Remodeling of skeletal muscle microvasculature in sickle cell trait and α-thalassemia

2010 ◽  
Vol 298 (2) ◽  
pp. H375-H384 ◽  
Author(s):  
Lucile Vincent ◽  
Léonard Féasson ◽  
Samuel Oyono-Enguéllé ◽  
Viviane Banimbek ◽  
Christian Denis ◽  
...  

The influence of sickle cell trait and/or α-thalassemia on skeletal muscle microvascular network characteristics was assessed and compared with control subjects [hemoglobin (Hb) AA] in 30 Cameroonian residents [10 HbAA, 5 HbAA α-thalassemia (α-t), 6 HbAS, and 9 HbASα-t] matched for maximal work capacity and daily energy expenditure. Subjects performed an incremental exercise to exhaustion and underwent a muscle biopsy. Muscle fiber type and surface area were not different among groups. However, sickle cell trait (SCT) was associated with lower capillary density ( P < 0.05), lower capillary tortuosity ( P < 0.001), and enlarged microvessels ( P < 0.01). SCT carriers had reduced counts of microvessels <5-μm diameter, but a higher percentage of broader microvessels, i.e., diameter >10 μm ( P < 0.05). α-Thalassemia seemed to be characterized by a higher capillary tortuosity and unchanged capillary density and diameter. Thus, while SCT is a priori clinically benign, we demonstrate for the first time that significant remodeling of the microvasculature occurs in SCT carriers. These modifications may possibly reflect protective adaptations against hemorheological and microcirculatory dysfunction induced by the presence of HbS. The remodeling of the microvascular network occurs to a lesser extent in α-thalassemia. In α-thalassemic subjects, increased capillary tortuosity would promote oxygen supply to muscle tissues and might compensate for the lower Hb content often reported in those subjects.

2010 ◽  
Vol 109 (3) ◽  
pp. 728-734 ◽  
Author(s):  
Lucile Vincent ◽  
Léonard Féasson ◽  
Samuel Oyono-Enguéllé ◽  
Viviane Banimbek ◽  
Géraldine Monchanin ◽  
...  

Previous studies have shown that subjects with sickle cell trait (SCT), α-thalassemia (α-t), and the dual hemoglobinopathy (SCT/α-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 α-t (α-t), 6 SCT carriers (SCT) and 9 SCT carriers with α-t (SCT/α-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), β-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 (V̇o2max) 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.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
William S Jones ◽  
Brian D Duscha ◽  
Jennifer L Robbins ◽  
Amy J Aldrich ◽  
Judy G Regensteiner ◽  
...  

Background : Peripheral arterial disease (PAD) is a disorder characterized by impaired blood flow to the legs and maladaptive changes in the skeletal muscle. It is generally accepted that the skeletal muscle characteristics in patients with PAD include decreased capillary density and an altered percentage of oxidative myofibers. The scientific literature is conflicting, and it is based on studies with small sample size and older methodologies of skeletal muscle analysis. In addition, women are under-represented or not included at all in these studies. Hypothesis : We hypothesized that there would be differences in skeletal muscle composition in PAD patients compared to healthy controls. We further hypothesized that there would be gender differences in skeletal muscle composition in PAD patients versus healthy controls. Methods : Thirty -one patients with PAD and 31 age-, gender-, and activity-matched healthy controls underwent gastrocnemius muscle biopsy. Capillary density analysis and muscle fiber type determination were performed using immunohistochemistry techniques. Capillary density was measured as endothelial cells per muscle fiber and endothelial cells per area (mm 2 ). Results : There was no significant difference in capillary density in patients with PAD versus healthy controls when measured as endothelial cells per fiber (mean = 1.45 ± 0.43 vs. 1.50 ± 0.35, NS) or area (mean = 1.20 ± 0.29 vs. 1.29 ± 0.33, NS). There was also no difference in muscle fiber type composition between the groups. In the PAD cohort, capillary density was significantly lower in the men versus the women (mean = 1.36 ± 0.35 vs. 1.59 ± 0.51, p=0.005). In our cohort of women, there was no difference in capillary density in patients with PAD versus healthy controls (N=12). In men, capillary density was significantly lower in the PAD group versus healthy controls (N=19, mean = 1.09 ± 0.20 vs. 1.28 ± 0.34, p=0.043). Conclusions : Our data fail to confirm the belief that patients with PAD have a decreased capillary density and an altered percentage of oxidative myofibers. However, we did find that gender has an important impact on these characteristics. Further study of skeletal muscle composition in PAD may help to better understand the functional relevance of the gender differences.


1987 ◽  
Vol 80 (2) ◽  
pp. 415-424 ◽  
Author(s):  
S Lillioja ◽  
A A Young ◽  
C L Culter ◽  
J L Ivy ◽  
W G Abbott ◽  
...  

2004 ◽  
Vol 287 (5) ◽  
pp. C1342-C1348 ◽  
Author(s):  
Richard E. Waters ◽  
Svein Rotevatn ◽  
Ping Li ◽  
Brian H. Annex ◽  
Zhen Yan

Adult skeletal muscle undergoes adaptation in response to endurance exercise, including fast-to-slow fiber type transformation and enhanced angiogenesis. The purpose of this study was to determine the temporal and spatial changes in fiber type composition and capillary density in a mouse model of endurance training. Long-term voluntary running (4 wk) in C57BL/6 mice resulted in an approximately twofold increase in capillary density and capillary-to-fiber ratio in plantaris muscle as measured by indirect immunofluorescence with an antibody against the endothelial cell marker CD31 (466 ± 16 capillaries/mm2 and 0.95 ± 0.04 capillaries/fiber in sedentary control mice vs. 909 ± 55 capillaries/mm2 and 1.70 ± 0.04 capillaries/fiber in trained mice, respectively; P < 0.001). A significant increase in capillary-to-fiber ratio was present at day 7 with increased concentration of vascular endothelial growth factor (VEGF) in the muscle, before a significant increase in percentage of type IIa myofibers, suggesting that exercise-induced angiogenesis occurs first, followed by fiber type transformation. Further analysis with simultaneous staining of endothelial cells and isoforms of myosin heavy chains (MHCs) showed that the increase in capillary contact manifested transiently in type IIb + IId/x fibers at the time ( day 7) of significant increase in total capillary density. These findings suggest that endurance training induces angiogenesis in a subpopulation of type IIb + IId/x fibers before switching to type IIa fibers.


2014 ◽  
Vol 116 (8) ◽  
pp. 998-1005 ◽  
Author(s):  
Bart B. L. Groen ◽  
Henrike M. Hamer ◽  
Tim Snijders ◽  
Janneau van Kranenburg ◽  
Dionne Frijns ◽  
...  

Adequate muscle perfusion is required for the maintenance of skeletal muscle mass. Impairments in microvascular structure and/or function with aging and type 2 diabetes have been associated with the progressive loss of skeletal muscle mass. Our objective was to compare muscle fiber type specific capillary density and endothelial function between healthy young men, healthy older men, and age-matched type 2 diabetes patients. Fifteen healthy young men (24 ± 1 yr), 15 healthy older men (70 ± 2 yr), and 15 age-matched type 2 diabetes patients (70 ± 1 yr) were selected to participate in the present study. Whole body insulin sensitivity, muscle fiber type specific capillary density, sublingual microvascular density, and dimension of the erythrocyte-perfused boundary region were assessed to evaluate the impact of aging and/or type 2 diabetes on microvascular structure and function. Whole body insulin sensitivity was significantly lower at a more advanced age, with lowest values reported in the type 2 diabetic patients. In line, skeletal muscle capillary contacts were much lower in the older and older type 2 diabetic patients when compared with the young. Sidestream darkfield imaging showed a significantly greater thickness of the erythrocyte perfused boundary region in the type 2 diabetic patients compared with the young. Skeletal muscle capillary density is reduced with aging and type 2 diabetes and accompanied by impairments in endothelial glycocalyx function, which is indicative of compromised vascular function.


1990 ◽  
Vol 68 (5) ◽  
pp. 1896-1901 ◽  
Author(s):  
A. R. Coggan ◽  
R. J. Spina ◽  
M. A. Rogers ◽  
D. S. King ◽  
M. Brown ◽  
...  

Many older athletes are capable of endurance performances equal to those of young runners who have higher maximal O2 uptakes (VO2max). To determine whether this is a result of differences in skeletal muscle characteristics, gastrocnemius muscle biopsy samples were obtained from eight master athletes [aged 63 +/- 6 (SD) yr] and eight young (aged 26 +/- 3 yr) runners. The young runners were matched with the master athletes for 10-km running performance and for their volume, pace, and type of training. Despite similar 10-km run times, VO2max was 11% lower (P less than 0.05) in the master athletes. Fiber type distribution did not differ between groups, with both groups having 60% type I and very few type IIb fibers. Succinate dehydrogenase and beta-hydroxyacyl-CoA dehydrogenase activities, however, were 31 and 24% higher in the master athletes compared with the matched young runners, whereas lactate dehydrogenase activity was 46% lower (all P less than 0.05). The capillary-to-fiber ratio was also greater in the master athletes; however, capillary density was similar in the two groups, because of the master athletes' 34% larger (P less than 0.05) type I fibers. These differences in skeletal muscle characteristics may explain the master athletes' ability to perform as well as some young runners despite having a lower VO2max.


2008 ◽  
Vol 294 (5) ◽  
pp. E882-E888 ◽  
Author(s):  
John J. Dubé ◽  
Francesca Amati ◽  
Maja Stefanovic-Racic ◽  
Frederico G. S. Toledo ◽  
Sarah E. Sauers ◽  
...  

We previously reported an “athlete's paradox” in which endurance-trained athletes, who possess a high oxidative capacity and enhanced insulin sensitivity, also have higher intramyocellular lipid (IMCL) content. The purpose of this study was to determine whether moderate exercise training would increase IMCL, oxidative capacity of muscle, and insulin sensitivity in previously sedentary overweight to obese, insulin-resistant, older subjects. Twenty-five older (66.4 ± 0.8 yr) obese (BMI = 30.3 ± 0.7 kg/m2) men ( n = 9) and women ( n = 16) completed a 16-wk moderate but progressive exercise training program. Body weight and fat mass modestly but significantly ( P < 0.01) decreased. Insulin sensitivity, measured using the euglycemic hyperinsulinemic clamp, was increased (21%, P = 0.02), with modest improvements (7%, P = 0.04) in aerobic fitness (V̇o2peak). Histochemical analyses of IMCL (Oil Red O staining), oxidative capacity [succinate dehydrogenase activity (SDH)], glycogen content, capillary density, and fiber type were performed on skeletal muscle biopsies. Exercise training increased IMCL by 21%. In contrast, diacylglycerol and ceramide, measured by mass spectroscopy, were decreased ( n = 13; −29% and −24%, respectively, P < 0.05) with exercise training. SDH (19%), glycogen content (15%), capillary density (7%), and the percentage of type I slow oxidative fibers (from 50.8 to 55.7%), all P ≤ 0.05, were increased after exercise. In summary, these results extend the athlete's paradox by demonstrating that chronic exercise in overweight to obese older adults improves insulin sensitivity in conjunction with favorable alterations in lipid partitioning and an enhanced oxidative capacity within muscle. Therefore, several key deleterious effects of aging and/or obesity on the metabolic profile of skeletal muscle can be reversed with only moderate increases in physical activity.


1985 ◽  
Vol 59 (1) ◽  
pp. 190-197 ◽  
Author(s):  
D. Parsons ◽  
T. I. Musch ◽  
R. L. Moore ◽  
G. C. Haidet ◽  
G. A. Ordway

The purpose of this study was to determine whether 8–12 wk of endurance training produces biochemical and histochemical adaptations in skeletal muscle in foxhounds. Analyses were performed on samples removed from gastrocnemius, triceps, and semitendinosus muscles of foxhounds before and after a treadmill running program. Biochemical analysis showed that training did not alter the activities of phosphofructokinase, beta-hydroxyacyl-CoA dehydrogenase, succinate dehydrogenase, or total phosphorylase. Histochemical analysis of myofibrillar actomyosin ATPase demonstrated three distinct classes of type II fibers and one type I fiber in the semitendinosus and triceps muscles and two type II and two type I fibers in the gastrocnemius muscle. Fiber type distribution and oxidative and glycolytic potentials, as indicated by nicotinamide adenine dinucleotide tetrazolium reductase or alpha-glycerophosphate dehydrogenase staining intensity, were unaltered by training. Similarly, capillary density, capillary-to-fiber ratios, and capillary area-to-fiber area ratios did not change with training. Thus, unlike humans and other mammals (i.e., rat), these foxhounds did not manifest biochemical or histochemical adaptations in skeletal muscle as the result of endurance training. This is consistent with the results of the study in which endurance training produced a 27% increase in maximal cardiac output and a 4% increase in maximal arteriovenous O2 extraction in foxhounds.


1977 ◽  
Vol 137 (3) ◽  
pp. 281a-281
Author(s):  
P. E. Mickelson

2020 ◽  
pp. 1-2
Author(s):  
Michael Alperovich ◽  
Eric Park ◽  
Michael Alperovich ◽  
Omar Allam ◽  
Paul Abraham

Although sickle cell disease has long been viewed as a contraindication to free flap transfer, little data exist evaluating complications of microsurgical procedures in the sickle cell trait patient. Reported is the case of a 55-year-old woman with sickle cell trait who underwent a deep inferior epigastric perforator (DIEP) microvascular free flap following mastectomy. The flap developed signs of venous congestion on postoperative day two but was found to have patent arterial and venous anastomoses upon exploration in the operating room. On near-infrared indocyanine green angiography, poor vascular flow was noted despite patent anastomoses and strong cutaneous arterial Doppler signals. Intrinsic microvascular compromise or sickling remains a risk in the sickle cell trait population as it does for the sickle cell disease population. Just like in sickle cell disease patients, special care should be taken to optimize anticoagulation and minimize ischemia-induced sickling for patients with sickle cell trait undergoing microsurgery.


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