, Atul (2018) Prone positioning in acute respiratory distress syndrome: why aren't we using it more? J Thorac Dis 10:S1020-S1024
Malhotra, Atul; Morrell, Mary J; Eastwood, Peter R (2018) Update in respiratory sleep disorders: Epilogue to a modern review series. Respirology 23:16-17

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