Skeletal muscle structural and energetic characteristics in subjects with sickle cell trait, α-thalassemia, or dual hemoglobinopathy

Abstract

Previous studies have shown that subjects with sickle cell trait (SCT), alpha-thalassemia (alpha-t), and the dual hemoglobinopathy (SCT/alpha-t) manifest subtle, albeit significant, differences during exercise. To better understand such differences, we assessed skeletal muscle histomorphological and energetic characteristics in 10 control HbAA subjects (C), 5 subjects with alpha-t (alpha-t), 6 SCT carriers (SCT) and 9 SCT carriers with alpha-t (SCT/alpha-t). Subjects underwent a muscle biopsy and also performed an incremental maximal exercise and a time to exhaustion test. There were no observable differences in daily energy expenditure, maximal power output (Pmax), or time to exhaustion at 110% Pmax (Tex) among the groups. Blood lactate concentrations measured at the end of the Tex, muscle fiber type distribution, and mean phosphofructokinase (PFK), lactate dehydrogenase (LDH), beta-hydroxyacyl-CoA-dehydrogenase (HAD), and citrate synthase (CS) activities were all similar among the four groups. However, SCT was associated with a lower cytochrome-c oxidase (COx) activity in type IIa fibers (P<0.05), and similar trends were observed in fiber types I and IIx. Trends toward lower creatine kinase (CK) activity (P=0.0702) and higher surface area of type IIx fibers were observed in SCT (P=0.0925). In summary, these findings support most of the previous observations in SCT, such as 1) similar maximal power output and associated maximal oxygen consumption (VO2max) values and 2) lower exercise performances during prolonged submaximal exercise. Furthermore, performances during short supramaximal exercise were not different in SCT. Finally, the dual hemoglobinopathy condition does not seem to affect muscle characteristics.

Effects of regular physical activity on skeletal muscle structural, energetic, and microvascular properties in carriers of sickle cell trait

“…Before giving their written consent, all subjects were fully informed of the objectives, possible discomforts, and potential benefits of the experiments. Part of the results has been published elsewhere for other purpose (55,56).…”

“…Although similar in terms of maximal aerobic performance (12), muscle fiber type distribution, and key enzyme activities of glycolytic or tricarboxylic acid cycle pathways (56), we (50) recently reported that compared with HbAA counterparts, carriers of SCT displayed particular muscle functional characteristics including 1) a trend toward a higher type IIx fiber surface area, 2) a significantly lower cytochrome c oxidase (COX) activity in type IIa fibers while similar trends were observed in type I and IIx fibers, and 3) a trend toward a lower creatine kinase (CK) activity, an enzyme also known for playing a key role in oxidative energy metabolism. However, the main changes observed in carriers of SCT consisted in their profound skeletal muscle microvasculature remodeling characterized by lower capillary density (CD) and tortuosity and a general enlargement of microvessels (55).…”

Reduced Physical Activity Patterns In Patients With Thalassemia Compared To Healthy Controls

“…Poor exercise performance and overall less activity have been observed in both adults and adolescent patients with sickle-cell disease 19,20 . Very few studies have examined physical activity in patients with Thal, and those that have focused primarily on the effect of iron overload on physical activity 2 .…”

ACSM and CHAMP Summit on Sickle Cell Trait

“…Similarly, when SCT carriers and controls repeated three incremental exercise bouts to exhaustion, interspaced with 10 min of recovery, no differences in any cardiorespiratory parameters were detected (60). However, Vincent et al (94) found lower cytochrome C oxidase activity in muscle fibers from SCT carriers relative to controls, which could limit oxidative energy metabolism and lower aerobic capacity in this population (23).…”

“…Importantly, SCT carriers have been shown to achieve superior performance during jumpand-reaeh tests compared with non-SCT controls (46). Whereas a potential underlying mechanism has yet to be identified, a 2010 study reported SCT carriers tended to have a higher cross-sectional surface area of Type IIx fibers-the muscle fibers recruited during brief, single explosive movements (94).…”