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. 2022 Oct 26;12(11):1025.
doi: 10.3390/metabo12111025.

Influence of 24 h Simulated Altitude on Red Blood Cell Deformability and Hematological Parameters in Patients with Fontan Circulation

Julian Alexander Härtel  1 , Nicole Müller  1 , Johannes Breuer  1 , Jens Jordan  2   3 , Jens Tank  2 , Janina Bros  4 , Benedikt Seeger  4 , Emily Zollmann  4 , Wilhelm Bloch  4 , Marijke Grau  4
Affiliations

Influence of 24 h Simulated Altitude on Red Blood Cell Deformability and Hematological Parameters in Patients with Fontan Circulation

Julian Alexander Härtel et al. Metabolites. .

Abstract

Patients with Fontan circulation are particularly dependent on low pulmonary vascular resistance because their lungs are passively perfused. Hypoxia drives pulmonary vasoconstriction; thus, red blood cell (RBC) deformability and stability of hematological parameters might be of particular importance, because alterations during hypoxia might further influence circulation. This study aimed to measure respective parameters in patients with Fontan circulation exposed to normobaric hypoxia. A total of 18 patients with Fontan circulation (16 to 38 years) were exposed to normobaric hypoxia (15.2% ambient oxygen). Blood samples were taken in normoxia, after 24 h in hypoxia, and 60 min after return to normoxia. Blood count, RBC age distribution, EPO, RBC deformability, marker of RBC nitric oxide, oxidative state, and RBC ATP were measured. Hypoxia increased oxidative stress in RBC, but without affecting RBC deformability. RBC age distribution remained unaffected, although EPO concentrations increased, followed by a rise in reticulocyte count at an already high hematocrit. NO metabolism was not affected by hypoxia. Modest normobaric hypoxia for 24 h did not impair RBC deformability in patients with Fontan circulation; however, the oxidative system seemed to be stressed. Given the high baseline Hct in these patients, hypoxia-induced erythropoiesis could adversely affect rheology with more prolonged hypoxia exposure.

Keywords: Fontan circulation; RBC deformability; altitude capability; congenital heart defect; hemorheology; hypoxia; red blood cells.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
(a) Distribution of RBC subfractions in % with n = 11 at measured timepoints (T1, T2, and T3), indicating no significant changes due to hypoxia, Y = young RBC fraction, M = middle RBC fraction, O = old RBC fraction; (b) RBC deformability shown as SS1/2:EImax ratio, demonstrating no influence by hypoxia.
Figure 2
Figure 2
Deformability parameters under an osmotic gradient measured by Osmoscan, indicating no changes due to hypoxia with unaffected (a) Omin, (b) Ohyper, and (c) EImax. Datasets included in this figure: (a–c) T1: n = 14, T2: n = 11, T3: n = 8.
Figure 3
Figure 3
(a) Phosphorylation of RBC-NOS at serine 1177 residue and (b) corresponding RBC nitrite/RSNP/Fe-NO concentration were not affected by hypoxia. (a) n = 16 and (b) n = 17.
Figure 4
Figure 4
Oxidative status of RBC, indicating (a) significantly reduced total antioxidant capacity (TAC) and (b) significantly increased free ROS/RNS due to hypoxia. (c) Nitrotyrosine concentration remained unaffected during the study. (a–c) n = 16. * p ≤ 0.05, ** p ≤ 0.01.
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