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Decreased erythrocyte aggregation in Glenn and Fontan: univentricular circulation as a rheologic disease model

Pediatric Research volume 95, pages 1335–1345 (2024)Cite this article

Abstract

Background

In the Fontan palliation for single ventricle heart disease (SVHD), pulmonary blood flow is non-pulsatile/passive, low velocity, and low shear, making viscous power loss a critical determinant of cardiac output. The rheologic properties of blood in SVHD patients are essential for understanding and modulating their limited cardiac output and they have not been systematically studied. We hypothesize that viscosity is decreased in single ventricle circulation.

Methods

We evaluated whole blood viscosity, red blood cell (RBC) aggregation, and RBC deformability to evaluate changes in healthy children and SVHD patients. We altered suspending media to understand cellular and plasma differences contributing to rheologic differences.

Results

Whole blood viscosity was similar between SVHD and healthy at their native hematocrits, while viscosity was lower at equivalent hematocrits for SVHD patients. RBC deformability is increased, and RBC aggregation is decreased in SVHD patients. Suspending SVHD RBCs in healthy plasma resulted in increased RBC aggregation and suspending healthy RBCs in SVHD plasma resulted in lower RBC aggregation.

Conclusions

Hematocrit corrected blood viscosity is lower in SVHD vs. healthy due to decreased RBC aggregation and higher RBC deformability, a viscous adaptation of blood in patients whose cardiac output is dependent on minimizing viscous power loss.

Impact

  • Patients with single ventricle circulation have decreased red blood cell aggregation and increased red blood cell deformability, both of which result in a decrease in blood viscosity across a large shear rate range.

  • Since the unique Fontan circulation has very low-shear and low velocity flow in the pulmonary arteries, blood viscosity plays an increased role in vascular resistance, therefore this work is the first to describe a novel mechanism to target pulmonary vascular resistance as a modifiable risk factor.

  • This is a novel, modifiable risk factor in this patient population.

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Fig. 1: Whole blood viscosities as measured by two different viscometers were not significantly different between Glenn, Fontan and healthy control groups.
Fig. 2: Viscosities in SVHD groups were lower than in healthy controls when adjusted to the same hematocrits.
Fig. 3: Hematocrit to viscosity ratios (HVR) were higher in SVHD groups than in healthy controls.
Fig. 4: RBC deformability in SVHD were significantly higher than in healthy group at most shear stresses between 0.5 and 50 Pa.
Fig. 5: RBC aggregation in SVHD groups were both lower than healthy controls.
Fig. 6: RBC aggregation was lower in both Glenn (panels a and c) and Fontan (panels b and d) and was increased when RBC from Glen and Fontan was resuspended in plasma from healthy controls.

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Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to acknowledge the clinical teams in the cardiac catheterization laboratory and the magnetic resonance imaging center at Children’s Hospital Los Angeles, without these incredible teams this research could not have happened.

Funding

This work is supported by funding from National Heart, Lung and Blood Institute, NIH# 1 K23 HL 119627–01A1 (J.A.D.), NIH# 1 U01 HL 117718–01 (J.A.D., T.D.C., J.C.W.), and Additional Ventures Foundation (J.A.D., J.C.W.).

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Authors and Affiliations

  1. Division of Cardiology, Children’s Hospital of Los Angeles, Los Angeles, CA, USA

    Silvie Suriany, Honglei Liu, Andrew L. Cheng, Neil Patel, John C. Wood & Jon A. Detterich

  2. Department of Physiology and Neuroscience, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Rosalinda Wenby, Herbert J. Meiselman & Jon A. Detterich

  3. Division of Pediatric and Congenital Cardiology, Helen Devos Children’s Hospital at Spectrum Health, Grand Rapids, MI, USA

    Sarah Badran

  4. Division of Cardiology, Department of Medicine, Michigan State University, East Lansing, MI, USA

    Sarah Badran

  5. Division of Hematology, Children’s Hospital of Los Angeles, Los Angeles, CA, USA

    Christopher Denton & Thomas D. Coates

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Contributions

J.A.D. and S.S. designed the study. S.S., H.L., R.W., A.L.C. and J.A.D. conducted the experiments and acquired data. S.S., J.A.D., J.C.W., and H.J.M. analyzed data. All authors were involved in writing the manuscript. All authors reviewed the results and approved the final version of the manuscript.

Corresponding author

Correspondence to Jon A. Detterich.

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Competing interests

JAD served on the scientific advisory board for Alcor Scientific in 2022 but this has no relation to the research presented in this article.

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The Institutional Review Board at Children’s Hospital Los Angeles reviewed and approved the research protocol. Consent and/or Assent was required from all parents and/or participants in this research study.

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Suriany, S., Liu, H., Cheng, A.L. et al. Decreased erythrocyte aggregation in Glenn and Fontan: univentricular circulation as a rheologic disease model. Pediatr Res 95, 1335–1345 (2024). https://doi.org/10.1038/s41390-023-02969-5

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