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S Egginton

Publications and source records attributed to S Egginton.

At least 19 recordsLinked to original sources

Regional capillary perfusion in muscles with limited blood supply: effects of torbafylline.

Severe limitation of blood supply mainly affects the oxidative regions of skeletal muscles. In mammals, they are located medially and are thus not accessible to direct observation. We therefore investigated capillary perfusion in rat tibialis anterior, which has a predominantly glycolytic cortex and oxidative core, using timed intraarterial injection of the fluorochrome thioflavine S conjugated with serum albumin. Muscles with intact blood supply were compared with those in which the blood supply had been limited for 5 weeks by unilateral ligation of the common iliac artery. The effect of a new xanthine derivative, torbafylline (1% solution, 12.5 mg/kg, in two daily doses by gavage, 7 days/week), was also studied. The capillary/fibre ratio was estimated for perfused capillaries (those filled with fluorochrome within 7.5 s after injection; Cp) and all capillaries (those subsequently stained for alkaline phosphatase; Ct), from micrographs of cryostat sections. Regional differentiation in relative capillary perfusion was evident in all muscles samples. Cp:Ct was 0.406 +/- 0.086 (mean +/- 95% CI) in the glycolytic cortex of the contralateral normal muscle, and 0.255 +/- 0.071 in the oxidative core. Muscles with limited blood supply had a significantly lower proportion of perfused capillaries, 0.119 +/- 0.056 in glycolytic and 0.034 +/- 0.038 in oxidative regions. Torbafylline treatment nearly doubled perfusion in the glycolytic regions (Cp:Ct = 0.216 +/- 0.137) and nearly quadrupled it in oxidative (Cp:Ct = 0.121 +/- 0.151) regions of ischaemic muscles. It also improved perfusion in the contralateral muscles (Cp:Ct = 0.705 +/- 0.085 in the glycolytic cortex and 0.583 +/- 0.230 in the oxidative core).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

The effect of torbafylline on enzyme activities in fast and slow muscles with limited blood supply.

1. Activities of a glycolytic enzyme--lactate dehydrogenase, LDH, and two oxidative enzymes--citrate synthase (CS), a marker for TCA cycle entry, and 3-hydroxyacyl-CoA dehydrogenase (HAD), which indicates the capacity for beta-oxidation of endogenous lipids, were measured in fast (tibialis anterior, TA, and extensor digitorum longus, EDL) and slow (soleus, SOL) muscles of Sprague-Dawley rats with intact and limited blood supply, and following treatment with the xanthine derivative torbafylline (Hoechst, Werk Albert, Wiesbaden). 2. Limitation of blood supply by unilateral ligation of the common iliac artery increased activity of LDH in fast muscles, and activity of CS and HAD in soleus. 3. Torbafylline treatment caused an increased LDH activity in intact fast muscles and decreased it in soleus, although the relative capacity for anaerobic and aerobic metabolism (indicated by the ratio of LDH and CS activities) remained unchanged in all cases. 4. Whilst having little effect on oxidative enzyme activity of fast muscles, torbafylline decreased the activity of CS but increased activity of HAD in soleus, suggesting a greater reliance on lipid metabolism. 5. The effect of arterial ligation on enzyme activity was ameliorated by treatment with torbafylline, possibly due to its effect on the microcirculation.

3-Hydroxyacyl CoA Dehydrogenases

Changes in capillary perfusion induced by different patterns of activity in rat skeletal muscle.

The proportion of "perfused" capillaries was evaluated in rat tibialis anterior at rest and during two different types of contraction after timed injection of thioflavine S. Capillary/fibre (C/F) ratio was estimated for "perfused" capillaries--those filled with fluorochrome--(Cp) from photomicrographs. Sections were subsequently stained for alkaline phosphatase and C/F ratio was estimated for all capillaries (Ct). At 7.5 sec after injection of fluorochrome, Cp:Ct at rest was 0.32 +/- 0.092 in the oxidative core and 0.43 +/- 0.058 in the glycolytic cortex (means +/- SEM). This increased to 0.83 +/- 0.045 and 0.88 +/- 0.026, respectively, during selective activation of glycolytic fibres. Activation of all fibres led to a modest further increase (0.92 +/- 0.040 in the core and 0.91 +/- 0.035 in the cortex). Blood flow (measured by radiolabelled microspheres increased to a similar extent (fivefold) in both regions of the muscle during activation of glycolytic fibres; the further increase during maximal activation was much smaller in the cortex (from 4 to 41 ml/100 g/min) than in the core (from 7 to 196 ml/100 g/min). Increased capillary perfusion during muscle contractions was thus independent of the type of activity, while muscle blood flow increased more in oxidative than in glycolytic regions during maximal activation. Thus the increase in muscle blood flow with maximal activation cannot be accounted for by further recruitment of "unperfused" capillaries and must result from a significant increase in the velocity of capillary blood flow.

Animals

Numerical and areal density estimates of fibre type composition in a skeletal muscle (rat extensor digitorum longus).

The composition of a mixed fast skeletal muscle (rat extensor digitorum longus) was examined to quantify the difference between the relative number of the three major fibre types in a representative muscle and their relative contribution to muscle cross-section, i.e. numerical (NN) and areal (AA) densities, respectively. These two indices clearly differ in their physiological relevance. While the former may be useful in describing hyperplasia, the latter allows for differences in size among fibre types. When estimated as NN, over 20% of fields contained 5-10% SO fibres and less than 5% had 75-80% FG fibres. In contrast, only 2% of fields had an AA of 5-10% for SO fibres while around 30% contained 75-80% FG fibres. The importance of a direct method for estimating AA is emphasised, as an indirect approach may have an error of 20-30% when used for oxidative fibre types. The use of an unbiased sampling regime to minimise error in determining both numerical and areal densities of different fibre types is illustrated.

Animals

Quantifying capillary distribution in four dimensions.

Analysis of spatial distribution using numerical (O-D) distribution is limited to global estimates, while linear (1-D) separation of capillaries may be used to describe unrealistic spatial patterns. Intramuscular diffusion is best viewed as an integration of all distances between surrounding capillaries, or area (2-D) of influence for individual vessels. True planar analysis also accommodates other forms of heterogeneity, and may be extrapolated to give the volume (3-D) of tissue supplied by capillaries. Temporal (4-D) heterogeneity in functional spacing may then be quantified.

Animals

Influence of muscle phenotype on local capillary supply.

The general method used to compute a local capillary fibre ratio for each fibre is as follows. The selected area of the section is covered by a tessellation of domains. For each fibre, the contribution of each capillary whose domain intersects the fibre is computed as the proportion of the domain area which overlaps the fibre. The sum of all the contributions from overlapping domains is taken to be the effective number of capillaries contributing to that fibre, and is called here the local capillary fibre ratio (LCFR). This parameter may be normalised by dividing by fibre area to give an index, independent of fibre size, which is capable of identifying the differential capillary supply to fibre types within a mixed muscle.

Animals

Thermal acclimation induces adaptive changes in subcellular structure of fish skeletal muscle.

Stereological analyses of electron micrographs were used to quantify physiologically important ultrastructures of slow-twitch oxidative (red) and fast-twitch glycolytic (white) muscle fibers from striped bass (Morone saxatilis) acclimated to 25 and 5 degrees C. The fraction of cell volume occupied by the mitochondria [volume density, Vv (mit,f)] of red fibers increases from 0.286 +/- 0.018 to 0.448 +/- 0.024 between 25 and 5 degrees C; Vv (mit,f) of white fibers increased from 0.027 +/- 0.003 and 0.040 +/- 0.004 at 25 and 5 degrees C, respectively. Because of a concomitant increase in the mass of oxidative muscle, acclimation from 25 to 5 degrees C results in an increase in total mitochondrial volume per 100 g body wt from 2.58 to 6.73 cm3 in oxidative muscle and from 2.46 to 3.40 cm3 in fast glycolytic muscle. Mitochondria of red fibers are in more clustered arrays after cold acclimation. Size and cristae surface densities of individual mitochondria are not affected markedly by acclimation, suggesting true cold-induced proliferation rather than enlargement of organelles. Harmonic means of intermitochondrial spacing in red fibers decreases from 2.64 to 1.43 micron between 25 and 5 degrees C. This reduces diffusion path lengths between sarcoplasmic and mitochondrial compartments proportionately, compensating for decreases in diffusivity of aqueous solutes. Intracellular lipid droplets of red fibers markedly increase in volume density from 0.006 +/- 0.003 at 25 degrees C to 0.079 +/- 0.014 at 5 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Adaptation, Physiological

Capillary density and fine structure in rabbit papillary muscles after a high dose of norepinephrine.

Two days after an iv infusion of norepinephrine (NE) (4 micrograms.kg-1.min-1 X 60 min) in rabbits, patchy myocardial damage in frozen cross sections of right and left papillary muscles was associated with loss of staining for alkaline phosphatase (ALP), an enzyme present in normal capillary endothelium, whereas a regular pattern of staining was observed in control normal muscles. Semithin cross sections of the same muscles after resin embedment gave comparable estimates of capillary density in control muscles and undamaged regions of norepinephrine-treated muscles. In damaged regions the complete absence of ALP staining corresponded with an apparent reduction in number, but not absence, of capillaries identifiable in semithin sections with light microscopy. Electron microscopy, however, revealed capillaries present in these regions in numbers similar to control undamaged tissue. Around 90% of these capillaries exhibited marked morphological abnormalities, with an 18% increase in endothelial cell volume density and a corresponding reduction in luminal volume density. These changes are similar to those reported after ischemia in cardiac and skeletal muscle. Myocardial damage induced by a high dose of NE is therefore associated 48 hr later with loss of ALP staining and endothelial cell disruption and edema, which may impair capillary perfusion and contribute to limited working cardiac performance observed previously.

Alkaline Phosphatase

Differing patterns of capillary distribution in fish and mammalian skeletal muscle.

The heterogeneity of capillary supply to muscles of different metabolic capacity and fibre size was assessed in slow and fast muscles from a fish and a mammal. The area surrounding each capillary delineated by equidistant boundaries from adjacent vessels, the capillary domain, was derived from morphometric analysis of histological sections. This 2-D integration of intercapillary distances may reveal heterogeneity of supply that is hidden by a global approach, especially when compared with the more usual 0- and 1-D indices of capillarisation. Mean radii of the equivalent Kroghian tissue cylinders (R) and heterogeneity of their lognormal distribution, represented by the logarithmic standard deviation (LogSD), were calculated. In eel slow muscle there was a 35-fold greater capillary density (CD) than fast muscle (698 vs 20 mm-2) although heterogeneity of capillary spacing was similar (LogSD congruent to 0.06). The difference in CD between slow and fast muscles of rat was less pronounced, but there was significantly lower heterogeneity in the aerobic tissue (LogSD = 0.08 vs 0.10) corresponding to a range in domain area of around 350-2300 microns 2 and 400-2900 microns 2, respectively. The overall capillary to fibre ratio (C:F) is inappropriate for sparse networks where many fibres lack direct capillary contact. The cumulative fraction of individual domains overlapping a muscle fibre (local capillary to fibre ratio, LCFR) plotted against fibre area showed the best correlation of any index in all tissue and was strongest in both fish muscles (r = 0.9), indicating a functionally homologous spatial distribution of capillaries with respect to muscle fibres in tissue of widely differing oxidative capacity. These data suggest that maximal oxygen supply to, or metabolite removal from, muscle fibres is not restricted to contiguous capillaries but also involves those remote from the fibre surface.

Animals

Metamorphosis of the American eel, Anguilla rostrata LeSeur: III. Contractile characteristics of skeletal muscle.

Previous work has suggested a common migratory strategy among fishes may involve changes in recruitment pattern of skeletal muscle types, allowing fast muscle to function continuously. In this study no evidence was found for changes in adenine nucleotide metabolism, thought to be important in fatigued muscle, with metamorphosis from the nonmigratory yellow to migratory silver eel in either slow or fast muscle tissue. Myofibrillar ATPase activity was found to be lower than reported values for other teleosts, around 0.075 and 0.17 microM inorganic phosphate mg-1 min-1 for slow and fast muscle, respectively. No change was found in the Ca++-kinetics of the enzyme within either muscle type. Likewise, no change in the contractile performance of fast muscle was evident, arguing against changes in activity pattern. In contrast to mammalian endurance exercise training where major changes in aerobic capacity occur in fast muscle, migratory pre-adaptation in eel appears to be restricted to changes in slow muscle performance. A displacement of the slow muscle force-velocity curve to the right upon metamorphosis results in 30% increase in the tension developed at maximal power output from 2.4 to 3.2 N cm-2. The difference in migratory potential between yellow and silver eels was shown previously to involve an increased aerobic capacity. The change in contractile characteristics may further improve endurance by permitting a portion of the tissue to periodically replenish endogenous energy stores.

AMP Deaminase

Morphometric analysis of sparse capillary networks.

Two methods were used to assess the heterogeneity of capillary supply to muscles of widely differing metabolic capacity and fibre size. Using the method of capillary domains (DOM; Hoofd et al., 1985) and the closest-individual method (CI; Kayar et al., 1981) radii of Kroghian cylinders (R) can be calculated, and the heterogeneity of their lognormal distribution represented by the logarithmic standard deviation (Log SD). Both methods yield similar values for mean R in a tissue. DOM is more direct and quicker than CI, and may be particularly useful in the analysis of capillary oxygen supply during functional hypertrophy and in muscle regeneration where a broad distribution of fibre areas may be found. Despite a 500-fold range of capillary density, to a minimum of 20 capillaries mm-2, heterogeneity of capillary supply was similar in all muscles, indicating a functionally homologous spatial distribution. The relationship between number of fibres overlapped by a capillary domain, and domain area has zero correlation in most tissues but shows a negative trend in fish fast muscle, reflecting hyperplastic and hypertrophic growth. Capillary/fibre ratio is inappropriate for sparse networks whereas the cumulative fraction of domains vs fibre area shows a strong correlation, suggesting that maximal oxygen supply to muscle fibres is not restricted to contiguous capillaries, but also involves those remote from the fibre surface.

Animals

Effects of an anabolic hormone on striated muscle growth and performance.

Chronic administration of an anabolic hormone, nandrolone phenylpropionate, in sedentary female rats for 6 weeks gave a 20% increase in body weight and the same proportional increase in all muscles sampled (heart, diaphragm, soleus, TA, EHP and EDL), such that the muscle/body weight ratio was unchanged. Cardiac muscle was unresponsive to treatment. Acute stimulation of EDL via lateral popliteal nerve gave similar values for contraction time, 1/2 relaxation time and twitch:tetanus ratio in both groups suggesting no slowing of the muscle. Fatigue resistance of EDL was improved with 0.29 +/- 0.029 vs. 0.46 +/- 0.071 of maximum isometric twitch tension being developed after 10 min repetitive stimulation at 4 Hz. This improved endurance was not accompanied by any increase in strength and could not be explained on the basis of cellular hypertrophy, but appears to reflect an increased aerobic capacity of skeletal muscle. The proportion of FOG fibres in EDL increased, 38 +/- 1.1% vs. 46 +/- 1.1%, and this was paralleled in the other skeletal muscles. Specific hypertrophy of FOG and FG fibres could be conclusively demonstrated in soleus and TA, respectively.

Adenosine Triphosphatases

Effects of an anabolic hormone on aerobic capacity of rat striated muscle.

The effect of chronic administration for 6 weeks of an anabolic steroid, nandrolone phenylpropionate (Durabolin), was studied in three predominantly glycolytic muscles, and three oxidative muscles of sedentary female rats. Mean blood pressure and resting heart rate (HR) were lower in the anabolic-treated group, while the increase in HR during stimulation of EDL was reduced. No change was noted in the aerobic capacity of ventricular myocardium, although there was an increase in skeletal muscles due to a combination of increased capillary supply and/or TCA cycle enzyme activity. Capillary:fibre ratio (C:F) increased around 10% in glycolytic muscle with little effect on resting blood flow (BF). In EDL C:F was 1.1 +/- 0.02 vs. 1.2 +/- 0.01 and BF was 7.0 +/- 1.45 vs. 6.2 +/- 1.82 ml min-1 100 g-1 for control and Durabolin treated animals, respectively (means +/- SEM, n = 7). No increase in citrate synthase (CS) activity was evident. In soleus, where C:F was not significantly different between groups, CS activity increased from 3.9 +/- 0.34 to 5.9 +/- 0.40 microM g-1 min-1 (means +/- SEM, n = 7). Glycolytic capacity, indicated by pyruvate kinase activity, increased only in diaphragm. These data demonstrate that total oxidative metabolism of striated muscle does not necessarily increase with greater proportion of FOG fibres, nor is it always correlated with capillary supply. The positive myotrophic effect of Durabolin represents the sum of modest changes at different levels of organisation.

Aerobiosis

Metamorphosis of the American eel, Anguilla rostrata LeSeur: I. Changes in metabolism of skeletal muscle.

Unequivocal demarcation between immature, nonmigratory yellow eels and migratory silver eels of greater sexual maturity is possible by measuring eye diameter and retinal capillary length, which undergo a 1.5- and 2.3-fold increase during metamorphosis, respectively. Anatomical arrangement of trunk musculature is similar in the two groups except for an increased depth of slow muscle in silver eel. Histochemical analysis reveals a progressive increase in numbers of "displaced" fast fibres within slow muscle of the lateral line triangle in maturing eels, although these are unlikely to affect recruitment pattern of muscle fibre types. Previous studies have suggested greater involvement of fast muscle in locomotion of migratory eels. In contrast, estimates of enzyme activity in fast muscle suggest an inadequate aerobic capacity to fuel sustained activity. Myoglobin content is extremely low, around 0.4 nM g wet wt-1. Prolonged anaerobic metabolism is also discounted as a migratory strategy. Increased energy provision for migration is apparently derived from increased capacity for both aerobic carbohydrate metabolism and mitochondrial fatty acid oxidation within slow muscle of silver eels. Activity of hexokinase (HK) shows a 1.6-fold increase (to 0.51 microM g wet wt-1) and carnitine palmitoyltransferase (CPT) a 3.1-fold increase (to 0.22 microM g wet wt-1 min-1), suggesting a maximal flux through these pathways of 18 and 14 ATP equivalents, respectively. However, the fatty acyl transferase system of skeletal muscle mitochondria displays up to threefold greater activity with palmitoleoyl CoA (C16:1) as substrate than with the usual palmitoyl CoA (C16:0). Slow muscle of silver eel is therefore capable of deriving aerobic energy from free fatty acids and carbohydrate in the ratio 2.3:1. Differences in aerobic enzyme activities are not paralleled by myoglobin content of slow muscle, being 15 and 16 nM g wet wt-1 for yellow and silver eel, respectively. Structural reorganization of muscle fibres during metamorphosis, however, results in a twofold elevation of cytoplasmic myoglobin concentration in silver eel. It would appear that dramatic differences in metabolic capacity between life history stages of eel is required to overcome locomotory inefficiency of yellow eels and to "preadapt" silver eels for migratory activity. This increased locomotory capacity may be amplified by a subsequent training response.

Aging