Abstract 4030: Resuscitation with Intraosseous Infusion of Artificial Oxygen Carrier of Liposome-Encapsulated Hemoglobin (LHb) from Lethal Hemorrhagic Shock and Its Effect on Cytokines

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Bonpei Takase ◽  
Satoshi Shono ◽  
Manabu Kinoshita ◽  
Yashiro Nogami ◽  
Yoshitaka Ogata ◽  
...  

Liposome-encapsulated hemoglobin (LHb), which is structurally similar to red blood cells (RBC) except smaller size (250 nm), can serve as blood substitute comparable to RBC. We have reported that intraosseous blood infusion (IOI) is effective treatment in shock mice model. IOI is alternative to peripheral i.v. infusion and is expected as an important field treatment in civilian emergency because of no collapse of intramedullary blood vessels in the bone marrow in shock. However, we did not evaluate the side effects of LHb in IOI. Total 70% hemorrhagic shock was induced by femoral vein bleeding. Immediately after bleeding, 17 mice were resuscitated with tibial bone IOI of 5% albumin (5% albumin), 18 mice resuscitated with mouse-washed RBC (Wash RBC) and 14 mice resuscitated with LHb (LHb-group). Survival rates were compared and the temporal changes in cytokins (TNF, INFγ) as well as liver and renal function (s-ALT, s-creatinine) were measured. All mice survived 48 h after IOI of LHb whereas only 47% and 45% mice survived in 5% albumin and Wash RBC, respectively (Fig. 1 ). The changes in TNF and INFγlevels after IOI were not statistically different among 3 groups (Fig. 2 ) and no side effects were found on liver and renal function.. Conclusions: LHb has a better anti-shock effect than RBC by using IOI probably due to smaller size and IOI of LHb could be useful in disaster medicine. In addition, IOI of LHb shows no significant effects on cytokins, liver and renal function. Figure 1 Figure 2

1982 ◽  
Vol 242 (5) ◽  
pp. R465-R470 ◽  
Author(s):  
A. Monks ◽  
R. L. Cysyk

The isolated rat liver was used to investigate the role of the liver in the regulation of circulating uridine concentrations. A synthetic blood substitute (Fluosol-43) was utilized as an alternative oxygen-carrying perfusion medium to a simplified blood preparation and produced no apparent hepatotoxicity within the perfusion period. The isolated rat liver excreted uridine into a circulating perfusion medium achieving concentrations similar to those found in rat plasma (1.4 +/- 0.6 microM). The mean output of uridine over 2 h was 107 nmol.h-1.g liver-1, but if the perfusate was recirculated the net output of uridine was reduced to 12.7 nmol.h-1.g-1. The rate of depletion of nonphysiological concentrations of circulating uridine was found to be concentration dependent up to 25 microM. At a steady state of circulating uridine, a radioactive uridine spike was cleared with a half-life of 7.4 min and an elimination constant of 0.094 min-1; 30% of the radioactivity appeared in the perfusate as metabolites of uridine within 40 min. Thus the perfused rat liver acts to maintain circulating uridine concentrations similar to those measured in plasma.


2021 ◽  
Vol 12 ◽  
Author(s):  
Lei Kuang ◽  
Yu Zhu ◽  
Yue Wu ◽  
Kunlun Tian ◽  
Xiaoyong Peng ◽  
...  

Background: Hypotensive resuscitation is widely applied for trauma and war injury to reduce bleeding during damage-control resuscitation, but the treatment time window is limited in order to avoid hypoxia-associated organ injury. Whether a novel hemoglobin-based oxygen carrier (HBOC), YQ23 in this study, could protect organ function, and extend the Golden Hour for treatment is unclear.Method: Uncontrolled hemorrhagic shock rats and miniature pigs were infused with 0.5, 2, and 5% YQ23 before bleeding was controlled, while Lactate Ringer’s solution (LR) and fresh whole blood plus LR (WB + LR) were set as controls. During hypotensive resuscitation the mean blood pressure was maintained at 50–60 mmHg for 60 min. Hemodynamics, oxygen delivery and utilization, blood loss, fluid demand, organ function, animal survival as well as side effects were observed. Besides, in order to observe whether YQ23 could extend the Golden Hour, the hypotensive resuscitation duration was extended to 180 min and animal survival was observed.Results: Compared with LR, infusion of YQ23 in the 60 min pre-hospital hypotensive resuscitation significantly reduced blood loss and the fluid demand in both rats and pigs. Besides, YQ23 could effectively stabilize hemodynamics, and increase tissue oxygen consumption, increase the cardiac output, reduce liver and kidney injury, which helped to reduce the early death and improve animal survival. In addition, the hypotensive resuscitation duration could be extended to 180 min using YQ23. Side effects such as vasoconstriction and renal injury were not observed. The beneficial effects of 5% YQ23 are equivalent to similar volume of WB + LR.Conclusion: HBOC, such as YQ23, played vital roles in damage-control resuscitation for emergency care and benefited the uncontrolled hemorrhagic shock in the pre-hospital treatment by increasing oxygen delivery, reducing organ injury. Besides, HBOC could benefit the injured and trauma patients by extending the Golden Hour.


ASAIO Journal ◽  
2005 ◽  
Vol 51 (2) ◽  
pp. 48A
Author(s):  
Koichi Kobayashi ◽  
Hiromi Sakai ◽  
Masataka Yamazaki ◽  
Manabu Yamamoto ◽  
Hirohisa Horinouchi ◽  
...  

2021 ◽  
Vol 8 ◽  
Author(s):  
Min Cao ◽  
Yong Zhao ◽  
Hongli He ◽  
Ruiming Yue ◽  
Lingai Pan ◽  
...  

If not cured promptly, tissue ischemia and hypoxia can cause serious consequences or even threaten the life of the patient. Hemoglobin-based oxygen carrier-201 (HBOC-201), bovine hemoglobin polymerized by glutaraldehyde and stored in a modified Ringer's lactic acid solution, has been investigated as a blood substitute for clinical use. HBOC-201 was approved in South Africa in 2001 to treat patients with low hemoglobin (Hb) levels when red blood cells (RBCs) are contraindicated, rejected, or unavailable. By promoting oxygen diffusion and convective oxygen delivery, HBOC-201 may act as a direct oxygen donor and increase oxygen transfer between RBCs and between RBCs and tissues. Therefore, HBOC-201 is gradually finding applications in treating various ischemic and hypoxic diseases including traumatic hemorrhagic shock, hemolysis, myocardial infarction, cardiopulmonary bypass, perioperative period, organ transplantation, etc. However, side effects such as vasoconstriction and elevated methemoglobin caused by HBOC-201 are major concerns in clinical applications because Hbs are not encapsulated by cell membranes. This study summarizes preclinical and clinical studies of HBOC-201 applied in various clinical scenarios, outlines the relevant mechanisms, highlights potential side effects and solutions, and discusses the application prospects. Randomized trials with large samples need to be further studied to better validate the efficacy, safety, and tolerability of HBOC-201 to the extent where patient-specific treatment strategies would be developed for various clinical scenarios to improve clinical outcomes.


1947 ◽  
Vol 86 (6) ◽  
pp. 477-487 ◽  
Author(s):  
Paul B. Hamilton ◽  
Alma Hiller ◽  
Donald D. Van Slyke

The immediate effects of treating hemorrhagic shock in dogs by replacing lost blood with 7 per cent hemoglobin solution were favorable, both on renal function and on general condition. However, subsequent transitory depression of the urea clearance for several days, shown by some of the treated animals, but not by untreated bled controls, indicates sufficient possibility of renal damage by the hemoglobin solution to prevent its recommendation at present as a blood substitute.


1991 ◽  
Vol 112 (2) ◽  
pp. 1094-1096
Author(s):  
E. A. Selivanov ◽  
N. I. Kochetygov ◽  
K. A. Gerbut ◽  
M. A. Azhigirova ◽  
E. P. Vyazova ◽  
...  

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Bonpei Takase ◽  
Yoshihiro Tanaka

Lethal ventricular arrhythmias (VT/VF) is serious complications in severe hemorrhagic shock (HS). Cardiac autonomic imbalance and dysfunction are well known unfavorable conditions. However, the effect of oxygenation including artificial oxygen carrier is not fully understood. To investigate the role of oxygenation in lethal HS, cardiac autonomic activity measures, cardiac function test, optical mapping analysis (OMP), and electrophysiological study (EPS) were performed in rats lethal HS. Methods and Results: 1) Over the course of 150 min, rats were subjected to blood withdrawal (0.2 mL/min; total 85% bleeding) and simultaneously transfused with washed rat red blood cells (wRBC), liposome-encapsulated hemoglobin (LHb) or 5% albumin (5%ALB). Temporal changes in cardiac function by 2-D Echocardiography, heart-type fatty acid-binding protein (hFAB) levels, plasma levels of catecholamines, heart rate variability (HRV), and hypoxia-inducible factor 1α expression (HIF1) were measured. As results, > 85% of the rats transfused with either LHb or wRBC survived for 8 days. LHb transfusion suppressed HIF1 expression in the heart, maintained low levels of hFAB, and attenuated sympathetic nerve activity as reflected by changes in HRV and catecholamines. 2) After cannulating 22G catheter into the abdominal aorta, acute HS was induced by withdrawing 30% of total blood for 25 min. After HS, the rats were immediately resuscitated by transfusing the same amount of wRBC, LHb, or 5%ALB. After excising the heart, OMP and EPS were performed in Langendorff-perfused hearts. OMP revealed abnormal ventricular conduction delay in conjunction with impaired action potential duration (APD) dispersion in 5%ALB. In contrast, myocardial conduction velocity and APD dispersion were substantially attenuated in wRBC or LHb. Sustained VT/VF was easily provoked by burst pacing stimulus to the LV in 5%ALB whereas no VT/VF was induced with wRBC or LHb. Conclusions: The results indicate that wRBC and LHb attenuates cardiac dysfunction and sympathetic overactivity during lethal HS. Oxygenated hemoglobin transfusion by using either wRBC or LHb prevents VT/VF by preserving myocardial electrical structures caused by ischemia-reperfusion injury in HS.


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