Prolonged low blood pressure <40 mmHg in hemorrhagic shock (HS) causes irreversible heart dysfunction, ‘Shock Heart Syndrome’ (SHS), which is associated with lethal arrhythmias (ventricular tachycardia or ventricular fibrillation [VT/VF]) leading to a poor prognosis.
To investigate whether the liposome-encapsulated human hemoglobin oxygen carrier (HbV) is comparable in effectiveness to autologous washed red blood cells (wRBCs) for improving arrhythmogenic properties in SHS, optical mapping analysis (OMP), electrophysiological study (EPS), and pathological examinations were performed in Sprague-Dawley rat hearts obtained from rats subjected to acute HS by withdrawing 30% of total blood volume. After acute HS, the rats were immediately resuscitated by transfusing exactly the same amount of saline (SAL), 5% albumin (5% ALB), HbV, or wRBCs. After excising the heart, OMP and EPS were performed in Langendorff-perfused hearts.
OMP showed a tendency for abnormal conduction and significantly impaired action potential duration dispersion (APDd) in both ventricles with SAL and 5% ALB. In contrast, myocardial conduction and APDd were substantially preserved with HbV and wRBCs. Sustained VT/VF was easily provoked by a burst pacing stimulus to the left ventricle with SAL and 5% ALB. No VT/VF was induced with HbV and wRBCs. Pathology showed myocardial structural damage characterized by worse myocardial cell damage and Connexin43 with SAL and 5% ALB, whereas it was attenuated with HbV and wRBCs.
Ventricular structural remodeling after HS causes VT/VF in the presence of APDd. Transfusion of HbV prevents VT/VF, similarly to transfusion of wRBCs, by preventing electrical remodeling and preserving myocardial structures in HS-induced SHS.
*Department of Intensive Care Medicine, National Defense Medical College, Saitama, Japan
†Department of Critical Care Medicine, National Defense Medical College, Saitama, Japan
‡Division of Biomedical Engineering, National Defense Medical College Research Institute, Saitama, Japan
§Department of Chemistry, School of Medicine, Nara Medical University, Japan
Address reprint requests to Bonpei Takase, MD, Department of Intensive Care Medicine, National Defense Medical College, 3-2 Namiki, Tokorozawa, Saitama 359-8513, Japan. E-mail: firstname.lastname@example.org
Received 4 April, 2018
Revised 4 May, 2018
Accepted 31 August, 2018
Grant support: 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.
The authors report no conflicts of interest.