Effects of Exchange Transfusion With Liposome‐Encapsulated Hemoglobin on VO₂/DO₂

Abstract

We clarified the effect of exchange transfusion with liposome-encapsulated hemoglobin (neo red cells, NRCs) with low O₂ affinity (P₅₀O₂ = 50 mm Hg) on O₂ metabolism. Rabbits were randomly assigned to receive serial exchange transfusions with NRC (NRC group, n = 5), shed blood diluted 1:1 with saline (red blood cell (RBC) group, n = 5), or saline alone (plasma group, n = 4) under hemodynamic monitoring. Cardiac tamponade was then induced and successively reversed to determine relationships between O₂ consumption (VO₂) and O₂ delivery (DO₂) using the dual-line method. Mean values of Hb concentration after exchange transfusion were 5.7 (NRC), 6.0 (RBC), and 1.5 (plasma) g/dL. The plasma group could not even survive the initial exchange hemodilution due to a critical decrease in DO₂. The NRC, but not the RBC group, developed progressive metabolic acidosis and lactatemia, as well as increases in PaCO₂ and decreases in tissue PO₂ in skeletal muscle after exchange transfusion. Nonetheless, systemic O₂ uptake indices obtained from an analysis of the VO₂/DO₂ relationship in the NRC and RBC groups were comparable. These findings suggested that systemic O₂ uptake was maintained in rabbits after exchange transfusion with NRC, although progressive tissue hypoxia with systemic acidosis is indicative of inadequate peripheral circulation and insufficient aerobic metabolism during extended hemodilution in which 86% of the circulating blood is replaced.

Artificial Oxygen Carrier to Regulate Hypoxic Signal Transduction

“…Cellular response to innate immunity , as well as nuclear factor kappa‐B, has also been interrelated with HIF‐1α to control the microenvironment against hypoxia, infection, and inflammation . Observations compatible with this theory include milder wound adhesion , decreased inflammatory cell infiltration , reduced proinflammatory cytokines , and a widened therapeutic window late after ischemic events (11) involving reperfusion rather than permanent ischemia. The extended dose‐response relationship (minimal effective dose as little as 0.4 mL/kg []), and plateaued efficacy at the other end suggests that aerobic energy generation per se was not the sole mechanism(s) behind the benefits so far accredited to AOC or its O 2 delivery.…”

Nanolipodendrosome-loaded glatiramer acetate and myogenic differentiation 1 as augmentation therapeutic strategy approaches in muscular dystrophy

“…Inflammation, along with muscular degeneration, causes intensification of the muscle pathobiology state by destroying the remaining tissue and preparing it to rebuild. [1][2][3][15][16][17][18][19][20][21][22][23][24][25][26][27] For instance, in an mdx mice model of Duchenne MD (DMD), T-cells had a major part in skeletal muscle fibrogenesis and death. [17][18][19][20][21] Additionally, two fibrosis markers -fibronectin and vimentin -had a significant increase in comparison with normal models among patients suffering from DMD compared with healthy humans.…”

“…On the contrary, recovery factors of MyoD and Myogenin reduced in value. [17][18][19][20][21][22][23][24][25][26][27] Myogenic differentiation 1 (MyoD) is a key protein regulating muscular differentiation. MyoD expression is necessary as one of the primary myogenic regulatory factors in transforming satellite cells into myoblasts.…”

“…5,15,22,41 Because of the similarity between a two-layer liposomal membrane and cellular two-layer membrane, liposomes are commonly used as artificial tissue. 18,22 Liposomes in drug delivery have some special characteristics. For instance, liposomes can target a drug to a specific position in the body, which increases treatment efficiency (direction).…”

“…Among the other characteristics of this nanoparticle are controlled release and amplification. 18,20,22,25 The efficiency of the drug delivery can be increased by connecting other nanocarriers to the liposomes. Nanolipodendrosome is a type of dendritic family formed by connecting dendritic nanoparticles to liposomes.…”