Transfused older stored red blood cells improve the clinical course and outcome in a canine lethal hemorrhage and reperfusion model

Steven B. Solomon, Irene Cortés-Puch, Junfeng Sun, Kenneth E. Remy, Dong Wang, Jing Feng, Sameena S. Khan, Derek Sinchar, Daniel B. Kim-Shapiro, Harvey G. Klein, Charles Natanson

Research output: Contribution to journalArticle

Abstract

BACKGROUND In canine models, transfused older stored red blood cells (RBCs) hemolyze in vivo resulting in significantly increased intravascular cell-free hemoglobin (CFH) and non-transferrin-bound iron (NTBI). During canine bacterial pneumonia with septic shock, but not in controls, older stored RBCs were associated with significantly increased lung injury and mortality. It is unknown if in shock without infection transfusion of older RBCs will result in similar adverse effects. STUDY DESIGN AND METHODS Two-year-old purpose-bred beagles (n = 12) were transfused similar quantities of either older (42-day) or fresher (7-day) stored universal donor canine RBCs 2.5 hours after undergoing controlled hemorrhage (55 mL/kg). RESULTS With older transfused RBCs, CFH (p <0.0001) and NTBI (p = 0.004) levels increased, but lung injury (p = 0.01) and C-reactive protein levels (p = 0.002) declined and there was a trend toward lower mortality (18% vs. 50%). All three deaths after transfused fresher RBCs resulted from hepatic fractures. Lowered exogenous norepinephrine requirements (p <0.05) and cardiac outputs (p <0.05) after older transfused RBCs were associated with increased CFH levels that have known vasoconstrictive nitric oxide scavenging capability. CONCLUSIONS In hemorrhagic shock, older RBCs altered resuscitation physiology but did not worsen clinical outcomes. Elevated CFH may lower norepinephrine requirements and cardiac outputs ameliorating reperfusion injuries. With hemorrhagic shock, NTBI levels persist in contrast to the increased clearance, lung injury, and mortality in the previously reported infection model. These preclinical data suggest that whereas iron derived from older RBCs promotes bacterial growth, worsening septic shock mortality during infection, release of CFH and NTBI during hemorrhagic shock is not necessarily harmful.

Original languageEnglish (US)
Pages (from-to)2552-2563
Number of pages12
JournalTransfusion
Volume55
Issue number11
DOIs
StatePublished - Nov 1 2015
Externally publishedYes

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Reperfusion
Canidae
Erythrocytes
Hemorrhage
Hemoglobins
Iron
Hemorrhagic Shock
Lung Injury
Mortality
Septic Shock
Cardiac Output
Norepinephrine
Infection
Bacterial Pneumonia
Erythrocyte Transfusion
Reperfusion Injury
Resuscitation
C-Reactive Protein
Shock
Nitric Oxide

ASJC Scopus subject areas

  • Hematology
  • Immunology
  • Immunology and Allergy

Cite this

Solomon, S. B., Cortés-Puch, I., Sun, J., Remy, K. E., Wang, D., Feng, J., ... Natanson, C. (2015). Transfused older stored red blood cells improve the clinical course and outcome in a canine lethal hemorrhage and reperfusion model. Transfusion, 55(11), 2552-2563. https://doi.org/10.1111/trf.13213

Transfused older stored red blood cells improve the clinical course and outcome in a canine lethal hemorrhage and reperfusion model. / Solomon, Steven B.; Cortés-Puch, Irene; Sun, Junfeng; Remy, Kenneth E.; Wang, Dong; Feng, Jing; Khan, Sameena S.; Sinchar, Derek; Kim-Shapiro, Daniel B.; Klein, Harvey G.; Natanson, Charles.

In: Transfusion, Vol. 55, No. 11, 01.11.2015, p. 2552-2563.

Research output: Contribution to journalArticle

Solomon, SB, Cortés-Puch, I, Sun, J, Remy, KE, Wang, D, Feng, J, Khan, SS, Sinchar, D, Kim-Shapiro, DB, Klein, HG & Natanson, C 2015, 'Transfused older stored red blood cells improve the clinical course and outcome in a canine lethal hemorrhage and reperfusion model', Transfusion, vol. 55, no. 11, pp. 2552-2563. https://doi.org/10.1111/trf.13213
Solomon, Steven B. ; Cortés-Puch, Irene ; Sun, Junfeng ; Remy, Kenneth E. ; Wang, Dong ; Feng, Jing ; Khan, Sameena S. ; Sinchar, Derek ; Kim-Shapiro, Daniel B. ; Klein, Harvey G. ; Natanson, Charles. / Transfused older stored red blood cells improve the clinical course and outcome in a canine lethal hemorrhage and reperfusion model. In: Transfusion. 2015 ; Vol. 55, No. 11. pp. 2552-2563.
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abstract = "BACKGROUND In canine models, transfused older stored red blood cells (RBCs) hemolyze in vivo resulting in significantly increased intravascular cell-free hemoglobin (CFH) and non-transferrin-bound iron (NTBI). During canine bacterial pneumonia with septic shock, but not in controls, older stored RBCs were associated with significantly increased lung injury and mortality. It is unknown if in shock without infection transfusion of older RBCs will result in similar adverse effects. STUDY DESIGN AND METHODS Two-year-old purpose-bred beagles (n = 12) were transfused similar quantities of either older (42-day) or fresher (7-day) stored universal donor canine RBCs 2.5 hours after undergoing controlled hemorrhage (55 mL/kg). RESULTS With older transfused RBCs, CFH (p <0.0001) and NTBI (p = 0.004) levels increased, but lung injury (p = 0.01) and C-reactive protein levels (p = 0.002) declined and there was a trend toward lower mortality (18{\%} vs. 50{\%}). All three deaths after transfused fresher RBCs resulted from hepatic fractures. Lowered exogenous norepinephrine requirements (p <0.05) and cardiac outputs (p <0.05) after older transfused RBCs were associated with increased CFH levels that have known vasoconstrictive nitric oxide scavenging capability. CONCLUSIONS In hemorrhagic shock, older RBCs altered resuscitation physiology but did not worsen clinical outcomes. Elevated CFH may lower norepinephrine requirements and cardiac outputs ameliorating reperfusion injuries. With hemorrhagic shock, NTBI levels persist in contrast to the increased clearance, lung injury, and mortality in the previously reported infection model. These preclinical data suggest that whereas iron derived from older RBCs promotes bacterial growth, worsening septic shock mortality during infection, release of CFH and NTBI during hemorrhagic shock is not necessarily harmful.",
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T1 - Transfused older stored red blood cells improve the clinical course and outcome in a canine lethal hemorrhage and reperfusion model

AU - Solomon, Steven B.

AU - Cortés-Puch, Irene

AU - Sun, Junfeng

AU - Remy, Kenneth E.

AU - Wang, Dong

AU - Feng, Jing

AU - Khan, Sameena S.

AU - Sinchar, Derek

AU - Kim-Shapiro, Daniel B.

AU - Klein, Harvey G.

AU - Natanson, Charles

PY - 2015/11/1

Y1 - 2015/11/1

N2 - BACKGROUND In canine models, transfused older stored red blood cells (RBCs) hemolyze in vivo resulting in significantly increased intravascular cell-free hemoglobin (CFH) and non-transferrin-bound iron (NTBI). During canine bacterial pneumonia with septic shock, but not in controls, older stored RBCs were associated with significantly increased lung injury and mortality. It is unknown if in shock without infection transfusion of older RBCs will result in similar adverse effects. STUDY DESIGN AND METHODS Two-year-old purpose-bred beagles (n = 12) were transfused similar quantities of either older (42-day) or fresher (7-day) stored universal donor canine RBCs 2.5 hours after undergoing controlled hemorrhage (55 mL/kg). RESULTS With older transfused RBCs, CFH (p <0.0001) and NTBI (p = 0.004) levels increased, but lung injury (p = 0.01) and C-reactive protein levels (p = 0.002) declined and there was a trend toward lower mortality (18% vs. 50%). All three deaths after transfused fresher RBCs resulted from hepatic fractures. Lowered exogenous norepinephrine requirements (p <0.05) and cardiac outputs (p <0.05) after older transfused RBCs were associated with increased CFH levels that have known vasoconstrictive nitric oxide scavenging capability. CONCLUSIONS In hemorrhagic shock, older RBCs altered resuscitation physiology but did not worsen clinical outcomes. Elevated CFH may lower norepinephrine requirements and cardiac outputs ameliorating reperfusion injuries. With hemorrhagic shock, NTBI levels persist in contrast to the increased clearance, lung injury, and mortality in the previously reported infection model. These preclinical data suggest that whereas iron derived from older RBCs promotes bacterial growth, worsening septic shock mortality during infection, release of CFH and NTBI during hemorrhagic shock is not necessarily harmful.

AB - BACKGROUND In canine models, transfused older stored red blood cells (RBCs) hemolyze in vivo resulting in significantly increased intravascular cell-free hemoglobin (CFH) and non-transferrin-bound iron (NTBI). During canine bacterial pneumonia with septic shock, but not in controls, older stored RBCs were associated with significantly increased lung injury and mortality. It is unknown if in shock without infection transfusion of older RBCs will result in similar adverse effects. STUDY DESIGN AND METHODS Two-year-old purpose-bred beagles (n = 12) were transfused similar quantities of either older (42-day) or fresher (7-day) stored universal donor canine RBCs 2.5 hours after undergoing controlled hemorrhage (55 mL/kg). RESULTS With older transfused RBCs, CFH (p <0.0001) and NTBI (p = 0.004) levels increased, but lung injury (p = 0.01) and C-reactive protein levels (p = 0.002) declined and there was a trend toward lower mortality (18% vs. 50%). All three deaths after transfused fresher RBCs resulted from hepatic fractures. Lowered exogenous norepinephrine requirements (p <0.05) and cardiac outputs (p <0.05) after older transfused RBCs were associated with increased CFH levels that have known vasoconstrictive nitric oxide scavenging capability. CONCLUSIONS In hemorrhagic shock, older RBCs altered resuscitation physiology but did not worsen clinical outcomes. Elevated CFH may lower norepinephrine requirements and cardiac outputs ameliorating reperfusion injuries. With hemorrhagic shock, NTBI levels persist in contrast to the increased clearance, lung injury, and mortality in the previously reported infection model. These preclinical data suggest that whereas iron derived from older RBCs promotes bacterial growth, worsening septic shock mortality during infection, release of CFH and NTBI during hemorrhagic shock is not necessarily harmful.

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