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Therapeutic effect of carbon monoxide-releasing molecule-3 on acute lung injury after hemorrhagic shock and resuscitation.
Kumada, Yuta; Takahashi, Toru; Shimizu, Hiroko; Nakamura, Ryu; Omori, Emiko; Inoue, Kazuyoshi; Morimatsu, Hiroshi.
Affiliation
  • Kumada Y; Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
  • Takahashi T; Faculty of Health and Welfare Science, Okayama Prefectural University, Soja, Okayama 719-1197, Japan.
  • Shimizu H; Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
  • Nakamura R; Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
  • Omori E; Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
  • Inoue K; Department of Anesthesiology, Kagawa Prefectural Central Hospital, Takamatsu, Kagawa 760-8557, Japan.
  • Morimatsu H; Department of Anesthesiology and Resuscitology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.
Exp Ther Med ; 17(5): 3429-3440, 2019 May.
Article in En | MEDLINE | ID: mdl-30988722
Hemorrhagic shock and resuscitation (HSR) induces a pulmonary inflammatory response and frequently causes acute lung injury. Carbon monoxide-releasing molecule-3 (CORM-3) has been reported to liberate and deliver CO under physiological conditions, which exerts organ-protective effects during systemic insults. The present study aimed to determine whether the administration of CORM-3 following HSR exerts a therapeutic effect against HSR-induced lung injury without any detrimental effects on oxygenation and hemodynamics. To induce hemorrhagic shock, rats were bled to a mean arterial blood pressure of 30 mmHg for 45 min and then resuscitated with the shed blood. CORM-3 or a vehicle was intravenously administered immediately following the completion of resuscitation. The rats were divided into four groups, including sham, HSR, HSR/CORM-3 and HSR/inactive CORM-3 groups. Arterial blood gas parameters and vital signs were recorded during HSR. The histopathological changes to the lungs were evaluated using a lung injury score, while pulmonary edema was evaluated on the basis of the protein concentration in bronchoalveolar lavage fluid and the lung wet/dry ratio. We also investigated the pulmonary expression levels of inflammatory mediators and apoptotic markers such as cleaved caspase-3 and transferase-mediated dUTP-fluorescein isothiocyanate nick-end labeling (TUNEL) staining. Although HSR caused significant lung histopathological damage and pulmonary edema, CORM-3 significantly ameliorated this damage. CORM-3 also attenuated the HSR-induced upregulation of tumor necrosis factor-α, inducible nitric oxide synthase and interleukin-1ß genes, and the expression of interleukin-1ß and macrophage inflammatory protein-2. In addition, the expression of interleukin-10, an anti-inflammatory cytokine, was inversely enhanced by CORM-3, which also reduced the number of TUNEL-positive cells and the expression of cleaved caspase-3 following HSR. Although CORM-3 was administered during the acute phase of HSR, it did not exert any influence on arterial blood gas analysis data and vital signs during HSR. Therefore, treatment with CORM-3 ameliorated HSR-induced lung injury, at least partially, through anti-inflammatory and anti-apoptotic effects, without any detrimental effects on oxygenation and hemodynamics.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Exp Ther Med Year: 2019 Document type: Article Affiliation country: Country of publication:

Full text: 1 Collection: 01-internacional Database: MEDLINE Language: En Journal: Exp Ther Med Year: 2019 Document type: Article Affiliation country: Country of publication: