[Show abstract][Hide abstract] ABSTRACT: Longitudinal strain (LS) is a quantitative parameter that adds incremental value to wall motion analysis. The aim of this study was to compare the reproducibility of LS derived from Doppler tissue imaging and speckle-tracking between an expert and a novice strain reader during dobutamine stress echocardiography (DSE).
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 05/2014; DOI:10.1016/j.echo.2014.04.016 · 3.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Background
Longitudinal strain (LS) is a quantitative parameter that adds incremental value to wall motion analysis. The aim of this study was to compare the reproducibility of LS derived from Doppler tissue imaging and speckle-tracking between an expert and a novice strain reader during dobutamine stress echocardiography (DSE).
Forty-one patients (mean age, 65 ± 15 years; mean ejection fraction, 58 ± 11%) underwent DSE per clinical protocol. Global LS derived from speckle-tracking and regional LS derived from both speckle-tracking and Doppler tissue imaging were measured twice by an expert strain reader and also measured twice by a novice strain reader. Intraobserver and interobserver analyses were performed using intraclass correlation coefficients (ICC), Bland-Altman analysis, and absolute difference values (mean ± SD).
Global LS measured by the expert strain reader demonstrated high intraobserver measurement reproducibility (rest: ICC = 0.95, absolute difference = 5.5 ± 4.9%; low dose: ICC = 0.96, absolute difference = 5.7 ± 3.7%; peak dose: ICC = 0.87, absolute difference = 11.4 ± 8.4%). Global LS measured by the novice strain reader also demonstrated high intraobserver reproducibility (rest: ICC = 0.97, absolute difference = 4.1 ± 3.4%; low dose: ICC = 0.94, absolute difference = 5.4 ± 5.9%; peak dose: ICC = 0.94, absolute difference = 6.1 ± 4.8%). Global LS also showed high interobserver agreement between the expert and novice readers at all stages of DSE (rest: ICC = 0.90, absolute difference = 8.5 ± 7.5%; low dose: ICC = 0.90, absolute difference = 8.9 ± 7.1%; peak dose: ICC = 0.87, absolute difference = 10.8 ± 8.4%). Of all parameters studied, LS derived from Doppler tissue imaging had relatively low interobserver and intraobserver agreement.
Global LS is highly reproducible during all stages of DSE. This variable is a potentially reliable and reproducible measure of myocardial deformation.
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to determine whether global strains derived from three-dimensional (3D) speckle-tracking echocardiography (STE) are as accurate as left ventricular (LV) ejection fraction (LVEF) obtained by two-dimensional (2D) and 3D echocardiography in the quantification of LV function.
Two-dimensional and 3D echocardiography and 2D and 3D STE were performed in 88 patients (LVEF range, 17%-79%). Two-dimensional and 3D global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain, and global area strain were quantified and correlated with LV function determined by 2D and 3D echocardiographic LVEF. Reproducibility, feasibility, and duration of study to perform 3D STE were assessed by independent, blinded observers.
A total of 78 patients (89%) underwent 3D STE. All 3D speckle-tracking echocardiographic parameters had strong correlations with assessment of LV function determined by 2D and 3D echocardiographic LVEF. Three-dimensional GCS was the best marker of LV function (r = -0.89, P < .0001). Subgroup analysis demonstrated that 3D speckle-tracking echocardiographic parameters were particularly useful in identifying LV dysfunction (LVEF < 50%). Receiver operating characteristic curve analysis demonstrated areas under the curve of 0.97 for 3D GCS, 0.96 for 3D global radial strain, 0.95 for 3D global area strain, and 0.87 for 3D GLS. An optimal 3D GCS cutoff value of magnitude < -12% predicted LV dysfunction (LVEF obtained by 2D echocardiography < 50%) with 92% sensitivity and 90% specificity. There was good correlation between 2D GLS and 3D GLS (r = 0.85, P < .001; mean difference, -1.7 ± 6.5%). Good intraobserver, interobserver, and test-retest agreements were seen with 3D STE. Time for image acquisition to postprocessing analysis was significantly reduced with 3D STE (3.7 ± 1.0 minutes) compared with 2D STE (4.6 ± 1.5 min) (P < .05).
Global strain by 3D STE is a promising novel alternative to quantitatively assess LV function. Three-dimensional STE is reproducible, feasible, and time efficient.
Journal of the American Society of Echocardiography: official publication of the American Society of Echocardiography 12/2013; DOI:10.1016/j.echo.2013.11.002 · 3.99 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Re-programming of gene expression is fundamental for skeletal muscle adaptations in response to endurance exercise. This study investigated the time-course dependent changes in the muscular transcriptome following an endurance exercise trial consisting of 1 h of intense cycling immediately followed by 1 h of intense running. Skeletal muscle samples were taken at baseline, 3 h, 48 h, and 96 h post-exercise from eight healthy, endurance-trained, male individuals. RNA was extracted from muscle. Differential gene expression was evaluated using Illumina microarrays and validated with qPCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Three h post-exercise, 102 gene sets were up-regulated [family wise error rate (FWER), P < 0.05]; including groups of genes related with leukocyte migration, immune and chaperone activation, and cyclic AMP responsive element binding protein (CREB) 1-signaling. Forty-eight h post-exercise, among 19 enriched gene sets (FWER, P < 0.05), two gene sets related to actin cytoskeleton remodeling were up-regulated. Ninety-six h post-exercise, 83 gene sets were enriched (FWER, P < 0.05), 80 of which were up-regulated; including gene groups related to chemokine signaling, cell stress management, and extracellular matrix remodeling. These data provide comprehensive insights into the molecular pathways involved in acute stress, recovery, and adaptive muscular responses to endurance exercise. The novel 96 h post-exercise transcriptome indicates substantial transcriptional activity, potentially associated with the prolonged presence of leukocytes in the muscles. This suggests that muscular recovery, from a transcriptional perspective, is incomplete 96 h after endurance exercise involving muscle damage.
[Show abstract][Hide abstract] ABSTRACT: Although phosphorus magnetic resonance spectroscopy ((31)P-MRS) based evidence suggests that in vivo peak mitochondrial respiration rate in young untrained adults is limited by the intrinsic mitochondrial capacity of ATP synthesis, it remains unknown whether a large, locally targeted, increase in convective O2 delivery would alter this interpretation. Consequently, we examined the effect of superimposing reactive hyperaemia (RH), induced by a period of brief ischemia during the last min of exercise, on oxygen delivery and mitochondrial function in the calf muscle of 9 young adults in comparison to free-flow conditions (FF). To this aim, we used an integrative experimental approach combining (31)P-MRS, Doppler ultrasound imaging, and near-infrared spectroscopy. Limb blood flow [area under the curve (AUC), 1.4±0.8 L in FF and 2.5±0.3 L in RH, P<0.01] and convective O2 delivery (AUC, 0.30±0.16 L in FF and 0.54±0.05 L in RH, P<0.01) were significantly increased in RH in comparison to FF. RH was also associated with significantly higher capillary blood flow (P<0.05) and faster tissue re-oxygenation mean response times (70±15 s in FF and 24±15 s in RH, P<0.05). This resulted in a 43% increase in estimated peak mitochondrial ATP synthesis rate (29±13 mM.min(-1) in FF and 41±14 mM.min(-1) in RH, P<0.05) whereas the phosphocreatine (PCr) recovery time constant in RH was not significantly different (P=0.22). This comprehensive assessment of local skeletal muscle O2 availability and utilization in untrained subjects reveals that mitochondrial function, assessed in vivo by (31)P-MRS, is limited by convective O2 delivery rather than an intrinsic mitochondrial limitation.
[Show abstract][Hide abstract] ABSTRACT: AIM: Short-term exercise training may induce metabolic and performance adaptations before any changes in mitochondrial enzyme potential. However, there has not been a study that has directly assessed changes in mitochondrial oxidative capacity or metabolic control as a consequence of such training in vivo. Therefore, we used (31) P-magnetic resonance spectroscopy ((31) P-MRS) to examine the effect of short-term plantar flexion exercise training on phosphocreatine (PCr) recovery kinetics and the control of respiration rate. METHOD: To this aim, we investigated 12 healthy men, experienced with this exercise modality (TRA), and 7 time-control subjects (TC). RESULTS: After 5 days of training, maximum work rate during incremental plantar flexion exercise was significantly improved (P < 0.01). During the recovery period, the maximal rate of oxidative ATP synthesis (PRE: 28 ± 13 mM.min(-1) ; POST: 26 ± 15 mM.min(-1) ) and the PCr recovery time constant (PRE: 31 ± 19 s; POST: 29 ± 16) were not significantly altered. In contrast, the Hill coefficient (nH ) describing the cooperativity between respiration rate and ADP was significantly increased in TRA (PRE:nH =2.7 ± 1.4; POST: nH =3.4 ± 1.9, P < 0.05). Meanwhile, there were no systematic variations in any of these variables in TC. CONCLUSION: This study reveals that 5 days of training induces rapid adaptation in the allosteric control of respiration rate by ADP before any substantial improvement in muscle oxidative capacity occurs. This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Neutrophils serve as an intriguing model for the study of innate immune cellular activity induced by physiological stress. We measured changes in the transcriptome of circulating neutrophils following an experimental exercise trial (EXTRI) consisting of 1 hour (h) of intense cycling immediately followed by 1 h of intense running. Blood samples were taken at baseline, 3 h, 48 h, and 96 h post-EXTRI from eight healthy, endurance-trained, male subjects. RNA was extracted from isolated neutrophils. Differential gene expression was evaluated using Illumina microarrays, and validated with qPCR. Gene set enrichment analysis identified enriched molecular signatures chosen from the Molecular Signatures Database. Blood concentrations of muscle damage indices, neutrophils, interleukin (IL)-6 and IL-10 were increased (P<0.05) 3 h post-EXTRI. Up-regulated groups of functionally related genes 3 h post-EXTRI included gene sets associated with the recognition of tissue damage, the IL-1 receptor-, and toll-like receptor (TLR) pathways (FWER p-value<0.05). The core enrichment for these pathways included TLRs, low-affinity immunoglobulin receptors, S100 calcium binding protein A12, and negative regulators of innate immunity, e.g. IL-1 receptor antagonist, and IL-1 receptor associated kinase-3. Plasma myoglobin changes correlated with neutrophil TLR4 gene expression (r=0.74; P<0.05). Neutrophils had returned to their non-activated state 48 h post-EXTRI, indicating that their initial pro-inflammatory response was transient and rapidly counter-regulated. This study provides novel insight into the signaling mechanisms underlying the neutrophil responses to endurance exercise, suggesting that their transcriptional activity was particularly induced by damage-associated molecule patterns, hypothetically originating from the leakage of muscle components into the circulation.
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: To investigate the frequency of the ACTN3 R577X polymorphism in elite endurance triathletes, and whether ACTN3 R577X is significantly associated with performance time. DESIGN: Cross-sectional study. METHODS: Saliva samples, questionnaires, and performance times were collected for 196 elite endurance athletes who participated in the 2008 Kona Ironman championship triathlon. Athletes were of predominantly North American, European, and Australian origin. A one-way analysis of variance was conducted to compare performance times between genotype groups. Multiple linear regression analysis was performed to model the effect of questionnaire variables and genotype on performance time. Genotype and allele frequencies were compared to results from different populations using the chi-square test. RESULTS: Performance time did not significantly differ between genotype groups, and age, sex, and continent of origin were significant predictors of finishing time (age and sex: p<5×10(-6); continent: p=0.003) though genotype was not. Genotype and allele frequencies obtained (RR 26.5%, RX 50.0%, XX 23.5%, R 51.5%, X 48.5%) were found to be not significantly different from Australian, Spanish, and Italian endurance athletes (p>0.05), but were significantly different from Kenyan, Ethiopian, and Finnish endurance athletes (p<0.01). CONCLUSIONS: Genotype and allele frequencies agreed with those reported for endurance athletes of similar ethnic origin, supporting previous findings for an association between 577X allele and endurance. However, analysis of performance time suggests that ACTN3 does not alone influence endurance performance, or may have a complex effect on endurance performance due to a speed/endurance trade-off.
[Show abstract][Hide abstract] ABSTRACT: Impaired O(2) transport to skeletal muscle potentially contributes to the decline in aerobic capacity with aging. Thus, we examined whether (1) skeletal muscle oxidative capacity decreases with age and (2) O(2) availability or mitochondrial capacity limits the maximal rate of mitochondrial ATP synthesis in vivo in sedentary elderly individuals. We used (31)P-magnetic resonance spectroscopy ((31)P-MRS) to examine the PCr recovery kinetics in six young (26 ± 10 years) and six older (69 ± 3 years) sedentary subjects following 4 min of dynamic plantar flexion exercise under different fractions of inspired O(2) (FiO(2), normoxia 0.2; hyperoxia 1.0). End-exercise pH was not significantly different between old (7.04 ± 0.10) and young (7.05 ± 0.04) and was not affected by breathing hyperoxia (old 7.08 ± 0.08, P > 0.05 and young 7.05 ± 0.03). Likewise, end-exercise PCr was not significantly different between old (19 ± 4 mM) and young (24 ± 5 mM) and was not changed in hyperoxia. The PCr recovery time constant was significantly longer in the old (36 ± 9 s) compared to the young in normoxia (23 ± 8 s, P < 0.05) and was not significantly altered by breathing hyperoxia in both the old (35 ± 9 s) and young (29 ± 10 s) groups. Therefore, this study reveals that the muscle oxidative capacity of both sedentary young and old individuals is independent of O(2) availability and that the decline in oxidative capacity with age is most likely due to limited mitochondrial content and/or mitochondrial dysfunction and not O(2) availability.
Age 07/2012; 35(4). DOI:10.1007/s11357-012-9442-6 · 3.45 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Exercise triggers hormesis, conditioning hearts against damaging consequences of subsequent ischemia-reperfusion (I/R). We test whether "low-stress" voluntary activity modifies I/R tolerance and molecular determinants of cardiac survival. Male C57BL/6 mice were provided 7-day access to locked (7SED) or rotating (7EX) running-wheels before analysis of cardiac prosurvival (Akt, ERK 1/2) and prodeath (GSK3β) kinases, transcriptomic adaptations, and functional tolerance of isolated hearts to 25-min ischemia/45-min reperfusion. Over 7 days, 7EX mice increased running from 2.1 ± 0.2 to 5.3 ± 0.3 km/day (mean speed 38 ± 2 m/min), with activity improving myocardial I/R tolerance: 7SED hearts recovered 43 ± 3% of ventricular force with diastolic contracture of 33 ± 3 mmHg, whereas 7EX hearts recovered 63 ± 5% of force with diastolic dysfunction reduced to 23 ± 2 mmHg (P < 0.05). Cytosolic expression (total protein) of Akt and GSK3β was unaltered, while ERK 1/2 increased 30% in 7EX vs. 7SED hearts. Phosphorylation of Akt and ERK 1/2 was unaltered, whereas GSK3β phosphorylation increased ∼90%. Microarray interrogation identified significant changes (≥1.3-fold expression change, ≤5% FDR) in 142 known genes, the majority (92%) repressed. Significantly modified paths/networks related to inflammatory/immune function (particularly interferon-dependent), together with cell movement, growth, and death. Of only 14 induced transcripts, 3 encoded interrelated sarcomeric proteins titin, α-actinin, and myomesin-2, while transcripts for protective actin-stabilizing ND1-L and activator of mitochondrial biogenesis ALAS1 were also induced. There was no transcriptional evidence of oxidative heat-shock or other canonical "stress" responses. These data demonstrate that relatively brief voluntary activity substantially improves cardiac ischemic tolerance, an effect independent of shifts in Akt, but associated with increased total ERK 1/2 and phospho-inhibition of GSK3β. Transcriptomic data implicate inflammatory/immune and sarcomeric modulation in activity-dependent protection.
[Show abstract][Hide abstract] ABSTRACT: Heart rate variability (HRV) and haemorheology adaptations to 12 wk of varied-dose treadmill walking were investigated in women aged 65-74 yr with type 2 diabetes. Subjects were randomly allocated into two groups where exercise frequency and session duration were manipulated (Group 1: 2 × 60 min·wk(-1) or Group 2: 4 × 30 min·wk(-1)), but intensity and accumulated weekly duration of exercise were consistent between groups (100% gas-exchange threshold; 120 min·wk(-1)). Twelve weeks of exercise training significantly improved peak oxygen uptake, time to exhaustion, and gas-exchange threshold (p < 0.05), independent of exercise group. Exercise training did not significantly change glycaemic control or body mass. Red blood cell (RBC) aggregation and RBC deformability significantly decreased (p < 0.05) for both groups. No change in HRV was observed for Group 1, whereas several key indicators of HRV were significantly improved in Group 2 (p < 0.05). The present study was the first to report decreased RBC aggregation following an exercise-only intervention and that exercise training improved RBC aggregation without a concomitant improvement in glycaemic control. The accumulated weekly exercise duration may be the most important training component for the prescription of exercise in older women with type 2 diabetes.