Fluid resuscitation with hemoglobin-vesicle solution does not increase hypoxia or inflammatory responses in moderate hemorrhagic shock

Goto, Yoshitugu; Terajima, Katsuyuki; Tsueshita, Takaya; Miyashita, Masao; Horinouchi, Hirohisa; Sakai, Hiromi; Tsuchida, Eishun; Sakamoto, Atsuhiro

doi:10.2220/biomedres.27.283

Cited by 5 publications

(2 citation statements)

References 33 publications

(40 reference statements)

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“…Another promising development representing hemoglobin vesicles involves use of phospholipid vesicles (liposomes) that encapsulate purified human hemoglobin. Because experimental studies in hemorrhagic shock have shown that fluid resuscitation with hemoglobin vesicles maintained systemic oxygenation and did not induce either vasoconstriction or activation of the immune system, their further investigation in hemorrhagic shock is needed [ 123 , 124 ].…”

Section: Transfusionmentioning

confidence: 99%

Bench-to-bedside review: Latest results in hemorrhagic shock

2008

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Hemorrhagic shock is a leading cause of death in trauma patients worldwide. Bleeding control, maintenance of tissue oxygenation with fluid resuscitation, coagulation support, and maintenance of normothermia remain mainstays of therapy for patients with hemorrhagic shock. Although now widely practised as standard in the USA and Europe, shock resuscitation strategies involving blood replacement and fluid volume loading to regain tissue perfusion and oxygenation vary between trauma centers; the primary cause of this is the scarcity of published evidence and lack of randomized controlled clinical trials. Despite enormous efforts to improve outcomes after severe hemorrhage, novel strategies based on experimental data have not resulted in profound changes in treatment philosophy. Recent clinical and experimental studies indicated the important influences of sex and genetics on pathophysiological mechanisms after hemorrhage. Those findings might provide one explanation why several promising experimental approaches have failed in the clinical arena. In this respect, more clinically relevant animal models should be used to investigate pathophysiology and novel treatment approaches. This review points out new therapeutic strategies, namely immunomodulation, cardiovascular maintenance, small volume resuscitation, and so on, that have been introduced in clinics or are in the process of being transferred from bench to bedside. Control of hemorrhage in the earliest phases of care, recognition and monitoring of individual risk factors, and therapeutic modulation of the inflammatory immune response will probably constitute the next generation of therapy in hemorrhagic shock. Further randomized controlled multicenter clinical trials are needed that utilize standardized criteria for enrolling patients, but existing ethical requirements must be maintained. IntroductionTrauma is the leading cause of death worldwide in persons aged between 5 and 44 years, and it has an impact in every community regardless of demographics [1,2]. Up to 50% of early deaths are due to massive hemorrhage, which is a major contributor to the dilemmas associated with traumatic injury and its care [3]. Studies have shown that hemorrhagic shock is a predictor of poor outcome in the injured patient. Early hypotension with hemorrhage in the field or at initial hospital evaluation is associated with complications such as multiple organ failure (MOF) and the development of secondary infection such as pneumonia and sepsis [4][5][6].The complex pathophysiology of hemorrhagic shock is summarized in Figure 1. Briefly, the 'shock syndrome' during massive bleeding reflects an imbalance between systemic oxygen delivery and oxygen consumption [7,8]. Blood loss leads sequentially to hemodynamic instability, coagulopathy, decreased oxygen delivery, decreased tissue perfusion, and cellular hypoxia [3]. Such alterations lay the foundations for subsequent development of MOF, a systemic inflammatory process that leads to dysfunction of different vital organs and accou...

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Section: Transfusionmentioning

confidence: 99%

Bench-to-bedside review: Latest results in hemorrhagic shock

2008

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“…Extensive in vivo studies of such HbV suspended in plasma‐derived HSA or rHSA revealed sufficient O 2 transporting efficiency that is apparently comparable to RBCs in extreme blood exchange experiments [29–31, 33, 54–56] and fluid resuscitation from hemorrhagic shock [32, 57–60]. It was confirmed in rat models that haematopoietic activity was preserved and the decreased haematocrit returned to the original level within 1 or 2 weeks, whilst HbV captured in RES disappeared completely [33].…”

Section: Rheological Properties and Efficacy Of An Hb‐vesicle Suspensmentioning

confidence: 99%

Haemoglobin‐vesicles as artificial oxygen carriers: present situation and future visions

Sakai

Sou

Horinouchi

et al. 2007

Journal of Internal Medicine

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During the long history of development of haemoglobin (Hb)-based O2 carriers (HBOCs), many side effects of Hb molecules have become apparent. They imply the physiological importance of the cellular structure of red blood cells. Hb-vesicles (HbV) are artificial O2 carriers that encapsulate concentrated Hb solution with a thin lipid membrane. We have overcome the intrinsic issues of the suspension of HbV as a molecular assembly, such as stability for storage and in blood circulation, blood compatibility and prompt degradation in the reticuloendothelial system. Animal tests clarified the efficacy of HbV as a transfusion alternative and the possibility for other clinical applications. The results of ongoing HbV research make us confident in advancing further development of HbV, with the expectation of its eventual realization.

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