Exercise Training Improves Skeletal-Muscle Microvasculature in Sickle-Cell Disease

By Will Boggs MD

December 20, 2019

NEW YORK (Reuters Health) - An eight-week endurance exercise program improves skeletal-muscle microvasculature in adults with sickle-cell disease (SCD), researchers from France report.

"If these results are confirmed in a larger cohort, endurance exercise training may, in the future, enter in the therapeutic strategy of SCD patients, as hydroxyurea and, more recently, other molecules (such as GBT440/voxelotor) have," Dr. Laurent A. Messonnier of Universite Savoie Mont Blanc, in Chambery, told Reuters Health by email.

Patients with SCD have lower capillary density and tortuosity, compared with healthy people, which drastically reduces oxygen delivery to muscle tissues. Regular physical activity has been shown to increase capillary network and tortuosity in healthy individuals and in some pathophysiological conditions.

Dr. Messonnier and colleagues in the EXDRE collaborative study group assessed skeletal-muscle microvascular in 40 adult homozygous SCD patients without severe chronic complications before and after an eight-week personalized moderate-intensity endurance exercise training program.

Each of 24 exercise sessions on a cycle ergometer consisted of five minutes' warm-up at 70% of the training workload, 30 minutes of endurance exercise at 100% of the training workload, five minutes' cool-down at 70% of the training workload, and five minutes of light stretching. Thirty-three (83%) patients (mean age, 34 years) completed the study.

At the end of training, mean capillary density had increased by 17.3% in the 15 patients who completed training, compared with 2.6% of the 17 non-training patients (P=0.003), the researchers report in Blood.

Training patients showed a 48.5% increase in the length of contact (LC) between a muscle fiber and the surrounding capillaries, compared to a 6.1% decrease among non-training patients (P<0.001).

The exchange surface between muscle fibers and surrounding capillaries increased by 42% for all fibers, by 48% for type-I muscle fibers, and by 35% for type-IIa muscle fibers (all significant changes), mainly due to the increase in LC.

In contrast, there were no significant differences between the groups in capillary tortuosity, capillary perimeter, capillary surface area, or capillary outer diameter.

Endurance training was also associated with improvements in power output and maximal oxygen uptake and decreases in blood lactate concentration and self-perceived exertion, as reported in a separate paper in the The Lancet Haematology (https://bit.ly/35k3PWQ).

The most surprising finding "was how patients declared their feeling about the endurance exercise training and how they expressed their benefits," Dr. Messonnier said. "When discussing with the trained patients, they reported their better well-being, they slept better, they were more concentrated at work, they were more able to play with their children, they could go back to the dance class."

"The present study demonstrates for the first time that a moderate-intensity endurance exercise training program over 8 weeks improves skeletal muscle microvasculature and partly reverses the microvascular deficits previously observed in SCD patients," the authors conclude. "The present study suggests that training-induced rearrangement of the microvascular network due to capillary growth may contribute to the concomitant improvement in the patients' physical capacity."

"One should not be afraid any more of exercise in SCD patients, insofar as this exercise is done appropriately, i.e., at low intensity (corresponding to fundamental endurance)," Dr. Messonnier said. "It is paramount to evaluate the exercise intensity and be sure that this exercise intensity is doable and safe for the patients. In that matter, particular attention must be paid to avoid blood lactate accumulation and the associated systemic acidosis, which is a triggering factor of complications."

Dr. Philippe Connes of Universite Claude Bernard Lyon, Faculte de Medecine, in Lyon, France, who has reported beneficial effects of moderate endurance exercise on oxidative stress in patients with SCD, told Reuters Health by email, "One of the most important findings of this study is that sickle-cell patients are able to perform regular endurance exercise at moderate and individualized intensity without any complications, and that training is able to promote profound muscle microvascular remodeling in this population."

"These findings are particularly important since most of physicians involved in the management of sickle-cell disease in the past were reluctant to promote physical activity in this population or were not fully able to indicate what kind of sports/physical activities sickle cell patients could perform without the risk of developing vaso-occlusive crises," he said.

"The long-term impact of such training on the clinical severity has not yet been investigated, and this require further studies," said Dr. Connes, who was not involved in the new work. "Moreover, while muscle microvasculature is affected by sickle-cell disease, no study has demonstrated the involvement of muscle microvasculature in the modulation of clinical severity in this disease."

"Further studies will also have to investigate the effects of such an intervention on classical biomarkers known to participate directly to the modulation of the clinical severity and involved in the occurrence of various acute and chronic complications," he said.

SOURCE: https://bit.ly/35ot1vr Blood, published November 19, 2019.