Effect of acute exercise on RBC deformability and RBC nitric oxide synthase signalling pathway in young sickle cell anaemia patients

Abstract

Sickle cell anaemia (SCA) is characterized by reduced red blood cell (RBC) deformability and nitric oxide (NO) bioavailability. The aim of the study was to investigate whether exercise might affect these parameters in SCA. SCA patients and healthy controls (AA) performed an acute submaximal exercise test until subjects reached the first ventilatory threshold (VT 1). Blood was sampled at rest and at VT 1. At rest, free haemoglobin level was higher and RBC count, haemoglobin and haematocrit were lower in SCA compared to AA. RBC deformability was lower in SCA. Exercise had no effect on the tested parameters. RBC NO level was higher in SCA compared to AA at rest and significantly decreased after exercise in SCA. This might be related to a reduction in RBC-NO synthase (RBC-NOS) activation which was only observed in SCA after exercise. Free radical levels were higher in SCA at rest but concentration was not affected by exercise. Marker for lipid peroxidation and antioxidative capacity were similar in SCA and AA and not affected by exercise. In conclusion, a single acute submaximal bout of exercise has no deleterious effects on RBC deformability or oxidative stress markers in SCA, and seems to modulate RBC-NOS signalling pathway.

Blood Rheology: Key Parameters, Impact on Blood Flow, Role in Sickle Cell Disease and Effects of Exercise

“…This delayed effect of exercise on RBC aggregate strength could be beneficial from a clinical point of view since this parameter is associated with risk of acute chest syndrome (Lamarre et al, 2012), and is increased during vaso-occlusive crises (Lapoumeroulie et al, 2019). Grau et al (2019) recently confirmed that a short progressive and submaximal cycling exercise had no deleterious effect on RBC deformability and showed that this kind of effort does not exacerbate hemolysis. Finally, Barbeau et al (2001) previously reported that the repetition of 30 min of moderate exercise for three consecutive days increased plasma NO concentrations in subjects with SCA.…”

“…This could be viewed as a positive effect since NO bioavailability is reduced in SCA (Kato et al, 2007). It is important to note that none of these studies reported any clinical complications immediately or several days after the exercise (Barbeau et al, 2001; Balayssac-Siransy et al, 2011; Waltz et al, 2012; Faes et al, 2014; Grau et al, 2019). Overall, the results of these studies suggest that mild-to-moderate intensity exercise is probably safe in SCA, but longer or high-intensity exercise should be avoided, or recommended only on a case-by-case basis (Martin et al, 2018).…”

Impact of A Six Week Training Program on Ventilatory Efficiency, Red Blood Cell Rheological Parameters and Red Blood Cell Nitric Oxide Signaling in Young Sickle Cell Anemia Patients: A Pilot Study

“…As previously described, specific performance parameters including watt power at VT 1, time to VT 1 and VO 2 at VT 1 were lower in SCA patients compared to healthy controls [18,19]. The ventilatory threshold is considered a reliable marker to assess cardiorespiratory fitness and is defined as the point during exercise where pulmonary ventilation begins to disproportionately increase with regard to the increase in oxygen uptake.…”

“…Although RBC-NOS activation decreased during training, the substrate for NO production-L-arginine-but also the levels of the resulting product-RBC nitrite/RSNO/Fe-NO-remained unaffected by the training program. RBC-NOS activation was shown to be higher in SCA patients compared to healthy controls [60] and a recent study on acute exercise effects on RBC-NOS activation in young patients with SCA also indicates a reduction in RBC-NOS activation by exercise [18]. Given the fact that RBC NO levels were comparable between T0 and T1, although RBC-NOS activation was reduced, suggests that NO bioavailability increased by other factors and that reduction in RBC-NOS activation represents an adjustment mechanism because of changed NO availability.…”

“…However, physicians are often reluctant to promote regular physical activity in SCA patients [14][15][16] The main reason is that the metabolic changes occurring during exercise may promote HbS polymerization, RBC sickling, oxidative stress and inflammation, and ultimately lead to vaso-occlusive crises. Nevertheless, several studies showed that a moderate exercise of 10-20 min duration is well tolerated by both adults and children with SCA and does not cause further alterations in RBC rheology, hemolysis or inflammation [17][18][19][20][21][22] In addition, recent works in transgenic sickle cell mice (SAD and Townes models) showed that regular physical activity decreased oxidative stress and inflammation, and improved blood rheology [23][24][25][26]. These data support the fact that SCA patients are able to exercise [27] and that regular moderate physical activity could be beneficial for their health.…”