Artificial organs · 2024
Liposome-encapsulated hemoglobin rescues hemorrhagic shock heart through anti-ischemic and anti-arrhythmogenic effects on myocardium in repetitive 65% bleeding rat model.
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Takase Bonpei, Higashimura Yuko, Masaki Nobuyuki, Kinoshita Manabu, Adachi Takeshi, Sakai Hiromi
Аннотация
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.
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.