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Liposome-Encapsulated Hemoglobin Vesicle Improves Persistent Anti-arrhythmogenesis through Improving Myocardial Electrical Remodeling and Modulating Cardiac Autonomic Activity in a Hemorrhagic Shock-Induced Rat Heart Model

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Abstract

Objective

Shock heart syndrome (SHS) is associated with lethal arrhythmias (ventricular tachycardia/ventricular fibrillation, VT/VF). We investigated whether liposome-encapsulated human hemoglobin vesicles (HbVs) has comparable persistent efficacy to washed red blood cells (wRBCs) for improving arrhythmogenesis in the subacute to chronic phase of SHS.

Methods

Optical mapping analysis (OMP), electrophysiological study (EPS), and pathological examinations were performed on blood samples from Sprague-Dawley rats following induction of hemorrhagic shock. After hemorrhagic shock, the rats were immediately resuscitated by transfusing 5% albumin (ALB), HbV, or wRBCs. All rats survived for 1 week. OMP and EPS were performed on Langendorff-perfused hearts. Spontaneous arrhythmias and heart rate variability (HRV) were evaluated using awake 24-h telemetry, cardiac function by echocardiography, and pathological examination of Connexin43.

Results

OMP showed significantly impaired action potential duration dispersion (APDd) in the left ventricle (LV) in the ALB group whereas APDd was substantially preserved in the HbV and wRBCs groups. Sustained VT/VF was easily provoked by EPS in the ALB group. No VT/VF was induced in the HbV and wRBCs groups. HRV, spontaneous arrhythmias, and cardiac function were preserved in the HbV and wRBCs groups. Pathology showed myocardial cell damage and Connexin43 degradation in the ALB group, all of which were attenuated in the HbV and wRBCs groups.

Conclusion

LV remodeling after hemorrhagic shock caused VT/VF in the presence of impaired APDd. Similar to wRBCs, HbV persistently prevented VT/VF by inhibiting persistent electrical remodeling, preserving myocardial structures, and ameliorating arrhythmogenic modifying factors in the subacute to chronic phase of hemorrhagic shock-induced SHS.

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Acknowledgements

The authors express sincere gratitude to Professor Susumu Matsukuma in the Department of Pathology and Laboratory Medicine, National Defense Medical College for his expertise and for supervising and analyzing the pathological findings in this study. In addition, we would like to thank Editage (www.editage.com) for English language editing.

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Authors and Affiliations

  1. Department of Intensive Care Medicine, National Defense Medical College, Tokorozawa, 359-8513, Japan

    Bonpei Takase & Yuko Higashimura

  2. Division of Traumatology Research Institute, National Defense Medical College Research Institute, Tokorozawa, 359-8513, Japan

    Haruka Asahina

  3. Division of Biomedical Engineering, National Defense Medical College Research Institute, Tokorozawa, 359-8513, Japan

    Masayuki Ishihara

  4. Department of Chemistry, School of Medicine, Nara Medical University, Nara, 634-8521, Japan

    Hiromi Sakai

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  1. Bonpei Takase
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  2. Yuko Higashimura
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  3. Haruka Asahina
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  4. Masayuki Ishihara
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  5. Hiromi Sakai
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Correspondence to Bonpei Takase.

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Conflict of Interest Statement

The authors declare that they have no competing interests.

This work was supported in part by the Project Promoting Clinical Trials for Development of New Drugs and Medical Devices from the Japan Agency for Medical Research and Development (AMED), Japan.

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Takase, B., Higashimura, Y., Asahina, H. et al. Liposome-Encapsulated Hemoglobin Vesicle Improves Persistent Anti-arrhythmogenesis through Improving Myocardial Electrical Remodeling and Modulating Cardiac Autonomic Activity in a Hemorrhagic Shock-Induced Rat Heart Model. CURR MED SCI 43, 232–245 (2023). https://doi.org/10.1007/s11596-023-2706-9

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  • DOI: https://doi.org/10.1007/s11596-023-2706-9

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