Anabolic influences of insulin-like growth factor I and/or growth hormone on the diaphragm of young rats

Lewis, Michael I., Thomas J. LoRusso, and Mario Fournier.Anabolic influences of insulin-like growth factor I and/or growth hormone on the diaphragm of young rats. J. Appl. Physiol. 82(6): 1972-1978, 1997.It iscontroversial whether insulin-like growth factor I (IGF-I), growthhormone (GH), or their combination might enhance body growthand/or tissue anabolism in the well-fed animal with an intactsomatotrophic axis. To assess this further, we studied four groups ofadolescent rats: 1) control (Ctr),2) GH,3) IGF-I, and4) GH/IGF-I. IGF-I was given via anosmotic minipump, whereas GH was injected subcutaneously for a period of 72 h. Diaphragm (Dia) contractile and fatigue properties were determined in vitro. Quantitative histochemical and morphometric analyses were performed on Dia fibers. Total serum IGF-I levels weresignificantly increased in the groups receiving growth factors. Although body weight increased to a greater extent in the animals receiving growth factors, a further synergistic effect was noted in theGH/IGF-I animals compared with either GH or IGF-I groups. Costal Diamass was greater in the groups receiving growth factors. The Dia ofGH/IGF-I animals was more fatigue resistant than the Dia in Ctr. Thecross-sectional area of types IIa and IIx fibers were increased to asimilar extent in all groups receiving growth factors compared withCtr. Succinate dehydrogenase activity of type IIa fibers wassignificantly greater in the GH/IGF-I animals compared with the othergroups. We conclude that the short-term provision of growth factors towell-nourished, normally growing adolescent rats can accelerate bodygrowth and promote selective hypertrophy of predominantly type II Diafibers.

     

IGF-I and/or growth hormone preserve diaphragm fiber size with moderate malnutrition

Resistance to theanabolic effects of growth hormone (GH) occurs with severe caloricdeficit. This study examined whether moderate caloric deficit (50% ofdaily intake for 7 days) in the adolescent rat exceeds a criticalthreshold for GH action and whether a combination of GH andinsulin-like growth factor I (IGF-I) would have enhanced anaboliceffects on the diaphragm (Dia). Five groups of rats (4 wk old) werestudied: 1) control (Ctl),2) nutritionally deprived (ND),3) ND + GH,4) ND + IGF-I, and5) ND + GH + IGF-I. IGF-I was givenby continuous infusion (200 µg/day). GH was injected subcutaneously(250 µg every 12 h). Contractile and fatigue properties of the Diawere determined in vitro. Quantitative histochemical methods were usedto determine Dia fiber type proportions, cross-sectional areas, andsuccinate dehydrogenase activities. The body weight of Ctl ratsincreased 46% compared with 7% in ND animals, whereas that of ND ratsreceiving growth factors was intermediate. Serum IGF-I levels werereduced 54% in ND animals and maintained with the provision of growthfactors. Dia fatigue resistance was improved in ND animals receivinggrowth factors. There were no differences in Dia contractileproperties, fiber type proportions, or succinate dehydrogenaseactivities across groups. ND resulted in atrophy/growth arrest of allDia fibers (20-32%) compared with Ctl. Administration of IGF-Iand/or GH completely prevented atrophy/growth arrest of all Diafibers. No additive or synergistic effects were noted. We propose thatthese growth factors may provide useful short-term adjunctivenutritional support in circumstances in which the provision of optimalnutrition may be delayed or inadequate.

     

Growth hormone/IGF-I and/or resistive exercise maintains myonuclear number in hindlimb unweighted muscles

Allen, David L., Jon K. Linderman, Roland R. Roy, Richard E. Grindeland, Venkat Mukku, and V. Reggie Edgerton. Growth hormone/IGF-I and/or resistive exercise maintains myonuclearnumber in hindlimb unweighted muscles. J. Appl.Physiol. 83(5): 1857-1861, 1997.In the presentstudy of rats, we examined the role, during 2 wk ofhindlimb suspension, of growth hormone/insulin-like growth factor I(GH/IGF-I) administration and/or brief bouts of resistance exercise in ameliorating the loss of myonuclei in fibers of the soleusmuscle that express type I myosin heavy chain. Hindlimb suspensionresulted in a significant decrease in mean soleus wet weight that wasattenuated either by exercise alone or by exercise plus GH/IGF-Itreatment but was not attenuated by hormonal treatment alone. Both meanmyonuclear number and mean fiber cross-sectional area (CSA) of fibersexpressing type I myosin heavy chain decreased after 2 wk of suspensioncompared with control (134 vs. 162 myonuclei/mm and 917 vs. 2,076 µm², respectively). NeitherGH/IGF-I treatment nor exercise alone affected myonuclear number orfiber CSA, but the combination of exercise and growth-factor treatmentattenuated the decrease in both variables. A significant correlationwas found between mean myonuclear number and mean CSA across allgroups. Thus GH/IGF-I administration and brief bouts of muscle loadinghad an interactive effect in attenuating the loss of myonuclei inducedby chronic unloading.

     

Growth hormone, IGF-I, and exercise effects on non-weightbearing fast muscles of hypophysectomized rats

Grossman, Elena J., Richard E. Grindeland, Roland R. Roy,Robert J. Talmadge, Juliann Evans, and V. Reggie Edgerton. Growth hormone, IGF-I, and exercise effects on non-weight-bearing fast musclesof hypophysectomized rats. J. Appl.Physiol. 83(5): 1522-1530, 1997.The effects ofgrowth hormone (GH) or insulin-like growth factor I (IGF-I) with orwithout exercise (ladder climbing) in countering the effects ofunweighting on fast muscles of hypophysectomized rats during 10 days ofhindlimb suspension were determined. Compared with untreated suspendedrats, muscle weights were 16-29% larger in GH-treated and5-15% larger in IGF-I-treated suspended rats. Exercise alone hadno effect on muscle weights. Compared with ambulatory control, themedial gastrocnemius weight in suspended, exercised rats was largerafter GH treatment and maintained with IGF-I treatment. The combinationof GH or IGF-I plus exercise in suspended rats resulted in an increasein the size of each predominant fiber type, i.e., types I, I+IIa andIIa+IIx, in the medial gastrocnemius compared with untreated suspendedrats. Normal ambulation or exercise during suspension increased theproportion of fibers expressing embryonic myosin heavy chain inhypophysectomized rats. The phenotype of the medial gastrocnemius wasminimally affected by GH, IGF-I, and/or exercise. These resultsshow that there is an IGF-I, as well as a GH, and exercise interactiveeffect in maintaining medial gastrocnemius fiber size in suspendedhypophysectomized rats.

     

Effect of intermittent weight bearing on soleus fiber force-velocity-power and force-pCa relationships

Bangart, J. J., J. J. Widrick, and R. H. Fitts. Effectof intermittent weight bearing on soleus fiber force-velocity-power andforce-pCa relationships. J. Appl.Physiol. 82(6): 1905-1910, 1997.Ratpermeabilized type I soleus fibers displayed a 33% reduction in peakpower output and a 36% increase in the freeCa²⁺ concentration required forone-half maximal activation after 14 days of hindlimb non-weightbearing (NWB). We examined the effectiveness of intermittent weightbearing (IWB; consisting of four 10-min periods of weight bearing/day)as a countermeasure to these functional changes. At peak power output,type I fibers from NWB animals produced 54% less force and shortenedat a 56% greater velocity than did type I fibers from controlweight-bearing animals while type I fibers from the IWB rats produced26% more absolute force than did fibers from the NWB group andshortened at a velocity that was only 80% of the NWB group mean. As aresult, no difference was observed in the average peak power of fibers from the IWB and NWB animals. Hill plot analysis of force-pCa relationships indicated that fibers from the IWB group required similarlevels of free Ca²⁺ to reachhalf-maximal activation in comparison to fibers from the weight-bearinggroup. However, at forces <50% of peak force, the force-pCa curvefor fibers from the IWB animals clearly fell between the relationshipsobserved for the other two groups. In summary, IWB treatments1) attenuated the NWB-inducedreduction in fiber Ca²⁺sensitivity but 2) failed to preventthe decline in peak power that occurs during NWB because of opposingeffects on fiber force (an increase vs. NWB) and shortening velocity (adecrease vs. NWB).

     

Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure

Delp, Michael D., Changping Duan, John P. Mattson, andTimothy I. Musch. Changes in skeletal muscle biochemistry and histology relative to fiber type in rats with heart failure.J. Appl. Physiol. 83(4):1291-1299, 1997.One of the primary consequences of leftventricular dysfunction (LVD) after myocardial infarction is adecrement in exercise capacity. Several factors have been hypothesizedto account for this decrement, including alterations in skeletal musclemetabolism and aerobic capacity. The purpose of this study was todetermine whether LVD-induced alterations in skeletal muscle enzymeactivities, fiber composition, and fiber size are1) generalized in muscles orspecific to muscles composed primarily of a given fiber type and2) related to the severity of theLVD. Female Wistar rats were divided into three groups: sham-operatedcontrols (n = 13) and rats withmoderate (n = 10) and severe(n = 7) LVD. LVD was surgicallyinduced by ligating the left main coronary artery and resulted inelevations (P < 0.05) in leftventricular end-diastolic pressure (sham, 5 ± 1 mmHg; moderate LVD,11 ± 1 mmHg; severe LVD, 25 ± 1 mmHg). Moderate LVDdecreased the activities of phosphofructokinase (PFK) and citratesynthase in one muscle composed of type IIB fibers but did not modifyfiber composition or size of any muscle studied. However, severe LVDdiminished the activity of enzymes involved in terminal and-oxidation in muscles composed primarily of type I fibers, type IIAfibers, and type IIB fibers. In addition, severe LVD induced areduction in the activity of PFK in type IIB muscle, a 10% reductionin the percentage of type IID/X fibers, and a corresponding increase inthe portion of type IIB fibers. Atrophy of type I fibers, type IIAfibers, and/or type IIB fibers occurred in soleus and plantarismuscles of rats with severe LVD. These data indicate that rats withsevere LVD after myocardial infarction exhibit1) decrements in mitochondrialenzyme activities independent of muscle fiber composition,2) a reduction in PFK activity in type IIB muscle, 3) transformationof type IID/X to type IIB fibers, and4) atrophy of type I, IIA, and IIBfibers.

     

Maintenance of myonuclear domain size in rat soleus after overload and growth hormone/IGF-I treatment

The purpose ofthis study was to determine the effects of functional overload (FO)combined with growth hormone/insulin-like growth factor I (GH/IGF-I)administration on myonuclear number and domain size in rat soleusmuscle fibers. Adult female rats underwent bilateral ablation of theplantaris and gastrocnemius muscles and, after 7 days of recovery, wereinjected three times daily for 14 days with GH/IGF-I (1 mg/kg each; FO + GH/IGF-I group) or saline vehicle (FO group). Intact rats receivingsaline vehicle served as controls (Con group). Muscle wet weight was32% greater in the FO than in the Con group: 162 ± 8 vs. 123 ± 16 mg. Muscle weight in the FO + GH/IGF-I group (196 ± 14 mg) was59 and 21% larger than in the Con and FO groups, respectively. Meansoleus fiber cross-sectional area of the FO + GH/IGF-I group (2,826 ± 445 µm²) was increasedcompared with the Con (2,044 ± 108 µm²) and FO (2,267 ± 301 µm²) groups. The difference infiber size between the FO and Con groups was not significant. Meanmyonuclear number increased in FO (187 ± 15 myonuclei/mm) and FO + GH/IGF-I (217 ± 23 myonuclei/mm) rats compared with Con (155 ± 12 myonuclei/mm) rats, although the difference between FO and FO + GH/IGF-I animals was not significant. The mean cytoplasmic volume permyonucleus (myonuclear domain) was similar across groups. These resultsdemonstrate that the larger mean muscle weight and fibercross-sectional area occurred when FO was combined with GH/IGF-Iadministration and that myonuclear number increased concomitantly withfiber volume. Thus there appears to be some mechanism(s) that maintainsthe myonuclear domain when a fiber hypertrophies.

     

Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training

McCall, G. E., W. C. Byrnes, A. Dickinson, P. M. Pattany,and S. J. Fleck. Muscle fiber hypertrophy, hyperplasia, and capillary density in college men after resistance training.J. Appl. Physiol. 81(5):2004-2012, 1996.Twelve male subjects with recreationalresistance training backgrounds completed 12 wk of intensifiedresistance training (3 sessions/wk; 8 exercises/session; 3 sets/exercise; 10 repetitions maximum/set). All major muscle groupswere trained, with four exercises emphasizing the forearm flexors.After training, strength (1-repetition maximum preacher curl) increasedby 25% (P < 0.05). Magneticresonance imaging scans revealed an increase in the biceps brachiimuscle cross-sectional area (CSA) (from 11.8 ± 2.7 to 13.3 ± 2.6 cm²;n = 8;P < 0.05). Muscle biopsies of thebiceps brachii revealed increases(P < 0.05) in fiber areas for type I(from 4,196 ± 859 to 4,617 ± 1,116 µm²;n = 11) and II fibers (from 6,378 ± 1,552 to 7,474 ± 2,017 µm²;n = 11). Fiber number estimated fromthe above measurements did not change after training (293.2 ± 61.5 × 10³ pretraining; 297.5 ± 69.5 × 10³ posttraining;n = 8). However, the magnitude ofmuscle fiber hypertrophy may influence this response because thosesubjects with less relative muscle fiber hypertrophy, but similarincreases in muscle CSA, showed evidence of an increase in fibernumber. Capillaries per fiber increased significantly(P < 0.05) for both type I(from 4.9 ± 0.6 to 5.5 ± 0.7;n = 10) and II fibers (from 5.1 ± 0.8 to 6.2 ± 0.7; n = 10). Nochanges occurred in capillaries per fiber area or muscle area. Inconclusion, resistance training resulted in hypertrophy of the totalmuscle CSA and fiber areas with no change in estimated fiber number,whereas capillary changes were proportional to muscle fiber growth.

     

Exercise-induced changes in circulating growth factors with cyclic variation in plasma estradiol in women

Hornum, Mette, Dan M. Cooper, Jo Anne Brasel, Alina Bueno,and Kathy E. Sietsema. Exercise-induced changes in circulating growth factors and cyclic variation in plasma estradiol in women. J. Appl. Physiol. 82(6):1946-1951, 1997.The effect of 10 min of high-intensity cyclingexercise on circulating growth hormone (GH), insulin-like growthfactors I and II (IGF-I and -II), and insulin-like growth factorbinding protein 3 (IGF BP-3) was studied in nine eumenorrheic women(age 19-48 yr) at two different phases of the menstrual cycle.Tests were performed on separate mornings corresponding to thefollicular phase and to the periovulatory phase of the menstrual cycle,during which plasma levels of endogenous estradiol(E₂) were relatively low (272 ± 59 pmol/l) and high (1,112 ± 407 pmol/l), respectively. GHincreased significantly in response to exercise under bothE₂ conditions. Plasma GH before exercise (2.73 ± 2.48 vs. 1.71 ± 2.09 µg/l) and total GH over 10 min of exercise and 1-h recovery (324 ± 199 vs. 197 ± 163 ng) were both significantly greater for periovulatory phase than for follicular phase studies. IGF-I, but not IGF-II, increased acutely after exercise. IGF BP-3, assayed by radioimmunoassay, was not significantly different at preexercise, end exercise, or at 30-min recovery time points and was not different between the two study days.When assayed by Western blot, however, there was a significant increasein IGF BP-3 30 min after exercise for the periovulatory study. Thesefindings indicate that the modulation of GH secretion associated withmenstrual cycle variations in circulatingE₂ affects GH measured afterexercise, at least in part, by an increase in baseline levels. Theacute increase in IGF-I induced by exercise appears to be independentof the GH response and is not affected by menstrual cycle timing.

     

Hypothyroidism alters diaphragm muscle development

Sieck, Gary C., Louise E. Wilson, Bruce D. Johnson, andWen-Zhi Zhan. Hypothyroidism alters diaphragm muscle development. J. Appl. Physiol. 81(5):1965-1972, 1996.The impact of hypothyroidism (Hyp) onmyosin heavy chain (MHC) isoform expression, maximum specific force(P_o), fatigability, and maximumunloaded shortening velocity(V_o) wasdetermined in the rat diaphragm muscle (Dia) at 0, 7, 14, 21, and 28 days of age. Hyp was induced by treating pregnant rats with6-n-propyl-2-thiouracil (0.05% indrinking water) beginning at gestational day10 and was confirmed by reduced plasma levels of3,5,3-triiodothyronine and thyroxine. MHC isoforms wereseparated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis gels and analyzed by densitometry. IsometricP_o and fatigue resistance of theDia were measured in vitro at 26°C, andV_o was determined at 15°C with the slack test. Compared with control muscles,expression of MHC-slow was higher and expression of adult fast MHCisoforms was lower in Hyp Dia at all ages. The neonatal isoform of MHC continued to be expressed in the Hyp Dia until day28. At each age,P_o and fatigability were reducedand V_o was slowerin the Hyp Dia. We conclude that Hyp-induced alterations in MHC isoform expression do not fully predict the changes in Dia contractile properties.

     

Combined myofibrillar and mitochondrial creatine kinase deficiency impairs mouse diaphragm isotonic function

Watchko, Jon F., Monica J. Daood, Gary C. Sieck, John J. LaBella, Bill T. Ameredes, Alan P. Koretsky, and BeWieringa. Combined myofibrillar and mitochondrialcreatine kinase deficiency impairs mouse diaphragm isotonic function.J. Appl. Physiol. 82(5): 1416-1423, 1997.Creatine kinase (CK) is an enzyme central to cellular high-energy phosphate metabolism in muscle. To characterize the physiological role of CK in respiratory muscle during dynamic contractions, we compared the force-velocity relationships, power, andwork output characteristics of the diaphragm (Dia) from mice withcombined myofibrillar and sarcomeric mitochondrial CK deficiency (CK[/]) with CK-sufficient controls (Ctl).Maximum velocity of shortening was significantly lower inCK[/] Dia (14.1 ± 0.9 L_o/s,where L_o isoptimal fiber length) compared with Ctl Dia (17.5 ± 1.1 L_o/s)(P < 0.01). Maximum power wasobtained at 0.4-0.5 tetanic force in both groups; absolute maximumpower (2,293 ± 138 W/m²) andwork (201 ± 9 J/m²) werelower in CK[/] Dia compared with Ctl Dia(2,744 ± 146 W/m² and 284 ± 26 J/m², respectively)(P < 0.05). The ability ofCK[/] Dia to sustain shortening duringrepetitive isotonic activation (75 Hz, 330-ms duration repeated eachsecond at 0.4 tetanic force load) was markedly impaired, withCK[/] Dia power and work declining to zero by 37 ± 4 s, compared with 61 ± 5 s in Ctl Dia. We conclude that combined myofibrillar and sarcomeric mitochondrial CK deficiency profoundly impairs Dia power and work output, underscoring the functional importance of CK during dynamic contractions in skeletal muscle.

     

Effect of 17days of bed rest on peak isometric force and unloaded shortening velocity of human soleus fibers

The purpose of this study was to examine the effect of prolongedbed rest (BR) on the peak isometric force(P_o) and unloaded shorteningvelocity (V_o)of single Ca²⁺-activated musclefibers. Soleus muscle biopsies were obtained from eight adult malesbefore and after 17 days of 6° head-down BR. Chemicallypermeabilized single fiber segments were mounted between a forcetransducer and position motor, activated with saturating levels ofCa²⁺, and subjected to slacklength steps. V_owas determined by plotting the time for force redevelopment vs. theslack step distance. Gel electrophoresis revealed that 96% of the pre-and 87% of the post-BR fibers studied expressed only the slow type Imyosin heavy chain isoform. Fibers with diameter >100 µm made uponly 14% of this post-BR type I population compared with 33% of thepre-BR type I population. Consequently, the post-BR type I fibers(n = 147) were, on average, 5%smaller in diameter than the pre-BR type I fibers(n = 218) and produced 13% lessabsolute P_o. BR had no overalleffect on P_o per fibercross-sectional area(P_o/CSA), even though halfof the subjects displayed a decline of 9-12% inP_o/CSA after BR. Type Ifiber V_oincreased by an average of 34% with BR. Although the ratio of myosinlight chain 3 to myosin light chain 2 also rose with BR, there was nocorrelation between this ratio andV_o for either thepre- or post-BR fibers. In separate fibers obtained from the originalbiopsies, quantitative electron microscopy revealed a 20-24%decrease in thin filament density, with no change in thick filamentdensity. These results raise the possibility that alterations in thegeometric relationships between thin and thick filaments may be atleast partially responsible for the elevatedV_o of the post-BRtype I fibers.

     

Influence of complete spinal cord injury on skeletal muscle within 6mo of injury

This study examined the influence of spinal cord injury (SCI) onaffected skeletal muscle. The right vastus lateralis muscle wasbiopsied in 12 patients as soon as they were clinically stable (average6 wk after SCI), and 11 and 24 wk after injury. Samples were also takenfrom nine able-bodied controls at two time points 18 wk apart. Surfaceelectrical stimulation (ES) was applied to the left quadriceps femorismuscle to assess fatigue at these same time intervals. Biopsies wereanalyzed for fiber type percent and cross-sectional area (CSA), fibertype-specific succinic dehydrogenase (SDH) and -glycerophosphatedehydrogenase (GPDH) activities, and myosin heavy chainpercent. Controls showed no change in any variable overtime. Patients showed 27-56% atrophy(P = 0.000) of type I, IIa, andIIax+IIx fibers from 6 to 24 wk after injury, resulting in fiber CSAapproximately one-third that of controls. Their fiber type specific SDHand GPDH activities increased (P  0.001) from 32 to 90% over the 18 wk, thereby approaching or surpassing control values. The relative CSA of type I fibers and percentage of myosin heavy chain type I did not change. There wasapparent conversion among type II fiber subtypes; type IIa decreasedand type IIax+IIx increased (P  0.012). Force loss during ES did not change over time for either groupbut was greater (P = 0.000) for SCIpatients than for controls overall (27 vs. 9%). The results indicatethat vastus lateralis muscle shows marked fiber atrophy, no change inthe proportion of type I fibers, and a relative independence ofmetabolic enzyme levels from activation during the first 24 wk afterclinically complete SCI. Over this time, quadriceps femoris muscleshowed moderately greater force loss during ES in patients than incontrols. It is suggested that the predominant response of mixed humanskeletal muscle within 6 mo of SCI is loss of contractile protein.Therapeutic interventions could take advantage of this to increasemuscle mass.

     

Alignment of microvascular units along skeletal muscle fibers of hamster retractor

Emerson, Geoffrey G., and Steven S. Segal. Alignment ofmicrovascular units along skeletal muscle fibers of hamster retractor.J. Appl. Physiol. 82(1): 42-48, 1997.When muscle fibers contract, blood flow requirements increasealong their entire length. However, the organization of capillaryperfusion along muscle fibers is unclear. The microvascular unit (MVU)is defined as a terminal arteriole and the group of capillaries itsupplies. We investigated whether neighboring MVUs along the fiber axis perfused the same group of muscle fibers by using the parallel-fibered retractor muscle. Hamsters were anesthetized and perfused with Microfilto visualize MVUs relative to muscle fibers. Fields of study, whichencompassed five to seven neighboring MVUs along a muscle fiber, werechosen from the interior of muscles and along muscle edges. On average,MVUs were 1 mm in length, 0.50 mm in width, and 0.1 mm deep; segmentsof ~30 fibers were contained in this tissue volume of 0.05 mm³ (20 MVUs/mg muscle). The totaldistance across muscle fibers encompassed by a pair of MVUs isdesignated "union" (U); the fraction of this distance common toboth MVUs is designated "intersection" (I). The ratio of I to Ufor the widths of neighboring MVUs provides an index of MVU alignmentalong muscle fibers (e.g., I/U = 1.0 indicates complete alignment,where the fibers perfused by one MVU are the same as those perfused bythe neighboring MVU). We found that I/U along muscle edges (0.71 ± 0.02) was greater (P < 0.05) thanthe ratio measured within muscles (0.66 ± 0.02). A model predicteda maximum I/U of 0.58 with random MVU alignment. Thus measured valueswere closer to random than to complete alignment. These findingsindicate that an increase in blood flow along muscle fibers requiresthe perfusion of many MVUs and imply that vasodilation is coordinatedamong the parent arterioles from which corresponding MVUsarise.

     

Simulation of motor unit recruitment and microvascular unit perfusion: spatial considerations

Fuglevand, Andrew J., and Steven S. Segal. Simulationof motor unit recruitment and microvascular unit perfusion: spatial considerations. J. Appl. Physiol.83(4): 1223-1234, 1997.Muscle fiber activity is the principalstimulus for increasing capillary perfusion during exercise. Thecontrol elements of perfusion, i.e., microvascular units (MVUs), supplyclusters of muscle fibers, whereas the control elements of contraction,i.e., motor units, are composed of fibers widely scattered throughoutmuscle. The purpose of this study was to examine how the discordantspatial domains of MVUs and motor units could influence the proportion of open capillaries (designated as perfusion) throughout a muscle crosssection. A computer model simulated the locations of perfused MVUs inresponse to the activation of up to 100 motor units in a muscle with40,000 fibers and a cross-sectional area of 100 mm². The simulation increasedcontraction intensity by progressive recruitment of motor units. Foreach step of motor unit recruitment, the percentage of active fibersand the number of perfused MVUs were determined for several conditions:1) motor unit fibers widely dispersed and motor unit territories randomly located (whichapproximates healthy human muscle),2) regionalized motor unitterritories, 3) reversed recruitmentorder of motor units, 4) denselyclustered motor unit fibers, and 5)increased size but decreased number of motor units. The simulationsindicated that the widespread dispersion of motor unit fibersfacilitates complete capillary (MVU) perfusion of muscle at low levelsof activity. The efficacy by which muscle fiber activity inducedperfusion was reduced 7- to 14-fold under conditions that decreased thedispersion of active fibers, increased the size of motor units, orreversed the sequence of motor unit recruitment. Such conditions aresimilar to those that arise in neuromuscular disorders, with aging, orduring electrical stimulation of muscle, respectively.

     

Effects of bovine colostrum supplementation on serum IGF-I, IgG, hormone, and saliva IgA during training

Mero, Antti, Heidi Miikkulainen, Jarmo Riski, RaimoPakkanen, Jouni Aalto, and Timo Takala. Effects of bovinecolostrum supplementation on serum IGF-I, IgG, hormone, and saliva IgAduring training. J. Appl. Physiol.83(4): 1144-1151, 1997.The purpose of this study was to examinethe effects of bovine colostrum supplementation (Bioenervi) on seruminsulin-like growth factor I (IGF-I), immunoglobulin G, hormone, andamino acid and saliva immunoglobulin A concentrations during a strengthand speed training period. Nine male sprinters and jumpersunderwent three randomized experimental training treatments of 8 daysseparated by 13 days. The only difference in the treatments was thedrink of 125 ml consumed per day. Posttraining increases were noticedfor serum IGF-I in the 25-ml Bioenervi treatment (125 ml contained 25 ml Bioenervi) and especially in the 125-ml Bioenervi treatment (125 mlcontained 125 ml Bioenervi) compared with the placebo (normal milkwhey) treatment (P < 0.05). The change in IGF-I concentration during the 8-day periods correlated positively with the change in insulin concentration during the sameperiods with 25-ml Bioenervi treatment(r = 0.68;P = 0.045) and with 125-ml Bioenervitreatment (r = 0.69;P = 0.038). Serum immunoglobulin G,hormone, and amino acid and saliva immunoglobulin A responses weresimilar during the three treatments. It appears that a bovine colostrumsupplement (Bioenervi) may increase serum IGF-I concentration inathletes during strength and speed training.

     

Human growth hormone response to repeated bouts of aerobic exercise

Kanaley, J. A., J. Y. Weltman, J. D. Veldhuis, A. D. Rogol,M. L. Hartman, and A. Weltman. Human growth hormone response torepeated bouts of aerobic exercise. J. Appl.Physiol. 83(5): 1756-1761, 1997.We examinedwhether repeated bouts of exercise could override growth hormone (GH)auto-negative feedback. Seven moderately trained men were studied onthree occasions: a control day (C), a sequential exercise day (SEB; at1000, 1130, and 1300), and a delayed exercise day (DEB; at 1000, 1400, and 1800). The duration of each exercise bout was 30 min at 70%maximal O₂ consumption (O_{2 max}) on a cycleergometer. Standard meals were provided at 0600 and 2200. GH wasmeasured every 5-10 min for 24 h (0800-0800). Daytime(0800-2200) integrated GH concentrations were ~150-160% greater during SEB and DEB than during C: 1,282 ± 345, 3,192 ± 669, and 3,389 ± 991 min · µg · l¹for C, SEB, and DEB, respectively [SEB > C(P < 0.06), DEB > C(P < 0.03)]. There were nodifferences in GH release during sleep (2300-0700). Deconvolutionanalysis revealed that the increase in 14-h integrated GH concentrationon DEB was accounted for by an increase in the mass of GH secreted perpulse (per liter of distribution volume,l_v): 7.0 ± 2.9 and 15.9 ± 2.6 µg/l_v for C and DEB,respectively (P < 0.01). Comparisonof 1.5-h integrated GH concentrations on the SEB and DEB days (30 minexercise + 60 min recovery) revealed that, with each subsequentexercise bout, GH release apparently increased progressively, with aslightly greater increase on the DEB day [SEB vs. DEB: 497 ± 162 vs. 407 ± 166 (bout 1), 566 ± 152 vs. 854 ± 184 (bout2), and 633 ± 149 vs. 1,030 ± 352 min · µg · l¹(bout 3),P < 0.05]. We conclude thatthe GH response to acute aerobic exercise is augmented with repeatedbouts of exercise.

     

Anabolic steroids in part reverse glucocorticoid-induced alterations in rat diaphragm

Animal and clinical studies have shownrespiratory muscle dysfunction caused by treatment withglucocorticoids. The present study was designed to investigate whetheranabolic steroids are able to antagonize the loss of diaphragm forceinduced by long-term low-dose methylprednisolone (MP) administration.Male adult rats were randomized to receive saline or MP (0.2 mg · kg¹ · day¹sc) during 9 mo, with or without nandrolone decanoate (ND; 1 mg · kg¹ · wk¹im) during the last 3 mo. The ~10% reduction in force generation ofisolated diaphragm bundles induced by MP was completely abolished byaddition of ND. The MP-induced decrease in number of fibers expressingtype IIb myosin heavy chains was not reversed by ND. MP slightlyreduced type I, IIa, and IIx fiber cross-sectional areas(CSA), but not type IIb fiber CSA. Addition of ND abolished thereduction in IIa and IIx fiber CSA. The MP-induced alterations inglycogenolytic activity and fatty acid oxidation capacity were notreversed by ND. In conclusion, the marked reduction in diaphragm forcecaused by long-term low-dose MP was completely abolished by addition ofND. ND in part also antagonized the effects of MP on diaphragmmorphology but showed no beneficial effects on biochemical changes.

     

Lower limb skeletal muscle function after 6wk of bed rest

Berg, H. E., L. Larsson, and P. A. Tesch. Lower limbskeletal muscle function after 6 wk of bed rest. J. Appl. Physiol. 82(1): 182-188, 1997.Force,electromyographic (EMG) activity, muscle mass, and fibercharacteristics were studied in seven healthy men before and after 6 wkof bed rest. Maximum voluntary isometric and concentric knee extensortorque decreased (P < 0.05)uniformly across angular velocities by 25-30% after bed rest.Maximum quadricep rectified EMG decreased by 19 ± 23%, whereassubmaximum (100-Nm isometric action) EMG increased by 44 ± 28%.Knee extensor muscle cross-sectional area (CSA), assessed by usingmagnetic resonance imaging, decreased by 14 ± 4%. Maximum torqueper knee extensor CSA decreased by 13 ± 9%. Vastus lateralis fiberCSA decreased 18 ± 14%. Neither type I, IIA, and IIB fiberpercentages nor their relative proportions of myosin heavy chain (MHC)isoforms were altered after bed rest. Because the decline in strengthcould not be entirely accounted for by decreased muscle CSA, it issuggested that the strength loss is also due to factors resulting indecreased neural input to muscle and/or reduced specifictension of muscle, as evidenced by a decreased torque/EMG ratio.Additionally, it is concluded that muscle unloading in humans does notinduce important changes in fiber type or MHC composition or in vivomuscle contractile properties.

     

Mechanical overload and skeletal muscle fiber hyperplasia: a meta-analysis

Kelley, George. Mechanical overload and skeletal musclefiber hyperplasia: a meta-analysis. J. Appl.Physiol. 81(4): 1584-1588, 1996.With use of themeta-analytic approach, the purpose of this study was to examine theeffects of mechanical overload on skeletal muscle fiber number inanimals. A total of 17 studies yielding 37 data points and 360 subjectsmet the initial inclusion criteria:1) "basic" research studiespublished in journals, 2) animals(no humans) as subjects, 3) controlgroup included, 4) some type ofmechanical overload (stretch, exercise, or compensatory hypertrophy)used to induce changes in muscle fiber number, and 5) sufficient data to accuratelycalculate percent changes in muscle fiber number. Across all designsand categories, statistically significant increases were found formuscle fiber number [15.00 ± 19.60% (SD), 95% confidenceinterval = 8.65-21.53], muscle fiber area (31.60 ± 44.30%, 95% confidence interval = 16.83-46.37), and muscle mass(90.50 ± 86.50%, 95% confidence interval = 61.59-119.34). When partitioned according to the fiber-counting technique, larger increases in muscle fiber number were found by using the histological vs. nitric acid digestion method (histological = 20.70%, nitric aciddigestion = 11.10%; P = 0.14).Increases in fiber number partitioned according to species weregreatest among those groups that used an avian vs. mammalian model(avian = 20.95%, mammalian = 7.97%;P = 0.07). Stretch overload yieldedlarger increases in muscle fiber number than did exercise andcompensatory hypertrophy (stretch = 20.95%, exercise = 11.59%,compensatory hypertrophy = 5.44%; P = 0.06). No significant differences between changes in fiber number werefound when data were partitioned according to type of control(intra-animal = 15.20%, between animal = 13.90%; P = 0.82) or fiber arrangement ofmuscle (parallel = 15.80%, pennate = 11.60%;P = 0.61). The results of this studysuggest that in several animal species certain forms of mechanicaloverload increase muscle fiber number.