Timing of microcirculatory injury from ischemia reperfusion

The low flow state that results from ischemia and reperfusion injury is a potentially reversible process that is important in numerous clinical situations. However, the point in time during the course of reperfusion where tissue injury becomes irreversible is unknown. This experiment evaluated the continuum of tissue damage in skeletal muscle after ischemic insult by quantifying the number of flowing capillaries and percentage muscle necrosis in a male Wistar rat skeletal muscle model. A gracilis muscle flap was raised on the vascular pedicle of 39 male Wistar rats and examined at 832x using intravital videomicroscopy. The numbers of flowing capillaries in five consecutive high-power fields were counted for baseline values. The flap was then subjected to 4 hours of global ischemia (except in sham animals, n = 7) by placing a microvascular clamp on the pedicle artery and vein. Upon reperfusion, flowing capillaries were counted in the same five high-power fields at intervals of 5, 15, 30, and 60 minutes, then at 2 to 8 (1-hour intervals), 24, and 48 hours. The gracilis muscle was then harvested at these intervals during reperfusion and assessed for viability. Compared with baseline, flowing capillaries from the ischemia and reperfusion group (mean +/- SEM) decreased significantly in the first 8 hours of reperfusion (7.7 +/- 0.2 to 3.2 +/- 0.3, p < 0.001) with minimal change noted from 8 to 48 hours. Percentage muscle necrosis increased progressively in ischemia and reperfusion preparations from 1 to 7 hours of reperfusion (16.5 +/- 2.6 percent to 38.9 +/- 1.2 percent, p < 0.001). No significant change in muscle necrosis in the ischemia and reperfusion group was noted between 7 and 48 hours. Sham preparations showed no change in the number of flowing capillaries through 3 hours of reperfusion, with a slight decrease at 24 hours. This rat gracilis microcirculation skeletal muscle model demonstrates a heterogeneous reperfusion injury. The decrease in flowing capillaries correlated with the increase in percentage necrosis and appeared to stabilize at the 7- to 8-hour interval. This finding may have important implications for the timing of interventions aimed at minimizing tissue damage from ischemia-reperfusion.     

Effects of long-duration bed rest on structural compartments of m. soleus in man

Magnetic resonance imaging (MRI), histomorphometry and electron microscopy of muscle demonstrate that long-term exposure to actual or simulated weightlessness (including head down bed rest) leads to decreased volume of antigravity muscles in mammals. In muscles interbundle space is occupied by the connective tissue. Rat studies show that hindlimb unloading induces muscle fiber atrophy along with increase in muscle non-fiber connective tissue compartment. Beside that, usually 20% of the muscle fiber volume is comprised by non-contractile (non-myofibrillar) compartment. The aim of the present study was to compare changes in muscle volume, and in muscle fiber size with alterations in myofibrillar apparatus, and in connective tissue compartment in human m. soleus under conditions of 120 day long head down bed rest (HDBR).     

Paretic muscle atrophy and non-contractile tissue content in individual muscles of the post-stroke lower extremity

Muscle atrophy is one of many factors contributing to post-stroke hemiparetic weakness. Since muscle force is a function of muscle size, the amount of muscle atrophy an individual muscle undergoes has implications for its overall force-generating capability post-stroke. In this study, post-stroke atrophy was determined bilaterally in fifteen leg muscles with volumes quantified using magnetic resonance imaging (MRI). All muscle volumes were adjusted to exclude non-contractile tissue content, and muscle atrophy was quantified by comparing the volumes between paretic and non-paretic sides. Non-contractile tissue or intramuscular fat was calculated by determining the amount of tissue excluded from the muscle volume measurement. With the exception of the gracilis, all individual paretic muscles examined had smaller volumes in the non-paretic side. The average decrease in volume for these paretic muscles was 23%. The gracilis volume, on the other hand, was approximately 11% larger on the paretic side. The amount of non-contractile tissue was higher in all paretic muscles except the gracilis, where no difference was observed between sides. To compensate for paretic plantar flexor weakness, one idea might be that use of the paretic gracilis actually causes the muscle to increase in size and not develop intramuscular fat. By eliminating non-contractile tissue from our volume calculations, we have presented volume data that more appropriately represents force-generating muscle tissue. Non-uniform muscle atrophy was observed across muscles and may provide important clues when assessing the effect of muscle atrophy on post-stroke gait.     

Evaluation of exercise muscle energetics by NMR

Magnetic resonance imaging (MRI) is superior to ultrasonography and X-CT especially in density resolution in soft tissue. 31P NMR provides information on metabolism, which has not been obtained in vivo by conventional methods, such as phosphocreatine (PCr), inorganic phosphate (Pi), ATP, and intracellular pH. We used MRI and 31P NMR spectroscopy to study skeletal muscle metabolism of human and rat. These NMR results suggested that 1) estimation of muscle fiber composition, 2) evaluation of muscle ATP turnover and 3) imaging of local muscle fatigue are possible.     

Magnetic Resonance Imaging Allows the Evaluation of Tissue Damage and Regeneration in a Mouse Model of Critical Limb Ischemia

Magnetic resonance imaging (MRI) provides non-invasive, repetitive measures in the same individual, allowing the study of a physio-pathological event over time. In this study, we tested the performance of 7 Tesla multi-parametric MRI to monitor the dynamic changes of mouse skeletal muscle injury and regeneration upon acute ischemia induced by femoral artery dissection. T2-mapping (T2 relaxation time), diffusion-tensor imaging (Fractional Anisotropy) and perfusion by Dynamic Contrast-Enhanced MRI (K-trans) were measured and imaging results were correlated with histological morphometric analysis in both Gastrocnemius and Tibialis anterior muscles. We found that tissue damage positively correlated with T2-relaxation time, while myofiber regeneration and capillary density positively correlated with Fractional Anisotropy. Interestingly, K-trans positively correlated with capillary density. Accordingly, repeated MRI measurements between day 1 and day 28 after surgery in ischemic muscles showed that: 1) T2-relaxation time rapidly increased upon ischemia and then gradually declined, returning almost to basal level in the last phases of the regeneration process; 2) Fractional Anisotropy dropped upon ischemic damage induction and then recovered along with muscle regeneration and neoangiogenesis; 3) K-trans reached a minimum upon ischemia, then progressively recovered. Overall, Gastrocnemius and Tibialis anterior muscles displayed similar patterns of MRI parameters dynamic, with more marked responses and less variability in Tibialis anterior. We conclude that MRI provides quantitative information about both tissue damage after ischemia and the subsequent vascular and muscle regeneration, accounting for the differences between subjects and, within the same individual, between different muscles.     

Venous malformations of skeletal muscle

Intramuscular venous malformations are often mistaken for tumors because of a similar presentation and improper nomenclature. This is a review of 176 patients with venous malformations localized to skeletal muscle compiled from the Vascular Anomalies Center at Children's Hospital from 1980 through 1999. The female-to-male ratio was 2:1. Two-thirds of skeletal muscle venous malformations were noted at birth; the remainder manifested in childhood and adolescence. Venous malformations occurred in every muscle group, most often in the head and neck and extremities. Pain and swelling were the usual presenting complaints. Skeletal problems, such as fracture, deformation, or growth abnormalities, were rare. Hormonal exacerbation and intralesional bleeding were infrequent. Magnetic resonance imaging showed the lesions to be isointense to surrounding muscle on T1-weighted sequences and hyperintense on T2-weighted images. Characteristic tubular or serpentine components were oriented along the muscular long axis. Thrombi were hyperintense on T1-weighted and hypointense on T2-weighted sequences; phleboliths were seen as signal voids on all sequences. Gross examination of resected specimens revealed multicolored tissue with dilated vascular channels, frequently containing phleboliths. Light microscopy showed aggregates of primarily medium-sized, thin-walled vascular channels with flat endothelium and variable smooth muscle, most closely resembling dysplastic veins. Three lesions had a different histologic appearance consisting predominantly of small vessels with capillary structure and proliferative activity admixed with large feeding and draining vessels, similar to a lesion called intramuscular capillary hemangioma in the literature. The endothelium in these three lesions was negative for glucose transporter-1 by immunostaining. Eight percent of the patients, who had minor or no symptoms, were not treated. Twenty-four percent of the patients were managed conservatively (with aspirin and compressive garments); for 17 of these patients (10 percent of 176), noninvasive therapy was not successful, and they proceeded to sclerotherapy, excision, or both. A total of 31 percent of the patients had sclerotherapy, 20 percent had excision, and 27 percent had combined sclerotherapy and excision. Sclerotherapy was used for diffuse lesions, except for those with multiple intralesional thromboses, neurologic impairment, or compressive signs and symptoms. Resection was preferred for venous malformations well localized to a single muscle or muscle group, particularly if the muscles are expendable. Therapeutic outcomes were recorded in the charts or obtained by telephone interview in 122 of the patients (69 percent). Of these, compression garment and aspirin, resection, sclerotherapy, or combined excision and sclerotherapy improved symptoms in 121 patients (92 percent); no change was noted in 10 patients (8 percent). Only one patient was worse (self-reported) after intervention.     

Magnetic Resonance Imaging at 7T Reveals Common Events in Age-Related Sarcopenia and in the Homeostatic Response to Muscle Sterile Injury

Skeletal muscle remodeling in response to various noxae physiologically includes structural changes and inflammatory events. The possibility to study those phenomena in-vivo has been hampered by the lack of validated imaging tools. In our study, we have relied on multiparametric magnetic resonance imaging for quantitative monitoring of muscle changes in mice experiencing age-related sarcopenia or active regeneration after sterile acute injury of tibialis anterior muscle induced by cardiotoxin (CTX) injection. The extent of myofibrils’ necrosis, leukocyte infiltration, and regeneration have been evaluated and compared with parameters from magnetic resonance imaging: T2-mapping (T2 relaxation time; T2-rt), diffusion-tensor imaging (fractional anisotropy, F.A.) and diffusion weighted imaging (apparent diffusion coefficient, ADC). Inflammatory leukocytes within the perimysium and heterogeneous size of fibers characterized aged muscles. They displayed significantly increased T2-rt (P<0.05) and F.A. (P<0.05) compared with young muscles. After acute damage T2-rt increased in otherwise healthy young muscles with a peak at day 3, followed by a progressive decrease to basal values. F.A. dropped 24 hours after injury and afterward increased above the basal level in the regenerated muscle (from day 7 to day 15) returning to the basal value at the end of the follow up period. The ADC displayed opposite kinetics. T2-rt positively correlated with the number of infiltrating leucocytes retrieved by immunomagnetic bead sorting from the tissue (r = 0.92) and with the damage/infiltration score (r = 0.88) while F.A. correlated with the extent of tissue regeneration evaluated at various time points after injury (r = 0.88). Our results indicate that multiparametric MRI is a sensitive and informative tool for monitoring inflammatory and structural muscle changes in living experimental animals; particularly, it allows identifying the increase of T2-rt and F.A. as common events reflecting inflammatory infiltration and muscle regeneration in the transient response of the tissue to acute injury and in the persistent adaptation to aging.     

Aging mechanism associated with a function of biowater.

Magnetic resonance imaging (MRI) pictures of the forearms of four human subjects belonging respectively to each of four generations of the same family were taken, and aging-associated changes in the humerus, epithelium, fat tissue, muscle and blood observed. It was found that together with morphological changes the proton density and the spin-lattice relaxation time (T1) of biowater in each tissue underwent chronological aging-induced changes. An aging mechanism associated with the function of biowater is deduced from the present result and from related experimental findings previously reported.     

In ovo monitoring of smooth muscle fiber development in the chick embryo: diffusion tensor imaging with histologic correlation

Background

Magnetic resonance imaging is a noninvasive method of evaluating embryonic development. Magnetic resonance diffusion tensor imaging, which is based on the measuring the directional diffusivity of water molecules, is an established method of evaluating tissue structure. Prolonged imaging times have precluded the use of embryonic diffusion tensor imaging due to motion artifact. Using temperature-based motion suppression, we aimed to investigate whether diffusion tensor imaging can be used to monitor embryonic smooth muscle development in ovo, and to determine the correlation between histologically-derived muscle fiber fraction, day of incubation and diffusion tensor imaging fractional anisotropy values and length of tracked fibers.

Methodology/Principal Findings

From a set of 82 normally developing fertile chicken eggs, 5 eggs were randomly chosen each day from incubation days 5 to 18 and cooled using a dual-cooling technique prior to and during magnetic resonance imaging at 3.0 Tesla. Smooth muscle fibers of the gizzard were tracked using region of interests placed over the gizzard. Following imaging, the egg was cracked and the embryo was fixated and sectioned, and a micrograph most closely corresponding to the acquired magnetic resonance image was made. Smooth muscle fiber fraction was determined using an automated computer algorithm.

Conclusions/Significance

We show that diffusion tensor images of smooth muscle within the embryonic gizzard can be acquired in ovo from incubation day 11 through hatching. Length of tracked fibers and day of incubation were found to have statistical significance (p<0.05) by multiple linear regression correlation with histologic specimens of sacrificed embryos from day 11 of incubation through hatching. The morphologic pattern of development in our histologic specimens corresponds to the development of embryonic gizzard as reported in the literature. These results suggest that diffusion tensor imaging can provide a noninvasive method of evaluating in ovo development of smooth muscle tissue.     

Effect of total venous occlusion on capillary flow and necrosis in skeletal muscle

Limb replantation and microvascular transfer of flaps are sometimes complicated by postoperative venous thrombosis. Total venous occlusion can lead to complete shutdown of microvascular perfusion, resulting in failure of the transfer or replantation. Once venous return stops, it must be restored within a critical period of time for tissue survival. The purpose of this experiment was to delineate this critical period of time at which no reflow and irreversible muscle necrosis occurs by the use of a rat gracilis flap microcirculation model. The gracilis muscle of 40 male Wistar rats (135.3 +/- 37.2 g) was elevated on its vascular pedicle and mounted on a raised platform for videomicroscopic analysis. Animals were randomly assigned to one of four groups: (1) sham (no total venous occlusion), (2) 10 minutes of total venous occlusion, (3) 30 minutes of total venous occlusion, and (4) 60 minutes of total venous occlusion. Total venous occlusion was established by placing a microvascular clamp across the femoral vein at the junction of the gracilis pedicle. The number of flowing capillaries in five consecutive high-power fields (832x) were counted at baseline and at 5, 15, 30, 60, 120, 180 minutes, and 24 hours after reperfusion. At 24 hours after reperfusion, the gracilis muscles were harvested and stained with nitroblue tetrazolium. Percentage of muscle necrosis was measured by using computer planimetry. The data were reported as mean +/- standard error of mean and were compared between groups by analysis of variance and appropriate post hoc comparisons. Total venous occlusion for 10, 30, and 60 minutes showed a significant decrease in the number of flowing capillaries through 24-hour postreversal. There was a significant drop (p < 0.01) in the number of flowing capillaries from 30 minutes of total venous occlusion to 60 minutes of total venous occlusion at all times. Muscle necrosis was significantly increased in all three groups of total venous occlusion compared with the sham group (36.1 +/- 1.7 percent, 45.5 +/- 3.4 percent, 74.1 +/- 4.7 percent versus 14.3 +/- 1.7 percent, and p < 0.01). These results indicate that irreversible tissue damage occurs in a very short time interval (60 minutes) in this model, making the early detection of venous occlusion critical to the successful correction of this complication.     

Non-Invasive MRI and Spectroscopy of mdx Mice Reveal Temporal Changes in Dystrophic Muscle Imaging and in Energy Deficits

In Duchenne muscular dystrophy (DMD), a genetic disruption of dystrophin protein expression results in repeated muscle injury and chronic inflammation. Magnetic resonance imaging shows promise as a surrogate outcome measure in both DMD and rehabilitation medicine that is capable of predicting clinical benefit years in advance of functional outcome measures. The mdx mouse reproduces the dystrophin deficiency that causes DMD and is routinely used for preclinical drug testing. There is a need to develop sensitive, non-invasive outcome measures in the mdx model that can be readily translatable to human clinical trials. Here we report the use of magnetic resonance imaging and spectroscopy techniques for the non-invasive monitoring of muscle damage in mdx mice. Using these techniques, we studied dystrophic mdx muscle in mice from 6 to 12 weeks of age, examining both the peak disease phase and natural recovery phase of the mdx disease course. T2 and fat-suppressed imaging revealed significant levels of tissue with elevated signal intensity in mdx hindlimb muscles at all ages; spectroscopy revealed a significant deficiency of energy metabolites in 6-week-old mdx mice. As the mdx mice progressed from the peak disease stage to the recovery stage of disease, each of these phenotypes was either eliminated or reduced, and the cross-sectional area of the mdx muscle was significantly increased when compared to that of wild-type mice. Histology indicates that hyper-intense MRI foci correspond to areas of dystrophic lesions containing inflammation as well as regenerating, degenerating and hypertrophied myofibers. Statistical sample size calculations provide several robust measures with the ability to detect intervention effects using small numbers of animals. These data establish a framework for further imaging or preclinical studies, and they support the development of MRI as a sensitive, non-invasive outcome measure for muscular dystrophy.     

Nonsurgical breast enlargement using an external soft-tissue expansion system

Less than 1 percent of the women interested in having larger breasts elect to have surgical augmentation mammaplasty with insertion of breast implants. The purpose of this report is to describe and test the efficacy of a nonsurgical method for breast enlargement that is based on the ability of tissues to grow when subjected to controlled distractive mechanical forces. Seventeen healthy women (aged 18 to 40 years) who were motivated to achieve breast enlargement were enrolled in a single-group study. The participants were asked to wear a brassiere-like system that applies a 20-mmHg vacuum distraction force to each breast for 10 to 12 hours/day over a 10-week period. Breast size was measured by three separate methods at regular intervals during and after treatment. Breast tissue water density and architecture were visualized before and after treatment by magnetic resonance imaging scans obtained in the same phase of the menstrual cycle. Twelve subjects completed the study; five withdrawals occurred due to protocol noncompliance. Breast size increased in all women over the 10-week treatment course and peaked at week 10 (final treatment); the average increase per woman was 98 +/- 67 percent over starting size. Partial recoil was seen in the first week after terminating treatment, with no significant further size reduction after up to 30 weeks of follow-up. The stable long-term increase in breast size was 55 percent (range, 15 to 115 percent). Magnetic resonance images showed no edema and confirmed the proportionate enlargement of both adipose and fibroglandular tissue components. A statistically significant decrease in body weight occurred during the course of the study, and scores on the self-esteem questionnaire improved significantly. All participants were very pleased with the outcome and reported that the device was comfortable to wear. No adverse events were recorded during the use of the device or after treatment. We conclude that true breast enlargement can be achieved with the daily use of an appropriately designed external expansion system. This nonsurgical and noninvasive alternative for breast enlargement is effective and well tolerated.     

The effects of deformation, ischemia, and reperfusion on the development of muscle damage during prolonged loading

Deep tissue injury (DTI) is a severe form of pressure ulcer where tissue damage starts in deep tissues underneath intact skin. In the present study, the contributions of deformation, ischemia, and reperfusion to skeletal muscle damage development were examined in a rat model during a 6-h period. Magnetic resonance imaging (MRI) was used to study perfusion (contrast-enhanced MRI) and tissue integrity (T2-weighted MRI). The levels of tissue deformation were estimated using finite element models. Complete ischemia caused a gradual homogeneous increase in T2 (～20% during the 6-h period). The effect of reperfusion on T2 was highly variable, depending on the anatomical location. In experiments involving deformation, inevitably associated with partial ischemia, a variable T2 increase (17-66% during the 6-h period) was observed reflecting the significant variation in deformation (with two-dimensional strain energies of 0.60-1.51 J/mm) and ischemia (50.8-99.8% of the leg) between experiments. These results imply that deformation, ischemia, and reperfusion all contribute to the damage process during prolonged loading, although their importance varies with time. The critical deformation threshold and period of ischemia that cause muscle damage will certainly vary between individuals. These variations are related to intrinsic factors, such as pathological state, which partly explain the individual susceptibility to the development of DTI and highlight the need for regular assessments of individual subjects.     

Arteriolar and systemic autoregulatory responses during the development of hypertension in the spontaneously hypertensive rat

Pressure-flow curves were constructed to determine whether acute autoregulation in rat skeletal muscle was altered during the development of hypertension in the spontaneously hypertensive rat (SHR). Under chloralose:urethane anesthesia, hindlimb blood flow and pressure, plus diameter changes of gracilis muscle arterioles, were simultaneously measured in the 6- and 9-week Wistar-Kyoto (WKY) and SHR. Femoral blood flow was measured by electromagnetic flowmetry and hindlimb pressure controlled with an hydraulic occluder. Arteriolar diameters were measured using image shearing techniques. Acute autoregulatory capacity was assessed by comparing the closed-loop gain and the regression lines over the regulated and passive pressure ranges of the pressure-flow curves. The lower pressure limit of autoregulation (LPLAR) shifted upward as the blood pressure increased in the SHR with age; it did not shift in the WKY. Resting hindlimb flow, elevated in the SHR at 6 weeks, was also elevated at the LPLAR. At 9 weeks hindlimb blood flow was comparable in the WKY and SHR. As blood pressure was increased autoregulation was accompanied by vasoconstriction of gracilis arterioles. However, neither the gain of the autoregulatory system nor the regression lines describing the pressure-flow curves were different between the hypertensive and normotensive animals at either age. These results indicate that the acute autoregulatory response mechanism was not affected by the developing hypertension in the SHR, and is consistent with a structural basis for the chronic maintenance of the elevated peripheral vascular resistance.     

Magnetic resonance imaging findings of vascular malformations of the lower extremity

Vascular malformations are congenital lesions resulting from a defect during embryogenesis. Magnetic resonance imaging (MRI) is a very effective method for demonstrating detailed information regarding involved structures, extent, and flow characteristics of vascular malformations. In previous MRI studies, most of the emphasis is laid on the difference between high- and low-flow lesions, whereas little detailed information is available about the extent of local tissue involvement. These additional characteristics may influence the approach in treating these malformations and improve understanding of the pathogenesis. We retrospectively reviewed MRI scans of 40 patients with vascular malformations of the lower extremity. Thirty-four patients had low-flow lesions, and six had high-flow lesions. Of the low-flow lesions, 23 patients (67.6 percent) had muscle infiltration, with four of the six high-flow lesions having muscle infiltration. Nine of the 11 male patients (81.8 percent) with low-flow lesions had associated muscle infiltration, in comparison with 14 of the 23 female patients (60.9 percent) with low-flow lesions (p = 0.206). Eighty percent of the vascular malformations located on the thigh with muscle involvement had involvement of the anterior muscle group, whereas 86.6 percent of the patients with a vascular malformation located on the leg and with associated muscle involvement had at least the posterior muscle group involved (p = 0.0049). Ten patients (25 percent) of the whole group had bone infiltration. Low-flow lesions often had multifocal lesions (20.6 percent), whereas associated muscle atrophy was visible in 10 low-flow lesions and in two high-flow lesions. In low-flow lesions with muscle infiltration (n = 23), 43 percent (n = 10) had associated surrounding muscle atrophy (p = 0.009). Hypertrophy of the subcutaneous tissue was visible in 11 low-flow patients (32.4 percent). The high amount of muscle and bone involvement in vascular malformations of the lower extremity is emphasized with this study. Of particular interest was the difference in affected muscle groups. The angiosome concept is used to explain this preponderance, and we feel the angiosome concept could also be used when assessing possible intervention. The surrounding muscle atrophy and multifocal nature of these anomalies are further important considerations when assessing the possibility of intervention.     

Proteomic analysis of rat soleus muscle undergoing hindlimb suspension-induced atrophy and reweighting hypertrophy

A proteomic analysis was performed comparing normal rat soleus muscle to soleus muscle that had undergone either 0.5, 1, 2, 4, 7, 10 and 14 days of hindlimb suspension-induced atrophy or hindlimb suspension-induced atrophied soleus muscle that had undergone 1 hour, 8 hour, 1 day, 2 day, 4 day and 7 days of reweighting-induced hypertrophy. Muscle mass measurements demonstrated continual loss of soleus mass occurred throughout the 21 days of hindlimb suspension; following reweighting, atrophied soleus muscle mass increased dramatically between 8 hours and 1 day post reweighting. Proteomic analysis of normal and atrophied soleus muscle demonstrated statistically significant changes in the relative levels of 29 soleus proteins. Reweighting following atrophy demonstrated statistically significant changes in the relative levels of 15 soleus proteins. Protein identification using mass spectrometry was attempted for all differentially regulated proteins from both atrophied and hypertrophied soleus muscle. Five differentially regulated proteins from the hindlimb suspended atrophied soleus muscle were identified while five proteins were identified in the reweighting-induced hypertrophied soleus muscles. The identified proteins could be generally grouped together as metabolic proteins, chaperone proteins and contractile apparatus proteins. Together these data demonstrate that coordinated temporally regulated changes in the skeletal muscle proteome occur during disuse-induced soleus muscle atrophy and reweighting hypertrophy.     

Water exchange induced by unilateral exercise in active and inactive skeletal muscles.

Water exchange was evaluated in active (E-leg) and inactive skeletal muscles by using (1)H-magnetic resonance imaging. Six healthy subjects performed one-legged plantar flexion exercise at low and high workloads. Magnetic resonance imaging measured calf cross-sectional area (CSA), transverse relaxation time (T2), and apparent diffusion capacity (ADC) at rest and during recovery. After high workload, inactive muscle decreased CSA and T2 by 2.1% (P < 0.05) and 3.1% (P < 0.05), respectively, and left ADC unchanged. E-leg simultaneously increased CSA, T2, and ADC by 4.2% (P < 0.001), 15.5% (P < 0.05), and 12.5% (P < 0.001), respectively. In conclusion, ADC and T2 correlated highly with muscle volume, indicative of extravascular water displacement closely related to muscle activity and perfusion, which was presumably a combined effect of increased intracellular osmoles and hydrostatic forces as driving forces. A distinguishable muscle temperature release was initially detected in the E-leg after high workload, and the ensuing recovery of ADC and T2 indicated delayed interstitial restitution than restitution of the intracellular compartment. Furthermore, absorption of extravascular water was detected in inactive muscles at contralateral high-intensity exercise.     

Hormonal studies of young lean and obese Zucker rats

Plasma concentrations of insulin, corticosterone, T3, T4 and glucose were measured at 6 hour intervals throughout 24 hours in undisturbed, 34-day-old lean (Fa/?) and genetically obese (fa/fa) Zucker rats. fa/fa rats had higher plasma concentrations of insulin at all sampling times and higher plasma concentrations of corticosterone at 0300 and 0900 hours. Neither T3 nor T4 levels differed between phenotypes at any sampling time. Fasting for 24 hours at 34 days abolished the hyperinsulinaemia of fa/fa rats and raised the plasma corticosterone concentrations of both phenotypes. Before weaning there were no phenotypic differences in the plasma insulin or corticosterone concentrations measured at two sampling times in undisturbed rats. Following an intra-gastric glucose load however, fa/fa rats became hyper-insulinaemic compared with similarly treated Fa/? animals. Pancreatic insulin contents were higher in fa/fa rats at 34 days of age, but not before weaning. Somatostatin contents of the pancreas, hypothalamus and cerebral cortex did not differ between phenotypes at either 18 or 34 days of age. In conclusion, the elevated plasma concentrations of insulin and corticosterone in young fa/fa rats may contribute to their greater lipid deposition and lower protein deposition.     

Training increases muscle blood flow in rats with peripheral arterial insufficiency

This study investigated the effect of physical training on muscle blood flow (BF) in rats with peripheral arterial insufficiency during treadmill running. Bilateral stenosis of the femoral artery of adult rats (300-350 g) was performed to reduce exercise hyperemia in the hindlimb but not limit resting muscle BF. Rats were divided into normal sedentary, acute stenosed (stenosed 3 days before the experiment), stenosed sedentary (limited to cage activity), and stenosed trained (run on a treadmill by a progressively intense program, up to 50-60 min/day, 5 days/wk for 6-8 wk). Hindlimb BF was determined with 85Sr- and 141Ce-labeled microspheres at a low (20 m/min) and high treadmill speed (30-40 m/min depending on ability). Maximal hindlimb BF was reduced to approximately 50% normal in the acute stenosed group. Total hindlimb BF (81 +/- 5 ml.min-1.100 g-1) did not change in stenosed sedentary animals with 6-8 wk of cage activity, but a redistribution of BF occurred within the hindlimb. Two factors contributed to a higher BF to the distal limb muscle of the trained animals. A redistribution BF within the hindlimb occurred in stenosed trained animals; distal limb BF increased to approximately 80% (P less than 0.001) of the proximal tissue. In addition, an increase in total hindlimb BF with training indicates that collateral BF has been enhanced (P less than 0.025). The associated increase in oxygen delivery to the relatively ischemic muscle probably contributed to the markedly improved exercise tolerance evident in the trained animals.     

Exercise selectively increases G4 AChe activity in fast-twitch muscle

Acetylcholinesterase (AChe) molecular forms were studied in hindlimb skeletal muscles from adult male Fischer 344 rats subjected to treadmill exercise for periods ranging between 1 and 30 days. Groups of three animals were exercised for 1 h/day at a treadmill speed of 8.5 m/min, with 1-min sprints at 15 m/min every 10 min. This exercise protocol led to a significant increase in the activity of G4 AChe in fast-twitch (gracilis and tibialis) but not in slow-twitch (soleus) muscles. Other AChe forms and muscle protein content remained unaltered. Such a selective enzymatic change was detected after a single exercise session, became more apparent after three daily sessions, and persisted for at least 30 days of exercise. A larger increment in G4 AChe activity was observed in gracilis muscle end-plate vs. non-end-plate regions. These findings show a specific adaptive reaction of fast-twitch muscles to enhanced motor activity, suggest that individual AChe forms in motor end plates are regulated through separate mechanisms, and support the hypothesis that membrane-bound G4 AChe plays an essential role in neuro-muscular transmission.