A novel cross-linked haemoglobin-based oxygen carrier is beneficial to sepsis in rats

Abstract

Pathological hypoxia-induced organ dysfunction contributes to the high mortality of sepsis. Because of the microcirculation dysfunction following severe sepsis, it is difficult for erythrocytes to transport oxygen to hypoxic tissues. Haemoglobin-based oxygen carriers (HBOCs) are capable of delivering oxygen to hypoxic tissues. The aim of this study is to observe the potential benefits of a novel bovinederived, non-polymerized, cell-free HBOC solution, YQ23, on sepsis in rats. Cecum ligation and puncture was performed to induce sepsis in Sprague-Dawley rats. Effects of Lactate Ringer's solution (LR), YQ23, and whole blood on oxygen delivery and consumption, mitochondrial function, organ protection and animal survival were observed. LR failed to restore oxygen delivery and the therapeutic effects were limited, whereas low dosage of YQ23 and whole blood significantly increased the tissue oxygen delivery and consumption, improved the mitochondrial function of heart, liver, kidney and intestine, prevented the vital organs injuries and improved the animal survival. The effects of 0.15 gÁkg À1 YQ23 resembled that of the whole blood. In addition, YQ23 did not induce renal toxicity, severe oxidative effect and acute vasoconstriction. Thus, YQ23 is a safe and effective resuscitation fluid for sepsis. ARTICLE HISTORY

Protective effects of HBOC on pulmonary vascular leakage after haemorrhagic shock and the underlying mechanisms

“…Previous studies found that HBOC improved oxygen delivery and consumption of the body by carrying oxygen. Our previous studies found that HBOC could improve oxygen delivery and consumption in rats with haemorrhagic shock and sepsis [11,19]; Li et al's [16] study found that HBOC could very much improve the survival rate of haemorrhagic shock as well as the PaO 2 of the body. The present study showed that HBOC could improve mitochondrial function after haemorrhagic shock.…”

“…In addition to improving the survival rate, HBOC also has protective effects on organ function in various diseases. A study by Li and Kuang found that HBOC had excellent protective effects on the liver, kidney, brain and other important organs in rats with haemorrhagic shock and sepsis [11,19]; Li et al's study found that HBOC had (HA, green, A), heparan sulphate (HS, green, B) and chondroitin sulphate (CS, green, C) levels in VECs (bar ¼ 25 lm) (n ¼ 8 observations per group). Data are presented as mean ± SD, each group contains eight observations, Ã p < 0.05 and ÃÃ p < 0.01 as compared with normal group, #p < 0.05 and ##p < 0.01 as compared with hypoxia group, @p < 0.05 and @@p < 0.01 as compared with LR group.…”

Safety profile of high molecular weight polymerized hemoglobins

“…To better understand differences in the efficacy between T‐state and R‐state PolybHb, further studies in animals under pathological conditions are necessary, since high or low O 2 affinity might be beneficial depending on the type of pathological model used. Other HBOCs have been tested and show that HBOCs improve recovery from septic shock, hemorrhagic shock, and myocardial infarction 34–38 . The high viscosity of these materials may preclude their use in certain scenarios where the PolybHb comprises most of the blood (such as after significant hemorrhage), as patients may not tolerate the increased cardiac load, particularly when the heart is already compromised.…”

Neuregulin‑1: An underlying protective force of cardiac dysfunction in sepsis (Review)

“…cardiac injury and cardiac insufficiency can be as high as 40-50% in patients with sepsis (1). in case of impaired cardiac function, the mortality rate can increase from 20 to 70%, and it continues to increase in a number of countries (2).…”

“…in case of impaired cardiac function, the mortality rate can increase from 20 to 70%, and it continues to increase in a number of countries (2). Studies have shown that early improvement of cardiac function can be achieved to significantly improve patient survival rates (1,2). The mechanism of cardiac insufficiency in sepsis is complex.…”