Jillian L. Clarke

Two-dimensional myocardial strain imaging detects changes in left ventricular systolic function immediately after anthracycline chemotherapy

AIMS The efficacy of anthracyclines is undermined by potential life-threatening cardiotoxicity. Cardiotoxicity is dependent upon several factors and the timing to its development is variable. Moreover, as adjuvant therapy with trastuzumab often follows, a close monitoring of cardiac function in those treated with anthracyclines is mandatory. Left ventricular ejection fraction (LVEF) by echocardiography is currently used for monitoring cardiotoxicity; however, LVEF has numerous limitations. Two-dimensional strain imaging may provide a more sensitive measure of altered LV systolic function, so the aim of the present study was to compare LVEF and LV systolic strain before and after anthracyclines. METHODS AND RESULTS Fifty-two women with histologically confirmed breast cancer were prospectively studied. Echocardiographic LVEF (by Simpsons method), global and regional peak longitudinal, radial, and circumferential 2D systolic strain were measured 1 week before and 1 week after chemotherapy. Global and regional longitudinal LV systolic strain was significantly reduced after treatment; global longitudinal strain decreased from -17.7 to -16.3% (P < 0.01) with 48% of global measurements reduced by >10%. Global and regional radial LV systolic strain after treatment was also significantly reduced; global radial strain dropped from 40.5 to 34.5% (P < 0.01) with 59% of global measurements reduced by >10%. In contrast, no reduction in LVEF >10% after chemotherapy was observed. CONCLUSION Reduced LV systolic strain immediately after anthracycline treatment may indicate early impairment of myocardial function before detectable change in LVEF.

In vivo passive mechanical behaviour of muscle fascicles and tendons in human gastrocnemius muscle-tendon units

Non‐Technical Summary  Relaxed skeletal muscles behave like springs that resist joint motion. There have been few in vivo studies of the spring‐like properties of relaxed muscles. In this study, ultrasound was used to image human calf muscles while muscle length was changed by rotating the ankle of relaxed subjects. The muscles of some subjects buckled at short lengths. At short lengths most muscle fascicles (bundles of muscle cells) are slack. As the muscle is lengthened the slack is progressively taken up, first in some fascicles then in others. The increase in muscle length is due partly to increases in the length of muscle fascicles but most of the increase in muscle length occurs in the tendons.

Altered left ventricular longitudinal diastolic function correlates with reduced systolic function immediately after anthracycline chemotherapy

AIMS The benefits from anthracycline chemotherapy are undermined by potentially life-threatening cardiotoxicity. Transthoracic echocardiography is the most commonly used method for monitoring cardiotoxicity, and centres on the measurement of left ventricular systolic function. The aim of this study was to utilize two-dimensional speckle tracking echocardiography (2DSTE) at baseline and immediately after anthracycline chemotherapy to investigate whether patients with significant changes in systolic function after anthracycline therapy would also develop alterations in diastolic parameters. METHODS AND RESULTS Fifty-two women with histologically confirmed breast cancer were prospectively recruited. Echocardiograms were performed 1 week prior to and 1 week following chemotherapy (always before adjuvant trastuzumab or thoracic radiotherapy). Conventional Doppler, tissue velocity imaging (TVI), and 2DSTE were used to measure diastolic function. 2DSTE measurements included longitudinal diastolic strain, early (E-Sr), and late (A-Sr) myocardial strain rate. 2DSTE and left ventricular ejection fraction (LVEF) were used to measure longitudinal systolic function. Altered LV diastolic function (including E-Sr) was observed in the entire cohort after chemotherapy, with a differential reduction in participants with a post therapy LVEF <55%. Pre-chemotherapy systolic strain was found to predict reduced E-Sr post therapy (P = 0.04). Univariate predictors of E-Sr were LVEF post therapy (P = 0.049) and systolic strain post-therapy (P = 0.01). In a multivariate analysis, systolic strain after chemotherapy was the strongest independent predictor (P = 0.001). CONCLUSION Altered LV diastolic function was observed immediately after the administration of therapeutic doses of anthracycline chemotherapy. Furthermore, our analysis indicates that the changes in diastolic function are associated with reduced systolic function.

Passive Mechanical Properties of Gastrocnemius Muscles of People With Ankle Contracture After Stroke

OBJECTIVE To investigate the mechanisms of contracture after stroke by comparing passive mechanical properties of gastrocnemius muscle-tendon units, muscle fascicles, and tendons in people with ankle contracture after stroke with control participants. DESIGN Cross-sectional study. SETTING Laboratory in a research institution. PARTICIPANTS A convenience sample of people with ankle contracture after stroke (n=20) and able-bodied control subjects (n=30). INTERVENTIONS Not applicable. MAIN OUTCOME MEASURES Stiffness and lengths of gastrocnemius muscle-tendon units, lengths of muscle fascicles, and tendons at specific tensions. RESULTS At a tension of 100N, the gastrocnemius muscle-tendon unit was significantly shorter in participants with stroke (mean, 436mm) than in able-bodied control participants (mean, 444mm; difference, 8mm; 95% confidence interval [CI], 0.2-15mm; P=.04). Muscle fascicles were also shorter in the stroke group (mean, 44mm) than in the control group (mean, 50mm; difference, 6mm; 95% CI, 1-12mm; P=.03). There were no significant differences between groups in the mean stiffness or length of the muscle-tendon units and fascicles at low tension, or in the mean length of the tendons at any tension. CONCLUSIONS People with ankle contracture after stroke have shorter gastrocnemius muscle-tendon units and muscle fascicles than control participants at high tension. This difference is not apparent at low tension.

Left ventricular systolic function in HER2/neu negative breast cancer patients treated with anthracycline chemotherapy: A comparative analysis of left ventricular ejection fraction and myocardial strain imaging over 12 months

AIM Anthracycline agents are undermined by their cardiotoxicity. As life expectancy following treatment is greatly improved, techniques that ensure early detection and timely management of cardiotoxicity are essential. The aim of the present study was to evaluate left ventricular (LV) systolic function with LV ejection fraction (LVEF) and two-dimensional myocardial strain up to 12 months after anthracycline chemotherapy, specifically in HER2/neu negative breast cancer patients. METHODS Seventy-eight consecutive anthracycline naïve breast cancer patients were studied before and immediately after anthracycline chemotherapy. Fifty HER2/neu negative patients were studied over 12 months with serial echocardiograms at four time points. All patients were treated with standard regimens containing anthracyclines. RESULTS Global systolic strain was significantly reduced immediately after, and 6 months after anthracyclines (-19.0 ± 2.3% to -17.5 ± 2.3% (P<0.001) and -18.2 ± 2.2% (P=0.01) respectively). A non-uniform reduction in strain was observed each time with relative sparing of the LV apex. LVEF remained largely unchanged at both time points. Global strain normalised by 12 months in the majority of patients. Persistently reduced strain was observed in 16% (n=8); these patients had a greater reduction in strain at 6 months (≤ -17.2%), and had received higher cumulative anthracycline doses. CONCLUSION Myocardial strain imaging is more sensitive than LVEF for the early detection and intermediate term monitoring of LV systolic function following anthracycline chemotherapy in HER2/neu negative breast cancer patients, and may aid in the development of improved monitoring protocols.

Passive mechanical properties of the gastrocnemius after spinal cord injury

In this study we compared passive mechanical properties of gastrocnemius muscle–tendon units, muscle fascicles, and tendons in control subjects and people with ankle contractures after spinal cord injury.

Gastrocnemius Muscle Contracture After Spinal Cord Injury: A Longitudinal Study

Objective The aim of this study was to examine changes in passive length and stiffness of the gastrocnemius muscle-tendon unit in people after spinal cord injury. Design In a prospective longitudinal study, eight wheelchair-dependent participants with severe paralysis were assessed 3 and 12 mos after spinal cord injury. Passive torque-angle data were obtained as the ankle was slowly rotated through range at six knee angles. Differences in passive ankle torque-angle data recorded at different knee angles were used to derive passive length-tension curves of the gastrocnemius muscle-tendon unit. Ultrasound imaging was used to determine fascicle and tendon contributions to the muscle-tendon unit length-tension curves. Results The participants had ankle contractures (mean [SD] maximum passive ankle dorsiflexion angle, 88 [9] degrees) 3 mos after spinal cord injury. Ankle range did not worsen significantly during the subsequent 9 mos (mean change, −5 degrees; 95% confidence interval, −16 to 6 degrees). There were no changes in the mean slack length or the stiffness of the gastrocnemius muscle-tendon unit or in the slack lengths of the fascicles or the tendon between 3 and 12 mos after spinal cord injury. There were no consistent patterns of the change in slack length or stiffness with the changes in ankle range in the data from the individual participants. Conclusions This study, the first longitudinal study of muscle length and stiffness after spinal cord injury, showed that the length and the stiffness of the gastrocnemius did not change substantially between 3 and 12 mos after injury.

Chondroitin sulphate glycosaminoglycans contribute to widespread inferior biomechanics in tendon after focal injury

Both mechanical and structural properties of tendon change after injury however the causal relationship between these properties is presently unclear. This study aimed to determine the extent of biomechanical change in post-injury tendon pathology and whether the sulphated glycosaminoglycans (glycosaminoglycans) present are a causal factor in these changes. Equine superficial digital flexor tendons (SDF tendons) were surgically-injured in vivo (n=6 injured, n=6 control). Six weeks later they were harvested and regionally dissected into twelve regions around the lesion (equal medial/lateral, proximal/distal). Glycosaminoglycans were removed by enzymatic (chondroitinase) treatment. Elastic modulus (modulus) and ultimate tensile strength (UTS) were measured under uniaxial tension to failure, and tendon glycosaminoglycan content was measured by spectrophotometry. Compared to healthy tendons, pathology induced by the injury decreased modulus (-38%; 95%CI -49% to -28%; P<0.001) and UTS (-38%; 95%CI -48% to -28%; P<0.001) and increased glycosaminoglycan content (+52%; 95%CI 39% - 64%; P<0.001) throughout the tendon. Chondroitinase-mediated glycosaminoglycan removal (50%; 95%CI 21-79%; P<0.001) in surgically-injured pathological tendons caused a significant increase in modulus (5.6MPa/µg removed; 95%CI 0.31-11; P=0.038) and UTS (1.0MPa per µg removed; 95%CI 0.043-2; P=0.041). These results demonstrate that the chondroitin/dermatan sulphate glycosaminoglycans that accumulate in pathological tendon post-injury are partly responsible for the altered biomechanical properties.

Mechanisms of increased passive compliance of hamstring muscle-tendon units after spinal cord injury

BACKGROUND People with spinal cord injury sometimes develop abnormally compliant hamstring muscle-tendon units. This study investigated whether the increased muscle-tendon compliance is due to a change in the passive properties of the muscle fascicles or tendons, or to muscle tears. METHODS Semimembranosus muscle fascicle lengths were measured from ultrasound images obtained from 15 spinal cord injured subjects and 20 control subjects while the hip was passively flexed with the knee extended. Semimembranosus muscles of spinal cord injured subjects were inspected for tears using ultrasound imaging. FINDINGS The mean (SD) hip angle at 30 Nm was 97 (SD 24) degrees in spinal cord injured subjects and 70 (SD 11) degrees in control subjects, indicating that spinal cord injured subjects had very compliant hamstring muscle-tendon units. The ratio of change in fascicle length to change in muscle-tendon length was not statistically different between spinal cord injured subjects and control subjects: muscle fascicles lengthened by 0.30 (SD 0.24) mm/mm in spinal cord injured subjects and 0.42 (SD 0.29) mm/mm in control subjects. These data were used to show that there was evidence of increased tendon compliance of spinal cord injured subjects compared to control subjects, but no evidence of increased muscle fascicle compliance. No tears were observed in semimembranosus muscles of spinal cord injured subjects. INTERPRETATION The increased hamstring muscle-tendon compliance apparent in some spinal cord injured subjects is due, at least in part, to increased tendon compliance. There was no evidence that the increased muscle-tendon compliance was due to muscle tears.

Effects of a Modified German Volume Training Program on Muscular Hypertrophy and Strength.

Abstract Amirthalingam, T, Mavros, Y, Wilson, GC, Clarke, JL, Mitchell, L, and Hackett, DA. Effects of a modified German volume training program on muscular hypertrophy and strength. J Strength Cond Res 31(11): 3109–3119, 2017—German Volume Training (GVT), or the 10 sets method, has been used for decades by weightlifters to increase muscle mass. To date, no study has directly examined the training adaptations after GVT. The purpose of this study was to investigate the effect of a modified GVT intervention on muscular hypertrophy and strength. Nineteen healthy men were randomly assign to 6 weeks of 10 or 5 sets of 10 repetitions for specific compound resistance exercises included in a split routine performed 3 times per week. Total and regional lean body mass, muscle thickness, and muscle strength were measured before and after the training program. Across groups, there were significant increases in lean body mass measures, however, greater increases in trunk (p = 0.043; effect size [ES] = −0.21) and arm (p = 0.083; ES = −0.25) lean body mass favored the 5-SET group. No significant increases were found for leg lean body mass or measures of muscle thickness across groups. Significant increases were found across groups for muscular strength, with greater increases in the 5-SET group for bench press (p = 0.014; ES = −0.43) and lat pull-down (p = 0.003; ES = −0.54). It seems that the modified GVT program is no more effective than performing 5 sets per exercise for increasing muscle hypertrophy and strength. To maximize hypertrophic training effects, it is recommended that 4–6 sets per exercise be performed, as it seems gains will plateau beyond this set range and may even regress due to overtraining.