Abstract 7: Myocardial Electrical Remodeling and Arrhythmogenic Substrate in Hemorrhagic Shock-Induced Heart

Abstract

Rationale: Lethal arrhythmias such as ventricular tachycardia and ventricular fibrillation (VT/VF) is one of the most serious complications after the resuscitation of severe hemorrhagic shock, even though systemic hemodynamics seems to recover. Objectives: To investigate the mechanisms of arrhythmogenesis after hemorrhagic shock and a role of oxygenated hemoglobin transfusion, optical mapping analysis (OMP), electrophysiological study (EPS), and pathological examination were performed using an acute hemorrhagic shock model of rats. Measurement and Main Results: After cannulating 22G catheter into the lower abdominal aorta, rats were subjected to acute hemorrhagic shock by withdrawing 30% of total blood volume (TBV) for 25 min, and observed for 15 min (shock alone). After acute hemorrhagic shock, the rats were immediately resuscitated by transfusing exactly the same amount of saline, 5% albumin (5%ALB), oxygenated liposome-encapsulated human hemoglobin (LHb), or oxygenated autologous washed red blood cells (wRBC) (n = 7, per group). After excising the heart, OMP and EPS were performed in isolated Langendorff-perfused hearts. OMP revealed abnormal ventricular conduction delay in conjunction with impaired action potential duration (APD) dispersion in both ventricles in shock alone, saline, and 5%ALB. In contrast, myocardial conduction velocity and APD dispersion in both ventricles were substantially attenuated in LHb or wRBC. VT/VF spontaneously occurred in shock alone. Furthermore, sustained VT/VF was easily provoked by burst pacing stimulus to the LV in saline and 5%ALB. No VT/VF was induced in the LV when the heart was resuscitated with oxygenated LHb or wRBC. Pathology including electron microscopy and immunohistochemistry demonstrated myocardial structural damages characterized by degradation of sarcometric actin and connexin43 in shock, saline, and 5%ALB. However, these histological changes were substantially attenuated in LHb and wRBC. Conclusion: Ventricular structural remodeling after hemorrhagic shock causes VT/VF only in the presence with APD dispersion. Oxygenated hemoglobin transfusion prevents VT/VF by preserving myocardial structures caused by ischemia-reperfusion injury in hemorrhagic shock.