Obstructive sleep apnea (OSA) is a very common disease with major health consequences. The fundamental problem leading to OSA is a failure of the neural control of the upper airway muscles during sleep in those anatomically predisposed. Some progress has been made in the understanding of the mechanisms underlying OSA by performing multi-unit electromyography recordings on upper airway dilator muscles such as the genioglossus (GG). Although these studies have been useful in establishing the importance of these muscles in protecting upper airway patency, and the potential stimuli of importance, we still have a relatively cursory understanding of apnea pathogenesis. Using a newer technique in this area, we are now actively recording single motor units (SMUs) in order to establish the characteristics of the various components contributing to overall genioglossus activity. We have characterized six different SMU patterns of genioglossus firing, some with activity predominantly during inspiration, some with constant activity throughout the respiratory cycle, and some with various combinations. Of note these various SMUs appear to have different response characteristics from standpoint of their activity, for example in going from wakefulness to sleep. Similarly, the response of these various SMUs to standard respiratory stimuli appears to be quite different. Specifically, the change in behavior of SMUs in the transitions from wakefulness to sleep is predicated on the discharge pattern during prior wakefulness. We have also observed major differences in SMUs in OSA patients compared to controls and during REM sleep. Also, certain types of motor units appear to be critically involved in the development of upper airway collapse. Based on animal and human data, we are in the process of developing a working neurobiological model to understand the major pathways regulating GG activity, and how these may be dysfunctional in OSA. We therefore strongly believe that the detailed characterization of SMUs in normal subjects and OSA patients and how SMU behavior changes from wakefulness to NREM and REM sleep will lead to major advances in our understanding of apnea pathogenesis. Ultimately, the development of this working model of upper airway motor control, and the characterization of the muscle control abnormalities in OSA will facilitate the identification of therapeutic targets for the treatment of OSA.
. Obstructive sleep apnea is a highly prevalent and debilitating disease with well established consequences to the brain and cardiovascular system. Current understanding of why sleep apnea occurs is incomplete, although the control of upper airway dilator muscles such as the genioglossus are thought to be important. Single motor unit technology allows scientists to understand the various different groups of neurons that are controlling the muscle and to draw inferences regarding how these neurons are being controlled;such studies will be critical for new treatments for this condition to emerge, such as drug treatment of sleep apnea.
|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|
|Pépin, Jean-Louis D; Woehrle, Holger; Liu, Dongquan et al. (2018) Adherence to Positive Airway Therapy After Switching From CPAP to ASV: A Big Data Analysis. J Clin Sleep Med 14:57-63|
|Sánchez-de-la-Torre, Alicia; Soler, Xavier; Barbé, Ferran et al. (2018) Cardiac Troponin Values in Patients With Acute Coronary Syndrome and Sleep Apnea: A Pilot Study. Chest 153:329-338|
Showing the most recent 10 out of 271 publications