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Exposure of stored packed erythrocytes to NO prevents transfusion-associated pulmonary hypertension

Exposure of stored packed erythrocytes to NO prevents transfusion-associated pulmonary hypertension
Exposure of stored packed erythrocytes to NO prevents transfusion-associated pulmonary hypertension
Background: Transfusion of packed erythrocytes stored for a long duration is associated with increased pulmonary arterial pressure and vascular resistance. Prolonged storage decreases erythrocyte deformability, and older erythrocytes are rapidly removed from the circulation after transfusion. The authors studied whether treating stored packed ovine erythrocytes with NO before transfusion could prevent pulmonary vasoconstriction, enhance erythrocyte deformability, and prolong erythrocyte survival after transfusion.

Methods: Ovine leukoreduced packed erythrocytes were treated before transfusion with either NO gas or a short-lived NO donor. Sheep were transfused with autologous packed erythrocytes, which were stored at 4°C for either 2 (“fresh blood”) or 40 days (“stored blood”). Pulmonary and systemic hemodynamic parameters were monitored before, during, and after transfusion. Transfused erythrocytes were labeled with biotin to measure their circulating lifespan. Erythrocyte deformability was assessed before and after NO treatment using a microfluidic device.

Results: NO treatment improved the deformability of stored erythrocytes and increased the number of stored erythrocytes circulating at 1 and 24?h after transfusion. NO treatment prevented transfusion-associated pulmonary hypertension (mean pulmonary arterial pressure at 30?min of 21?±?1 vs. 15?±?1 mmHg in control and NO–treated packed erythrocytes, P < 0.0001). Washing stored packed erythrocytes before transfusion did not prevent pulmonary hypertension.

Conclusions: NO treatment of stored packed erythrocytes before transfusion oxidizes cell-free oxyhemoglobin to methemoglobin, prevents subsequent NO scavenging in the pulmonary vasculature, and limits pulmonary hypertension. NO treatment increases erythrocyte deformability and erythrocyte survival after transfusion. NO treatment might provide a promising therapeutic approach to prevent pulmonary hypertension and extend erythrocyte survival.
0003-3022
1-12
Muenster, Stefan
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Beloiartsev, Arkadi
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Yu, Binglan
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Du, E
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Abidi, Sabia
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Dao, Ming
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Fabry, Gregor
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Graw, Jan A.
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Wepler, Martin
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Malhotra, Rajeev
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Fernandez, Bernadette O.
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Feelisch, Martin
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Bloch, Kenneth D.
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Bloch, Donald B.
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Zapol, Warren M.
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Muenster, Stefan
bb8d5da1-d6cd-4035-8d91-7da0ad8d1215
Beloiartsev, Arkadi
dfe99c9e-1998-4e2c-8756-65726412452b
Yu, Binglan
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Du, E
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Abidi, Sabia
ef146984-803c-4ddf-909e-629703b277ac
Dao, Ming
a14a71c0-18d9-427e-af73-8c9e5cc5ab5a
Fabry, Gregor
bcbbc012-3e97-4bb4-a445-42e5064a6b29
Graw, Jan A.
a61a439c-4e63-41c1-97d0-07f982d14849
Wepler, Martin
8647d16b-7d6b-4bb4-8a41-0cc40b8fea39
Malhotra, Rajeev
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Fernandez, Bernadette O.
9890aabc-1fe6-4530-a51e-31182e537131
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Bloch, Kenneth D.
25d43ddf-77d4-448b-b618-079a0492aba1
Bloch, Donald B.
bce63551-89d0-4ccc-b03a-4a2a5278eaf7
Zapol, Warren M.
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Muenster, Stefan, Beloiartsev, Arkadi, Yu, Binglan, Du, E, Abidi, Sabia, Dao, Ming, Fabry, Gregor, Graw, Jan A., Wepler, Martin, Malhotra, Rajeev, Fernandez, Bernadette O., Feelisch, Martin, Bloch, Kenneth D., Bloch, Donald B. and Zapol, Warren M. (2016) Exposure of stored packed erythrocytes to NO prevents transfusion-associated pulmonary hypertension. Anesthesiology, 1-12. (doi:10.1097/ALN.0000000000001294). (PMID:27517645)

Record type: Article

Abstract

Background: Transfusion of packed erythrocytes stored for a long duration is associated with increased pulmonary arterial pressure and vascular resistance. Prolonged storage decreases erythrocyte deformability, and older erythrocytes are rapidly removed from the circulation after transfusion. The authors studied whether treating stored packed ovine erythrocytes with NO before transfusion could prevent pulmonary vasoconstriction, enhance erythrocyte deformability, and prolong erythrocyte survival after transfusion.

Methods: Ovine leukoreduced packed erythrocytes were treated before transfusion with either NO gas or a short-lived NO donor. Sheep were transfused with autologous packed erythrocytes, which were stored at 4°C for either 2 (“fresh blood”) or 40 days (“stored blood”). Pulmonary and systemic hemodynamic parameters were monitored before, during, and after transfusion. Transfused erythrocytes were labeled with biotin to measure their circulating lifespan. Erythrocyte deformability was assessed before and after NO treatment using a microfluidic device.

Results: NO treatment improved the deformability of stored erythrocytes and increased the number of stored erythrocytes circulating at 1 and 24?h after transfusion. NO treatment prevented transfusion-associated pulmonary hypertension (mean pulmonary arterial pressure at 30?min of 21?±?1 vs. 15?±?1 mmHg in control and NO–treated packed erythrocytes, P < 0.0001). Washing stored packed erythrocytes before transfusion did not prevent pulmonary hypertension.

Conclusions: NO treatment of stored packed erythrocytes before transfusion oxidizes cell-free oxyhemoglobin to methemoglobin, prevents subsequent NO scavenging in the pulmonary vasculature, and limits pulmonary hypertension. NO treatment increases erythrocyte deformability and erythrocyte survival after transfusion. NO treatment might provide a promising therapeutic approach to prevent pulmonary hypertension and extend erythrocyte survival.

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Accepted/In Press date: 7 July 2016
e-pub ahead of print date: 18 August 2016
Organisations: Clinical & Experimental Sciences

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Local EPrints ID: 400522
URI: https://eprints.soton.ac.uk/id/eprint/400522
ISSN: 0003-3022
PURE UUID: 05bd553a-18a2-4390-86e7-a41b19946c46
ORCID for Bernadette O. Fernandez: ORCID iD orcid.org/0000-0001-6337-0381
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 19 Sep 2016 09:22
Last modified: 10 Dec 2019 06:24

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Contributors

Author: Stefan Muenster
Author: Arkadi Beloiartsev
Author: Binglan Yu
Author: E Du
Author: Sabia Abidi
Author: Ming Dao
Author: Gregor Fabry
Author: Jan A. Graw
Author: Martin Wepler
Author: Rajeev Malhotra
Author: Bernadette O. Fernandez ORCID iD
Author: Martin Feelisch ORCID iD
Author: Kenneth D. Bloch
Author: Donald B. Bloch
Author: Warren M. Zapol

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