Hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm

Abstract Mechanical ventilation (MV) is a clinical tool providing adequate alveolar ventilation in patients that require respiratory support. Although a life‐saving intervention for critically ill patients, prolonged MV results in the rapid development of inspiratory muscle weakness due to both diap...

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Autores principales:	Noriko Ichinoseki‐Sekine, Ashley J. Smuder, Aaron B. Morton, James M. Hinkley, Andres Mor Huertas, Scott K. Powers
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
Acceso en línea:	https://doaj.org/article/7d170cf563a6460aa9f8669b55a66868
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spelling	oai:doaj.org-article:7d170cf563a6460aa9f8669b55a668682021-11-19T17:51:34ZHydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm1752-80621752-805410.1111/cts.13081https://doaj.org/article/7d170cf563a6460aa9f8669b55a668682021-11-01T00:00:00Zhttps://doi.org/10.1111/cts.13081https://doaj.org/toc/1752-8054https://doaj.org/toc/1752-8062Abstract Mechanical ventilation (MV) is a clinical tool providing adequate alveolar ventilation in patients that require respiratory support. Although a life‐saving intervention for critically ill patients, prolonged MV results in the rapid development of inspiratory muscle weakness due to both diaphragmatic atrophy and contractile dysfunction; collectively known as “ventilator‐induced diaphragm dysfunction” (VIDD). VIDD is a severe clinical problem because diaphragmatic weakness is a risk factor for difficulties in weaning patients from MV. Currently, no standard treatment to prevent VIDD exists. Nonetheless, growing evidence reveals that hydrogen sulfide (H2S) possesses cytoprotective properties capable of protecting skeletal muscles against several hallmarks of VIDD, including oxidative damage, accelerated proteolysis, and mitochondrial damage. Therefore, we used an established animal model of MV to test the hypothesis that treatment with sodium sulfide (H2S donor) will defend against VIDD. Our results confirm that sodium sulfide was sufficient to protect the diaphragm against both MV‐induced fiber atrophy and contractile dysfunction. H2S prevents MV‐induced damage to diaphragmatic mitochondria as evidenced by protection against mitochondrial uncoupling. Moreover, treatment with sodium sulfide prevented the MV‐induced activation of the proteases, calpain, and caspase‐3 in the diaphragm. Taken together, these results support the hypothesis that treatment with a H2S donor protects the diaphragm against VIDD. These outcomes provide the first evidence that H2S has therapeutic potential to protect against MV‐induced diaphragm weakness and to reduce difficulties in weaning patients from the ventilator. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Mechanical ventilation (MV) results in diaphragm atrophy and contractile dysfunction, known as ventilator‐induced diaphragm dysfunction (VIDD). VIDD is important because diaphragm weakness is a risk factor for problems in weaning patients from MV. Currently, no accepted treatment exists to protect against VIDD. Growing evidence reveals that hydrogen sulfide (H2S) donors protect skeletal muscle against ischemia‐reperfusion‐induced injury. Nonetheless, it is unknown if treatment with a H2S donor can protect against VIDD. WHAT QUESTION DID THIS STUDY ADDRESS? Can treatment with an H2S donor protect against VIDD? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? This study provides the first evidence that treatment with a H2S donor protects against VIDD. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? These new findings provide the basis for further exploration of H2S donors as a therapy to prevent VIDD and reduce the risk of problems in weaning patients from MV.Noriko Ichinoseki‐SekineAshley J. SmuderAaron B. MortonJames M. HinkleyAndres Mor HuertasScott K. PowersWileyarticleTherapeutics. PharmacologyRM1-950Public aspects of medicineRA1-1270ENClinical and Translational Science, Vol 14, Iss 6, Pp 2139-2145 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270
spellingShingle	Therapeutics. Pharmacology RM1-950 Public aspects of medicine RA1-1270 Noriko Ichinoseki‐Sekine Ashley J. Smuder Aaron B. Morton James M. Hinkley Andres Mor Huertas Scott K. Powers Hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm
description	Abstract Mechanical ventilation (MV) is a clinical tool providing adequate alveolar ventilation in patients that require respiratory support. Although a life‐saving intervention for critically ill patients, prolonged MV results in the rapid development of inspiratory muscle weakness due to both diaphragmatic atrophy and contractile dysfunction; collectively known as “ventilator‐induced diaphragm dysfunction” (VIDD). VIDD is a severe clinical problem because diaphragmatic weakness is a risk factor for difficulties in weaning patients from MV. Currently, no standard treatment to prevent VIDD exists. Nonetheless, growing evidence reveals that hydrogen sulfide (H2S) possesses cytoprotective properties capable of protecting skeletal muscles against several hallmarks of VIDD, including oxidative damage, accelerated proteolysis, and mitochondrial damage. Therefore, we used an established animal model of MV to test the hypothesis that treatment with sodium sulfide (H2S donor) will defend against VIDD. Our results confirm that sodium sulfide was sufficient to protect the diaphragm against both MV‐induced fiber atrophy and contractile dysfunction. H2S prevents MV‐induced damage to diaphragmatic mitochondria as evidenced by protection against mitochondrial uncoupling. Moreover, treatment with sodium sulfide prevented the MV‐induced activation of the proteases, calpain, and caspase‐3 in the diaphragm. Taken together, these results support the hypothesis that treatment with a H2S donor protects the diaphragm against VIDD. These outcomes provide the first evidence that H2S has therapeutic potential to protect against MV‐induced diaphragm weakness and to reduce difficulties in weaning patients from the ventilator. Study Highlights WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC? Mechanical ventilation (MV) results in diaphragm atrophy and contractile dysfunction, known as ventilator‐induced diaphragm dysfunction (VIDD). VIDD is important because diaphragm weakness is a risk factor for problems in weaning patients from MV. Currently, no accepted treatment exists to protect against VIDD. Growing evidence reveals that hydrogen sulfide (H2S) donors protect skeletal muscle against ischemia‐reperfusion‐induced injury. Nonetheless, it is unknown if treatment with a H2S donor can protect against VIDD. WHAT QUESTION DID THIS STUDY ADDRESS? Can treatment with an H2S donor protect against VIDD? WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE? This study provides the first evidence that treatment with a H2S donor protects against VIDD. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE? These new findings provide the basis for further exploration of H2S donors as a therapy to prevent VIDD and reduce the risk of problems in weaning patients from MV.
format	article
author	Noriko Ichinoseki‐Sekine Ashley J. Smuder Aaron B. Morton James M. Hinkley Andres Mor Huertas Scott K. Powers
author_facet	Noriko Ichinoseki‐Sekine Ashley J. Smuder Aaron B. Morton James M. Hinkley Andres Mor Huertas Scott K. Powers
author_sort	Noriko Ichinoseki‐Sekine
title	Hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm
title_short	Hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm
title_full	Hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm
title_fullStr	Hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm
title_full_unstemmed	Hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm
title_sort	hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/7d170cf563a6460aa9f8669b55a66868
work_keys_str_mv	AT norikoichinosekisekine hydrogensulfidedonorprotectsagainstmechanicalventilationinducedatrophyandcontractiledysfunctionintheratdiaphragm AT ashleyjsmuder hydrogensulfidedonorprotectsagainstmechanicalventilationinducedatrophyandcontractiledysfunctionintheratdiaphragm AT aaronbmorton hydrogensulfidedonorprotectsagainstmechanicalventilationinducedatrophyandcontractiledysfunctionintheratdiaphragm AT jamesmhinkley hydrogensulfidedonorprotectsagainstmechanicalventilationinducedatrophyandcontractiledysfunctionintheratdiaphragm AT andresmorhuertas hydrogensulfidedonorprotectsagainstmechanicalventilationinducedatrophyandcontractiledysfunctionintheratdiaphragm AT scottkpowers hydrogensulfidedonorprotectsagainstmechanicalventilationinducedatrophyandcontractiledysfunctionintheratdiaphragm
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Hydrogen sulfide donor protects against mechanical ventilation‐induced atrophy and contractile dysfunction in the rat diaphragm

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