Perflubron Emulsion Improves Hepatic Microvascular Integrity and Mitochondrial Redox State After Hemorrhagic Shock

Abstract

Hemorrhagic shock is associated with decreased systemic oxygen delivery, but also with impaired microvascular perfusion, which can result in diminished local oxygen availability even in the presence of adequate cardiac output after resuscitation. Beside surgical interventions to control blood loss, transfusion of stored packed red blood cells represents the current standard of care in the management of severe hemorrhagic shock. Because stored red blood cells are less deformable and show a higher O2 affinity that affects the O2 off-load to tissues, perfluorocarbon-based artificial oxygen carriers might improve local O2 delivery under these conditions. To test this, rats were subjected to hemorrhagic shock (1 h, mean arterial pressure [MAP] 30-35 mmHg) and were resuscitated with fresh whole blood, pentastarch, stored red blood cells, perflubron emulsion (2.7 and 5.4 g/kg body weight) together with pentastarch, or stored red blood cells together with 2.7 g/kg perflubron emulsion. Hepatic microcirculation, tissue oxygenation, and mitochondrial redox state were investigated by intravital microscopy. In addition, hepatocellular function and liver enzyme release were determined. After hemorrhagic shock and resuscitation with perflubron emulsion, volumetric sinusoidal blood flow was significantly increased compared with resuscitation with stored red blood cells. Furthermore, resuscitation with perflubron emulsion resulted in higher hepatic tissue PO2 and normalized mitochondrial redox potential, which was accompanied by lessened hepatocellular injury as well as improved liver function. These results indicate that, in this model of hemorrhagic shock, asanguineous fluid resuscitation with addition of perflubron emulsion is superior to stored blood or pentastarch alone with respect to increased local O2 availability on the cellular level. This effect is primarily due to improved restoration of hepatic microcirculatory integrity.

RESUSCITATION FROM HEMORRHAGIC SHOCK WITH MalPEG-ALBUMIN: COMPARISON WITH MalPEG-HEMOGLOBIN

“…Persistent deficits in perfusion and oxygenation of various tissues after resuscitation from hemorrhagic shock with different plasma expanders and autologous blood have been described (2)(3)(4)(5)(6)(7)(8)(9)(10). In our laboratory, best results have been obtained with pegylated plasma expanders (1,11).…”

Effects of Colloid Resuscitation on Peripheral Microcirculation, Hemodynamics, and Colloidal Osmotic Pressure During Acute Severe Hemorrhage in Rabbits

“…Flow velocity has been measured by laser Doppler flowmetry (4,5) and indirectly by monitoring partial oxygen pressure (6). The microcirculation has been microscopically examined in vivo during hemorrhagic shock (7,8), as well as after resuscitation (9,10). To our knowledge, however, the effects of colloid and crystalloid solutions on the peripheral microcirculation, hemodynamics, and colloidal osmotic pressure (COP) have not been directly compared microscopically during acute severe hemorrhage and resuscitation in vivo.…”

Blood Substitutes

“…In splenectomized dogs, Kemming and coworkers demonstrated beneficial effects on survival and tissue oxygenation attributable to the combined use of fluid resuscitation with hetastarch, hyperoxic ventilation, and infusion of 4.5 mL/kg Oxygent™ 60% [47]. The same treatment modality was found beneficial in rats subjected to hemorrhagic shock: hepatic microcirculation, tissue oxygenation, and hepatocellular energy metabolism were restored most sufficiently in PFCtreated animals when compared with colloidal fluid resuscitation alone or with the transfusion of stored RBCs [75,76].…”