Biomedical subjects

Krista Vandenborne

Publications and source records attributed to Krista Vandenborne.

At least 19 recordsLinked to original sources

PubMed2011

Long-term restoration of cardiac dystrophin expression in golden retriever muscular dystrophy following rAAV6-mediated exon skipping.

Although restoration of dystrophin expression via exon skipping in both cardiac and skeletal muscle has been successfully demonstrated in the mdx mouse, restoration of cardiac dystrophin expression in large animal models of Duchenne muscular dystrophy (DMD) has proven to be a challenge. In large animals, investigators have focused on using intravenous injection of antisense oligonucleotides (AO) to mediate exon skipping. In this study, we sought to optimize restoration of cardiac dystrophin expression in the golden retriever muscular dystrophy (GRMD) model using percutaneous transendocardial delivery of recombinant AAV6 (rAAV6) to deliver a modified U7 small nuclear RNA (snRNA) carrying antisense sequence to target the exon splicing enhancers of exons 6 and 8 and correct the disrupted reading frame. We demonstrate restoration of cardiac dystrophin expression at 13 months confirmed by reverse transcription-PCR (RT-PCR) and immunoblot as well as membrane localization by immunohistochemistry. This was accompanied by improved cardiac function as assessed by cardiac magnetic resonance imaging (MRI). Percutaneous transendocardial delivery of rAAV6 expressing a modified U7 exon skipping construct is a safe, effective method for restoration of dystrophin expression and improvement of cardiac function in the GRMD canine and may be easily translatable to human DMD patients.

Alternative Splicing↗

PubMed2006

Deficit in human muscle strength with cast immobilization: contribution of inorganic phosphate.

Metabolic factors have been proposed to explain strength deficits observed in skeletal muscle with immobilization that are not completely accounted for by changes in muscle cross-sectional area (CSA) and neural adaptations. The aim of this study was to quantify changes in the resting inorganic phosphate (Pi) concentration from the medial gastrocnemius muscle during immobilization, reloading and rehabilitation. Additionally, we assessed the contributions of CSA, muscle activation and Pi concentration to plantar flexor torque during rehabilitation following immobilization. Eight persons with a surgically stabilized ankle fracture participated. Subjects were immobilized for 6-8 weeks and subsequently participated in 10 weeks of rehabilitation. Localized (31)P-Magnetic resonance spectroscopy, magnetic resonance imaging, isometric torque and activation testing were performed on the immobilized and uninvolved limbs. At 6 weeks of immobilization, significant differences were noted between the immobilized and uninvolved limbs for the Pi concentration and the Pi/PCr ratio (P < 0.05). From 6 weeks of immobilization to 3-5 days of reloading, the increase in Pi concentration (15%, P = 0.26) and Pi/PCr (20%, P = 0.29) was not significant. During rehabilitation, the relative contributions of CSA, muscle activation and Pi concentration to plantarflexor torque were 32, 44 and 40%, respectively. Together, CSA, muscle activation and Pi concentration accounted for 76% of the variance in torque (P < 0.01). In summary, our findings suggest that immobilization, independent of reloading, leads to a significant increase in the resting Pi concentration of human skeletal muscle. Additionally, alterations in resting Pi concentration may contribute to strength deficits with immobilization not accounted for by changes in muscle CSA or neural adaptations.

Adult↗

PubMed2006

Changes in muscle T2 relaxation properties following spinal cord injury and locomotor training.

Magnetic resonance (MR) is frequently used to study structural and biochemical properties of skeletal muscle. Changes in proton transverse relaxation (T2) properties have been used to study muscle cellular damage, as well as muscle activation during exercise protocols. In this study, we implemented MR imaging to characterize the T2 relaxation properties of rat hindlimb muscles following spinal cord injury (SCI) and locomotor training. After moderate midthoracic contusion SCI, Sprague-Dawley rats were assigned to either treadmill training, cycle training or an untrained group. T2 weighted images were obtained and mean muscle T2 times were calculated in the tibialis anterior, soleus, and gastrocnemius (GAS) muscles at pre-injury as well as at 1, 2, 4, 8, and 12 weeks post-injury. Following SCI, hindlimb muscles in untrained animals showed a significant increase in muscle T2, with the most dramatic shift (+5.46 ms) observed in soleus muscle at 1 week post-SCI. Subsequently, all muscle groups showed a spontaneous recovery in muscle T2 with normalized T2 values in the GAS and tibilias anterior muscles at 4 weeks and the soleus at 12 weeks post-SCI. Both training paradigms, treadmill and cycling training, accelerated the recovery of soleus muscle T2. As a result, soleus muscle T2 recovered back to pre-injury values within 3 weeks of training in both training groups. Finally, in vitro histological assessments of rat skeletal muscles demonstrated that there was no apparent muscle injury in any of the muscles studied at 1 week post-SCI.

Animals↗

PubMed2006

Relative contributions of muscle activation and muscle size to plantarflexor torque during rehabilitation after immobilization.

Muscle atrophy is clearly related to a loss of muscle torque, but the reduction in muscle size cannot entirely account for the decrease in muscle torque. Reduced neural input to muscle has been proposed to account for much of the remaining torque deficits after disuse or immobilization. The purpose of this investigation was to assess the relative contributions of voluntary muscle activation failure and muscle atrophy to loss of plantarflexor muscle torque after immobilization. Nine subjects (ages 19-23) years with unilateral ankle malleolar fractures were treated by open reduction-internal fixation and 7 weeks of cast immobilization. Subjects participated in 10 weeks of rehabilitation that focused on both strength and endurance of the plantarflexors. Magnetic resonance imaging, isometric plantarflexor muscle torque and activation (interpolated twitch technique) measurements were performed at 0, 5, and 10 weeks of rehabilitation. Following immobilization, voluntary muscle activation (56.8 +/- 16.3%), maximal cross-sectional area (CSA) (35.3 +/- 7.6 cm(2)), and peak torque (26.2 +/- 12.7 N-m) were all significantly decreased ( p < 0.0056) compared to the uninvolved limb (98.0 +/- 2.3%, 48.0 +/- 6.8 cm(2), and 105.2 +/- 27.0 N-m, respectively). During 10 weeks of rehabilitation, muscle activation alone accounted for 56.1% of the variance in torque ( p < 0.01) and muscle CSA alone accounted for 35.5% of the variance in torque ( p < 0.01). Together, CSA and muscle activation accounted for 61.5% of the variance in torque ( p < 0.01). The greatest gains in muscle activation were made during the first 5 weeks of rehabilitation. Both increases in voluntary muscle activation and muscle hypertrophy contributed to the recovery in muscle strength following immobilization, with large gains in activation during the first 5 weeks of rehabilitation. In contrast, muscle CSA showed fairly comparable gains throughout both the early and later phase of rehabilitation.

Adult↗

PubMed2006

Lower-extremity muscle cross-sectional area after incomplete spinal cord injury.

OBJECTIVES: (1) To quantify skeletal muscle size in lower-extremity muscles of people after incomplete spinal cord injury (SCI), (2) to assess differences in muscle size between involved lower limbs, (3) to determine the impact of ambulatory status (using wheelchair for community mobility vs not using a wheelchair for community mobility) on muscle size after incomplete SCI, and (4) to determine if differential atrophy occurs among individual muscles after incomplete SCI. DESIGN: Case-control study. SETTING: University research setting. PARTICIPANTS: Seventeen people with incomplete SCI and 17 age-, sex-, weight-, and height-matched noninjured controls. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Maximum cross-sectional area (CSA) of individual lower-extremity muscles (soleus, medial gastrocnemius, lateral gastrocnemius, tibialis anterior, quadriceps femoris, hamstrings) as assessed by magnetic resonance imaging. RESULTS: Overall, subjects with incomplete SCI had significantly smaller (24%-31%) average muscle CSA in affected lower-extremity muscles as compared with control subjects (P<.05). Mean differences were highest in the thigh muscles ( approximately 31%) compared with the lower-leg muscles ( approximately 25%). No differences were noted between the self-reported more- and less-involved limbs within the incomplete SCI group. Dichotomizing the incomplete SCI group showed significantly lower muscle CSA values in both the wheelchair (range, 21%-39%) and nonwheelchair groups (range, 24%-38%). In addition, the wheelchair group exhibited significantly greater plantarflexor muscle atrophy compared with the dorsiflexors, with maximum atrophy in the medial gastrocnemius muscle (39%). CONCLUSIONS: Our results suggest marked and differential atrophic response of the affected lower-extremity muscles that is seemingly affected by ambulatory status in people with incomplete SCI.

Adult↗

PubMed2006

Changes in soleus muscle function and fiber morphology with one week of locomotor training in spinal cord contusion injured rats.

The purpose of this study is two-fold: (1) to examine skeletal muscle function in a rat model of midthoracic contusion spinal cord injury (SCI) and (2) to evaluate the therapeutic influence of a short bout (1 week) of treadmill locomotor training on soleus muscle function (peak force, fatigability, contractile properties, fiber types), size (fiber area), and motor deficit and recovery (BBB scores) after SCI. The rats were injured with a moderate T8 spinal cord contusion and were assigned to either receive treadmill locomotor training (TM), starting 1 week after SCI for 5 consecutive days (20 min/trial, 2 trials/day) or not to receive any exercise intervention (no TM). Locomotor training resulted in a significant improvement in overall locomotor function (32% improvement in BBB scores) when compared to no TM. Also, the injured animals that trained for 1 week had 38% greater peak soleus tetanic forces (p < 0.05), a 9% decrease in muscle fatigue (p < 0.05), 23% larger muscle fiber CSA (p < 0.05), and decreased immunoexpression of fast heavy chain fiber types than did rats receiving no TM. In addition, there was a good correlation (0.704) between the BBB scores of injured animals and peak soleus muscle force regardless of group assignment. No significant differences were seen in twitch or time to peak tension values across groups. Collectively, these results indicate that 1 week of treadmill locomotor training, initiated early after SCI, can significantly improve motor recovery following SCI. The magnitude of these changes is remarkable considering the relatively short training interval and clearly illustrates the potential that initiating treadmill locomotor training shortly after injury may have on countering some of the functional deficits resulting from SCI.

Animals↗

PubMed2006

Ambulatory continuous interscalene nerve blocks decrease the time to discharge readiness after total shoulder arthroplasty: a randomized, triple-masked, placebo-controlled study.

BACKGROUND: A continuous interscalene nerve block (CISB) may be used to provide analgesia after shoulder arthroplasty. Therefore, inpatient stays may be shortened if CISB (1) provides adequate analgesia without intravenous opioids and (2) improves shoulder mobilization. This study investigated the relationship between ambulatory CISB and the time to reach three discharge criteria after shoulder arthroplasty. METHODS: Preoperatively, patients received a CISB. All patients received a perineural 0.2% ropivacaine infusion from surgery until 06:00 the following morning, at which time they were randomly assigned either to continue perineural ropivacaine or to switch to normal saline. The primary endpoint was the time from the end of surgery until three discharge criteria were attained (adequate analgesia, independence from intravenous analgesics, and tolerance to 50% of shoulder motion targets). Patients were discharged home as early as the afternoon after surgery with their CISB using a portable infusion pump. RESULTS: Patients receiving perineural ropivacaine (n = 16) attained all three discharge criteria in a median (10th-90th percentiles) of 21 (16-41) h, compared with 51 (37-90) h for those receiving perineural normal saline (n = 13, P < 0.001). Unlike patients receiving perineural ropivacaine, patients receiving perineural normal saline often required intravenous morphine, but still experienced a higher degree of pain and tolerated less external rotation. CONCLUSIONS: An ambulatory CISB considerably decreases the time until readiness for discharge after shoulder arthroplasty, primarily by providing potent analgesia that permits greater passive shoulder movement and the avoidance of intravenous opioids. Additional research is required to define the appropriate subset of patients and assess the incidence of complications associated with earlier discharge.

Aged↗

PubMed2006

Total knee arthroplasty as an overnight-stay procedure using continuous femoral nerve blocks at home: a prospective feasibility study.

The average duration of hospitalization after total knee arthroplasty (TKA) in the United States is 4-5 days. In this two-phase study we investigated the feasibility of converting TKA into an overnight-stay procedure using a continuous femoral nerve block provided at home through postoperative day 4. Nine of 10 patients met discharge criteria and were discharged home the day after surgery. Pain was well controlled, opioid requirements and sleep disturbances were minimal, and patient satisfaction was high. Additional research is required to replicate these results in a controlled trial, define the appropriate subset of patients, and assess the incidence of complications associated with this practice before its mainstream use.

Adolescent↗

PubMed2005

Metabolic and phenotypic characteristics of human skeletal muscle fibers as predictors of glycogen utilization during electrical stimulation.

Characteristics of skeletal muscle such as fiber type composition and activities of key metabolic enzymes have been purported to affect glycogen utilization. However, the relative importance individual factors may have in predicting glycogen utilization of individual muscle fibers has not been addressed. Thus, we sought to determine the relative importance that metabolic characteristics and phenotypic expression of individual fibers have in predicting fiber specific glycogen utilization during neuromuscular electrical stimulation (NMES) exercise. Biopsies were taken from the m, vastus lateralis (VL) of eight recreationally active males before and immediately after 30 min of non-fatiguing NMES and analyzed for type (I, IIa and IIx), succinate dehydrogenase activity (SDH), glycerol-phosphate dehydrogenase activity (GPDH), quantitative-actomyosin adenosine triphosphatase activity (qATPase), and glycogen content. Our results demonstrate that a ratio of enzyme activities representing pathways for energy supply and energy demand (SDH: qATPase) accounted for more of the variance in glycogen utilization (y=0.2091 e(-0.0329x ), R2=0.622, P< or = 0.0001) than SDH (R2=0.321) or qATPase (R2=0.365) alone. Fiber phenotype was also a significant predictor of glycogen utilization, but to a lesser extent than the other variables studied (R2=0.201). A ratio of the activities of enzymes representing pathways of energy supply and energy demand, represented by SDH:qATPase, is a better predictor of glycogen utilization than either of its components independently while fiber phenotype, although a statistically significant predictor of glycogen utilization, may not be the most appropriate determinate of the functional characteristics of an individual fiber.

Adenosine Triphosphatases↗

PubMed2005

Noninvasive monitoring of muscle damage during reloading following limb disuse.

Cast immobilization causes skeletal muscle disuse atrophy and an increased susceptibility to muscle damage. The objective of this study was to explore the utility of noninvasive magnetic resonance (MR) imaging to monitor muscle damage in the lower hindlimb muscles of the mouse during reloading following cast immobilization and to compare the findings in different muscles. The hindlimbs of C57BL6 mice were immobilized for 2 weeks in plantarflexion using a bilateral casting model. Following immobilization the mice were allowed to reambulate and muscle damage was monitored at different times. Cage-restricted reloading following cast immobilization induced a significant shift (P < 0.0001) in the transverse (T2) relaxation characteristics of the postural slow-twitch soleus muscle, but not in the neighboring gastrocnemius. Soleus T2 values peaked at 2 days of reloading. Muscle-specific changes in MR T2 relaxation properties correlated with uptake of Evans blue dye, a histological marker of muscle damage. This study demonstrates that T2 MR imaging can be implemented to monitor noninvasively and sequentially muscle-specific damage during reloading following limb disuse.

Animals↗

PubMed2005

A model of muscle atrophy using cast immobilization in mice.

We describe a new cast-immobilization protocol to induce muscle atrophy in the lower hindlimb muscles of mice. Bilateral cast immobilization for 2 weeks in a shortened position resulted in a significant loss of muscle size and strength in the soleus and extensor digitorum longus. The availability of a model of cast immobilization in mice may benefit future studies targeting genetic or cell therapy interventions of muscle atrophy in transgenic and mutant mice strains.

Animals↗

PubMed2005

Total shoulder arthroplasty as an outpatient procedure using ambulatory perineural local anesthetic infusion: a pilot feasibility study.

We investigated the feasibility of converting total shoulder arthroplasty (TSA) into an outpatient procedure using ambulatory interscalene perineural ropivacaine infusion. Of the patients of the first phase (n = 8) who were required to remain hospitalized for at least 1 postoperative night, 5 met discharge criteria in the recovery room. Of the subsequent patients of the second phase (n = 6), all met discharge criteria in the recovery room after surgery, and 5 were discharged directly home. For all patients, postoperative pain was well controlled, oral opioid requirements and sleep disturbances were minimal, range-of-motion consistently reached or exceeded the surgeon's expectations, and patient satisfaction was high. These results suggest that TSA may be performed on an outpatient basis using perineural local anesthetic infusion. Additional research is required to define the appropriate subset of patients and assess the incidence of complications associated with this practice before its mainstream use.

Adult↗

PubMed2005

Early quadriceps strength loss after total knee arthroplasty. The contributions of muscle atrophy and failure of voluntary muscle activation.

BACKGROUND: While total knee arthroplasty reduces pain and provides a functional range of motion of the knee, quadriceps weakness and reduced functional capacity typically are still present one year after surgery. The purpose of the present investigation was to determine the role of failure of voluntary muscle activation and muscle atrophy in the early loss of quadriceps strength after surgery. METHODS: Twenty patients with unilateral knee osteoarthritis were tested an average of ten days before and twenty-seven days after primary total knee arthroplasty. Quadriceps strength and voluntary muscle activation were measured with use of a burst-superimposition technique in which a supramaximal burst of electrical stimulation is superimposed on a maximum voluntary isometric contraction. Maximal quadriceps cross-sectional area was assessed with use of magnetic resonance imaging. RESULTS: Postoperatively, quadriceps strength was decreased by 62%, voluntary activation was decreased by 17%, and maximal cross-sectional area was decreased by 10% in comparison with the preoperative values; these differences were significant (p < 0.01). Collectively, failure of voluntary muscle activation and atrophy explained 85% of the loss of quadriceps strength (p < 0.001). Multiple linear regression analysis revealed that failure of voluntary activation contributed nearly twice as much as atrophy did to the loss of quadriceps strength. The severity of knee pain with muscle contraction did not change significantly compared with the preoperative level (p = 0.31). Changes in knee pain during strength-testing did not account for a significant amount of the change in voluntary activation (p = 0.14). CONCLUSIONS: Patients who are managed with total knee arthroplasty have profound impairment of quadriceps strength one month after surgery. This impairment is predominantly due to failure of voluntary muscle activation, and it is also influenced, to a lesser degree, by muscle atrophy. Knee pain with muscle contraction played a surprisingly small role in the reduction of muscle activation.

Aged↗

PubMed2004

Changes in inorganic phosphate and force production in human skeletal muscle after cast immobilization.

Cast immobilization is associated with decreases in muscle contractile area, specific force, and functional ability. The pathophysiological processes underlying the loss of specific force production as well as the role of metabolic alterations are not well understood. The aim of this study was to quantify changes in the resting energy-rich phosphate content and specific force production after immobilization. (31)P-magnetic resonance spectroscopy, three-dimensional magnetic resonance imaging, and isometric strength testing were performed in healthy subjects and patients with an ankle fracture after 7 wk of immobilization and during rehabilitation. Muscle biopsies were obtained in a subset of patients. After immobilization, there was a significant decrease in the specific plantar flexor torque and a significant increase in the inorganic phosphate (P(i)) concentration (P < 0.001) and the P(i)-to-phosphocreatine (PCr) ratio (P < 0.001). No significant change in the PCr content or basal pH was noted. During rehabilitation, both the P(i) content and the P(i)-to-PCr ratio decreased and specific torque increased, approaching control values after 10 wk of rehabilitation. Regression analysis showed an inverse relationship between the in vivo P(i) concentration and specific torque (r = 0.65, P < 0.01). In vitro force mechanics performed on skinned human muscle fibers demonstrated that varying the P(i) levels within the ranges observed across individuals in vivo (4-10 mM) changed force production by approximately 16%. In summary, our findings clearly depict a change in the resting energy-rich phosphate content of skeletal muscle with immobilization, which may negatively impact its force generation.

Ankle Injuries↗

PubMed2004

Muscle adaptations with immobilization and rehabilitation after ankle fracture.

UNLABELLED: INTRODUCTION/ PURPOSE: The widespread occurrence of muscular atrophy during immobilization and its reversal presents an important challenge to rehabilitation medicine. We used 3D-magnetic resonance imaging (MRI) in patients with surgically-stabilized ankle mortise fractures to quantify changes in plantarflexor and dorsiflexor muscle size during immobilization and rehabilitation, as well as to evaluate changes in force generating capacity (specific torque). METHODS: Twenty-individuals participated in a 10 wk rehabilitation program after 7 wk of immobilization. MRIs were acquired at baseline, 2, and 7 wk of immobilization, and at 5 and 10 wk of rehabilitation. Isometric plantarflexor muscle strength testing was performed at 0, 5, and 10 wk of rehabilitation. RESULTS: Dorsiflexors and plantarflexors atrophied 18.9% and 24.4% respectively, the majority of which occurred during the first 2 wk of immobilization (dorsiflexors: 9.6%; plantarflexors: 14.1%). Likewise, more than 50% of hypertrophy during rehabilitation occurred within the first 5 wk of rehabilitation for both the dorsiflexors (12.9%) and plantarflexors (13.2%), when compared to the total amount of hypertrophy over 10 wk of rehabilitation (dorsiflexors: 17.6%, plantarflexors: 22.5%). There were no significant differences in hypertrophy or atrophy of the dorsiflexor or plantarflexor muscles, despite a rehabilitation emphasis on the plantarflexors. Patients had significantly lower plantarflexor specific torque (torque/CSA) than healthy, control subjects immediately after cast immobilization, which did not return to normal after 10 wk of rehabilitation (P < 0.05). CONCLUSION: Our investigation of the consequences of limb immobilization on rehabilitation outcomes in patients can be applied directly to optimizing rehabilitation programs. Although muscle hypertrophy occurred early during rehabilitation, plantarflexor muscle function (specific torque) should remain the focus of rehabilitation programs because although CSA recovered quickly, specific torque still lagged behind that of control subjects.

Adaptation, Physiological↗

PubMed2003

Effects of experimental weight perturbation on skeletal muscle work efficiency in human subjects.

Maintenance of reduced or elevated body weight results in respective decreases or increases in energy expended in physical activity, defined as 24-h energy expenditure excluding resting energy expenditure and the thermic effect of feeding, beyond those attributable to weight change. We examined skeletal muscle work efficiency by graded cycle ergometry and, in some subjects, rates of gastrocnemius muscle ATP flux during exercise by magnetic resonance spectroscopy (MRS), in 30 subjects (15 males, 15 females) at initial weight and 10% below initial weight and in 8 subjects (7 males, 1 female) at initial weight and 10% above initial weight to determine whether changes in skeletal muscle work efficiency at altered body weight were correlated with changes in the energy expended in physical activity. At reduced weight, muscle work efficiency was increased in both cycle ergometry [mean (SD) change = +26.5 (26.7)%, P < 0.001] and MRS [ATP flux change = -15.2 (23.2)%, P = 0.044] studies. Weight gain resulted in decreased muscle work efficiency by ergometry [mean (SD) change = -17.8 (20.5)%, P = 0.043]. Changes in muscle efficiency at altered body weight accounted for 35% of the change in daily energy expended in physical activity.

Body Composition↗

PubMed2003

Human and rat skeletal muscle adaptations to spinal cord injury.

Results of studies of rodent skeletal muscle plasticity are often extrapolated to humans. However, responses to "disuse" may be species specific, in part because of different inherent properties of anatomically similar muscles. Thus, this study quantified human and rat m. vastus lateralis (VL) fiber adaptations to 11 weeks of spinal cord injury (SCI). The m. VL was taken from 8 young (54 d) male Charles River rats after T-9 laminectomy (n = 4) or sham surgery (n = 4). In addition, the m. VL was biopsied in 7 able-bodied and in 7 SCI humans (31.3 +/- 4.7 years, mean +/- SE). Samples were sectioned and fibers were analyzed for type (I, IIa, IIb/x), cross-sectional area (CSA), succinate dehydrogenase (SDH), alpha-glycerol-phosphate dehydrogenase (GPDH), and actomyosin adenosine triphosphatase (qATPase) activities. Rat fibers had 1.5- to 2-fold greater SDH and GPDH activities while their fibers were 60% the size of those in humans. The most striking differences, however, were the absence of slow fibers in the rat and its four-fold greater proportion of IIb/x fibers (80% vs. 16% of the CSA) compared to humans. SCI decreased SDH activity more in rats whereas atrophy and IIa to IIb/x fiber shift occurred to a greater extent in humans. It is suggested that the rat is a reasonable model for studying the predominant response to SCI, atrophy. However, its high proportion of IIb/x fibers limits evaluation of the mechanical consequences of shifting to "faster" contractile machinery after SCI.

Adaptation, Physiological↗

PubMed2002

Metabolic costs of isometric force generation and maintenance of human skeletal muscle.

During isometric contractions, no true work is performed, so the force-time integral (FTI) is often used to approximate isometric work. However, the relationship between FTI and metabolic cost is not as linear. We tested the hypothesis that this nonlinearity was due to the cost of attaining a given force being greater than that of maintaining it. The ATP consumed per contraction in the human medial gastrocnemius muscle (n = 6) was determined by use of (31)P-NMR spectroscopy during eight different electrical stimulation protocols. Each protocol consisted of 8 trains of a single frequency (20 or 80 Hz) and duration (300, 600, 1,200, or 1,800 ms) performed under ischemic conditions. The cost of force generation was determined from the ATP turnover during the short-duration trains that did not attain a steady force level. Estimates of the cost of force maintenance at each frequency were determined by subtracting the ATP turnover during the shorter-duration trains from the turnover during the long-duration trains. The force generation phase of an isometric contraction was indeed more metabolically costly than the force maintenance phase during both 20- and 80-Hz stimulation. Thus the mean rate of ATP hydrolysis appeared to decline as contraction duration increased. Interestingly, the metabolic costs of maintaining force during 20-Hz and 80-Hz stimulation were comparable, although different levels of force were produced.

Adenosine Triphosphate↗