Research Opportunities in Autonomic Neural Mechanisms of Cardiopulmonary Regulation: A Report From the National Heart, Lung, and Blood Institute and the National Institutes of Health Office of the Director Workshop

Reena Mehra; Olga A Tjurmina; Olujimi A Ajijola; Rishi Arora; Donald C Bolser; Mark W Chapleau; Peng-Sheng Chen; Colleen E Clancy; Brian P Delisle; Michael R Gold; Jeffrey J Goldberger; David S Goldstein; Beth A Habecker; M Louis Handoko; Robert Harvey; James P Hummel; Thomas Hund; Christian Meyer; Susan Redline; Crystal M Ripplinger; Marc A Simon; Virend K Somers; Stavros Stavrakis; Thomas Taylor-Clark; Bradley Joel Undem; Richard L Verrier; Irving H Zucker; George Sopko; Kalyanam Shivkumar

doi:10.1016/j.jacbts.2021.11.003

Research Opportunities in Autonomic Neural Mechanisms of Cardiopulmonary Regulation: A Report From the National Heart, Lung, and Blood Institute and the National Institutes of Health Office of the Director Workshop

JACC Basic Transl Sci. 2022 Jan 26;7(3):265-293. doi: 10.1016/j.jacbts.2021.11.003. eCollection 2022 Mar.

Authors

Reena Mehra^{1

2}, Olga A Tjurmina³, Olujimi A Ajijola⁴, Rishi Arora⁵, Donald C Bolser⁶, Mark W Chapleau⁷, Peng-Sheng Chen⁸, Colleen E Clancy⁹, Brian P Delisle¹⁰, Michael R Gold¹¹, Jeffrey J Goldberger¹², David S Goldstein¹³, Beth A Habecker¹⁴, M Louis Handoko¹⁵, Robert Harvey¹⁶, James P Hummel¹⁷, Thomas Hund¹⁸, Christian Meyer¹⁹, Susan Redline²⁰, Crystal M Ripplinger²¹, Marc A Simon^{22

23}, Virend K Somers²⁴, Stavros Stavrakis²⁵, Thomas Taylor-Clark²⁶, Bradley Joel Undem²⁷, Richard L Verrier²⁸, Irving H Zucker²⁹, George Sopko³, Kalyanam Shivkumar⁴

Affiliations

¹ Cleveland Clinic, Cleveland, Ohio, USA.
² Case Western Reserve University, Cleveland, Ohio, USA.
³ National Heart, Lung, and Blood Institute, Bethesda, Maryland, USA.
⁴ David Geffen School of Medicine at UCLA, Los Angeles, California, USA.
⁵ Feinberg School of Medicine at Northwestern University, Chicago, Illinois, USA.
⁶ University of Florida, Gainesville, Florida, USA.
⁷ University of Iowa Carver College of Medicine, Iowa City, Iowa, USA.
⁸ Cedars-Sinai Medical Center, Los Angeles, California, USA.
⁹ University of California Davis, Davis, California, USA.
¹⁰ University of Kentucky, Lexington, Kentucky, USA.
¹¹ Medical University of South Carolina, Charleston, South Carolina, USA.
¹² University of Miami Miller School of Medicine, Miami, Florida, USA.
¹³ National Institute of Neurological Disorders and Stroke, Bethesda, Maryland, USA.
¹⁴ Oregon Health and Science University School of Medicine, Portland, Oregon, USA.
¹⁵ Amsterdam University Medical Centers, Amsterdam, the Netherlands.
¹⁶ University of Nevada Reno, Reno, Nevada, USA.
¹⁷ Yale University School of Medicine, New Haven, Connecticut, USA.
¹⁸ Ohio State University, Columbus, Ohio, USA.
¹⁹ University of Düsseldorf, Germany, Düsseldorf, Germany.
²⁰ Harvard Medical School, Boston, Massachusetts, USA.
²¹ University of California Davis School of Medicine, Davis, California, USA.
²² University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.
²³ University of California-San Francisco, San Francisco, California, USA.
²⁴ Mayo Clinic, Rochester, Minnesota, USA.
²⁵ University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA.
²⁶ University of South Florida, Tampa, Florida, USA.
²⁷ Johns Hopkins University, Baltimore, Maryland, USA.
²⁸ Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
²⁹ University of Nebraska Medical Center, Omaha, Nebraska, USA.

Abstract

This virtual workshop was convened by the National Heart, Lung, and Blood Institute, in partnership with the Office of Strategic Coordination of the Office of the National Institutes of Health Director, and held September 2 to 3, 2020. The intent was to assemble a multidisciplinary group of experts in basic, translational, and clinical research in neuroscience and cardiopulmonary disorders to identify knowledge gaps, guide future research efforts, and foster multidisciplinary collaborations pertaining to autonomic neural mechanisms of cardiopulmonary regulation. The group critically evaluated the current state of knowledge of the roles that the autonomic nervous system plays in regulation of cardiopulmonary function in health and in pathophysiology of arrhythmias, heart failure, sleep and circadian dysfunction, and breathing disorders. Opportunities to leverage the Common Fund's SPARC (Stimulating Peripheral Activity to Relieve Conditions) program were characterized as related to nonpharmacologic neuromodulation and device-based therapies. Common themes discussed include knowledge gaps, research priorities, and approaches to develop novel predictive markers of autonomic dysfunction. Approaches to precisely target neural pathophysiological mechanisms to herald new therapies for arrhythmias, heart failure, sleep and circadian rhythm physiology, and breathing disorders were also detailed.

Keywords: ACE, angiotensin-converting enzyme; AD, autonomic dysregulation; AF, atrial fibrillation; ANS, autonomic nervous system; Ach, acetylcholine; CNS, central nervous system; COPD, chronic obstructive pulmonary disease; CSA, central sleep apnea; CVD, cardiovascular disease; ECG, electrocardiogram; EV, extracellular vesicle; GP, ganglionated plexi; HF, heart failure; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; HRV, heart rate variability; LQT, long QT; MI, myocardial infarction; NE, norepinephrine; NHLBI, National Heart, Lung, and Blood Institute; NPY, neuropeptide Y; NREM, non-rapid eye movement; OSA, obstructive sleep apnea; PAH, pulmonary arterial hypertension; PV, pulmonary vein; REM, rapid eye movement; RV, right ventricular; SCD, sudden cardiac death; SDB, sleep disordered breathing; SNA, sympathetic nerve activity; SNSA, sympathetic nervous system activity; TLD, targeted lung denervation; asthma; atrial fibrillation; autonomic nervous system; cardiopulmonary; chronic obstructive pulmonary disease; circadian; heart failure; pulmonary arterial hypertension; sleep apnea; ventricular arrhythmia.

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Review

Abstract

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