Can angiogenesis induced by chronic electrical stimulation enhance latissimus dorsi muscle flap survival for application in cardiomyoplasty?

In cardiomyoplasty, the latissimus dorsi muscle is lifted on its primary neurovascular pedicle and wrapped around a failing heart. After 2 weeks, it is trained for 6 weeks using chronic electrical stimulation, which transforms the latissimus dorsi muscle into a fatigue-resistant muscle that can contract in synchrony with the beating heart without tiring. In over 600 cardiomyoplasty procedures performed clinically to date, the outcomes have varied. Given the data obtained in animal experiments, the authors believe these variable outcomes are attributable to distal latissimus dorsi muscle flap necrosis. The aim of the present study was to investigate whether the chronic electrical stimulation training used to transform the latissimus dorsi muscle into fatigue-resistant muscle could also be used to induce angiogenesis, increase perfusion, and thus protect the latissimus dorsi muscle flap from distal necrosis. After 14 days of chronic electrical stimulation (10 Hz, 330 microsec, 4 to 6 V continuous, 8 hours/day) of the right or left latissimus dorsi muscle (randomly selected) in 11 rats, both latissimus dorsi muscles were lifted on their thoracodorsal pedicles and returned to their anatomical beds. Four days later, the resulting amount of distal flap necrosis was measured. Also, at predetermined time intervals throughout the experiment, muscle surface blood perfusion was measured using scanning laser Doppler flowmetry. Finally, latissimus dorsi muscles were excised in four additional stimulated rats, to measure angiogenesis (capillary-to-fiber ratio), fiber type (oxidative or glycolytic), and fiber size using histologic specimens. The authors found that chronic electrical stimulation (1) significantly (p < 0.05) increased angiogenesis (mean capillary-to-fiber ratio) by 82 percent and blood perfusion by 36 percent; (2) did not reduce the amount of distal flap necrosis compared with nonchronic electrical stimulation controls (29 +/- 5.3 percent versus 26.6 +/- 5.1 percent); (3) completely transformed the normally mixed (oxidative and glycolytic) fiber type distribution into all oxidative fibers; and (4) reduced fiber size in the proximal and middle but not in the distal segments of the flap. Despite the significant increase in angiogenesis and blood perfusion, distal latissimus dorsi muscle flap necrosis did not decrease. This might be because of three reasons: first, the change in muscle metabolism from anaerobic to aerobic may have rendered the muscle fibers more susceptible to ischemia. Second, because of the larger diameter of the distal fibers in normal and stimulated latissimus dorsi muscle, the diffusion distance for oxygen to the center of the distal fibers is increased, making fiber survival more difficult. Third, even though angiogenesis was significantly increased in the flap, cutting all but the single vascular pedicle resulted in the newly formed capillaries not receiving enough blood to provide nourishment to the distal latissimus dorsi muscle. The authors' findings indicate that chronic electrical stimulation as tested in these experiments could not be used to prevent distal latissimus dorsi muscle flap ischemia and necrosis in cardiomyoplasty.     

Regional injury and the terminal differentiation of satellite cells in stretched avian slow tonic muscle.

In the avian stretch model, the application of a weight overload to the humerus induces enlargement of the anterior latissimus dorsi (ALD) muscle and an increase in muscle fiber number which is accompanied by satellite cell activation. Myofiber injury may be an important stimulus to muscle fiber hyperplasia; therefore, light and electron microscopic evaluation was undertaken to determine if myofiber injury occurs in the stretch-enlarged ALD muscle of the adult quail. Autoradiographic studies were used to determine the terminal differentiation of labeled myogenic cells. A weight equal to 10% of body mass was attached to one wing of 27 adult quail and 3 birds were euthanized at 9 intervals of stretch, from 1 to 30 days. Birds were injected with tritiated thymidine at intervals ranging from 1 hr to 3 days prior to euthanization. Labeled nuclei were detected by light microscopic examination and identified by electron microscopy of a serial section. Three regions of the muscle were examined for disorganization of contractile elements, presence of cytoplasmic vacuoles, and/or phagocytic cell infiltration. The percentage of fibers exhibiting one or more of these criterion was significantly greater in the stretched ALD by Days 5 and 7 and declined at Day 10, reaching near control values by Day 14. Myofiber necrosis and phagocytic cell infiltration were only observed in the middle and distal regions of the stretched ALD muscle. Traditional signs of regeneration and repair were observed, including clusters of labeled myoblast-like cells and myotube formation within an existing basal lamina. New myotube formation with labeled central nuclei was also noted in the interstitial space, outside of basal lamina of persisting fibers. Labeled myonuclei were observed in the stretched fibers. These results demonstrate that chronic stretch produces regional injury and fiber degeneration and resultant regeneration in the ALD muscle of the adult quail. This may be an important stimulus for new fiber formation in this model.     

Subcellular responses of p53 and Id2 in fast and slow skeletal muscle in response to stretch-induced overload.

Tumor suppressor p53 and inhibitor of DNA-binding/differentiation Id2 were examined after 7 or 21 days of wing weighting in fast patagialis (PAT) and slow anterior latissimus dorsi (ALD) wing muscles of young adult and old Japanese quails. The contralateral wing served as the intra-animal control. Seven days of loading increased PAT and ALD muscle weight by 28 and 96%, respectively, in young birds. PAT and ALD muscle weight was 49 and 179% greater, respectively, than control muscles after 21 days of loading in young birds. In aged birds, no PAT or ALD hypertrophy was found after 7 days of loading; however, PAT and ALD muscle weight increased by 29 and 102%, respectively, after 21 days of loading. Id2 protein in the nuclear muscle fraction increased in both PAT and ALD muscles from young adult and old birds that were loaded for 7 days and in ALD muscles after 21 days of loading relative to contralateral control muscles. Nuclear p53 protein was greater in 7- or 21-day loaded PAT and ALD muscles relative to control muscles in both age groups. Cytosolic Id2 and p53 protein contents were not changed in loaded PAT or ALD muscles relative to control muscles at any time point. These data suggest that nuclear, but not cytosolic, Id2 and p53 are responsive to stretch-induced muscle overload. Moreover, the attenuated ability of the aged skeletal muscle to achieve hypertrophy does not appear to be explained by the subcellular changes in Id2 and p53 content with overload.     

Effect of denervation and tenotomy on slow and fast muscles of the chicken

Summary Changes of muscle weights, fiber diameters and ultrastructure were studied in the slow anterior latissimus dorsi (ALD) and in the fast posterior latissimus dorsi (PLD) of the chick three weeks after denervation and tenotomy, and after combined denervation and tenotomy of the two muscles.The slow ALD muscle becomes hypertrophic after denervation (Feng, Jung and Wu, 1962). Three weeks after nerve section, wet weights of ALD muscles are increased by 60% and fiber diameters become by 30% larger than those of contralateral control muscles. In spite of this hypertrophy, degenerative changes are seen in the ultrastructure, similar to those described in denervated atrophic muscles. Areas of dedifferentiation with autophagic vacuoles and aggregates of tubules are found in superficial layers of some fibers. Disintegration of Z lines and filaments along one or two sarcomeres occurs in a number of myofibrils, especially in muscles of young animals.In contrast to denervation alone, simultaneous denervation and tenotomy of the ALD muscles results in atrophy. Decrease of muscle weights and reduction of fiber diameters are similar as after tenotomy; in both cases muscle fibers waste by degeneration and atrophy of myofibrils.The fast PLD muscles underwent extensive atrophy in all three series of experiments. Corresponding atrophic and degenerative changes of ultrastructure were found in all instances.The authors wish to acknowledge gratefully the skillful technical assistance of Mrs. M. Sobotková and Ing. M. Doubek, and editorial assistance of Miss Virginia Hamilton.     

Focal adhesion proteins FAK and paxillin increase in hypertrophied skeletal muscle

Components of signaling pathways for mechanotransduction duringload-induced enlargement of skeletal muscle have not been completelydefined. We hypothesized that loading of skeletal muscle would resultin an adaptive increase in the expression of two focal adhesion complex(FAC)-related proteins, focal adhesion kinase (FAK) and paxillin, aswell as increased FAK activity. FAK protein was immunolocalized to thesarcolemmal region of rooster anterior latissimus dorsi (ALD) myofibersin the middle of the ALD muscle. FAK (77 and 81%) and paxillin (206 and 202%) protein concentrations per unit of total protein in Westernblots increased significantly after 1.5 and 7 days, but not after 13 days, of stretch-induced hypertrophy-hyperplasia of the ALD muscle. FAK autokinase activity in immunoprecipitates was increased after 1.5, 7, and 13 days in stretched ALD muscles. To determine whether increasedFAK and paxillin protein concentrations are associated with hypertrophyand/or new fiber formation, two additional experiments were performed.First, during formation of primary chicken myotubes (a model of newfiber formation), FAK protein concentration (63%), FAK activity(157%), and paxillin protein concentration (97%) increased comparedwith myoblasts. Second, FAK (112% and 611%) and paxillin (87% and431%) protein concentrations per unit of total protein in the soleusmuscle increased at 1 and 8 days after surgical ablation of thesynergistic gastrocnemius muscle (a model of hypertrophy withouthyperplasia). Thus increases in components of the FAC occur inhypertrophying muscle of animals and in newly formed muscle fibers inculture. Furthermore, increased FAK activity suggests a possibleconvergence of signaling at the FAC in load-induced growth of skeletal muscle.

     

Tenotomy of the avian anterior latissimus dorsi muscle. I. Effect of age on fiber-type transformation and regeneration from the stump in chicks

The chick's anterior latissimus dorsi muscle (ALD) was tenotomized at its origin at either 1 day or 4 weeks of age, and investigated histochemically and ultrastructurally at intervals thereafter to determine whether muscle fiber-type transformation from a slow to a twitch type is greater in young birds than older birds. No transformation of fiber type occurred in either procedure, but a new muscular connection regenerated between the scar tissue at the end of the original tenotomized stump and the former origin. This regenerated muscle had a mosaic pattern of fiber types, as demonstrated by myofibrillar ATPase activity, and contained predominantly fast fibers, as contrasted with controls or the tenotomized portion, which contained predominantly slow tonic muscle fibers. The regenerated portion contained muscle spindles. The original portion of the tenotomized muscle was indistinguishable from the control muscle. These responses of the chick ALD to tenotomy are quite different from those in the pigeon, which are reported in the following study.     

Acetylcholinesterase in singly and multiply innervated muscles of normal and dystrophic chickens. II. Effects of denervation.

Neural regulation of mature normal fast twitch muscle of the chicken suppresses high activity, extrajunctional localization, and isozyme forms of acetylcholinesterase (AChE) characteristic of embryonic, denervated and dystrophic muscle. Normal adult slow tonic muscle ofthe chicken retains intermediate levels of activity and embryonic isozyme forms but not extrajunctional activity; it is not affected by muscular dystrophy. The hypothesis that neural regulation of the AChE system is lacking in slow tonic muscle and thus not affected by dystrophy was tested by denervating the fast twitch posterior latissimus dorsi and slow tonic anterior latissimus dorsi muscles of normal and dystrophic chickens. Extrajunctional AChE activity and embryonic isozyme forms increased, then declined, in both muscles. The results suggest that ocntrol of AChE is qualitatively similar in slow tonic and fast twitch muscle of the chicken.     

Vinculin in subsarcolemmal densities in chicken skeletal muscle: localization and relationship to intracellular and extracellular structures

Using immunocytochemical methods we have studied the distribution of vinculin in the anterior and posterior latissimus dorsi skeletal (ALD and PLD, respectively) muscles of the adult chicken. The ALD muscle is made up of both tonic (85%) and twitch (15%) myofibers, and the PLD muscle is made up entirely of twitch myofibers. In indirect immunofluorescence, antivinculin antibodies stained specific regions adjacent to the sarcolemma of the ALD and PLD muscles. In the central and myotendinous regions of the ALD, staining of the tonic fibers was intense all around the fiber periphery. Staining of the twitch fibers of both ALD and PLD muscles was intense only at neuromuscular junctions and myotendinous regions. Electron microscopy revealed subsarcolemmal, electron-dense plaques associated with the membrane only in those regions where vinculin was localized by immunofluorescence. Using antivinculin antibody and protein A conjugated to colloidal gold, we found that the electron-dense subsarcolemmal densities in the tonic fibers of the ALD contain vinculin; no other structures were labeled. The basal lamina overlying the densities appeared to be connected to the sarcolemma by fine, filamentous structures, more enriched at these sites than elsewhere along the muscle fiber. Increased amounts of endomysial connective tissue were often found just outside the basal lamina near the densities. In tonic ALD muscle fibers, the subsarcolemmal densities were present preferentially over the I-bands. In partially contracted ALD muscle, subsarcolemmal densities adjacent to the Z-disk appeared to be connected to that structure by short filaments. We propose that in the ALD muscle, through their association with the extracellular matrix, the densities stabilize the muscle membrane and perhaps assist in force transmission.     

Numbers of myonuclei and satellite cell nuclei in latissimus dorsi muscles of the chicken

Summary In the 3-, 33- and 66-day-old chicken, two muscles, the oxidative slow tonic anterior latissimus dorsi and the glycolytic fast twitch posterior latissimus dorsi were compared by the measurement of muscle fibre diameter and the fraction of total muscle tissue nuclei which were either myonuclei or satellite cell nuclei. Between 3 and 33 days there was a period of rapid growth (more marked in the posterior latissimus dorsi) which coincided with a sharp fall in numerical density of myonuclei and satellite cell nuclei (number per cubic millimetre muscle tissue). The fraction of all nuclei which were satellite cell nuclei declined steadily.The higher levels of myonuclei and satellite cell nuclei in the anterior latissimus dorsi were thought to be a reflection of its oxidative metabolism and the presence of multiple endplates.The volume of sarcoplasm occupied by single myonuclei in anterior and posterior latissimus dorsi muscles was shown to be considerably greater than that occupied by nuclei in other cell systems.     

Characterization of the C-protein from posterior latissimus dorsi muscle of the adult chicken: heterogeneity within a single sarcomere

Specific isoforms of myofibrillar proteins are expressed in different muscles and in various fiber types within a single muscle. We have isolated and characterized monoclonal antibodies against C-proteins from slow tonic (anterior latissimus dorsi, ALD) and fast twitch (pectoralis major) muscles of the chicken. Although the antibody against "fast" C-protein (MF-1) did not bind to the "slow" isoform and the antibody to the "slow" C-protein (ALD-66) did not bind to the "fast" isoform, we observed that both antibodies bound C-protein from the posterior latissimus dorsi (PLD) muscle. Here we demonstrate that in the PLD muscle the binding sites of these two antibodies reside in two different C-protein isoforms which have different molecular weights and can be separated by hydroxylapatite column chromatography. Since we have shown previously that both these antibodies stain all myofibers and myofibrils derived from PLD muscle, we conclude that all myofibers in this muscle contain both isoforms with all sarcomeres.     

Properties of standard avian slow muscle grafts following long-term regeneration

The tonic anterior latissimus dorsi (ALD) of adult pigeons was orthotopically homografted and evaluated after 11 months of regeneration for histological, histochemical, electromyographic (EMG), and mechanical properties. The resting EMG activity of the grafts was lower in amplitude than that of the controls, but showed the tonic pattern typical for these tonic muscles. The control and grafted muscles had a histochemically homogeneous population of fibers with moderate myofibrillar adenosine triphosphatase activity. Succinic dehydrogenase activity was moderate for the control muscles, but low for the grafts. The regenerated muscles had fewer and smaller fibers and had much larger intersynaptic distances. Both the regenerated and the contralateral control muscles were slow contracting and maintained tetanic tension for prolonged periods with direct electrical stimulation. The relaxation was slower in the grafted muscle than in the control. The grafts produced 40% of the maximum tension of the control muscles, but the rate of tension development was similar between the two groups. The results indicate that the tonic properties were regenerated, but the innervation pattern was altered and the grafted muscles did not have normal mature fibers even after long-term regeneration.     

Capillarity and diffusion distances in skeletal muscles in birds

Summary Tissue capillarity and diffusion distances were determined for red and white skeletal muscles of adult birds ranging in mass from 10.8 to 6200 g. In addition, literature values for capillarity and diffusion distances in skeletal muscles of mammals were incorporated into the data set. Muscle mass was closely coupled to body mass. However, no significant allometric relations were found for any of the other variables measured. Number of capillaries per fiber was not correlated with cross sectional area of individual muscle fibers. Thus, capillary density decreased in a hyperbolic manner against fiber area and diffusion distance decreased in a hyperbolic manner against the number of capillaries per muscle fiber. Red muscles had significantly higher numbers of capillaries per fiber and significantly shorter diffusion distances than did white muscles. The patterns for tissue capillarity and diffusion distances in avian muscle reported here are similar to values reported previously for mammalian muscles. In both taxanomic groups capillarity and diffusion distances are independent of body mass. In addition, diffusion distances are characteristic of capillaries distributed in random arrays through the muscle cross section.Abbreviations ALD muscle anterior latissimus dorsi - CD numerical density of capillaries in muscle cross section - C/F number of capillaries per individual muscle fiber - FCSA fiber cross sectional area - GST muscle gastrocnemius - LGST lateral head of muscle gastrocnemius - MGST medial head of muscle gastrocnemius - MM muscle mass - PLD muscle posterior latissimus dorsi     

Absence of changes in fiber type with aging in avian muscles

Summary The anterior latissimus dorsi of the pigeon, a slow tonic muscle, and biventer cervicis, a mixed muscle, of two age groups (1–2 years old versus 6–8 years old) were compared with respect to percentages of fiber types and activities of adenosine triphosphatase (ATPase) and succinic dehydrogenase (SDH), as estimated histochemically, to determine whether these became altered with old age. These parameters did not change between the young and old birds for either type of muscle.This investigation was supported in part by research grants PCM 77-15960 and PCM 79-16540 from the National Science Foundation     

A histochemical study of twitch and tonus fibers

The distribution of glycogen, lipids and succinic dehydrogenase (SDH) in twitch and tonus fibers of several amphibians and birds is described, and the correlation of histochemical properties with fiber structure and function is discussed. Twitch and tonus fibers were identified histologically by the presence of Fibrillenstruktur and Felderstruktur respectively. The rectus abdominis, sartorius and semitendinosus were studied in Rana pipiens, Xenopus laevis and Necturus maculosus; the pectoralis major, pectoralis minor, anterior latissimus dorsi and posterior latissimus dorsi were investigated in Gallus gallus and Passer domesticus. Periodic acid-Schiff was used to stain for glycogen, Sudan Black B for lipids and Nitro BT for localization of SDH activity. In amphibian muscles, fibers with Fibrillenstruktur and Felderstruktur constitute the rectus abdominis. Except in one case, only Fibrillenstruktur fibers were seen in the sartorius and semitendinosus. In the avian muscles, fibers with Fibrillenstruktur comprise the pectoralis major, pectoralis minor and posterior latissimus dorsi, while fibers with Felderstruktur constitute the anterior latissimus dorsi. These types of muscle fibers showed no consistent pattern in the distribution of glycogen, lipids and SDH. The evidence precludes the use of such data alone for distinguishing twitch (Fibrillenstruktur) and tonus (Felderstruktur) fibers.     

Effect of denervation on pigeon slow skeletal muscle

Summary The slow anterior latissimus dorsi muscle (ALD) of the pigeon was denervated surgically and examined after varying post-operative intervals. Muscles were studied with respect to changes in weight, histological and ultrastructural alterations, and changes in size and number of fibers. The weights of the denervated muscles increased over the contralateral control, reaching a maximum hypertrophy in the first 18 days, but the hypertrophy persisted for several months. The fibers of the denervated muscle did not hypertrophy. They showed a gradation in size from the posterior to the anterior border, with the fibers in the anterior third of the muscle being the smallest. After measuring cross-sectional sizes from the anterior, middle, and posterior thirds of the muscle, the overall fiber change was one of atrophy.Morphologically, the fibers showed various signs of pathological changes, including nuclear proliferation, swelling and migration away from the sarcolemmal position, vacuolation, myofibril degeneration, connective-tissue infiltration and replacement of the fibers, and regenerative activities in the form of budding and myoblast formation. A condition termed a peripheral rim of degeneration is described. Although many abnormal conditions were found in these denervated muscles, much of the muscle appeared normal; the neurotrophic relationship of slow muscle is discussed.This investigation was supported in part by a Public Health Service Fellowship, 2 F 2 NB 35, 582, from the National Institute of Neurological Diseases and Stroke, and by an Ohio University Research Grant to R. Hikida; and a grant 5 RO 1 AN 10856 from the National Institute of Arthritis and Metabolic Diseases to W. Bock.The authors wish to acknowledge gratefully the skillful technical assistance of Mr. Lawrence Mezza and Miss Sally Mitchell.     

Fiber number, area, and composition of mouse soleus muscle following enlargement

Muscle fiber number, cross-sectional area, and composition were studied in response to enlargement produced by synergistic ablation in the mouse soleus muscle. The effect of the location of a histological section on the number of fibers that appear in the section was also studied using the mouse soleus muscle. Enlargement was produced in the soleus muscle of 15 male and 15 female mice by ablation of the ipsilateral gastrocnemius muscle. Fiber counts, using the nitric acid digestion method, revealed no difference between control and enlarged muscles in male and female mice. Mean fiber area, determined by planimetry, was 49.1 and 34.5% greater following enlargement in male and female mice, respectively. Increase in muscle weight could be totally accounted for by the increase in fiber area following enlargement. A transformation of type II to type I fibers occurred following enlargement for both sexes. Counts of fibers from histological sections revealed that there was a progressive decrease in the fiber number as the section was moved from the belly to the distal end of the muscle. The results of these studies indicate that muscle enlargement in the mouse soleus muscle is due to hypertrophy of the existing muscle fibers.     

Regulation of expression of avian slow myosin heavy-chain isoforms.

The slow tonic anterior latissimus dorsi (ALD) muscle of the chicken contains two isomyosins, namely SM-1 and SM-2. The proportions of the two isoforms change with age, SM-2 expression increasing at the expense of SM-1. Applying a load on the wing increases the rate and extent of SM-1 replacement. Here we have demonstrated that decreasing the load by removal of the distal portion of the wing in 1-week-old chickens had an effect opposite to that of overloading in that it slowed muscle growth and the rate of SM-1 elimination. Experimental unloading of muscles previously weighted for 1 or 3 weeks slowed the growth rate of muscles, with consequent regression of relative hypertrophy; however, it did not lead to the reexpression of SM-1 myosin. This indicates that the overload-induced changes in myosin expression are not readily reversible. Nerve section produced unexpected results, in that it advanced the normal developmental shift in myosin expression toward predominance of the SM-2 isoform, similar to the effect of muscle overload.     

Turnover of muscle protein in the fowl (Gallus domesticus). Rates of protein synthesis in fast and slow skeletal, cardiac and smooth muscle of the adult fowl.

Rates of protein synthesis in skeletal, cardiac and smooth muscle of fully grown fowl (Gallus domesticus) were determined in vivo by means of the constant infusion method using [14C]proline. In the anterior latissimus dorsi muscle, containing predominantly slow fibres, the average synthesis rate of non-collagen muscle proteins was 17.0 +/- 3.1% per day, a value higher than that obtained for cardiac muscle (13.8 +/- 1.3% per day) and for smooth muscle of the gizzard (12.0 +/- 1.9% per day). In the posterior latissimus dorsi muscle, containing predominantly fast fibres, synthesis rates were much lower (6.9 +/- 1.8% per day). In each case these average rates for the non-collagen protein were similar to the average rate for the sarcoplasmic and myofibrillar protein fractions. The RNA concentration of these four muscles showed that relative rates of protein synthesis were determined mainly by the relative RNA concentrations. The rate of protein synthesis per unit of DNA (the DNA activity) was similar in the two skeletal muscles, but somewhat lower in cardiac muscle and gizzard, possibly reflecting the larger proportion of less active cell types in these two muscles. These quantitative aspects of protein turnover in the two skeletal muscles are discussed in terms of the determination of ultimate size of the DNA unit, and in relation to muscle ultrastructure.     

Expression of fibroblast growth factor family during postnatal skeletal muscle hypertrophy

The potential role of the fibroblast growth factor (FGF) familyduring stretch-induced postnatal skeletal muscle hypertrophy wasanalyzed by using an avian wing-weighting model. After 2 or 11 days ofweighted stretch, anterior latissimus dorsi (ALD) muscles were, onaverage, 34 (P < 0.01) and 85%(P < 0.01) larger, respectively, than unweighted ALD control muscles. By using quantitative RT-PCR, FGF-1 mRNA expression was found to be significantly decreased in ALDmuscles stretched for 2 or 11 days. In contrast, FGF-4 and FGF-10 mRNAexpression was significantly increased 2 days after initiation ofstretch. FGF-2, FGF-10, fibroblast growth factor receptor 1, andFREK mRNA expression was significantly increased at 11 days poststretch. Increases in FGF-2 and FGF-4 protein could bedetected throughout the myofiber periphery after 11 days of stretch. Ona cellular level, FGF-2 and FGF-4 proteins were differentiallylocalized. This differential expression pattern and proteinlocalization of the FGF family in response to stretch-induced hypertrophy suggest distinct roles for individual FGFs during thepostnatal hypertrophy process.

     

Parallel-fibered muscles transplanted with neurovascular repair into bipennate muscle sites in rabbits.

Experiments were performed on 20 New Zealand White male rabbits. Our hypotheses were that (1) latissimus dorsi (LTD) muscles transplanted into the site of a bipennate rectus femoris (RFM) muscle with neurovascular repair would retain their parallel-fibered structure and (2) the parallel-fibered structure of latissimus dorsi grafts would reduce their total fiber cross-sectional area and adversely affect force development relative to that of bipennate rectus femoris grafts and muscles. Compared with their respective donor muscles, 120 to 150 days after grafting, latissimus dorsi and rectus femoris grafts showed no change in the number of fibers and a decrease in the mean single-fiber cross-sectional area to approximately 70 percent. The latissimus dorsi grafts, which remained parallel-fibered, developed maximum forces 34 and 23 percent of the values for fully activated rectus femoris grafts and muscles, respectively. The deficit in the maximum force of the latissimus dorsi grafts resulted primarily from the smaller total-fiber cross-sectional area as a result of the parallel-fibered structure.