Chicken skeletal muscle-associated macroarray for gene discovery

Macro- and microarrays are well-established technologies to determine gene functions through repeated measurements of transcript abundance. We constructed a chicken skeletal muscle-associated array based on a muscle-specific EST database, which was used to generate a tissue expression dataset of similar to 4500 chicken genes across 5 adult tissues (skeletal muscle, heart, liver, brain, and skin). Only a small number of ESTs were sufficiently well characterized by BLAST searches to determine their probable cellular functions. Evidence of a particular tissue-characteristic expression can be considered an indication that the transcript is likely to be functionally significant. The skeletal muscle macroarray platform was first used to search for evidence of tissue-specific expression, focusing on the biological function of genes/transcripts, since gene expression profiles generated across tissues were found to be reliable and consistent. Hierarchical clustering analysis revealed consistent clustering among genes assigned to 'developmental growth', such as the ontology genes and germ layers. Accuracy of the expression data was supported by comparing information from known transcripts and tissue from which the transcript was derived with macroarray data. Hybridization assays resulted in consistent tissue expression profile, which will be useful to dissect tissue-regulatory networks and to predict functions of novel genes identified after extensive sequencing of the genomes of model organisms. Screening our skeletal-muscle platform using 5 chicken adult tissues allowed us identifying 43 'tissue-specific' transcripts, and 112 co-expressed uncharacterized transcripts with 62 putative motifs. This platform also represents an important tool for functional investigation of novel genes; to determine expression pattern according to developmental stages; to evaluate differences in muscular growth potential between chicken lines, and to identify tissue-specific genes.

The relative effects of severe burn injury and pre- and post-natal protein deprivation on mandibular condyle morphology

The mandible has a mixed embryological origin, and its growth is associated with the secondary cartilage of the condyle process (CP). In this area, growth depends on an array of intrinsic and extrinsic factors that influence protein metabolism. In the present study, we used an adolescent rat model to evaluate the growth and development of the CP under conditions of pre- and postnatal protein deficiency, combined with or without the stress of severe burn injury (BI). We found that protein deficiency severely undermined the growth of the CP, by altering the thickness of its constituent layers. BI is also capable of affecting CP growth, although the effect is less severe than protein deficiency. Interestingly, the summed effect of protein deficiency and BI on the CP is less severe than protein deficiency alone. A possible explanation is that the increased carbohydrates in a hypoproteic diet stimulate the production of endogenous insulin and protein synthesis, which partially compensates for the loss of lean body mass caused by BI.

Cross-Talk Between Mitochondria and NADPH Oxidase: Effects of Mild Mitochondrial Dysfunction on Angiotensin II-Mediated Increase in Nox Isoform Expression and Activity in Vascular Smooth Muscle Cells

Mitochondria and NADPH oxidase activation are concomitantly involved in pathogenesis of many vascular diseases. However, possible cross-talk between those ROS-generating systems is unclear. We induced mild mitochondrial dysfunction due to mitochondrial DNA damage after 24 h incubation of rabbit aortic smooth muscle (VSMC) with 250 ng/mL ethidium bromide (EtBr). VSMC remained viable and had 29% less oxygen consumption, 16% greater baseline hydrogen peroxide, and unchanged glutathione levels. Serum-stimulated proliferation was unaltered at 24 h. Although PCR amplification of several mtDNA sequences was preserved, D-Loop mtDNA region showed distinct amplification of shorter products after EtBr. Such evidence for DNA damage was further enhanced after angiotensin-II (AngII) incubation. Remarkably, the normally observed increase in VSMC membrane fraction NADPH oxidase activity after AngII was completely abrogated after EtBr, together with failure to upregulate Nox1 mRNA expression. Conversely, basal Nox4 mRNA expression increased 1.6-fold, while being unresponsive to AngII. Similar loss in AngII redox response occurred after 24 h antimycin-A incubation. Enhanced Nox4 expression was unassociated with endoplasmic reticulum stress markers. Protein disulfide isomerase, an NADPH oxidase regulator, exhibited increased expression and inverted pattern of migration to membrane fraction after EtBr. These results unravel functionally relevant cross-talk between mitochondria and NADPH oxidase, which markedly affects redox responses to AngII. Antioxid Redox Signal 11, 1265-1278.

Angiotensin receptor blockade improves the net balance of cardiac Ca(2+) handling-related proteins in sympathetic hyperactivity-induced heart failure

Aims: The clinical benefits of angiotensin II type 1 (AT1) receptor blockers (ARB) in heart failure (HF) include cardiac anti-remodeling and improved ventricular function. However, the cellular mechanisms underlying the benefits of ARB on ventricular function need to be better clarified. In the present manuscript, we evaluated the effects of AT1 receptor blockade on the net balance of Ca(2+) handling proteins in hearts of mice lacking alpha(2A) and alpha(2C) adrenoceptors (alpha(2A)/alpha(2C)ARKO), which develop sympathetic hyperactivity (SH) induced-HF. Main methods: A cohort of male wild-type (WT) and congenic alpha(2A)/alpha(2C)ARKO mice in a C57BL6/J genetic background (5-7 mo of age) was randomly assigned to receive either placebo or ARB (Losartan, 10 mg/kg for 8wks). Ventricular function (VF) was assessed by echocardiography, and cardiac myocyte width and ventricular fibrosis by a computer-assisted morphometric system. Sarcoplasmic reticulum Ca(2+) ATPase (SERCA2), phospholamban (PLN), phospho-Ser(16)-PLN, phospho-Thr(17)-PLN, phosphatase 1 (PP1), Na(+)-Ca(2+) exchanger (NCX), Ca(2+)/calmodulin-dependent protein kinase 11 (CaMKII) and phospho-Thr(286)-CaMKII were analyzed by Western blot. Key findings: alpha(2A)/alpha(2C)ARKO mice displayed ventricular dysfunction, cardiomyocyte hypertrophy and cardiac fibrosis paralleled by decreased SERCA2 and increased phospho-Thr(17)-PLN, CaMKII, phospho-Thr(286)-CaMKII and NCX levels. ARB induced anti-cardiac remodeling effect and improved VF in alpha(2A)/alpha(2C)ARKO associated with increased SERCA2 and phospho-Ser(16)-PLN levels, and SERCA2:NCX ratio. Additionally, ARB decreased phospho-Thr(17)-PLN levels as well as reestablished NCX, CaMKII and phospho-Thr(286)-CaMKII toward WT levels. Significance: Altogether, these data provide new insights on intracellular Ca(2+) regulatory mechanisms underlying improved ventricular function by ARB therapy in HF. (c) 2011 Elsevier Inc. All rights reserved.

Exercise training associated with diet improves heart rate recovery and cardiac autonomic nervous system activity in obese children

The purpose of this study was to test the hypotheses that in obese children: 1) hypocaloric diet (D) improves both heart rate recovery at 1 min (Delta HRR1) cfter an exercise test, and cardiac autonomic nervous system activity (CANSA) in obese children; 2) Diet and exercise training (DET) combined leads to greater improvement in both Delta HRR1 after an exercise test and in CANSA, than D alone. Moreover, we examined the relationships among Delta HRR1, CANSA, cardiorespiratory fitness and anthropometric variables (AV) in obese children submitted to D and to DET. 33 obese children (10 +/- 0.2 years; body mass index (BMI) >95(th) percentile) were divided into 2 groups: D (n = 15; BMI = 31 +/- 1 kg/m(2)) and DET (n = 18; 29 +/- 1 kg/m(2)). All children performed a maximal cardiopulmonary exercise test on a treadmill. The Delta HRR1 was defined as the difference between heart rate at peak and at 1-min post-exercise. CANSA was assessed using power spectral analysis of heart rate variability at rest. The sympathovagal balance (low frequency and high frequency ratio, LF/HF) was measured. After interventions, all obese children showed reduced body weight (P < 0.05). The D group did not improve in terms of peak VO(2), Delta HRR1 or LF/HF ratio (P > 0.05). In contrast, the DET group showed increased peak VO(2) (P = 0.01) and improved Delta HRR1 (Delta HRR1 = 37.3 +/- 2.6; P = 0.01) and LF/HF ratio (P = 0.001). The DET group demonstrated significant relationships among Delta HRR1, peak VO(2) and CANSA (P < 0.05). In conclusion, DET, in contrast to D, promoted improved Delta HRR1 and CANSA in obese children, suggesting a positive influence of increased levels of cardiorespiratory fitness by exercise training on cardiac autonomic activity.

Aerobic exercise training improves Ca(2+) handling and redox status of skeletal muscle in mice

Exercise training is known to promote relevant changes in the properties of skeletal muscle contractility toward powerful fibers. However, there are few studies showing the effect of a well-established exercise training protocol on Ca(2+) handling and redox status in skeletal muscles with different fiber-type compositions. We have previously standardized a valid and reliable protocol to improve endurance exercise capacity in mice based on maximal lactate steady-state workload (MLSSw). The aim of this study was to investigate the effect of exercise training, performed at MLSSw, on the skeletal muscle Ca(2+) handling-related protein levels and cellular redox status in soleus and plantaris. Male C57BL/6J mice performed treadmill training at MLSSw over a period of eight weeks. Muscle fiber-typing was determined by myosin ATPase histochemistry, citrate synthase activity by spectrophotometric assay, Ca(2+) handling-related protein levels by Western blot and reduced to oxidized glutathione ratio (GSH:GSSG) by high-performance liquid chromatography. Trained mice displayed higher running performance and citrate synthase activity compared with untrained mice. Improved running performance in trained mice was paralleled by fast-to-slow fiber-type shift and increased capillary density in both plantaris and soleus. Exercise training increased dihydropyridine receptor (DHPR) alpha 2 subunit, ryanodine receptor and Na(+)/Ca(2+) exchanger levels in plantaris and soleus. Moreover, exercise training elevated DHPR beta 1 subunit and sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) 1 levels in plantaris and SERCA2 levels in soleus of trained mice. Skeletal muscle GSH content and GSH:GSSG ratio was increased in plantaris and soleus of trained mice. Taken together, our findings indicate that MLSSw exercise-induced better running performance is, in part, due to increased levels of proteins involved in skeletal muscle Ca(2+) handling, whereas this response is partially dependent on specificity of skeletal muscle fiber-type composition. Finally, we demonstrated an augmented cellular redox status and GSH antioxidant capacity in trained mice.

Exercise training changes IL-10/TNF-alpha ratio in the skeletal muscle of post-MI rats

Heart failure (HF) is associated with changes in the skeletal muscle (SM) which might be a consequence of the unbalanced local expression of pro- (TNF-alpha) and anti- (IL-10) inflammatory cytokines, leading to inflammation-induced myopathy, and SM wasting. This local effect of HF on SM may, on the other hand, contribute to systemic inflammation, as this tissue actively secretes cytokines. Since increasing evidence points out to an anti-inflammatory effect of exercise training, the goal of the present study was to investigate its effect in rats with HF after post-myocardial infarction (MI), with special regard to the expression of TNF-alpha and IL-10 in the soleus and extensor digitorum longus (EDL), muscles with different fiber composition. Wistar rats underwent left thoracotomy with ligation of the left coronary artery, and were randomly assigned to either a sedentary (Sham-operated and MI sedentary) or trained (Sham-operated and MI trained) group. Animals in the trained groups ran on a treadmill (0% grade at 13-20 m/min) for 60 min/day, 5 days/week, for 8-10 weeks. The training protocol was able to reverse the changes induced by MI, decreasing TNF-alpha protein (26%, P < 0.05) and mRNA (58%, P < 0.05) levels in the soleus, when compared with the sedentary MI group. Training also increased soleus IL-10 expression (2.6-fold, P < 0.001) in post-MI HF rats. As a consequence, the IL-10/TNF-alpha ratio was increased. This ""anti-inflammatory effect"" was more pronounced in the soleus than in the EDL, suggesting a fiber composition dependent response. (C) 2009 Elsevier Ltd. All rights reserved.

Adaptations in autonomic function during exercise training in heart failure

Although neurohumoral excitation is the hallmark of heart failure (HF), the mechanisms underlying this alteration are not entirely known. Abnormalities in several systems contribute to neurohumoral excitation in HF, including arterial and cardiopulmonary baroreceptors, central and peripheral chemoreceptors, cardiac chemoreceptors, and central nervous system abnormalities. Exercise intolerance is characteristic of chronic HF, and growing evidence strongly suggests that exercise limitation in patients with chronic HF is not due to elevated filling pressures or inadequate cardiac output during exercise, but instead due to skeletal myopathy. Several lines of evidence suggest that sympathetic excitation contributes to the skeletal myopathy of HF, since sympathetic activity mediates vasoconstriction at rest and during exercise likely restrains muscle blood flow, arteriolar dilatation, and capillary recruitment, leading to underperfused areas of working muscle, and areas of muscle ischemia, release of reactive oxygen species (ROS), and inflammation. Although controversial, either unmyelinated, metabolite-sensitive afferent fibers, and/or myelinated, mechanosensitive afferent fibers in skeletal muscle underlie the exaggerated sympathetic activity in HF. Exercise training has emerged as a unique non-pharmacological strategy for the treatment of HF. Regular exercise improves functional capacity and quality of life, and perhaps prognosis in chronic HF patients. Recent studies have provided convincing evidence that these benefits in chronic HF patients are mediated by significant reduction in central sympathetic outflow as a consequence of improvement in arterial and chemoreflex controls, and correction of central nervous system abnormalities, and increase in peripheral blood flow with reduction in cytokines and increase in mass muscle.

Effect of eccentric contraction velocity on muscle damage in repeated bouts of elbow flexor exercise

Eccentric exercise induces muscle damage, but controversy exists concerning the effect of contraction velocity on the magnitude of muscle damage, and little is known about the effect of contraction velocity on the repeated-bout effect. This study examined slow (60 degrees.s(-1)) and fast (180 degrees.s(-1)) velocity eccentric exercises for changes in indirect markers of muscle damage following 3 exercise bouts that were performed every 2 weeks. Fifteen young men were divided into 2 groups based on the velocity of eccentric exercise: 7 in the Ecc60 (60 degrees.s(-1)) group, and 8 in the Ecc180 (180 degrees.s(-1)) group. The exercise consisted of 30 maximal eccentric contractions of the elbow flexors at each velocity, in which the elbow joint was forcibly extended from 60 degrees to 180 degrees (full extension) on an isokinetic dynamometer. Changes in maximal voluntary isometric contraction strength, range of motion, muscle soreness, and plasma creatine kinase activity before and for 4 days after the exercise were compared in the 2 groups using a mixed-model analysis (group x bout x time). No significant differences between groups were evident for changes in any variables following exercise bouts; however, the changes were significantly smaller (p < 0.05) after the second and third bouts than after the first bout. These results indicate that the contraction velocity does not influence muscle damage or the repeated-bout effect.

Influence of high- and low-carbohydrate diet following glycogen-depleting exercise on heart rate variability and plasma catecholamines

The purpose of this study was to investigate the effects of a short-term low-or high-carbohydrate (CHO) diet consumed after exercise on sympathetic nervous system activity. Twelve healthy males underwent a progressive incremental test; a control measurement of plasma catecholamines and heart rate variability (HRV); an exercise protocol to reduce endogenous CHO stores; a low-or high-CHO diet (counterbalanced order) consumed for 2 days, beginning immediately after the exercise protocol; and a second resting plasma catecholamine and HRV measurement. The exercise and diet protocols and the second round of measurements were performed again after a 1-week washout period. The mean (+/- SD) values of the standard deviation of R-R intervals were similar between conditions (control, 899.0 +/- 146.1 ms; low-CHO diet, 876.8 +/- 115.8 ms; and high-CHO diet, 878.7 +/- 127.7 ms). The absolute high-and low-frequency (HF and LF, respectively) densities of the HRV power spectrum were also not different between conditions. However, normalized HF and LF (i.e., relative to the total power spectrum) were lower and higher, respectively, in the low-CHO diet than in the control diet (mean +/- SD, 17 +/- 9 normalized units (NU) and 83 +/- 9 NU vs. 27 +/- 11 NU and 73 +/- 17 NU, respectively; p < 0.05). The LF/HF ratio was higher with the low-CHO diet than with the control diet (mean +/- SD, 7.2 +/- 6.2 and 4.2 +/- 3.2, respectively; p < 0.05). The mean values of plasma catecholamines were not different between diets. These results suggest that the autonomic control of the heart rate was modified after a short-term low-CHO diet, but plasma catecholamine levels were not altered.

Treatment of vitamin D deficiency increases lower limb muscle strength in institutionalized older people independently of regular physical activity: a randomized double-blind controlled trial

Aims: To investigate the effects of a 6-month supplementation with calcium and cholecalciferol on biochemical parameters and muscle strength of institutionalized elderly. Methods: This prospective, double-blind, placebo-controlled, randomized trial included Brazilian institutionalized people 6 60 years of age receiving a 6-month supplementation ( December to May) of daily calcium plus monthly placebo (calcium/placebo group) or daily calcium plus oral cholecalciferol (150,000 IU once a month during the first 2 months, followed by 90,000 IU once a month for the last 4 months; calcium/vitamin D group). Fasting blood samples for 25-(OH) D, PTH and calcium determination were collected (n = 56) and muscle tests were performed ( n = 46) to measure the strength of hip flexors (SHF) and knee extensors (SKE) before ( baseline) and after the 6-month intervention ( 6 months). Results: Due to seasonal variations, serum 25( OH) D significantly enhanced in both groups after treatment, but the calcium/vitamin D group had significantly higher 25-(OH) D levels than the calcium/placebo group (84 vs. 33%, respectively; p < 0.0001). No cases of hypercalcemia were observed. While the calcium/placebo group showed no improvement in SHF and SKE at 6 months (p = 0.93 and p = 0.61, respectively), SHF was increased in the calcium/vitamin D group by 16.4% (p = 0.0001) and SKE by 24.6% (p = 0.0007). Conclusions: The suggested cholecalciferol supplementation was safe and efficient in enhancing 25(OH)D levels and lower limb muscle strength in the elderly, in the absence of any regular physical exercise practice. Copyright (C) 2009 S. Karger AG, Basel

Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene

Negrão M.V, Alves CR, Alves G.B, Pereira A.C, Dias R.G, Laterza M.C, Mota G.F, Oliveira E.M, Bassaneze V, Krieger J.E, Negrão C.E, Rondon M.U.P. Exercise training improves muscle vasodilatation in individuals with T786C polymorphism of endothelial nitric oxide synthase gene. Physiol Genomics 42A: 71-77, 2010. First published July 6, 2010; doi:10.1152/physiolgenomics.00145.2009.-Allele T at promoter region of the eNOS gene has been associated with an increase in coronary disease mortality, suggesting that this allele increases susceptibility for endothelial dysfunction. In contrast, exercise training improves endothelial function. Thus, we hypothesized that: 1) Muscle vasodilatation during exercise is attenuated in individuals homozygous for allele T, and 2) Exercise training improves muscle vasodilatation in response to exercise for TT genotype individuals. From 133 preselected healthy individuals genotyped for the T786C polymorphism, 72 participated in the study: TT (n = 37; age 27 +/- 1 yr) and CT + CC (n = 35; age 26 +/- 1 yr). Forearm blood flow (venous occlusion plethysmography) and blood pressure (oscillometric automatic cuff) were evaluated at rest and during 30% handgrip exercise. Exercise training consisted of three sessions per week for 18 wk, with intensity between anaerobic threshold and respiratory compensation point. Resting forearm vascular conductance (FVC, P = 0.17) and mean blood pressure (P = 0.70) were similar between groups. However, FVC responses during handgrip exercise were significantly lower in TT individuals compared with CT + CC individuals (0.39 +/- 0.12 vs. 1.08 +/- 0.27 units, P = 0.01). Exercise training significantly increased peak VO(2) in both groups, but resting FVC remained unchanged. This intervention significantly increased FVC response to handgrip exercise in TT individuals (P = 0.03), but not in CT + CC individuals (P = 0.49), leading to an equivalent FVC response between TT and CT + CC individuals (1.05 +/- 0.18 vs. 1.59 +/- 0.27 units, P = 0.27). In conclusion, exercise training improves muscle vasodilatation in response to exercise in TT genotype individuals, demonstrating that genetic variants influence the effects of interventions such as exercise training.

Ethanol-induced vasoconstriction is mediated via redox-sensitive cyclo-oxygenase-dependent mechanisms

The present study investigated the role of ROS (reactive oxygen species) and COX (cyclooxygenase) in ethanol-induced contraction and elevation of [Ca(2+)](i) (intracellular [Ca(2+)]). Vascular reactivity experiments, using standard muscle bath procedures, showed that ethanol (1-800 mmol/l) induced contraction in endothelium-intact (EC(50): 306 +/- 34 mmol/l) and endothelium-denuded (EC(50): 180 +/- 40 mmol/l) rat aortic rings. Endothelial removal enhanced ethanol-induced contraction. Preincubation of intact rings with L-NAME [N(G)-nitro-L-arginine methyl ester; non-selective NOS (NO synthase) inhibitor, 100 mu mol/l], 7-nitroindazole [selective nNOS (neuronal NOS) inhibitor, 100 mu mol/l], oxyhaemoglobin (NO scavenger, 10 mu mol/l) and ODQ (selective inhibitor of guanylate cyclase enzyme, 1 mu mol/l) increased ethanol-induced contraction. Tiron [O(2)(-) (superoxide anion) scavenger, 1 mmol/l] and catalase (H(2)O(2) scavenger, 300 units/ml) reduced ethanol-induced contraction to a similar extent in both endothelium-intact and denuded rings. Similarly, indomethacin (non-selective COX inhibitor, 10 mu mol/l), SC560 (selective COX- I inhibitor, 1 mu mol/l), AH6809 [PGF(2 alpha) (prostaglandin F(2 alpha))] receptor antagonist, 10 mu mol/l] or SQ29584 [PGH(2)(prostaglandin H(2))/TXA(2) (thromboxane A(2)) receptor antagonist, 3 mu mol/l] inhibited ethanol-induced contraction in aortic rings with and without intact endothelium. In cultured aortic VSMCs (vascular smooth muscle cells), ethanol stimulated generation of O(2)(-) and H(2)O(2). Ethanol induced a transient increase in [Ca(2+)](i), which was significantly inhibited in VSMCs pre-exposed to tiron or indomethacin. Our data suggest that ethanol induces vasoconstriction via redox-sensitive and COX-dependent pathways, probably through direct effects on ROS production and Ca(2+) signalling. These findings identify putative molecular mechanisms whereby ethanol, at high concentrations, influences vascular reactivity. Whether similar phenomena occur in vivo at lower concentrations of ethanol remains unclear.

Utility of Quantitative Ultrasound of the Calcaneus in Diagnosing Osteoporosis in Spinal Cord Injury Patients

Bittar CK, Cliquet A Jr, dos Santos Floter M: Utility of quantitative ultrasound of the calcaneus in diagnosing osteoporosis in spinal cord injury patients. Am J Phys Med Rehabil 2011;90:477-481. Objective: The aim of this study was to assess the utility of quantitative ultrasound of the calcaneus in diagnosing osteoporosis in spinal cord injury patients in a Brazilian Teaching Hospital. Design: This is a diagnostic test criterion standard comparison study. Between January 2008 and October 2009, the bone density of 15 spinal cord injury patients was assessed for analysis before beginning rehabilitation using muscle stimulation. The bone density was assessed using bone densitometry examination (DEXA) and ultrasound examination of the calcaneus (QUS). The measurements acquired using QUS and DEXA were compared between patients with spinal cord injury and a control group of ten healthy individuals. Results: The T-score values for femoral neck using DEXA (P < 0.0022) and those using QUS of the calcaneus (P < 0.0005) differed significantly between the groups, and the means in the normal subjects were higher than those in spinal cord injury patients who would receive electrical stimulation. In spinal cord injury patients, the significant differences were found between the QUS T-score for calcaneus and the DEXA scores for the lumbar spine and femoral neck. Conclusions: Because of the low level of mechanical stress on the calcaneus, the results of the QUS could not be correlated with the DEXA results for diagnosing osteoporosis. Therefore, QUS seems to be not a good choice for diagnosis and follow-up.

Altered left ventricular diastolic function in subjects with spinal cord injury

Study design: This is cross-sectional study. Objectives: The aim of this study is to investigate the cardiac structure and function of subjects with spinal cord injury (SCI) and the impact of metabolic, hemodynamic and inflammatory factors on these parameters. Setting: Sao Paulo, Brazil. Methods: Sixty-five nondiabetic, nonhypertensive, sedentary, nonsmoker men (34 with SCI and 31 healthy subjects) were evaluated by medical history, anthropometry, laboratory tests, analysis of hemodynamic and inflammatory parameters and echocardiography. Results: Subjects with SCI had lower systolic blood pressure and higher levels of C-reactive protein and tumor necrosis factor receptors than the healthy ones. Echocardiography data showed that the SCI group presented similar left ventricular (LV) structural and systolic parameters, but lower initial diastolic velocity (Em) (9.2 +/- 0.5 vs 12.3 +/- 0.5 cm s(-1); P<0.001) and higher peak early inflow velocity (E)/Em ratio (7.7 +/- 0.5 vs 6.1 +/- 0.3; P = 0.009) compared with the able-bodied group, even after adjustment for systolic blood pressure and C-reactive protein levels. Furthermore, injured subjects with E/Em >8 had lower peak spectral longitudinal contraction (Sm) (9.0 +/- 0.7 vs 11.6 +/- 0.4cm s(-1); P<0.001) and cardiac output (4.2 +/- 0.2 vs 5.0 +/- 0.21 min(-1); P = 0.029), as well as higher relative wall thickness (0.38 +/- 0.01 vs 0.35 +/- 0.01; P = 0.005), than individuals with SCI with E/Em<8, but similar age, body mass index, blood pressure, injury level, metabolic parameters and inflammatory marker levels. Conclusion: Subjects with SCI presented impaired LV diastolic function in comparison with able-bodied ones. Moreover, worse LV diastolic function was associated with a pattern of LV concentric remodeling and subclinical decreases in systolic function among injured subjects. Overall, these findings might contribute to explain the increased cardiovascular risk reported for individuals with SCI. Spinal Cord (2011) 49, 65-69; doi: 10.1038/sc.2010.88; published online 27 July 2010