Abstract
Phase I clinical trial of Liposome-encapsulated hemoglobin vesicles (HbVs) was successfully accomplished. Since several ameliorating mechanisms are not fully understood on HbVs, to investigate its mechanisms of salutary effect on myocardium, optical mapping analysis (OMP) and electrophysiological study (EPS), immunostaining pathological examination for HIF1-alpha in heart and measurement of blood troponin I (TnI) were performed in 30% spontaneous arterial bleedings five times up to approximately total 65% hemorrhage in rats. Eighteen rats in each group were resuscitated by immediately after bleeding by same volume as bleedings each five times by transvenous infusion of 5%albumin solution (ALB-group), washed erythrocytes (wRBC-group) and HbVs (HbV-group). Survival effects over 24 hours were examined. After excising heart, OMP and EPS were performed. All rats died in ALB-group, whereas all survived in wRBC-group and HbV-group. OMP showed impaired (prolonged) action potential duration dispersion (APDd: which is arrhythmogenic index) in LV in ALB-group, whereas APDds were attenuated in HbV-group and wRBC-group (26±4 vs. 11±6, 14±5ms, P<0.05). Lethal arrhythmias (ventricular tachycardia [VT]/ventricular fibrillation [VF]; VT/VF) were provoked by EPS and/or spontaneously occurred in ALB-group whereas not in both wRBC-group and HbV-group. HIF1-alpha was positively stained and TnI levels were significantly elevated only in ALB-group (Peak TnI; 186±47 vs. 64±25, 91±24, 44±10pg/mL, P<0.05: Figure). Conclusions: HbVs rescue lethal hemorrhage through improving lethal arrhythmias and myocardial damages by reflected by inducing HIF1-alpha and elevated TnI. HbVs could be useful for resuscitation and saving life from gun-shot arterial bleeding on-site occurred in terrorisms.
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