Hypertonic saline reduces skeletal muscle injury and associated remote organ injury following ischemia reperfusion injury

Liver ischemia/reperfusion injury has been extensively studied during the last decades and has been implicated in the pathophysiology of many clinical entities following hepatic surgery and transplantation. Apart from its pivotal role in the pathogenesis of the organ’s post reperfusion injury, it has also been proposed as an underlying mechanism responsible for the dysfunction and injury of other organs as well. It seems that liver ischemia and reperfusion represent an event with “global” consequences that influence the function of many remote organs including the lung, kidney, intestine, pancreas, adrenals, and myocardium among others. The molecular and clinical manifestation of these remote organs injury may lead to the multiple organ dysfunction syndrome, frequently encountered in these patients. Remote organ injury seems to be in part the result of the oxidative burst and the inflammatory response following reperfusion. The present paper aims to review the existing literature regarding the proposed mechanisms of remote organ injury after liver ischemia and reperfusion.

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LOW VOLUME HYPERTONIC SALINE ABROGATES MESENTERIC ISCHEMIA/REPERFUSION INDUCED REMOTE ORGAN INJURY

Journal of Trauma and Acute Care Surgery ◽

10.1097/00005373-200508000-00091 ◽

2005 ◽

Vol 59 (2) ◽

pp. 527

Author(s):

Ernest A. Gonzalez ◽

Rosemary A. Kozar ◽

James W. Suliburk ◽

David W. Mercer ◽

Frederick A. Moore

Keyword(s):

Hypertonic Saline ◽

Mesenteric Ischemia ◽

Ischemia Reperfusion ◽

Organ Injury ◽

Remote Organ ◽

Remote Organ Injury ◽

Low Volume

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Simvastatin Plus Nitric Oxide Synthase Inhibition Modulates Remote Organ Damage Following Skeletal Muscle Ischemia-Reperfusion Injury

Journal of Investigative Surgery ◽

10.1080/08941930802046501 ◽

2008 ◽

Vol 21 (3) ◽

pp. 119-126 ◽

Cited By ~ 10

Author(s):

P. A. Cowled ◽

A. Khanna ◽

P. E. Laws ◽

J. B. F. Field ◽

R. A. Fitridge

Keyword(s):

Nitric Oxide ◽

Skeletal Muscle ◽

Nitric Oxide Synthase ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Organ Damage ◽

Muscle Ischemia ◽

Remote Organ ◽

Oxide Synthase

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Conventional Dose Hypertonic Saline Provides Optimal Gut Protection and Limits Remote Organ Injury After Gut Ischemia Reperfusion

Journal of Trauma and Acute Care Surgery ◽

10.1097/01.ta.0000224190.65542.e2 ◽

2006 ◽

Vol 61 (1) ◽

pp. 66-74 ◽

Cited By ~ 22

Author(s):

Ernest A. Gonzalez ◽

Rosemary A. Kozar ◽

James W. Suliburk ◽

Norman W. Weisbrodt ◽

David W. Mercer ◽

...

Keyword(s):

Hypertonic Saline ◽

Ischemia Reperfusion ◽

Organ Injury ◽

Conventional Dose ◽

Remote Organ ◽

Remote Organ Injury

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Differential Regulation of Damage-Associated Molecular Pattern Release in a Mouse Model of Skeletal Muscle Ischemia/Reperfusion Injury

Frontiers in Immunology ◽

10.3389/fimmu.2021.628822 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hiroaki Furubeppu ◽

Takashi Ito ◽

Midori Kakuuchi ◽

Tomotsugu Yasuda ◽

Chinatsu Kamikokuryo ◽

...

Keyword(s):

Skeletal Muscle ◽

Gastrocnemius Muscle ◽

Ischemia Reperfusion ◽

Histone H3 ◽

Organ Injury ◽

Hindlimb Ischemia ◽

Clinical Issue ◽

Muscle Ischemia ◽

Remote Organ ◽

Remote Organ Injury

BackgroundSkeletal muscle ischemia/reperfusion (I/R) injury is an important clinical issue that can cause remote organ injury. Although its pathogenesis has not been fully elucidated, recent studies have suggested that damage-associated molecular patterns (DAMPs) are mediators of remote organ injury in sterile inflammation. The purpose of this study was to investigate the possible involvement of DAMPs, including the nuclear proteins high-mobility group box 1 (HMGB1) and histone H3, in the pathogenesis of skeletal muscle I/R injury in mice.MethodsHindlimb ischemia was induced in mice through bilateral ligation of inguinal regions using rubber grommets. Reperfusion was induced by cutting the rubber grommets after 2–12 h of ischemic period. Survival rates, localization of HMGB1 and histone H3 in the gastrocnemius muscle, and circulating HMGB1 and histone H3 levels were analyzed. The effect of anti-HMGB1 and anti-histone H3 antibodies on survival was analyzed in mice with I/R injury.ResultsAll mice with hindlimb ischemia survived for at least 36 h, while all mice died within 24 h if the hindlimbs were reperfused after ischemia for 4–12 h. Immunohistochemical analysis revealed that HMGB1 translocated from the nucleus to the cytoplasm in the ischemic gastrocnemius muscle, while histone H3 was confined to the nucleus. Accordingly, serum HMGB1 levels were significantly elevated in mice with hindlimb I/R compared with normal mice or mice with hindlimb ischemia (P < 0.05). Serum histone H3 levels were not elevated after I/R. Treatment with anti-HMGB1 antibodies significantly improved survival of mice with hindlimb I/R injury compared with control antibodies (P < 0.05).ConclusionsHMGB1, but not histone H3, translocated to the cytoplasm during skeletal muscle ischemia, and was released into the systemic circulation after reperfusion in mice with I/R injury. Treatment with anti-HMGB1 antibodies partially improved survival.

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