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Effects of Red Blood Cell Sickling on Right Ventricular Afterload in vivo

  • Sp Iss: Experimental Advances in Cardiovascular Biomechanics
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Abstract

Background

Hemolysis in sickle cell disease (SCD) releases cell free hemoglobin, which scavenges nitric oxide (NO), leading to pulmonary vascular vasoconstriction, increased pulmonary vascular resistance (PVR), and the development of PH. However, PVR is only one component of right ventricular (RV) afterload. Whether sickled red blood cells increase the total RV afterload, including compliance and wave reflections, is unclear.

Objective

Patients with SCD and pulmonary hypertension (PH) have a significantly increased risk of sudden death compared to patients with SCD alone. Sickled red blood cells (RBCs) are fragile and lyse easily. Here, we sought to determine the acute effects of SCD RBCs and increased cell free hemoglobin on RV afterload.

Methods

Main pulmonary artery pressures and flows were measured in C57BL6 mice before and after exchanges of whole blood (~200 uL, Hct = 45%) with an equal volume of SCD RBCs in plasma (Hct = 45%) or cell free hemoglobin (Hb+) in solution. After transfusions, animals were additionally stressed with acute hypoxia (AH; 10% O2).

Results

SCD RBCs increased PVR only compared to control RBCs; cell free hemoglobin increased PVR and wave reflections. These increases in RV afterload increased further with AH.

Conclusions

The release of cell free hemoglobin from fragile SCD RBCs in vivo increases the total RV afterload and may impair RV function more than the SCD RBCs themselves.

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Acknowledgments

We thank Dr. Ron R. Magness for the use of the viscometer. We would also like to thank Gaoussou Diarra for his surgical expertise performing the in vivo hemodynamic measurements.

Funding

This study is supported by National Institutes of Health (NIH), NIH R21-HL086939 (NCC) and NIH F31 HL128088–01 (DAS).

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Wisconsin, 2146 ECB, 1550 Engineering Dr., Madison, WI, 53706, USA

    D. A. Schreier, D. M. Tabima & N. C. Chesler

  2. Department of Medicine, 1685 Highland Avenue, 5158 Medical Foundation Centennial Building, Madison, WI, 53705-2281, USA

    T. A. Hacker & N. C. Chesler

  3. Department of Biomedical Engineering, University of Georgia Tech, Engineered Biosystems Building, 950 Atlantic Drive, Suite 3015, Atlanta, GA, 30332, USA

    M. O. Platt

  4. Irvine, USA

    N. C. Chesler

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  1. D. A. Schreier
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Contributions

David Schreier1,2,3,4, Timothy Hacker1,2,4, Diana Tabima1,4, Manu O. Platt1,4, Naomi Chesler1,4

1. Designed research.

2. Performed research.

3. Analyzed data.

4. Wrote the paper.

Corresponding author

Correspondence to N. C. Chesler.

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Conflict of Interest

No conflicts of interest, financial or otherwise, are declared by the author(s). The University of Wisconsin-Madison Institutional Animal Care and Use Committee approved all procedures.

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Schreier, D.A., Hacker, T.A., Tabima, D.M. et al. Effects of Red Blood Cell Sickling on Right Ventricular Afterload in vivo. Exp Mech 61, 229–235 (2021). https://doi.org/10.1007/s11340-020-00669-3

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