J Appl Physiol 103: 2140-2141, 2007;
doi:10.1152/japplphysiol.00338.2007b
8750-7587/07 $8.00
POINT-COUNTERPOINT
Rebuttal from Prof. Le Gallais
Biological differences with subjects with normal hemoglobin (Hb) and data on morbidity and mortality led Connes and colleagues to suggest that sickle cell trait (SCT) should be considered as symptomatic and not as a benign condition during physical activity.
Several reports have pointed out the occurrence of splenic infarction, heat illness, rhabdomyolysis, coagulopathy, and finally sudden death in subjects with SCT. Unfortunately, these reports are anecdotal and the causal effect of HbS has never been demonstrated (4). An epidemiological study has reported a substantially higher risk of exercise-related sudden death unexplained by prior disease in recruits with SCT during the 1977–1981 period (5). However, this result has been contradicted by a recent study, unbiased, and during a longer period, 1977–2001 (9). Lastly, high blood viscosity, impaired red blood cell deformability, increased coagulation activity, high plasma levels of adhesion molecules (7), and decrease in heart rate variability have been reported in subjects with SCT. Together, these risk factors may have resulted in well-documented cardiovascular deaths in subjects with SCT participating in these studies. This was not the case, nor was it in the above epidemiological studies, nor in trained athletes throughout the United States during 10 years (6). One would thus suggest that the risk factors hypothesized in SCT may have been compensated by some advantages, such as an increase in plasma HDL cholesterol levels (8) and/or unidentified markers that may have protected subjects with SCT from cardiac events.
Sudden deaths during exercise remain rare in SCT. It thus appears unjustified to consider all subjects with SCT at risk for exercise-induced sudden death and SCT as a disease state. Since 1950, all data on SCT have failed to ascertain a causal relationship between HbS and sudden death. This means that the single HbS mutation may be asymptomatic and benign and that sudden deaths in SCT may be due not to HbS mutation but to another Hb-dependent or -independent associated mutation or coexistent disease, possibly diabetes (1). This hypothesis now can be tested using new technologies in genomics and proteomics (10). DNA chips may be used to analyze polymorphisms and mutations that may underlie SCT and SCT individual variations (2). The polymorphism of cardiovascular enzymes (3) and the gene expression in skeletal muscle and white blood cells may provide new insights into the mechanisms of possible rhabdomyolysis, heat shock, and sudden death reported in SCT during exercise and, thus, add to the debate.
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Copyright © 2007 by the American Physiological Society.
