Cognitive outcomes in patients treated with neuromuscular electrical stimulation after coronary artery bypass grafting

Vincenzina Lo Re; Giovanna Russelli; Emanuele Lo Gerfo; Rossella Alduino; Matteo Bulati; Gioacchin Iannolo; Danilo Terzo; Gennaro Martucci; Stefano Anzani; Giovanna Panarello; Gianvincenzo Sparacia; Giuseppe Parla; Federica Avorio; Giuseppe Raffa; Michele Pilato; Aurelio Speciale; Valentina Agnese; Giuseppe Mamone; Fabio Tuzzolino; Giovan Battista Vizzini; Pier Giulio Conaldi; Fabrisia Ambrosio

doi:10.3389/fneur.2023.1209905

Cognitive outcomes in patients treated with neuromuscular electrical stimulation after coronary artery bypass grafting

Front Neurol. 2023 Aug 25:14:1209905. doi: 10.3389/fneur.2023.1209905. eCollection 2023.

Authors

Vincenzina Lo Re¹, Giovanna Russelli², Emanuele Lo Gerfo^{1

2}, Rossella Alduino², Matteo Bulati², Gioacchin Iannolo², Danilo Terzo³, Gennaro Martucci⁴, Stefano Anzani^{1

2}, Giovanna Panarello⁴, Gianvincenzo Sparacia⁵, Giuseppe Parla⁵, Federica Avorio¹, Giuseppe Raffa⁶, Michele Pilato⁶, Aurelio Speciale³, Valentina Agnese², Giuseppe Mamone⁵, Fabio Tuzzolino², Giovan Battista Vizzini⁷, Pier Giulio Conaldi², Fabrisia Ambrosio^{8

9

10}

Affiliations

¹ Neurology Service, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione), University of Pittsburgh Medical Center (UPMC), Palermo, Italy.
² Department of Research, IRCCS ISMETT, UPMC, Palermo, Italy.
³ Rehabilitation Service, IRCCS ISMETT, Palermo, Italy.
⁴ Department of Anesthesiology and Intensive Care, IRCCS ISMETT, UPMC, Palermo, Italy.
⁵ Radiology Unit, Department of Diagnostic and Therapeutic Services, IRCCS ISMETT, Palermo, Italy.
⁶ Cardiac Surgery Unit, Department for the Treatment and Study of Cardiothoracic Diseases and Cardiothoracic Transplantation, IRCCS ISMETT, Palermo, Italy.
⁷ Salvator Mundi International Hospital, UPMC, Rome, Italy.
⁸ Discovery Center for Musculoskeletal Recovery, Schoen Adams Research Institute at Spaulding, Boston, MA, United States.
⁹ Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Charlestown, MA, United States.
¹⁰ Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, United States.

Abstract

Objective: Mechanisms of neurocognitive injury as post-operative sequelae of coronary artery bypass grafting (CABG) are not understood. The systemic inflammatory response to surgical stress causes skeletal muscle impairment, and this is also worsened by immobility. Since evidence supports a link between muscle vitality and neuroprotection, there is a need to understand the mechanisms by which promotion of muscle activity counteracts the deleterious effects of surgery on long-term cognition.

Methods: We performed a clinical trial to test the hypothesis that adding neuromuscular electrical stimulation (NMES) to standard rehabilitation care in post-CABG patients promotes the maintenance of skeletal muscle strength and the expression of circulating neuroprotective myokines.

Results: We did not find higher serum levels of neuroprotective myokines, except for interleukin-6, nor better long-term cognitive performance in our intervention group. However, a greater increase in functional connectivity at brain magnetic resonance was seen between seed regions within the default mode, frontoparietal, salience, and sensorimotor networks in the NMES group. Regardless of the treatment protocol, patients with a Klotho increase 3 months after hospital discharge compared to baseline Klotho values showed better scores in delayed memory tests.

Significance: We confirm the potential neuroprotective effect of Klotho in a clinical setting and for the first time post-CABG.

Keywords: coronary artery bypass grafting (CABG); klotho; myokines; neuromuscular electrical stimulation (NMES); post-operative cognitive decline (POCD).

Copyright © 2023 Lo Re, Russelli, Lo Gerfo, Alduino, Bulati, Iannolo, Terzo, Martucci, Anzani, Panarello, Sparacia, Parla, Avorio, Raffa, Pilato, Speciale, Agnese, Mamone, Tuzzolino, Vizzini, Conaldi and Ambrosio.