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  

作　　者：Bonpei Takase Yuko Higashimura Haruka Asahina Masayuki Ishihara Hiromi Sakai 

机构地区：[1]Department of Intensive Care Medicine,National Defense Medical College,Tokorozawa,359-8513,Japan [2]Division of Traumatology Research Institute,National Defense Medical College Research Institute,Tokorozawa,359-8513,Japan [3]Division of Biomedical Engineering,National Defense Medical College Research Institute,Tokorozawa,359-8513,Japan [4]Department of Chemistry,School of Medicine,Nara Medical University,Nara,634-8521,Japan

出　　处：《Current Medical Science》2023年第2期232-245,共14页当代医学科学（英文）

基　　金：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.

摘　　要：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.

关 键 词：artificial oxygen carrier hemorrhage lethal arrhythmia RESUSCITATION heart rate variability 

分 类 号：R541[医药卫生—心血管疾病]