Morphologic Changes of Red Blood Cells During Hemorrhagic Shock Replicate Changes of Aging

Red blood cells in hemorrhagic shock: a critical role for glutaminolysis in fueling alanine transamination in rats

“…31 These observations also confirm and expand on previous reports about the role of oxidative stress as a potential etiological factor of RBC morphological lesions and hemolysis in response to HS. [34][35][36] In addition, we show that glutaminederived glutamate is necessary to fuel pyruvate transamination to alanine, a phenomenon we observed in RBCs, plasma, liver, and lungs of HS rats. By contributing to pyruvate-to-alanine ratios, glutaminolysis indirectly influences NADH-to-NAD 1 ratios and thus influences ongoing glycolysis (lactate acidosis) and potentially the activities of enzymes relying on reducing cofactors, such as methemoglobin reductase, in analogy to what was observed in RBCs from glucose 6-phosphate dehydrogenase-deficient donors.…”

“…These results support and expand on previous observations by Deitch's group, suggesting a role for oxidative stress in morphological lesions and hemolysis of HS RBCs. [34][35][36] GSH synthesis, an ATP-dependent process, was previously observed in hypoxic RBCs under physiological conditions in vivo and proportionally to hypoxia in vitro in human and mouse RBCs. 26,31 On the other hand, several groups 26,28,29,50 including ours 15,32 have shown that hypoxia limits RBC antioxidant capacity by limiting metabolic fluxes through the pentose phosphate pathway, which generates reducing equivalents (NAD phosphate) for the reduction of oxidized GSH/recycling of antioxidant enzymes (eg, GSH reductase).…”

“…[25][26][27][28][29] Of note, plasma adenosine levels, which increase significantly upon early hemorrhage even before severe HS ensues in rats, 12 are important upstream contributors to these mechanisms through signaling via the RBC adenosine receptor A2B. 25,26 Previous studies by Deitch and colleagues [34][35][36] confirmed that HS adversely affects RBC morphology, probably due to oxidative stress.…”

Do We have Enough Direct Evidence to Postulate that Abnormally Shaped Red Blood Cells Impair Microvascular Blood Flow in Critical Conditions?

“…Smaller number of publications report RBC shape changes as a result of critical conditions [5,11,[12][13][14][15]. Experimental studies demonstrated that the number of abnormal (reversibly and irreversibly changed) RBCs after hemorrhagic shock was increased more than five times compared to control values and their proportion to normal discocytes exceeded 30% [5,13]. The similar phenomenon was observed in patients with severe trauma [14].…”

“…Numerous experimental and clinical studies have proven that these insults cause a significant decrease in RBC deformability [3][4][5][6][7][8][9][10][11]. Smaller number of publications report RBC shape changes as a result of critical conditions [5,11,[12][13][14][15]. Experimental studies demonstrated that the number of abnormal (reversibly and irreversibly changed) RBCs after hemorrhagic shock was increased more than five times compared to control values and their proportion to normal discocytes exceeded 30% [5,13].…”