Abstract Sun204: Artificial Oxygen Carrier (HbV) Ameliorates Prognosis through Persistently Improving Arrhythmogenicity, LV dysfunction, Systemic Organ Damages in Hemorrhagic Shock during Pneumonectomy

Abstract

Perioperative hemorrhagic shock (HS) is fetal in thoracic surgery. We previously reported acute salutary effects of Liposome-encapsulated hemoglobin vesicle (HbV) on organ dysfunction, hemodynamic deterioration and lethal arrhythmogenic property assessed by optical mapping analysis (OMP) with Langendorff's method in rat pneumonectomy HS model. In the previous study, immediately after pneumonectomy, repetitive 50% blood hemorrhage and resuscitation were conducted. HbV-administration (HbV-group), washed red blood cell-administration (wRBC-group), and 5% albumin-administration (ALB-group) were studied (Figure 1). Since extensive phase I clinical trial of HbV has now successfully being performed, investigating the chronic effects of HbV are suggested to be important for conducting future phase II clinical trials. Thus, we investigated serial effect of HbV on mean systemic blood pressure (MSP), mean RV pressure (MRVP), LV function (LVEF) by UCG, arrhythmogenicity by OMP (action potential duration dispersion [APDd, ms] in LV) with EPS for lethal arrhythmias (VT/VF) induction, organ dysfunction (troponin I [cTnI], CPK, AST, ALT, compliment C3[C3a]) and oxygen arterial content (CaO2) for respiratory function as studying chronic effects and/or side effects of HbV in SD rats (n=118). Each parameter was measured at 2 hours (Figure 1), and 1 week, 2 weeks, 4 weeks after resuscitation from pneumonectomy HS (F/U, chronic phase). Since very few rats in ALB-group, and most rats in HbV- and wRBC-groups could survive in chronic phase (Figure 2), each parameter was measured in limited number of ALB-group and almost all HbV-group and wRBC-group at F/U. MSPs of survived rats maintained normal all F/U among 3 groups. MRVPs were compensated to normal ranges in all 3 groups over 4 weeks (54±5, 44±3, 31±4, 27±6 mmHg; P<0.05). Except few survived ALB-group rats at F/U (impaired LVEF, cTnI, APDd, induced VF), Each parameter of survived rats in HbV-group and wRBC-group was normal at all 3 F/U phase (for example, data at 4 weeks) such as LVEF (91±4 vs. 92±3%), cTnI (0.09±0.1 vs. 0.06±0.08 ng/mL) and normal CPK, AST, ALT, C3a, as well as normal CaO2 (11±1.0 vs.11±1.5 ml/dl) and normal OMP findings with no VT/VF induced (Figure 3). Conclusions; Administration of HbV could have good prognosis in pneumonectomy with HS, not showing adverse effects of HbV. These findings are useful for conducting HbV human phase II clinical trials.