Liposome‐encapsulated hemoglobin rescues hemorrhagic shock heart through anti‐ischemic and anti‐arrhythmogenic effects on myocardium in repetitive 65% bleeding rat model

Abstract Background Phase I clinical trial of an artificial oxygen carrier (liposome‐encapsulated hemoglobin vesicles [HbVs]) is safely completed, considering the other clinical application. Herein, we aimed to investigate the resuscitation effects of HbVs in cases of lethal hemorrhage, including the mechanisms involved. Methods Optical mapping analysis (OMP) and electrophysiological studies (EPS), immunostaining pathological examination for hypoxia‐inducible factor‐1α (HIF1‐alpha) in the heart tissue, and blood troponin I (TnI) level measurements were performed in rats that underwent five rounds of spontaneous arterial bleeding with up to 65% hemorrhage. Results Ten rats in each group were resuscitated by a transvenous infusion of 5% albumin (ALB), washed erythrocytes (wRBC), HbVs (HbV), 50% HbV diluted by 5% albumin (50% HbV), and 66% HbV diluted by 5% albumin (66% HbV). The rats in the ALB and 50% HbV groups died, whereas those in the other groups survived. OMP showed impaired action potential duration dispersion (APDd) in the left ventricle in the ALB and 50% HbV groups, which was attenuated in the other groups. Lethal arrhythmias were provoked by EPS in the ALB and 50% HbV groups but not in the other groups. HIF1‐alpha was positively stained only in the ALB and 50% HbV groups. TnI levels were elevated in the ALB and 50% HbV groups. Conclusions Acute lethal hemorrhage causes myocardial ischemia with hypoxia and arrhythmias, which may be induced by impaired APDd and myocardial damage, reflected in the increased levels of HIF1‐alpha and TnI. HbVs could be useful for resuscitation and may help save patients with injuries such as gunshot wounds.