Skip to main content
Top
Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie 4/2012

01-04-2012 | Reports of Original Investigations

Plasma methemoglobin as a potential biomarker of anemic stress in humans

Authors: Gregory M. T. Hare, MD, PhD, Alexander Mu, MD, Alexander Romaschin, MD, Albert K.-Y. Tsui, PhD, Nadine Shehata, MD, W. Scott Beattie, MD, PhD, C. David Mazer, MD

Published in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Issue 4/2012

Login to get access

Abstract

Purpose

Transfusion of allogeneic red blood cells (RBCs) is one of the main treatments of acute anemia secondary to blood loss and fluid resuscitation within the operating room. Decisions to transfuse blood are based largely on intermediate biological markers (hemoglobin, arterial oxygen saturation, blood pressure, heart rate) which may not accurately reflect inadequacy of tissue oxygen delivery. Based on experimental studies, we hypothesized that anemia-induced tissue hypoxia activates adaptive mechanisms which promote local vascular nitric oxide (NO) production to improve tissue perfusion and survival during acute anemia. Hemoglobin (Hb) oxidation to methemoglobin (MetHb) may be a byproduct of such local NO production. Therefore, we tested the hypothesis that MetHb is a biomarker of hypoxic-anemic stress during acute hemodilution associated with cardiopulmonary bypass.

Methods

With institutional ethics approval, routine laboratory arterial blood gas and co-oximetry values were obtained from 295 patients undergoing heart surgery during February 1 to September 30, 2010, and the values were assessed retrospectively. All samples with an arterial oxygen saturation value ≥90% were included (n = 1,421). The maximal change in Hb associated with hemodilution on cardiopulmonary bypass was determined within 48 hr of surgery (n = 180). A chart review was performed to determine the incidence of RBC transfusion and exogenous nitrate administration. All anonymous data were analyzed by linear regression to determine the relationship between Hb and MetHb. A Wilcoxon Signed Rank Test and Student’s t test were used to determine changes in Hb, MetHb, and carboxyhemoglobin (CarboxHb) levels. All data are presented as mean and significance was assigned at P < 0.05.

Results

A significant decrease in Hb [118 (20) g·L−1 vs 94 (18) g·L−1] was associated with an increase in MetHb [0.88 (0.22)% vs 0.95 (0.24)%] (P < 0.001 for both), but not CarboxHb [1.08 (0.47)% vs 1.08 (0.49)%]. Regression analysis revealed a significant relationship between the change in Hb and MetHb (F = 40.3; P < 0.001) but not between the change in Hb and CarboxyHb (F = 0.2; P = 0.694). This correlation was not influenced by RBC transfusion or exogenous nitrate use.

Conclusions

A negative correlation was observed between the change in Hb and MetHb in patients undergoing cardiac surgery and cardiopulmonary bypass. These data support the previously unreported hypothesis that MetHb may be a marker of anemic stress associated with reduced tissue perfusion during acute hemodilution in humans. Further prospective studies are needed to determine if these changes in MetHb are linked to adverse outcomes in patients undergoing cardiac surgery.
Literature
1.
go back to reference Beattie WS, Karkouti K, Wijeysundera DN, Tait G. Risk associated with preoperative anemia in noncardiac surgery: a single-center cohort study. Anesthesiology 2009; 110: 574-81.PubMedCrossRef Beattie WS, Karkouti K, Wijeysundera DN, Tait G. Risk associated with preoperative anemia in noncardiac surgery: a single-center cohort study. Anesthesiology 2009; 110: 574-81.PubMedCrossRef
2.
go back to reference Karkouti K, Wijeysundera DN, Beattie WS. Reducing Bleeding in Cardiac Surgery (RBC) Investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study. Circulation 2008; 117: 478-84.PubMedCrossRef Karkouti K, Wijeysundera DN, Beattie WS. Reducing Bleeding in Cardiac Surgery (RBC) Investigators. Risk associated with preoperative anemia in cardiac surgery: a multicenter cohort study. Circulation 2008; 117: 478-84.PubMedCrossRef
3.
go back to reference Tsui AK, Dattani ND, Marsden PA, et al. Reassessing the risk of hemodilutional anemia: some new pieces to an old puzzle. Can J Anesth 2010; 57: 779-91.PubMedCrossRef Tsui AK, Dattani ND, Marsden PA, et al. Reassessing the risk of hemodilutional anemia: some new pieces to an old puzzle. Can J Anesth 2010; 57: 779-91.PubMedCrossRef
4.
go back to reference Hung M, Besser M, Sharples LD, Nair SK, Klein AA. The prevalence and association with transfusion, intensive care unit stay and mortality of pre-operative anaemia in a cohort of cardiac surgery patients. Anaesthesia 2011; 66: 812-8.PubMedCrossRef Hung M, Besser M, Sharples LD, Nair SK, Klein AA. The prevalence and association with transfusion, intensive care unit stay and mortality of pre-operative anaemia in a cohort of cardiac surgery patients. Anaesthesia 2011; 66: 812-8.PubMedCrossRef
5.
go back to reference Musallam KM, Tamim HM, Richards T, et al. Preoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort study. Lancet 2011; 378: 1396-407.PubMedCrossRef Musallam KM, Tamim HM, Richards T, et al. Preoperative anaemia and postoperative outcomes in non-cardiac surgery: a retrospective cohort study. Lancet 2011; 378: 1396-407.PubMedCrossRef
6.
go back to reference Ragoonanan TE, Beattie WS, Mazer CD, et al. Metoprolol reduces cerebral tissue oxygen tension after acute hemodilution in rats. Anesthesiology 2009; 111: 988-1000.PubMedCrossRef Ragoonanan TE, Beattie WS, Mazer CD, et al. Metoprolol reduces cerebral tissue oxygen tension after acute hemodilution in rats. Anesthesiology 2009; 111: 988-1000.PubMedCrossRef
7.
go back to reference Tsui AK, Marsden PA, Mazer CD, et al. Priming of hypoxia-inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anemia. Proc Natl Acad Sci USA 2011; 108: 17544-9.PubMedCrossRef Tsui AK, Marsden PA, Mazer CD, et al. Priming of hypoxia-inducible factor by neuronal nitric oxide synthase is essential for adaptive responses to severe anemia. Proc Natl Acad Sci USA 2011; 108: 17544-9.PubMedCrossRef
8.
go back to reference Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999; 340: 409-17.PubMedCrossRef Hebert PC, Wells G, Blajchman MA, et al. A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion Requirements in Critical Care Investigators, Canadian Critical Care Trials Group. N Engl J Med 1999; 340: 409-17.PubMedCrossRef
9.
go back to reference Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med 2008; 358: 1229-39.PubMedCrossRef Koch CG, Li L, Sessler DI, et al. Duration of red-cell storage and complications after cardiac surgery. N Engl J Med 2008; 358: 1229-39.PubMedCrossRef
10.
go back to reference Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 2009; 361: 2019-32.PubMedCrossRef Pfeffer MA, Burdmann EA, Chen CY, et al. A trial of darbepoetin alfa in type 2 diabetes and chronic kidney disease. N Engl J Med 2009; 361: 2019-32.PubMedCrossRef
11.
go back to reference Natanson C, Kern SJ, Lurie P, Banks SM, Wolfe SM. Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a meta-analysis. JAMA 2008; 299: 2304-12.PubMedCrossRef Natanson C, Kern SJ, Lurie P, Banks SM, Wolfe SM. Cell-free hemoglobin-based blood substitutes and risk of myocardial infarction and death: a meta-analysis. JAMA 2008; 299: 2304-12.PubMedCrossRef
12.
go back to reference Weiskopf RB. Emergency transfusion for acute severe anemia: a calculated risk. Anesth Analg 2010; 111: 1088-92.PubMedCrossRef Weiskopf RB. Emergency transfusion for acute severe anemia: a calculated risk. Anesth Analg 2010; 111: 1088-92.PubMedCrossRef
13.
go back to reference McLaren AT, Marsden PA, Mazer CD, et al. Increased expression of HIF-1 alpha, nNOS, and VEGF in the cerebral cortex of anemic rats. Am J Physiol Regul Integr Comp Physiol 2007; 292: R403-14.PubMedCrossRef McLaren AT, Marsden PA, Mazer CD, et al. Increased expression of HIF-1 alpha, nNOS, and VEGF in the cerebral cortex of anemic rats. Am J Physiol Regul Integr Comp Physiol 2007; 292: R403-14.PubMedCrossRef
14.
go back to reference McLaren AT, David MC, Zhang H, Liu E, Mok L, Hare GM. A potential role for inducible nitric oxide synthase in the cerebral response to acute hemodilution. Can J Anesth 2009; 56: 502-9.PubMedCrossRef McLaren AT, David MC, Zhang H, Liu E, Mok L, Hare GM. A potential role for inducible nitric oxide synthase in the cerebral response to acute hemodilution. Can J Anesth 2009; 56: 502-9.PubMedCrossRef
15.
go back to reference Shander A, Javidroozi M, Ozawa S, Hare GM. What is really dangerous - anaemia or transfusion? Br J Anaesth 2011; 107: i41-59.PubMedCrossRef Shander A, Javidroozi M, Ozawa S, Hare GM. What is really dangerous - anaemia or transfusion? Br J Anaesth 2011; 107: i41-59.PubMedCrossRef
16.
go back to reference Luchsinger BP, Rich EN, Gow AJ, Williams EM, Stamler JS, Singel DJ. Routes to S-nitrosohemoglobin formation with heme redox and preferential reactivity in the beta subunits. Proc Natl Acad Sci USA 2003; 100: 461-6.PubMedCrossRef Luchsinger BP, Rich EN, Gow AJ, Williams EM, Stamler JS, Singel DJ. Routes to S-nitrosohemoglobin formation with heme redox and preferential reactivity in the beta subunits. Proc Natl Acad Sci USA 2003; 100: 461-6.PubMedCrossRef
17.
go back to reference Angelo M, Singel DJ, Stamler JS. An S-nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate. Proc Natl Acad Sci USA 2006; 103: 8366-71.PubMedCrossRef Angelo M, Singel DJ, Stamler JS. An S-nitrosothiol (SNO) synthase function of hemoglobin that utilizes nitrite as a substrate. Proc Natl Acad Sci USA 2006; 103: 8366-71.PubMedCrossRef
18.
go back to reference Cosby K, Partovi KS, Crawford JH, et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 2003; 9: 1498-505.PubMedCrossRef Cosby K, Partovi KS, Crawford JH, et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med 2003; 9: 1498-505.PubMedCrossRef
19.
go back to reference Crawford JH, Isbell TS, Huang Z, et al. Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood 2006; 107: 566-74.PubMedCrossRef Crawford JH, Isbell TS, Huang Z, et al. Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood 2006; 107: 566-74.PubMedCrossRef
20.
go back to reference Gladwin MT, Raat NJ, Shiva S, et al. Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation. Am J Physiol Heart Circ Physiol 2006; 291: H2026-35.PubMedCrossRef Gladwin MT, Raat NJ, Shiva S, et al. Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation. Am J Physiol Heart Circ Physiol 2006; 291: H2026-35.PubMedCrossRef
21.
go back to reference Hobbs AJ, Gladwin MT, Patel RP, Williams DL, Butler AR. Haemoglobin: NO transporter, NO inactivator or NOne of the above? Trends Pharmacol Sci 2002; 23: 406-11.PubMedCrossRef Hobbs AJ, Gladwin MT, Patel RP, Williams DL, Butler AR. Haemoglobin: NO transporter, NO inactivator or NOne of the above? Trends Pharmacol Sci 2002; 23: 406-11.PubMedCrossRef
22.
go back to reference Huang Z, Shiva S, Kim-Shapiro DB, et al. Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control. J Clin Invest 2005; 115: 2099-107.PubMedCrossRef Huang Z, Shiva S, Kim-Shapiro DB, et al. Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control. J Clin Invest 2005; 115: 2099-107.PubMedCrossRef
23.
go back to reference van Bommel J, Trouwborst A, Schwarte L, Siegemund M, Ince C, Henny C. Intestinal and cerebral oxygenation during severe isovolemic hemodilution and subsequent hyperoxic ventilation in a pig model. Anesthesiology 2002; 97: 660-70.PubMedCrossRef van Bommel J, Trouwborst A, Schwarte L, Siegemund M, Ince C, Henny C. Intestinal and cerebral oxygenation during severe isovolemic hemodilution and subsequent hyperoxic ventilation in a pig model. Anesthesiology 2002; 97: 660-70.PubMedCrossRef
24.
go back to reference Weiskopf RB, Viele MK, Feiner J, et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 1998; 279: 217-21.PubMedCrossRef Weiskopf RB, Viele MK, Feiner J, et al. Human cardiovascular and metabolic response to acute, severe isovolemic anemia. JAMA 1998; 279: 217-21.PubMedCrossRef
25.
go back to reference Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine (Baltimore) 2004; 83: 265-73.CrossRef Ash-Bernal R, Wise R, Wright SM. Acquired methemoglobinemia: a retrospective series of 138 cases at 2 teaching hospitals. Medicine (Baltimore) 2004; 83: 265-73.CrossRef
26.
go back to reference Kane GC, Hoehn SM, Behrenbeck TR, Mulvagh SL. Benzocaine-induced methemoglobinemia based on the Mayo Clinic experience from 28 478 transesophageal echocardiograms: incidence, outcomes, and predisposing factors. Arch Intern Med 2007; 167: 1977-82.PubMedCrossRef Kane GC, Hoehn SM, Behrenbeck TR, Mulvagh SL. Benzocaine-induced methemoglobinemia based on the Mayo Clinic experience from 28 478 transesophageal echocardiograms: incidence, outcomes, and predisposing factors. Arch Intern Med 2007; 167: 1977-82.PubMedCrossRef
27.
go back to reference Shehata N, Burns LA, Nathan H, et al. A randomized controlled pilot study of adherence to transfusion strategies in cardiac surgery. Transfusion 2012; 52: 91-9.PubMedCrossRef Shehata N, Burns LA, Nathan H, et al. A randomized controlled pilot study of adherence to transfusion strategies in cardiac surgery. Transfusion 2012; 52: 91-9.PubMedCrossRef
28.
go back to reference Mohan RM, Golding S, Heaton DA, Danson EJ, Paterson DJ. Targeting neuronal nitric oxide synthase with gene transfer to modulate cardiac autonomic function. Prog Biophys Mol Biol 2004; 84: 321-44.PubMedCrossRef Mohan RM, Golding S, Heaton DA, Danson EJ, Paterson DJ. Targeting neuronal nitric oxide synthase with gene transfer to modulate cardiac autonomic function. Prog Biophys Mol Biol 2004; 84: 321-44.PubMedCrossRef
29.
go back to reference Sears CE, Ashley EA, Casadei B. Nitric oxide control of cardiac function: is neuronal nitric oxide synthase a key component? Philos Trans R Soc Lond B Biol Sci 2004; 359: 1021-44.PubMedCrossRef Sears CE, Ashley EA, Casadei B. Nitric oxide control of cardiac function: is neuronal nitric oxide synthase a key component? Philos Trans R Soc Lond B Biol Sci 2004; 359: 1021-44.PubMedCrossRef
30.
go back to reference Ward ME, Toporsian M, Scott JA, et al. Hypoxia induces a functionally significant and translationally efficient neuronal NO synthase mRNA variant. J Clin Invest 2005; 115: 3128-39.PubMedCrossRef Ward ME, Toporsian M, Scott JA, et al. Hypoxia induces a functionally significant and translationally efficient neuronal NO synthase mRNA variant. J Clin Invest 2005; 115: 3128-39.PubMedCrossRef
31.
go back to reference Iadecola C, Beitz AJ, Renno W, Xu X, Mayer B, Zhang F. Nitric oxide synthase-containing neural processes on large cerebral arteries and cerebral microvessels. Brain Res 1993; 606: 148-55.PubMedCrossRef Iadecola C, Beitz AJ, Renno W, Xu X, Mayer B, Zhang F. Nitric oxide synthase-containing neural processes on large cerebral arteries and cerebral microvessels. Brain Res 1993; 606: 148-55.PubMedCrossRef
32.
go back to reference Hudetz AG, Wood JD, Kampine JP. 7-Nitroindazole impedes erythrocyte flow response to isovolemic hemodilution in the cerebral capillary circulation. J Cereb Blood Flow Metab 2000; 20: 220-4.PubMedCrossRef Hudetz AG, Wood JD, Kampine JP. 7-Nitroindazole impedes erythrocyte flow response to isovolemic hemodilution in the cerebral capillary circulation. J Cereb Blood Flow Metab 2000; 20: 220-4.PubMedCrossRef
33.
go back to reference Plochl W, Liam BL, Cook DJ, Orszulak TA. Cerebral response to haemodilution during cardiopulmonary bypass in dogs: the role of nitric oxide synthase. Br J Anaesth 1999; 82: 237-43.PubMedCrossRef Plochl W, Liam BL, Cook DJ, Orszulak TA. Cerebral response to haemodilution during cardiopulmonary bypass in dogs: the role of nitric oxide synthase. Br J Anaesth 1999; 82: 237-43.PubMedCrossRef
34.
go back to reference Lopez A, Lorente JA, Steingrub J, et al. Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med 2004; 32: 21-30.PubMedCrossRef Lopez A, Lorente JA, Steingrub J, et al. Multiple-center, randomized, placebo-controlled, double-blind study of the nitric oxide synthase inhibitor 546C88: effect on survival in patients with septic shock. Crit Care Med 2004; 32: 21-30.PubMedCrossRef
35.
go back to reference Olofsson CI, Gorecki AZ, Dirksen R, et al. Evaluation of MP4OX for Prevention of perioperative hypotension in patients undergoing primary hip arthroplasty with spinal anesthesia: a randomized, double-blind, multicenter study. Anesthesiology 2011; 114: 1048-63.PubMedCrossRef Olofsson CI, Gorecki AZ, Dirksen R, et al. Evaluation of MP4OX for Prevention of perioperative hypotension in patients undergoing primary hip arthroplasty with spinal anesthesia: a randomized, double-blind, multicenter study. Anesthesiology 2011; 114: 1048-63.PubMedCrossRef
36.
go back to reference Renshaw GM, Dyson SE. Increased nitric oxide synthase in the vasculature of the epaulette shark brain following hypoxia. Neuroreport 1999; 10: 1707-12.PubMedCrossRef Renshaw GM, Dyson SE. Increased nitric oxide synthase in the vasculature of the epaulette shark brain following hypoxia. Neuroreport 1999; 10: 1707-12.PubMedCrossRef
37.
go back to reference Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anesth Analg 2009; 108: 837-45.PubMedCrossRef Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anesth Analg 2009; 108: 837-45.PubMedCrossRef
38.
go back to reference Lang JD Jr, Teng X, Chumley P, et al. Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation. J Clin Invest 2007; 117: 2583-91.PubMedCrossRef Lang JD Jr, Teng X, Chumley P, et al. Inhaled NO accelerates restoration of liver function in adults following orthotopic liver transplantation. J Clin Invest 2007; 117: 2583-91.PubMedCrossRef
39.
go back to reference Hermon MM, Burda G, Golej J, et al. Methemoglobin formation in children with congenital heart disease treated with inhaled nitric oxide after cardiac surgery. Intensive Care Med 2003; 29: 447-52.PubMed Hermon MM, Burda G, Golej J, et al. Methemoglobin formation in children with congenital heart disease treated with inhaled nitric oxide after cardiac surgery. Intensive Care Med 2003; 29: 447-52.PubMed
40.
go back to reference Stawicki SP, Sims C, Sarani B, Grossman MD, Gracias VH. Methylene blue and vasoplegia: who, when, and how? Mini Rev Med Chem 2008; 8: 472-90.PubMedCrossRef Stawicki SP, Sims C, Sarani B, Grossman MD, Gracias VH. Methylene blue and vasoplegia: who, when, and how? Mini Rev Med Chem 2008; 8: 472-90.PubMedCrossRef
41.
go back to reference Maslow AD, Stearns G, Butala P, Schwartz CS, Gough J, Singh AK. The hemodynamic effects of methylene blue when administered at the onset of cardiopulmonary bypass. Anesth Analg 2006; 103: 2-8.PubMedCrossRef Maslow AD, Stearns G, Butala P, Schwartz CS, Gough J, Singh AK. The hemodynamic effects of methylene blue when administered at the onset of cardiopulmonary bypass. Anesth Analg 2006; 103: 2-8.PubMedCrossRef
42.
go back to reference Jia L, Bonaventura C, Bonaventura J, Stamler JS. S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 1996; 380: 221-6.PubMedCrossRef Jia L, Bonaventura C, Bonaventura J, Stamler JS. S-nitrosohaemoglobin: a dynamic activity of blood involved in vascular control. Nature 1996; 380: 221-6.PubMedCrossRef
43.
go back to reference Jaffrey SR, Erdjument-Bromage H, Ferris CD, Tempst P, Snyder SH. Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat Cell Biol 2001; 3: 193-7.PubMedCrossRef Jaffrey SR, Erdjument-Bromage H, Ferris CD, Tempst P, Snyder SH. Protein S-nitrosylation: a physiological signal for neuronal nitric oxide. Nat Cell Biol 2001; 3: 193-7.PubMedCrossRef
44.
go back to reference Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 1990; 87: 1620-4.PubMedCrossRef Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: implications for endothelial injury from nitric oxide and superoxide. Proc Natl Acad Sci USA 1990; 87: 1620-4.PubMedCrossRef
45.
go back to reference Denicola A, Souza JM, Radi R. Diffusion of peroxynitrite across erythrocyte membranes. Proc Natl Acad Sci USA 1998; 95: 3566-71.PubMedCrossRef Denicola A, Souza JM, Radi R. Diffusion of peroxynitrite across erythrocyte membranes. Proc Natl Acad Sci USA 1998; 95: 3566-71.PubMedCrossRef
46.
go back to reference Batthyany C, Schopfer FJ, Baker PR, et al. Reversible post-translational modification of proteins by nitrated fatty acids in vivo. J Biol Chem 2006; 281: 20450-63.PubMedCrossRef Batthyany C, Schopfer FJ, Baker PR, et al. Reversible post-translational modification of proteins by nitrated fatty acids in vivo. J Biol Chem 2006; 281: 20450-63.PubMedCrossRef
Metadata
Title
Plasma methemoglobin as a potential biomarker of anemic stress in humans
Authors
Gregory M. T. Hare, MD, PhD
Alexander Mu, MD
Alexander Romaschin, MD
Albert K.-Y. Tsui, PhD
Nadine Shehata, MD
W. Scott Beattie, MD, PhD
C. David Mazer, MD
Publication date
01-04-2012
Publisher
Springer-Verlag
Published in
Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Issue 4/2012
Print ISSN: 0832-610X
Electronic ISSN: 1496-8975
DOI
https://doi.org/10.1007/s12630-011-9663-7

Other articles of this Issue 4/2012

Canadian Journal of Anesthesia/Journal canadien d'anesthésie 4/2012 Go to the issue