Calf Skeletal Muscle Research Articles

Peripheral artery disease, calf skeletal muscle mitochondrial DNA copy number, and functional performance.

In people without lower extremity peripheral artery disease (PAD), mitochondrial DNA copy number declines with aging, and this decline is associated with declines in mitochondrial activity and functional performance. However, whether lower extremity ischemia is associated with lower mitochondrial DNA copy number and whether mitochondrial DNA copy number is associated with the degree of functional impairment in people with PAD is unknown. In people with and without PAD, age 65 years and older, we studied associations of the ankle-brachial index (ABI) with mitochondrial DNA copy number and associations of mitochondrial DNA copy number with functional impairment. Calf muscle biopsies were obtained from 34 participants with PAD (mean age: 73.5 years (SD 6.4), mean ABI: 0.67 (SD 0.15), mean 6-minute walk distance: 1191 feet (SD 223)) and 10 controls without PAD (mean age: 73.1 years (SD 4.7), mean ABI: 1.14 (SD 0.07), mean 6-minute walk distance: 1387 feet (SD 488)). Adjusting for age and sex, lower ABI values were associated with higher mitochondrial DNA copy number, measured in relative copy number (ABI<0.60: 914, ABI 0.60-0.90: 731, ABI 0.90-1.50: 593; p trend=0.016). The association of mitochondrial DNA copy number with the 6-minute walk distance and 4-meter walking velocity differed significantly between participants with versus without PAD ( p-value for interaction=0.001 and p=0.015, respectively). The correlation coefficient between mitochondrial DNA copy number and the 6-minute walk distance was 0.653 ( p=0.056) among people without PAD and -0.254 ( p=0.154) among people with PAD and ABI < 0.90. In conclusion, lower ABI values are associated with increased mitochondrial DNA copy number. Associations of mitochondrial DNA copy number with the 6-minute walk distance and 4-meter walking velocity significantly differed between people with versus without PAD, with stronger positive associations observed in people without PAD than in people with PAD. The cross-sectional and exploratory nature of the analyses precludes conclusions regarding causal inferences. ClinicalTrials.gov Identifier: NCT02246660.

Body Composition Remodeling and Incident Mobility Limitations in African Ancestry Men.

Mobility limitations are common, with higher prevalence in African Americans compared with whites, and are associated with disability, institutionalization, and death. Aging is associated with losses of lean mass and a shift to central adiposity, which are more pronounced in African Americans. We aimed to examine the association of body composition remodeling with incident mobility limitations in older men of African ancestry. Seven-year changes in body composition were measured using peripheral quantitative computed tomography (pQCT) of the calf and whole-body dual x-ray absorptiometry (DXA) in 505 African ancestry men aged ≥60 years and free of self-reported mobility limitations at baseline. Self-reported incident mobility limitations were assessed at 7-year follow-up. Odds of developing mobility limitations associated with baseline and change in body composition were quantified using separate logistic regression models. Seventy-five men (14.9%) developed incident mobility limitations over 6.2 ± 0.6 years. Baseline body composition was not associated with incident mobility limitations. After adjustment for covariates, gaining total and intermuscular fat were associated with incident mobility limitations (odds ratio [OR]: 1.60; 95% confidence interval [CI]: 1.21-2.13; OR: 1.51; 95% CI: 1.18-1.94). Changes in DXA lean mass were not related to mobility limitations; however, maintaining pQCT calf muscle area was protective against mobility limitations (OR: 0.65; 95% CI: 0.48-0.87). Increases in body fat, and particularly intermuscular fat, and decreases in calf skeletal muscle area were associated with a higher risk of developing mobility limitations. Our findings emphasize the importance of body composition remodeling in the development of mobility limitations among African ancestry men.

IDH2 Deficiency Disrupts Energy Homeostasis and Skeletal Muscle Development by Upregulating UCP1 Expression in Mice

Isocitrate dehydrogenase 2 (IDH2) is a mitochondrial specific enzyme that catalyses the oxidative decarboxylation of isocitrate into α‐ketoglutarate with concurrent reduction of NADP+ to NADPH. We previous reported that IDH2 knock‐out (KO) increased obesity resistance via UCP1‐mediated enhanced energy expenditure in adipose and liver tissues. Since skeletal muscle is the most mitochondria abundant tissue and is a major site for energy expenditure, we here examined the effects of IDH2 KO on skeletal muscle energy homeostasis and its growth. Calf skeletal muscle samples (i.e., mixed part of soleus, gastrocnemius, and plantaris muscles) were harvested from 11‐week‐old male IDH2 KO (n=4) and wild type (WT; C57BL/6; n=4) mice, and a ratio of skeletal muscle weight to body weight was measured. Subsequently, marker of mitochondrial DNA to nucleic DNA ratio was measured by PCR analysis. In addition, mRNA expression levels involved in fatty acid β‐oxidation (CPT1 and FAT), adipogenesis (PPARγ, C/EBPα, C/EBPβ, aP2, and ZFP423), thermogenesis (UCP1, BMP7, and PRDM16), myogenesis (MRF4 and MyoD), and mitochondria biogenesis (PGC‐1α, TFAM, ERRα, and MFN2) were compared. Interestingly, a ratio of skeletal muscle weight to body weight was significantly lower in IDH2 KO mice compared to that of WT mice (P=0.0004). Further, mitochondrial content was relatively lower in skeletal muscle of IDH2 KO mice than the WT mice albeit it was not statistically significant (P=0.09). In consistent with the muscle mass, there were trends of decrease in the expressions of myogenesis (MyoD, P=0.07) as well as mitochondrial biogenesis genes in IDH2 KO mice (PGC‐1α, P&lt;0.05; TFAM, P=0.07). Last, the expression level of UCP1, a hallmark of thermogenesis, was remarkably increased in skeletal muscle whereas adipogenesis pathway (PPARγ, P&lt;0.005; C/EBPβ, P=0.06; ZFP423, P&lt;0.05) was down‐regulated in skeletal muscle of IDH2 KO mice. However, UCP1 seems not directly regulated by the expression of BMP7 or PRDM16 as the expression of BMP7 and PRDM16 was also down‐regulated in IDH2 KO mice. Taken together, our study suggests that IDH2 deficiency may upregulate UCP1‐mediated thermogenesis possibly to adopt limited NADPH supply. In turn, the thermogenesis‐induced energy imbalance may cause suppression of myogenesis, mitochondria biogenesis, adipogenic signaling pathway, and skeletal muscle growth. Our study will provide scientific background to further studies on the mechanistic functions of IDH2 in skeletal muscle development.Support or Funding InformationThis work was supported by the University of Arkansas, VPRED Start‐up fund (KJK, and PJH). Support has been provided in part by the Arkansas Biosciences Institute, a partnership of scientists from Arkansas Children's Hospital, Arkansas State University, the University of Arkansas‐Division of Agriculture, the University of Arkansas, Fayetteville, and the University of Arkansas for Medical Sciences. The Arkansas Biosciences Institute is the major research component of the Arkansas Tobacco Settlement Proceeds Act of 2000 (JKK, JHP, KEB, and BCK).This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Exercise versus vasodilator stress limb perfusion imaging for the assessment of peripheral artery disease.

Our aim was to determine whether pharmacologic vasodilation is an alternative to exercise stress during limb perfusion imaging for peripheral artery disease (PAD). Quantitative contrast-enhanced ultrasound (CEU) perfusion imaging of the bilateral anterior thigh and calf was performed in nine control subjects and nine patients with moderate to severe PAD at rest and during vasodilator stress with dipyridamole. For those who were able, CEU of the calf was then performed during modest plantar flexion exercise (20watts). CEU time-intensity data were analyzed to quantify microvascular blood flow (MBF) and its parametric components of microvascular blood volume and flux rate. Thigh and calf skeletal muscle MBF at rest was similar between control and PAD patients. During dipyridamole, MBF increased minimally (<twofold) for all groups and there were only nonsignificant trends for a reduction in calf MBF in those with PAD (13.5±6.9, 10.0±4.7, and 8.2±6.1IU/s, for controls, moderate, and severe PAD, respectively; P=.11). In contrast, MBF during modest planar flexion exercise increased markedly in controls but not PAD patients (87.9±79.9 vs 15.2±12.9 IU/s, P<.05). In three moderate PAD patients restudied after undergoing surgical revascularization, MBF during dipyridamole did not change, whereas exercise MBF increased by an average of sevenfold. Resting limb skeletal muscle MBF in patients with moderate to severe PAD is similar to that in normal subjects. However, differences in hyperemic flow during contractile exercise but not during dipyridamole allow evaluation of the degree of flow impairment from PAD and the degree of improvement with revascularization.

Abstract P363: Ectopic Adiposity is Associated With Abdominal Aorto-Illiac but Not Coronary Artery Calcification Independent of Total Body Adiposity in African Ancestry Men

Objective: While ectopic adiposity is considered a risk factor for many chronic diseases, including cardiovascular disease, the extent to which this association is independent of total adiposity is yet to be established. Vascular calcification, which is associated with greater adiposity, is a subclinical marker of cardiovascular disease that may have varying etiology and clinical implications in different vascular beds. Therefore, our objective was to assess the potential independent associations of total, regional and ectopic adiposity measures with abdominal aorto-iliac calcification (AAC) and coronary artery calcification (CAC). Methods: Detailed health history, clinical exam, dual x-ray absorptiometry and computed tomography (CT) scans were obtained in 798 African ancestry men aged ≥40 years (mean(SD): 62.0(8.6)years) recruited without regard to health status from the Tobago Heart Health Study. Vascular calcification was measured by CT in the abdomen (AAC) and chest (CAC). Calcification was scored using the Agatston method and a score ≥10 was considered to be a prevalent calcification. Severity of calcification was modeled using continuous Agatston score in those with any calcification. Multivariable logistic and linear regression models were used to assess the cross-sectional association of adiposity measures with vascular calcification prevalence and severity. All models were adjusted for age, hypertension, diabetes, dyslipidemia, smoking, alcohol intake and sedentary lifestyle. In addition, models of ectopic adiposity (abdominal visceral adipose tissue, liver attenuation and calf skeletal muscle fat) were adjusted for total body fat. Results: AAC was present in 63% and CAC was present in 29% of men. After adjustment for traditional cardiovascular risk factors, 1SD greater total, trunk, or abdominal subcutaneous adiposity was associated with 1.3-1.5-fold increased odds of AAC (all p&lt;0.05). After additional adjustment for total body fat, 1SD lower liver attenuation (indicative of greater liver adiposity) or 1SD greater skeletal muscle fat were each associated with a 1.2-1.3-fold increased odds of AAC. In fully adjusted models, only greater BMI or waist circumference was associated with increased odds of CAC (OR 1.2, p&lt;0.05 for both). In fully adjusted linear models of calcification severity, no significant association was observed between any adiposity measure and AAC or CAC. Conclusions: Independent of total adiposity, measures of ectopic adiposity were associated with greater AAC, but not CAC, prevalence in African ancestry men. These results highlight potential differences in the adiposity-vascular disease relationship that may vary by ectopic fat depot and vascular bed location. Future vascular disease research should explore potential underlying biologic mechanisms for these findings.

Abstract MP048: Ectopic Muscle and Liver Adiposity are Independently Associated with Type 2 Diabetes in African Ancestry Men

Although obesity is a major driver of type 2 diabetes (T2D), many obese individuals do not develop T2D. Indeed, fat around and within non-adipose tissue organs (i.e., ectopic fat) is emerging as a strong risk factor for diabetes. The potential differential contribution of ectopic fat depots throughout the body on T2D risk is unclear because studies have mainly focused on visceral and/or liver fat. No study, to our knowledge, has addressed the potential independent association of visceral, liver, and skeletal muscle adiposity with T2D. Such studies are particularly needed among African ancestry populations, as generalized obesity and other risk factors do not appear to explain the high T2D burden in this population segment. To address this knowledge gap, we measured total body fat by DXA, and visceral, liver, and calf skeletal muscle adiposity by computed tomography in 490 Afro-Caribbean men, aged 50-91 years (mean age=64 years, mean BMI=27.5 kg/m 2 ). The prevalence of T2D in this population was 22.3%. We employed multiple logistic regression using total body fat percent and ectopic fat depots as predictors (Table). We found that each 7.9 HU decrease in liver attenuation (indicative of greater liver adiposity) was associated with a 33% increased odds of T2D (p=0.011). Similarly, each 4.2 mg/cm 3 decrease in muscle attenuation (indicative of greater intra-muscular adiposity) was associated with a 31% increased odds of T2D (p=0.04). These associations were independent of total and visceral adiposity. Our results support the “ectopic fat syndrome” theory, as opposed to the “portal theory”, in the pathogenesis of diabetes among African ancestry men. Longitudinal studies are needed to clarify the exact role of specific ectopic fat depots in T2D, particularly in high-risk African ancestry populations.

Rest-Stress Limb Perfusion Imaging in Humans with Contrast Ultrasound Using Intermediate-Power Imaging and Microbubbles Resistant to Inertial Cavitation

Contrast-enhanced ultrasound (CEU) limb perfusion imaging is a promising approach for evaluating peripheral artery disease (PAD). However, low signal enhancement in skeletal muscle has necessitated high-power intermittent imaging algorithms, which are not clinically feasible. We hypothesized that CEU using a combination of intermediate power and a contrast agent resistant to inertial cavitation would allow real-time limb stress perfusion imaging. In normal volunteers, CEU of the calf skeletal muscle was performed on separate days with Sonazoid,Optison, or Definity. Progressive reduction in the ultrasound pulsing interval was used to assess the balance between signal enhancement and agent destruction at escalating mechanical indices (MI, 0.1-0.4). Real-time perfusion imaging at MI 0.1-0.4 using postdestructive replenishment kinetics was performedat rest and during 25W plantar flexion contractile exercise. For Optison, limb perfusion imaging was unreliable at rest due to very low signal enhancement generated at all MIs and was possible during exercise-induced hyperemia only at MI 0.1 due to agent destruction at higher MIs. For Definity, signal intensity progressively increased with MI but was offset by microbubble destruction, which resulted in modest signal enhancement during CEU perfusion imaging and distortion of replenishment curves at MI≥0.2. For Sonazoid, there strong signal enhancement at MI≥0.2, with little destruction detected only at MI 0.4. Accordingly, high signal intensity and nondistorted perfusion imaging was possible at MI 0.2-0.3 and detected an 8.0- ± 5.7-fold flow reserve. Rest-stress limb perfusion imaging in humans with real-time CEU, which requires only seconds to perform, is possible using microbubbles with viscoelastic properties that produce strong nonlinear signal generation without destruction at intermediate acoustic pressures.

Measurement of skeletal muscle perfusion dynamics with pseudo-continuous arterial spin labeling (pCASL): Assessment of relative labeling efficiency at rest and during hyperemia, and comparison to pulsed arterial spin labeling (PASL).

To compare calf skeletal muscle perfusion measured with pulsed arterial spin labeling (PASL) and pseudo-continuous arterial spin labeling (pCASL) methods, and to assess the variability of pCASL labeling efficiency in the popliteal artery throughout an ischemia-reperfusion paradigm. At 3T, relative pCASL labeling efficiency was experimentally assessed in five subjects by measuring the signal intensity of blood in the popliteal artery just distal to the labeling plane immediately following pCASL labeling or control preparation pulses, or without any preparation pulses throughout separate ischemia-reperfusion paradigms. The relative label and control efficiencies were determined during baseline, hyperemia, and recovery. In a separate cohort of 10 subjects, pCASL and PASL sequences were used to measure reactive hyperemia perfusion dynamics. Calculated pCASL labeling and control efficiencies did not differ significantly between baseline and hyperemia or between hyperemia and recovery periods. Relative to the average baseline, pCASL label efficiency was 2 ± 9% lower during hyperemia. Perfusion dynamics measured with pCASL and PASL did not differ significantly (P > 0.05). Average leg muscle peak perfusion was 47 ± 20 mL/min/100g or 50 ± 12 mL/min/100g, and time to peak perfusion was 25 ± 3 seconds and 25 ± 7 seconds from pCASL and PASL data, respectively. Differences of further metrics parameterizing the perfusion time course were not significant between pCASL and PASL measurements (P > 0.05). No change in pCASL labeling efficiency was detected despite the almost 10-fold increase in average blood flow velocity in the popliteal artery. pCASL and PASL provide precise and consistent measurement of skeletal muscle reactive hyperemia perfusion dynamics. J. MAGN. RESON. IMAGING 2016;44:929-939.

Dynamic Quantitative Contrast-enhanced Ultrasound for Assessment of Cilostazol Induced Pro-angiogenic Therapeutic Effects on Skeletal Muscle Microcirculation in Peripheral Arterial Disease

Purpose: To assess the effect of cilostazol on muscular microperfusion in patients with peripheral artery occlusive disease (PAOD) using dynamic quantitative contrast-enhanced ultrasound (CEUS). Materials and Methods: 20 patients with PAOD, Rutherford classification grade I, category III were evaluated performing CEUS with the arterial occlusion paradigm, ankle-brachial-index (ABI) and treadmill walking distance test before and after oral treatment with cilostazol for three months. Microperfusion of the calf skeletal muscle was assessed using quantitative CEUS parameters which were extracted from time signal-intensity curves (TIC). Results: 10 patients had to be taken off medication secondary to side effects. Maximum CEUS signal enhancement prior to therapy was 104 ± 69 ~mL compared to 114±68 ~mL post treatment (P=0.26). tmax was 34 ± 20 s before and 36 ± 23 s post treatment (P=0.51). Maximum slope of the TIC (m2) prior to therapy was 6.06 ± 5.55 ~mL/s and revealed to be 5.12 ± 3.30 ~mL/s post treatment (P=0.62). Area under the curve after the occlusion (AUCpost) was 3975.38 ± 2856.52 ~mL/s prior to cilostazol therapy compared to 4210.98 ± 2816.33 ~mL/s after therapy (P=0.39). The values for ABI and treadmill walking distance test did not differ significantly differ, either. Conclusion: In patients with PAOD, medical therapy with cilostazol seems not to be associated with significant improvement of muscular microperfusion as assessed by dynamic quantitative CEUS. This study demonstrates the feasibility of the CEUS technique to evaluate response to pro-angiogenic drug treatment and confirmation of results in a larger population is warranted.

New continuous-flow total artificial heart and vascular permeability

BackgroundWe tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability. MethodsTen calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10–25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho–VE-cadherin, and CD31 were analyzed by immunohistochemistry. ResultsThere were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho–VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance. ConclusionsThere was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability.

Lower extremity manifestations of peripheral artery disease: the pathophysiologic and functional implications of leg ischemia.

Lower extremity peripheral artery disease (PAD) is frequently underdiagnosed, in part because of the wide variety of leg symptoms manifested by patients with PAD and in part because of the high prevalence of asymptomatic PAD. In primary care medical practices, 30% to 60% of patients with PAD report no exertional leg symptoms and ≈45% to 50% report exertional leg symptoms that are not consistent with classic intermittent claudication. The prevalence and extent of functional impairment and functional decline in PAD may also be underappreciated. Functional impairment and functional decline are common in PAD, even among those who are asymptomatic. Lower extremity ischemia is also associated with pathophysiologic changes in calf skeletal muscle, including smaller calf muscle area, increased calf muscle fat content, impaired leg strength, and impaired metabolic function. People with severe PAD have poorer peroneal nerve conduction velocity compared with people with mild PAD or no PAD. The degree of ischemia-related pathophysiologic changes in lower extremity muscles and peripheral nerves of people with PAD are associated with the degree of functional impairment. New interventions are needed to improve functional performance and prevent mobility loss in the large number of patients with PAD, including in those who are asymptomatic or who have exertional leg symptoms other than claudication.

Abstract P261: Skeletal Muscle Density: A Novel Risk Factor for Hypertension in Aging African Ancestry Men

Background: Intramuscular fat is greater in African compared with European ancestry men and is now recognized as a major risk factor for cardio-metabolic diseases, independent of general obesity. However, prospective studies examining health consequences of this important ectopic fat depot are lacking, particularly in high-risk African ancestry populations. Therefore, we sought to determine if change in skeletal muscle density, a measure of intramuscular fat, predicts subsequent development of hypertension in African ancestry men. Methods: We measured at two time points calf skeletal muscle density (MD; mg/cm 3 ) using computed tomography in 1504 Afro-Caribbean men aged 40-92 years (mean, 59 years), who were recruited without regard to their health status. Hypertension was defined as having a systolic blood pressure of 140 mm Hg or greater, having a diastolic blood pressure of 90 mm Hg or greater, or taking antihypertensive medications. Logistic regression was used to estimate the association between change in MD and incident hypertension adjusting for follow-up time, baseline age and muscle density, and covariates known to be associated with hypertension and intramuscular fat (baseline body weight, body weight change, waist circumference, waist circumference change, current smoking, alcohol intake, physical activity, and baseline type 2 diabetes status). Results were expressed as the odds (95% CI) of hypertension per one standard deviation decrease in muscle density. Results: During the 6.2 years follow-up (range of follow-up years: 4.9-9.1 years), we observed a significant annualized percent decrease in muscle density (-0.43 %/yr; P&lt;0.0001). Among the 777 men who were normotensive at the baseline visit, 224 (28.8%) developed hypertension during follow-up. Decreased MD during follow-up was associated with an increased risk of hypertension (odds ratio [95% CI] per SD decrease in MD: 1.31 [1.03, 1.67]). This association remained significant after additional adjustment for baseline waist circumference and change in waist circumference in a separate model (odds ratio [95% CI] per SD decrease in MD: 1.27 [1.02, 1.59]). Conclusions: Our novel findings show that ectopic intramuscular fat increases with advancing age, and support a causal role of intramuscular fat in hypertension risk among middle-aged and elderly African ancestry men. Additional studies are needed to elucidate the mechanisms behind this association, and to confirm our findings in other populations.

Quantification of residual limb skeletal muscle perfusion with contrast-enhanced ultrasound during application of a focal junctional tourniquet

Focal junctional tourniquets (JTs) have been developed to control hemorrhage from proximal limb injuries. These devices may permit greater collateral perfusion than circumferential tourniquets. We hypothesized that JTs eliminate large-vessel pulse pressure yet allow a small amount of residual limb perfusion that could be useful for maintaining tissue viability. Ten healthy control subjects were studied. Transthoracic echocardiography, Doppler ultrasound of the femoral artery (FA) and posterior tibial artery, and contrast-enhanced ultrasound (CEU) perfusion imaging of the anterior thigh extensor and calf plantar flexor muscles were performed at baseline and during application of a JT over the common FA. Intramuscular arterial pulsatility index was also measured from CEU intensity variation during the cardiac cycle. FA flow was eliminated by JTs in all subjects; posterior tibial flow was eliminated in all but one. Perfusion measured in the thigh and calf muscles was similar at baseline (0.33 ± 0.29 vs 0.29 ± 0.22 mL/min/g). Application of the JT resulted in a reduction of perfusion (P < .05) that was similar for the thigh and calf (0.08 ± 0.07 and 0.10 ± 0.03 mL/min/g). On CEU, microvascular flux rate was reduced by ≈55%, and functional microvascular blood volume was reduced by ≈35%. Arterial pulsatility index was reduced by ≈90% in the calf. JT inflation did not alter left ventricle dimensions, fractional shortening, cardiac output, or arterial elastance as a measure of total systolic load. Application of a JT eliminates conduit arterial pulse and markedly reduces intramuscular pulse pressure, but thigh and calf skeletal muscle perfusion is maintained at 25% to 35% of basal levels. These data suggest that JTs that are used to control limb hemorrhage allow residual tissue perfusion even when pulse pressure is absent.

Skeletal muscle adiposity is associated with serum lipid and lipoprotein levels in Afro‐Caribbean men

ObjectiveCompared to other ethnic groups, African ancestry individuals have lower triglycerides and higher HDL-C levels, although the mechanisms for these differences remain unclear. Our objective was to evaluate a comprehensive array of factors potentially related to fasting serum lipid and lipoprotein levels in African ancestry men.Design and Methods1821 men underwent DXA measures of total body fat and quantitative computed tomography assessments of calf skeletal muscle adiposity (subcutaneous and intermuscular adipose tissue (AT), and muscle density as a measure of intra-muscular AT).ResultsMultivariable linear regression analysis identified age (−), total body fat (+), subcutaneous AT (−), fasting glucose (+), fasting insulin (+), diastolic blood pressure (+) and non-African ancestry (+) as independent correlates of triglycerides (all P<0.05). Total body fat (+), intra-muscular AT (−) and diastolic blood pressure (+) were independent correlates of LDL-C (all P<0.001). Age (+), waist circumference (−), fasting insulin (−), physical activity (+) and alcohol intake (+) were independent correlates of HDL-C (all P<0.05).ConclusionsOur study illuminates a novel relationship between skeletal muscle adiposity and serum lipid and lipoprotein levels in African ancestry men, independent of total and central adiposity. Our finding also suggests that in African ancestry populations, genetic factors are likely a significant determinant of triglycerides levels.

Bioimpedance spectroscopy as a measure of physical functioning in nursing home residents.

Intracellular resistance (Ri), a raw measure of bioimpedance spectroscopy (BIS), has been suggested for assessment of muscle health. The associations of repeated BIS measurements with functioning and nutritional status were investigated in nursing home residents suffering from poor health and disabilities. A total of 106 nursing home residents (age 83±8 yrs, 75% women) were recruited. Whole body and calf BIS measures (lean body mass, resistance at 50 kHz, and Ri), height and calf electrode distance (D) were used to calculate six muscle indices. Hand grip and knee extension strengths were measured and data on Activities of Daily Living (ADL), mobility score, and Mini Nutritional Assessment (MNA) collected. Repeated measurements were performed at 3 (BIS) and 6 months (BIS, muscle strength, ADL, mobility, and MNA). All bioimpedance muscle indices were lower in women than men and associated with MNA. However, the calf skeletal muscle index (SMI=D2/Ri) associated with muscle strength measurements at baseline and consistently with mobility and ADL also at 6-month re-examination. When compared to the highest tertile of SMI percent change (cut point +0.7%), the patients in the lowest tertile (cut point - 11.6%) had a 5.3-fold risk (p=0.004) for mobility decline within the 6-month follow-up. This risk association also remained significant after controlling for age, gender, baseline mobility, and percent change in body weight. Calf intracellular resistance related to electrode distance is associated with the activities of daily living reflecting mobility in typical nursing home residents and a decrease in this index indicates a markedly increased risk for mobility decline.

Lower Extremity Nerve Function, Calf Skeletal Muscle Characteristics, and Functional Performance in Peripheral Arterial Disease

To determine whether poor lower extremity nerve function is associated with less-favorable calf muscle characteristics and greater functional impairment in people with and without peripheral arterial disease (PAD). Cross-sectional. Three Chicago-area medical centers. Four hundred thirteen participants with PAD (ankle-brachial index (ABI)<0.90) and 255 without. Electrodiagnostic testing of the peroneal nerve was performed. Calf muscle cross-sectional area and percentage fat were measured using computed tomography at 66.7% of the distance between the distal and proximal tibia. Six-minute walk performance was measured. Adjusting for age, sex, race, ABI, leg symptoms, smoking, physical activity, comorbidities, and other covariates, lower peroneal nerve conduction velocity (NCV) was associated with lower calf muscle area (first quartile 4,770.3mm(2) , fourth quartile 5,571mm(2) , P<.001) and poorer 6-minute walk distance (first quartile 989.2feet, fourth quartile 1,210.8feet, P<.001) in participants without diabetes mellitus with PAD. Lower peroneal NCV was associated with lower calf muscle area (first quartile 5,166.0mm(2) , fourth quartile 6,003.8mm(2) , P=.01) and poorer 6-minute walk distance (first quartile 866.4feet, fourth quartile 1,082.5feet, P=.01) in participants with diabetes mellitus and PAD as well. In participants without PAD, lower peroneal NCV was not associated with lower calf muscle area but was associated with poorer 6-minute walk distance only in participants without diabetes mellitus (first quartile 1,317.0feet, fourth quartile 1,570.4feet, P-trend<.001). Lower peroneal nerve function is associated with smaller calf muscle area and greater functional impairment in individuals with PAD. Future study is needed to determine whether improving peroneal NCV prevents loss of calf muscle and functional decline in people with PAD.

Local heating, but not indirect whole body heating, increases human skeletal muscle blood flow

For decades it was believed that direct and indirect heating (the latter of which elevates blood and core temperatures without directly heating the area being evaluated) increases skin but not skeletal muscle blood flow. Recent results, however, suggest that passive heating of the leg may increase muscle blood flow. Using the technique of positron-emission tomography, the present study tested the hypothesis that both direct and indirect heating increases muscle blood flow. Calf muscle and skin blood flows were evaluated from eight subjects during normothermic baseline, during local heating of the right calf [only the right calf was exposed to the heating source (water-perfused suit)], and during indirect whole body heat stress in which the left calf was not exposed to the heating source. Local heating increased intramuscular temperature of the right calf from 33.4 ± 1.0°C to 37.4 ± 0.8°C, without changing intestinal temperature. This stimulus increased muscle blood flow from 1.4 ± 0.5 to 2.3 ± 1.2 ml·100 g⁻¹·min⁻¹ (P < 0.05), whereas skin blood flow under the heating source increased from 0.7 ± 0.3 to 5.5 ± 1.5 ml·100 g⁻¹·min⁻¹ (P < 0.01). While whole body heat stress increased intestinal temperature by ∼1°C, muscle blood flow in the calf that was not directly exposed to the water-perfused suit (i.e., indirect heating) did not increase during the whole body heat stress (normothermia: 1.6 ± 0.5 ml·100 g⁻¹·min⁻¹; heat stress: 1.7 ± 0.3 ml·100 g⁻¹·min⁻¹; P = 0.87). Whole body heating, however, reflexively increased calf skin blood flow (to 4.0 ± 1.5 ml·100 g⁻¹·min⁻¹) in the area not exposed to the water-perfused suit. These data show that local, but not indirect, heating increases calf skeletal muscle blood flow in humans. These results have important implications toward the reconsideration of previously accepted blood flow distribution during whole body heat stress.

Bioactive androgens and glucuronidated androgen metabolites are associated with subcutaneous and ectopic skeletal muscle adiposity among older black men

Aging is associated with declining serum levels of androgenic hormones and with increased skeletal muscle fat infiltration, an emerging risk factor for type 2 diabetes mellitus (T2DM). Androgens regulate fat mass and glucose homeostasis, but the effect of androgenic hormones on skeletal muscle fat infiltration is largely unknown. Thus, the aim of the current study was to examine the association of serum androgens and their precursors and metabolites with skeletal muscle fat infiltration and T2DM in a black male population group at high risk of T2DM. Serum androgens, estrogens, and androgen precursors and metabolites were measured using mass spectrometry; and calf skeletal muscle fat distribution (subcutaneous and intermuscular fat; skeletal muscle density) was measured using quantitative computed tomography in 472 Afro-Caribbean men 65 years and older. Bioactive androgens, testosterone, free testosterone, and dihydrotestosterone were associated with less skeletal muscle fat infiltration (r = −0.14 to −0.18, P < .05) and increased skeletal muscle density (r = 0.10 to 0.14, P < .05), independent of total adiposity. In addition, glucuronidated androgen metabolites were associated with less subcutaneous fat (r = −0.11 to −0.15, P < .05). Multivariate logistic regression analysis identified an increased level of 3α-diol-3 glucuronide (odds ratio = 1.38, P < .01) and a decreased level of dihydrotestosterone (odds ratio = 0.66, P < .01) to be significantly associated with T2DM. Our findings suggest that, in elderly black men, independent of total adiposity, bioactive androgens and glucuronidated androgen metabolites may play previously unrecognized role in skeletal muscle fat distribution. Longitudinal studies are needed to further evaluate the relationship between androgens and androgen metabolites with changes in skeletal muscle fat distribution with aging and the incidence of T2DM.

Associations of calf skeletal muscle characteristics and peripheral nerve function with self-perceived physical functioning and walking ability in persons with peripheral artery disease

We determined whether more adverse calf muscle characteristics and poorer peripheral nerve function were associated with impairments in self-perceived physical functioning and walking ability in persons with lower extremity peripheral artery disease (PAD). Participants included 462 persons with PAD; measures included the ankle-brachial index (ABI), medical history, electrophysiologic characteristics of nerves, and computed tomography of calf muscle. Self-perceived physical functioning and walking ability were assessed using the 36-Item Short Form Health Survey (SF-36) and the Walking Impairment Questionnaire (WIQ). Results were adjusted for age, sex, race, ABI, body mass index, comorbidities, and other confounders. Lower calf muscle area was associated with a poorer SF-36 physical function (PF) score (overall p-trend < 0.001, 33.76 PF score for the lowest quartile versus 59.74 for the highest, pairwise p < 0.001) and a poorer WIQ walking distance score (p-trend = 0.001, 29.71 WIQ score for the lowest quartile versus 48.43 for the highest, pairwise p < 0.001). Higher calf muscle percent fat was associated with a poorer SF-36 PF score (p-trend < 0.001, 53.76 PF score for the lowest quartile versus 40.28 for the highest, pairwise p = 0.009). Slower peroneal nerve conduction velocity was associated with a poorer WIQ speed score ( p-trend = 0.023, 30.49 WIQ score for the lowest quartile versus 40.48 for the highest, pairwise p = 0.031). In summary, adverse calf muscle characteristics and poorer peripheral nerve function are associated significantly and independently with impairments in self-perceived physical functioning and walking ability in PAD persons.

Orthostatic intolerance in the heat: are the α-adrenergic receptors the culprit?

Orthostatic intolerance in the heat: are the α-adrenergic receptors the culprit?