Cell-Free Hemoglobin-Based Blood Substitutes and Risk of Myocardial Infarction and Death

Natanson, Charles; Kern, Steven J.; Lurie, Peter; Banks, Steven M.; Wolfe, Sidney M.

doi:10.1001/jama.299.19.jrv80007

Cited by 562 publications

(430 citation statements)

References 34 publications

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“…These adverse outcomes may have been due to reduced NO bioavailability. 11,35 Thus, generalized NOS inhibition or NO scavenging has been associated with adverse cardiovascular outcomes and increased mortality.…”

Section: Discussionmentioning

confidence: 99%

“…3,6,7 The complex nature of the cellular mechanisms involved may explain why anemiainduced mortality is not necessarily improved by therapies which increase blood oxygen content, including red blood cell (RBC) transfusions, 8,9 use of erythropoiesis stimulating agents (ESAs), 10 or hemoglobin-based oxygen carriers (HBOCs). 11 Each of these strategies is capable of increasing blood oxygen content but may not increase tissue oxygen delivery. Indeed, some of these treatment strategies (transfusion, HBOCs) may limit tissue perfusion by reducing nitric oxide (NO) bioavailability, thereby increasing tissue hypoxia and mortality.…”

Section: Résumémentioning

confidence: 99%

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Plasma methemoglobin as a potential biomarker of anemic stress in humans

Hare

Romaschin

et al. 2012

Can J Anesth/J Can Anesth

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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 C90% 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 Author contributions Gregory M.T. Hare designed the research, performed the research, contributed novel intellectual input, analyzed the data, and wrote the paper. Alexander Mu performed the research, contributed novel intellectual input, and analyzed the data. Alexander Romaschin designed the research, performed the research, contributed novel intellectual input, and analyzed the data. Nadine Shehata designed the research, performed the research, contributed novel intellectual input, and analyzed the data. W. Scott Beattie designed the research, performed the research, contributed novel intellectual input, analyzed the data, and wrote the paper. C. David Mazer designed the research, performed the research, contributed novel intellectual input, analyzed the data, and wrote the paper. Albert K.Y. Tsui contributed novel intellectual input, analyzed the data, and wrote the paper. RésuméObjectif La transfusion de globules rouges alloge´niques est l'un des principaux traitements de l'ane´mie aigues econdaire a`une perte sanguine et au remplissage liquidien en salle d'ope´ration. La de´cision de transfuser du sang repose essentiellement sur des marqueurs biologiques interme´diaires (he´moglobine, saturation en oxyge`ne du sang arte´riel, pression arte´rielle, fre´quence cardiaque) qui pourraient ne pas refle´ter avec pre´cision l'insuffisance d'apport d'oxyge`ne aux tissus. A`partir d'e´tudes expe´rimentales nous avons fait l'hypothe`se qu'une hypoxie tissulaire induite par l'ane´mie act...

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Section: Discussionmentioning

confidence: 99%

Section: Résumémentioning

confidence: 99%

Plasma methemoglobin as a potential biomarker of anemic stress in humans

Hare

Romaschin

et al. 2012

Can J Anesth/J Can Anesth

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show abstract

“…92 In addition, other strategies that globally reduce systemic NO availability (transfusion of hemoglobin-based oxygen carriers) have also led to an observed increase in myocardial infarction and mortality. 96 These clinical studies provide evidence that an acute and generalized reduction in systemic NOS activity and/or NO scavenging by plasma phase Hb may impair compensatory mechanisms that maintain organ perfusion and cellular integrity, especially in the presence of vascular disease and endothelial dysfunction. Fig.…”

Section: Clinical Relevance Of Understanding Nos-mediated Cardiovascumentioning

confidence: 96%

“…99 Although the initial results provided evidence of improved tissue perfusion with methylene blue, these results must be interpreted with caution, since previous attempts to reduce NO bioavailability have led to increased mortality. 92,96 Methylene blue acts by restricting NO bioavailability by three mechanisms: 1) inhibition of NOS; 2) direct scavenging of NO; and 3) inhibiting the action of downstream soluble guanylate cyclase ( Figure 6). 100 Thus, methylene blue may improve blood pressure at the expense of impairing NO-mediated tissue perfusion and oxygen delivery.…”

Section: Anemia Increases Risk 787mentioning

confidence: 99%

“…Inhibition of NO-mediated pathways by methylene blue may paradoxically impair mechanisms that are directed at optimizing perfusion, resulting in negative clinical outcomes. 92,96 Thus, further mechanistic studies are required to determine the role of NOS-derived NO during conditions of hemodynamic stress, including acute hemodilution and CPB.…”

Section: Anemia Increases Risk 787mentioning

confidence: 99%

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