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.

     

Modulation of MHC isoforms in functionally overloaded and exercised rat plantaris fibers

Roy, Roland R., Robert J. Talmadge, Kenneth Fox, MichaelLee, Aki Ishihara, and V. Reggie Edgerton. Modulation of MHC isoforms in functionally overloaded and exercised rat plantaris fibers.J. Appl. Physiol. 83(1): 280-290, 1997.The effects of 1 and 10 wk of functional overload (FO) of therat plantaris with (FO_Tr) andwithout daily endurance treadmill training on its myosin heavy chain(MHC) composition were studied. After 1 and 10 wk of FO, plantaris masswas 22 and 56% greater in FO and 37 and 94% greater, respectively, inFO_Tr rats compared withage-matched controls. At 1 wk, pure type I and pure type IIa MHC fiberswere hypertrophied in FO (39 and 44%) andFO_Tr (70 and 87%) rats. By 10 wkall fiber types comprising >5% of the fibers sampled showed ahypertrophic response in both FO groups. One week of FO increased thepercentage of hybrid (containing both type I and type IIa MHC) fibersand of fibers containing embryonic MHC. By 10 wk, the percentage ofpure type I MHC fibers was ~40% in both FO groups compared with 15%in controls, and the percentage of fibers containing embryonic MHC wassimilar to that in controls. Sodium dodecyl sulfate-polyacrylamide gelelectrophoresis analyses showed an increase in type I MHC and adecrease in type IIb MHC in both FO groups at 10 wk, whereas littlechange was observed at 1 wk. These data are consistent with hypertrophyand transformation from faster to slower MHC isoforms in chronicallyoverloaded muscles. The additional overload imposed by daily endurancetreadmill training employed in this study (1.6 km/day; 10% incline)results in a larger hypertrophic response but appears to have a minimaleffect on the MHC adaptations.

     

Influence of treadmill running on femoral bone in young orchidectomized rats

Horcajada, M.-N., V. Coxam, M.-J. Davicco, N. Gaumet, P. Pastoureau, C. Leterrier, J. Culioli, and J.-P. Barlet. Influence of treadmill running on femoral bone in young orchidectomized rats.J. Appl. Physiol. 83(1): 129-133, 1997.Forty 6-wk-old male Wistar rats weighing 308 ± 24 g weredivided into two groups. On day 0, the20 animals in one group were surgically castrated and the other groupwas sham operated. Within each group, 10 rats were selected fortreadmill running (60% maximal O₂consumption, 1 h/day, 6 days/wk for 15 wk). The 20 sedentary rats wereused as controls. At the time the rats were killed(day 105), running had nosignificant effect on femoral mechanical properties either in castratedor in sham-operated rats. Femoral bone density was lowerin orchidectomized than in sham-operated rats. Nevertheless, it washigher in exercised than in sedentary rats. Femoral Ca contentparalleled changes in bone density. Treadmill running had nosignificant effect on plasma osteocalcin concentration but inhibitedthe increase in urinary deoxypyridinoline excretion observed incastrated rats. Image analysis (measured at the distal femoraldiaphysis) revealed that these effects mainly resulted from decreasedtrabecular bone resorption in castrated exercised rats.

     

Diaphragm thickening during inspiration

Cohn, David, Joshua O. Benditt, Scott Eveloff, and F. DennisMcCool. Diaphragm thickening during inspiration.J. Appl. Physiol. 83(1): 291-296, 1997.Ultrasound has been used to measure diaphragm thickness(T_di) in thearea where the diaphragm abuts the rib cage (zone of apposition).However, the degree of diaphragm thickening during inspiration reportedas obtained by one-dimensional M-mode ultrasound was greater than thatpredicted by using other radiographic techniques. Becausetwo-dimensional (2-D) ultrasound provides greater anatomic definitionof the diaphragm and neighboring structures, we used this technique toreevaluate the relationship between lung volume andT_di. We firstestablished the accuracy and reproducibility of 2-D ultrasound bymeasuring T_diwith a 7.5-MHz transducer in 26 cadavers. We found thatT_di measured byultrasound correlated significantly with that measured by ruler (R² = 0.89), withthe slope of this relationship approximating a line of identity(y = 0.89x + 0.04 mm). The relationship between lung volume andT_di was thenstudied in nine subjects by obtaining diaphragm images at the fivetarget lung volumes [25% increments from residual volume (RV) tototal lung capacity (TLC)]. Plots ofT_di vs. lungvolume demonstrated that the diaphragm thickened as lung volumeincreased, with a more rapid rate of thickening at the higher lungvolumes[T_di = 1.74 vital capacity (VC)² + 0.26 VC + 2.7 mm] (R² = 0.99; P < 0.001) where lung volumeis expressed as a fraction of VC. The mean increase inT_di between RVand TLC for the group was 54% (range 42-78%). We conclude that2-D ultrasound can accurately measureT_di and that theaverage thickening of the diaphragm when a subject is inhaling from RVto TLC using this technique is in the range of what would be predictedfrom a 35% shortening of the diaphragm.

     

Ultrasound evaluation of piglet diaphragm function before and after fatigue

Kocis, Keith C., Peter J. Radell, Wayne I. Sternberger, JaneE. Benson, Richard J. Traystman, and David G. Nichols. Ultrasound evaluation of piglet diaphragm function before and after fatigue. J. Appl. Physiol. 83(5):1654-1659, 1997.Clinically, a noninvasive measure of diaphragmfunction is needed. The purpose of this study is to determine whetherultrasonography can be used to 1)quantify diaphragm function and 2)identify fatigue in a piglet model. Five piglets were anesthetized withpentobarbital sodium and halothane and studied during the followingconditions: 1) baseline (spontaneous breathing); 2) baseline + CO₂ [inhaledCO₂ to increase arterial PCO₂ to 50-60 Torr (6.6-8kPa)]; 3) fatigue + CO₂ (fatigue induced with 30 minof phrenic nerve pacing); and 4)recovery + CO₂ (recovery after 1 hof mechanical ventilation). Ultrasound measurements of the posteriordiaphragm were made (inspiratory mean velocity) in the transverseplane. Images were obtained from the midline, just inferior to thexiphoid process, and perpendicular to the abdomen. M-mode measures weremade of the right posterior hemidiaphragm in the plane just lateral tothe inferior vena cava. Abdominal and esophageal pressures weremeasured and transdiaphragmatic pressure (Pdi) was calculated duringspontaneous (Sp) and paced (Pace) breaths. Arterial blood gases werealso measured. Pdi(Sp) and Pdi(Pace)during baseline + CO₂ were 8 ± 0.7 and 49 ± 11 cmH₂O, respectively, anddecreased to 6 ± 1.0 and 27 ± 7 cmH₂O,respectively, during fatigue + CO₂. Mean inspiratory velocityalso decreased from 13 ± 2 to 8 ± 1 cm/s during theseconditions. All variables returned to baseline during recovery + CO₂. Ultrasonography can beused to quantify diaphragm function and identify piglet diaphragm fatigue.

     

Effect of chronic resistive loading on hypoxic ventilatory responsiveness

Greenberg, Harly E., Rammohan S. Rao, Anthony L. Sica, andSteven M. Scharf. Effect of chronic resistive loading on hypoxicventilatory responsiveness. J. Appl.Physiol. 82(2): 500-507, 1997.Depression ofventilation mediated by endogenous opioids has been observed acutelyafter resistive airway loading. We evaluated the effects of chronicallyincreased airway resistance on hypoxic ventilatory responsivenessshortly after load imposition and 6 wk later. A circumferentialtracheal band was placed in 200-g rats, tripling tracheal resistance.Sham surgery was performed in controls. Ventilation and the ventilatoryresponse to hypoxia were measured by using barometric plethysmographyat 2 days and 6 wk postsurgery in unanesthetized rats during exposureto room air and to 12% O₂-5%CO₂-balanceN₂. Trials were performed with andwithout naloxone (1 mg/kg ip). Room air arterial blood gases demonstrated hypercapnia with normoxia in obstructed rats at 2 days and6 wk postsurgery. During hypoxia, a 30-Torr fall inPO₂ occurred with no change inPCO₂. Hypoxic ventilatory responsiveness was suppressed in obstructed rats at 2 days postloading. Naloxone partially reversed this suppression. However, hypoxic responsiveness at 6 wk was not different from control levels. Naloxonehad a small effect on ventilatory pattern at this time with no overalleffect on hypoxic responsiveness. This was in contrast to previouslydemonstrated long-term suppression ofCO₂ sensitivity in this model,which was partially reversible by naloxone only during the immediateperiod after load imposition. Endogenous opioids apparently modulateventilatory control acutely after load imposition. Their effect waneswith time despite persistence of depressedCO₂ sensitivity.

     

Skeletal muscle chemoreflex and pHi in exercise ventilatory control

Oelberg, David A., Allison B. Evans, Mirko I. Hrovat, PaulP. Pappagianopoulos, Samuel Patz, and David M. Systrom. Skeletal muscle chemoreflex and pH_i inexercise ventilatory control. J. Appl.Physiol. 84(2): 676-682, 1998.To determinewhether skeletal muscle hydrogen ion mediates ventilatory drive inhumans during exercise, 12 healthy subjects performed three bouts ofisotonic submaximal quadriceps exercise on each of 2 days in a 1.5-Tmagnet for ³¹P-magnetic resonancespectroscopy(³¹P-MRS). Bilaterallower extremity positive pressure cuffs were inflated to 45 Torr duringexercise (BLPP_ex) or recovery(BLPP_rec) in a randomized orderto accentuate a muscle chemoreflex. Simultaneous measurements were madeof breath-by-breath expired gases and minute ventilation, arterializedvenous blood, and by ³¹P-MRS ofthe vastus medialis, acquired from the average of 12 radio-frequencypulses at a repetition time of 2.5 s. WithBLPP_ex, end-exercise minuteventilation was higher (53.3 ± 3.8 vs. 37.3 ± 2.2 l/min;P < 0.0001), arterializedPCO₂ lower (33 ± 1 vs. 36 ± 1 Torr; P = 0.0009), and quadricepsintracellular pH (pH_i) more acid (6.44 ± 0.07 vs. 6.62 ± 0.07; P = 0.004), compared withBLPP_rec. Bloodlactate was modestly increased withBLPP_ex but without a change inarterialized pH. For each subject, pH_i was linearly relatedto minute ventilation during exercise but not to arterialized pH. Thesedata suggest that skeletal muscle hydrogen ion contributes to theexercise ventilatory response.

     

Contractile function of single muscle fibers after hindlimb unweighting in aged rats

Thompson, L. V., and J. A. Shoeman. Contractilefunction of single muscle fibers after hindlimb unweighting in aged rats. J. Appl. Physiol. 84(1):229-235, 1998.This investigation determined how muscle atrophyproduced by hindlimb unweighting (HU) alters the contractile functionof single muscle fibers from older animals (30 mo). After 1 wk of HU,small bundles of fibers were isolated from the soleus muscles and thedeep region of the lateral head of the gastrocnemius muscles. Singleglycerinated fibers were suspended between a motor lever and forcetransducer, functional properties were studied, and the myosin heavychain (MHC) composition was determined electrophoretically. After HU, the diameter of type I MHC fibers of the soleus declined (88 ± 2 vs. 80 ± 4 µm) and reductions were observed in peak active force (47 ± 3 vs. 28 ± 3 mg) and peak specific tension(P_o; 80 ± 5 vs. 56 ± 5 kN/m²). The maximal unloadedshortening velocity increased. The type I MHC fibers from thegastrocnemius showed reductions in diameter (14%), peak active force(41%), and P_o (24%), whereas thetype IIa MHC fibers showed reductions in peak active force andP_o. Thus 1 wk ofinactivity has a significant effect on the force-generating capacity ofsingle skeletal muscle fibers from older animals in a fibertype-specific manner (type I MHC > type IIa MHC > type I-IIa MHC).The decline in the functional properties of single skeletal musclefibers in the older animals appears to be more pronounced than what hasbeen reported in younger animal populations.

     

Corticosteroid effects on isotonic contractile properties of rat diaphragm muscle

Van Balkom, Roland H. H., Wen-Zhi Zhan, Y. S. Prakash, P. N. Richard Dekhuijzen, and Gary C. Sieck. Corticosteroid effects on isotonic contractile properties of rat diaphragm muscle. J. Appl. Physiol. 83(4):1062-1067, 1997.The effects of corticosteroids (CS) on diaphragmmuscle (Dia_m) fiber morphologyand contractile properties were evaluated in three groups of rats:controls (Ctl), surgical sham and weight-matched controls (Sham), andCS-treated (6 mg · kg¹ · day¹prednisolone at 2.5 ml/h for 3 wk). In the CS-treatedDia_m, there was a selectiveatrophy of type IIx and IIb fibers, compared with a generalized atrophyof all fibers in the Sham group. Maximum isometric force was reduced by20% in the CS group compared with both Ctl and Sham. Maximumshortening velocity in the CS Dia_m was slowed by ~20% compared with Ctl and Sham. Peak power output ofthe CS Dia_m was only 60% of Ctland 70% of Sham. Endurance to repeated isotonic contractions improvedin the CS-treated Dia_m comparedwith Ctl. We conclude that the atrophy of type IIx and IIb fibers inthe Dia_m can only partiallyaccount for the CS-induced changes in isotonic contractile properties.Other factors such as reduced myofibrillar density or alteredcross-bridge cycling kinetics are also likely to contribute to theeffects of CS treatment.

     

Gender-specific effects of dexamethasone treatment on rat diaphragm structure and function

Prezant, D. J., M. L. Karwa, B. Richner, D. Maggiore, E. I. Gentry, and J. Cahill. Gender-specific effects of dexamethasone treatment on rat diaphragm structure and function. J. Appl. Physiol. 82(1): 125-133, 1997.The effectsof long-term dexamethasone treatment on diaphragm muscle were studiedin female and male rats. Compared with pair-fed control animals,dexamethasone treatment did not significantly affect estrous cycling orpeak serum estradiol levels; however, testosterone levels weresignificantly increased in females and decreased in males.Dexamethasone significantly reduced body and costal diaphragm weights,but to a lesser extent in females than in males. Reductions indiaphragm weight were proportional to reductions in body weight. Infemales and males, dexamethasone treatment significantly decreaseddiaphragm fiber (types I and II) cross-sectional area and the relativeexpression of myosin heavy chain isoform 2B. With the exception of typeI fiber atrophy, these changes occurred to a lesser extent in females.Dexamethasone did not significantly affect specific forces.Dexamethasone significantly increased twitch one-half relaxation timeand fatigue resistance indexes in males but not in females. Inconclusion, the effects of long-term dexamethasone treatment weregender specific, with significantly fewer effects in females, andchanges in serum testosterone levels were associated with thesefindings.

     

Strain-induced growth of the immature lung

Zhang, Shaoping, Vicki Garbutt, and John T. McBride.Strain-induced growth of the immature lung. J. Appl. Physiol. 81(4): 1471-1476, 1996.Toinvestigate the relationship between strain and postnatal lung growth,two groups of weanling ferrets were tracheotomized: the study group wasexposed for 2 wk to a continuous positive airway pressure (CPAP) of 6 cmH₂O and the other group wasexposed to atmospheric pressure (control). Total lung capacity after 2 wk was ~40% higher in the CPAP-exposed animals than in the controlanimals (n = 19 for the control groupand 18 for the study group; P < 0.01). CPAP exposure was also associated with increases in lung weightand total lung protein and DNA contents. Lung recoil, measured in asubgroup of animals, was characterized by air-filled and saline-filledstatic expiratory pressure-volume curves. Neither in the air-filledlungs nor in the saline-filled lungs was there a significant differencebetween CPAP-exposed and control animals in lung recoil at equalfractions of total lung capacity. These data indicate that mechanicalstrain was associated with an acceleration of lung growth in immatureferrets. The preservation of volume-corrected lung recoil and theexpected contribution of surface forces and tissue forces to lungrecoil in CPAP-exposed animals suggest that this response did notinvolve simple lung distension but included a remodeling of the lungparenchyma.

     

In vivo assessment of changes in air and tissue volumes after pneumonectomy

Takeda, S., E. Y. Wu, R. H. Epstein, A. S. Estrera, and C. C. W. Hsia. In vivo assessment of changes in air and tissue volumes after pneumonectomy. J. Appl.Physiol. 82(4): 1340-1348, 1997.We examined theprogression and topographical distribution of postpneumonectomy volumechanges in immature foxhounds undergoing right pneumonectomy (R-Pnx,n = 5) or sham pneumonectomy (Sham, n = 6) at 2 mo of age and subsequentlyraised to maturity. Volumes of lung air (Vair) and tissue(Vti) were estimated by computerized tomography (CT) scan at 7, 22, and52 wk after surgery at a transpulmonary pressure of 20 cmH₂O. Estimates of Vti by CT scanincluded both septal tissue as well as nonseptal tissue (small- andmedium-sized airways and blood vessels); these were compared withestimates of septal Vti by an acetylene rebreathing (Rb) method. Wefound significant correlations between these techniques(Vair_CT = 0.83 Vair_Rb + 275, R = 0.97;Vti_CT = 1.62 Vti_Rb  30, R = 0.81). Extravascular septal Vtireturned to normal 7 wk after R-Pnx and remained normal up to maturity.Nonseptal Vti remained significantly below normal. The greatestincrease in Vti occurred in the midlung region just cephalad and caudalto the heart. After an early period of accelerated tissue growth afterR-Pnx, the rate of septal tissue growth matched that of somatic growth,whereas nonseptal tissue growth lagged behind. Compensatory growth ofthe remaining left lung was not associated with selectivealterations in thoracic development.

     

Changes in maximum oxygen uptake during prolonged training, overtraining, and detraining in horses

Tyler, Catherine M., Lorraine C. Golland, David L. Evans,David R. Hodgson, and Reuben J. Rose. Changes in maximum oxygenuptake during prolonged training, overtraining, and detraining inhorses. J. Appl. Physiol. 81(5):2244-2249, 1996.Thirteen standardbred horses were trained asfollows: phase 1 (endurance training, 7 wk),phase 2 (high-intensity training, 9 wk),phase 3 (overload training, 18 wk), andphase 4 (detraining, 12 wk). Inphase 3, the horses were divided intotwo groups: overload training (OLT) and control (C). The OLT groupexercised at greater intensities, frequencies, and durations than groupC. Overtraining occurred after 31 wk of training and was defined as asignificant decrease in treadmill run time in response to astandardized exercise test. In the OLT group, there was a significantdecrease in body weight (P < 0.05).From pretraining values of 117 ± 2 (SE)ml ^· kg^{1 ·} min¹,maximal O₂ uptake(O_{2 max}) increased by15% at the end of phase 1, and when signs of overtraining werefirst seen in the OLT group,O_{2 max} was 29%higher (151 ± 2 ml ^· kg^{1 ·} min¹in both C and OLT groups) than pretraining values. There was nosignificant reduction inO_{2 max} until after 6 wk detraining whenO_{2 max} was 137 ± 2 ml ^· kg^{1 ·} min¹.By 12 wk detraining, meanO_{2 max} was134 ± 2 ml ^· kg^{1 ·} min¹,still 15% above pretraining values. When overtraining developed, O_{2 max} was notdifferent between C and OLT groups, but maximal values forCO₂ production (147 vs. 159 ml ^· kg^{1 ·} min¹)and respiratory exchange ratio (1.04 vs. 1.11) were lower in the OLTgroup. Overtraining was not associated with a decrease inO_{2 max} and, afterprolonged training, decreases inO_{2 max} occurredslowly during detraining.

     

Aerobic fitness effects on exercise-induced low-frequency diaphragm fatigue

Babcock, Mark A., David F. Pegelow, Bruce D. Johnson, andJerome A. Dempsey. Aerobic fitness effects on exercise-induced low-frequency diaphragm fatigue. J. Appl.Physiol. 81(5): 2156-2164, 1996.We usedbilateral phrenic nerve stimulation (BPNS; at 1, 10, and 20 Hz atfunctional residual capacity) to compare the amount of exercise-induceddiaphragm fatigue between two groups of healthy subjects, a high-fitgroup [maximal O₂consumption (O_{2 max}) = 69.0 ± 1.8 ml ^· kg^{1 ·} min¹,n = 11] and a fit group(O_{2 max} = 50.4 ± 1.7 ml ^· kg^{1 ·} min¹,n = 13). Both groups exercised at88-92% O_{2 max}for about the same duration (15.2 ± 1.7 and 17.9 ± 2.6 min forhigh-fit and fit subjects, respectively,P > 0.05). The supramaximal BPNS test showed a significant reduction (P < 0.01) in the BPNS transdiaphragmatic pressure (Pdi) immediatelyafter exercise of 23.1 ± 3.1% for the high-fit group and23.1 ± 3.8% (P > 0.05)for the fit group. Recovery of the BPNS Pdi took 60 min in both groups.The high-fit group exercised at a higher absolute workload, whichresulted in a higher CO₂production (+26%), a greater ventilatory demand (+16%) throughout theexercise, and an increased diaphragm force output (+28%) over theinitial 60% of the exercise period. Thereafter, diaphragm force outputdeclined, despite a rising minute ventilation, and it was not differentbetween most of the high-fit and fit subjects. In summary, the high-fitsubjects showed diaphragm fatigue as a result of heavy enduranceexercise but were also partially protected from excessive fatigue,despite high ventilatory requirements, because their hyperventilatoryresponse to endurance exercise was reduced, their diaphragm wasutilized less in providing the total ventilatory response, and possiblytheir diaphragm aerobic capacity was greater.

     

A model for phosphocreatine resynthesis

Nevill, Alan M., David A. Jones, David McIntyre, Gregory C. Bogdanis, and Mary E. Nevill. A model forphosphocreatine resynthesis. J. Appl.Physiol. 82(1): 329-335, 1997.A model for phosphocreatine (PCr) resynthesis is proposed based on a simple electric circuit, where the PCr store in muscle is likened to thestored charge on the capacitor. The solution to the second-order differential equation that describes the potential around the circuitsuggests the model for PCr resynthesis is given byPCr(t) = R  [d₁ ^· exp(k₁ ^· t) ± d₂ ^· exp(k₂ ^· t)],where R is PCr concentration at rest,d₁,d₂, k₁, andk₂ are constants, andt is time. By using nonlinear leastsquares regression, this double-exponential model was shown to fit thePCr recovery data taken from two studies involving maximal exerciseaccurately. In study 1, when themuscle was electrically stimulated while occluded, PCr concentrations rose during the recovery phase to a level above that observed at rest.In study 2, after intensive dynamicexercise, PCr recovered monotonically to resting concentrations. Thesecond exponential term in the double-exponential model was found tomake a significant additional contribution to the quality of fit inboth study 1 (P < 0.05) andstudy 2 (P < 0.01).

     

Sprint training attenuates myocyte hypertrophy and improves Ca2+ homeostasis in postinfarction myocytes

Zhang, Xue-Qian, Yuk-Chow Ng, Timothy I. Musch, Russell L. Moore, R. Zelis, and Joseph Y. Cheung. Sprint training attenuates myocyte hypertrophy and improvesCa²⁺ homeostasis in postinfarctionmyocytes. J. Appl. Physiol. 84(2): 544-552, 1998.Myocytes isolated from rat hearts 3 wk aftermyocardial infarction (MI) had decreasedNa⁺/Ca²⁺exchange currents(I_Na/Ca; 3 Na⁺ out:1Ca²⁺ in) and sarcoplasmicreticulum (SR)-releasable Ca²⁺contents. These defects in Ca²⁺regulation may contribute to abnormal contractility in MI myocytes. Because exercise training elicits positive adaptations in cardiac contractile function and myocardialCa²⁺ regulation, thepresent study examined whether 6-8 wk ofhigh-intensity sprint training (HIST) would ameliorate some of thecellular maladaptations observed in post-MI rats with limited exerciseactivity (Sed). In MI rats, HIST did not affect citrate synthaseactivities of plantaris muscles but significantly increased thepercentage of cardiac -myosin heavy chain (MHC) isoforms (57.2 ± 1.9 vs. 49.3 ± 3.5 in MI-HIST vs. MI-Sed, respectively;P  0.05). At the single myocytelevel, HIST attenuated cellular hypertrophy observed post-MI, asevidenced by reductions in cell lengths (112 ± 4 vs. 130 ± 5 µm in MI-HIST vs. MI-Sed, respectively;P  0.005) and cell capacitances (212 ± 8 vs. 242 ± 9 pF in MI-HIST vs. MI-Sed, respectively; P  0.015). ReverseI_Na/Ca wassignificantly lower (P  0.0001) inmyocytes from MI-Sed rats compared with those from rats that were shamoperated and sedentary. HIST significantly increased reverseI_Na/Ca(P  0.05) without affecting theamount ofNa⁺/Ca²⁺exchangers (detected by immunoblotting) in MI myocytes. SR-releasable Ca²⁺ content, as estimated byintegrating forwardI_Na/Ca duringcaffeine-induced SR Ca²⁺ release,was also significantly increased (P  0.02) by HIST in MI myocytes. We conclude that the enhanced cardiacoutput and stroke volume in post-MI rats subjected to HIST aremediated, at least in part, by reversal of cellular maladaptationspost-MI.

     

Endurance training affects myosin heavy chain phenotype in regenerating fast-twitch muscle

Bigard, Xavier A., Chantal Janmot, Danièle Merino,Françoise Lienhard, Yannick C. Guezennec, and Anne D'Albis.Endurance training affects myosin heavy chain phenotype inregenerating fast-twitch muscle. J. Appl.Physiol. 81(6): 2658-2665, 1996.The aim of thisstudy was to analyze the effects of treadmill training (2 h/day, 5 days/wk, 30 m/min, 7% grade for 5 wk) on the expression of myosinheavy chain (MHC) isoforms during and after regeneration of afast-twitch white muscle [extensor digitorum longus (EDL)]. Male Wistar rats were randomly assigned to a sedentary(n = 10) or an endurance-trained (ET;n = 10) group. EDL muscle degeneration and regeneration were induced by two subcutaneous injections of a snaketoxin. Five days after induction of muscle injury, animals were trainedover a 5-wk period. It was verified that ~40 days after venomtreatment, central nuclei were present in the treated EDL muscles fromsedentary and ET rats. The changes in the expression of MHCs in EDLmuscles were detected by using a combination of biochemical andimmunocytochemical approaches. Compared with contralateral nondegenerated muscles, relative concentrations of types I, IIa, andIIx MHC isoforms in ET rats were greater in regenerated EDL muscles(146%, P < 0.05; 76%,P < 0.01; 87%,P < 0.01, respectively). Their elevation corresponded to a decreasein the relative concentration of type IIb MHC (36%,P < 0.01). Although type I accountedfor only 3.2% of total myosin in regenerated muscles from the ETgroup, the cytochemical analysis showed that the proportion of positive staining with the slow MHC antibody was markedly greater in regenerated muscles than in contralateral ones. Collectively, these results demonstrate that the regenerated EDL muscle is sensitive to endurance training and suggest that the training-induced shift in MHC isoforms observed in these muscles resulted from an additive effect of regeneration and repeated exercise.

     

Task failure with lack of diaphragm fatigue during inspiratory resistive loading in human subjects

McKenzie, D. K., G. M. Allen, J. E. Butler, and S. C. Gandevia. Task failure with lack of diaphragm fatigue during inspiratory resistive loading in human subjects. J. Appl. Physiol. 82(6): 2011-2019, 1997.Taskfailure during inspiratory resistive loading is thought to beaccompanied by substantial peripheral fatigue of the inspiratorymuscles. Six healthy subjects performed eight resistive breathingtrials with loads of 35, 50, 75 and 90% of maximal inspiratorypressure (MIP) with and without supplemental oxygen. MIP measuredbefore, after, and at every minute during the trial increased slightlyduring the trials, even when corrected for lung volume (e.g., for 24 trials breathing air, 12.5% increase, P < 0.05). In some trials, taskfailure occurred before 20 min (end point of trial), and in thesetrials there was an increase in end-tidalPCO₂(P < 0.01), despite the absence of peripheral muscle fatigue. In four subjects (6 trials with task failure), there was no decline in twitch amplitude with bilateral phrenic stimulation or in voluntary activation of the diaphragm, eventhough end-tidal PCO₂ rose by 1.6 ± 0.9%. These results suggest that hypoventilation,CO₂ retention, and ultimate taskfailure during resistive breathing are not simply dependent on impairedforce-generating capacity of the diaphragm or impaired voluntaryactivation of the diaphragm.

     

Recovery of diaphragmatic function in awake sheep after two approaches to thoracic surgery

Imanaka, Hideaki, William R. Kimball, John C. Wain, MasajiNishimura, Kenichi Okubo, Dean Hess, and Robert M. Kacmarek. Recovery of diaphragmatic function in awake sheep after two approaches to thoracic surgery. J. Appl.Physiol. 83(5): 1733-1740, 1997.Video-assistedthoracoscopic surgery (VATS) is replacing thoracotomy, but no study hasaddressed the extent or duration of VATS-induced diaphragmaticalteration. We hypothesized that VATS would impair diaphragmaticfunction less and return diaphragmatic function faster thanthoracotomy. In eight sheep, sonomicrometers were randomly implanted onthe right costal diaphragm via VATS or thoracotomy. Diaphragmaticresting length, shortening fraction, and respiratory function weremeasured weekly during quiet breathing (QB) andCO₂ rebreathing for 4 wk. ForVATS, shortening fraction was smallest onpostoperative days 1 (POD 1) (6.4 ± 3.4 and12.9 ± 8.7% during QB and 10%CO₂ rebreathing, respectively) and7 (6.3 ± 3.4 and 16.9 ± 4.0%during QB and 10% CO₂rebreathing, respectively) and recovered by 3 wk (13.2 ± 1.8 and28.9 ± 8.0% during QB and 10%CO₂ rebreathing, respectively).For thoracotomy, shortening fraction at 10%CO₂ rebreathing was smaller onPODs 1, 7, 14 (15.9 ± 7.1, 13.6 ± 5.4, and 19.0 ± 6.9%) than onPOD 28 (29.9 ± 8.2%), but notduring QB on POD 1 or7 (7.5 ± 3.8 and 3.4 ± 2.6%)compared with POD 28 (10.7 ± 8.7%). Shortening fraction did not differ between surgeries. There wasno group difference in minute ventilation, respiratory rate,transdiaphragmatic pressure, or esophageal and gastric pressures. Inconclusion, although shortening fraction recovered faster for VATS,this translated into insignificant functional differences.

     

Metabolic and phenotypic adaptations of diaphragm muscle fibers with inactivation

Zhan, Wen-Zhi, Hirofumi Miyata, Y. S. Prakash, and Gary C. Sieck. Metabolic and phenotypic adaptations of diaphragm musclefibers with inactivation. J. Appl.Physiol. 82(4):1145-1153, 1997.We hypothesizedthat metabolic adaptations to muscle inactivity are most pronouncedwhen neurotrophic influence is disrupted. In ratdiaphragm muscle(Dia_m), 2 wk ofunilateral denervation or tetrodotoxin nerve blockade resulted in areduction in succinate dehydrogenase (SDH) activity of type I, IIa, andIIx fibers (~50, 70, and 24%, respectively) and a decrease in SDHvariability among fibers (~63%). In contrast, inactivity induced byspinal cord hemisection at C₂ (ST)resulted in much less change in SDH activity of type I and IIa fibers(~27 and 24%, respectively) and only an ~30% reduction in SDHvariability among fibers. Actomyosin adenosinetriphosphatase (ATPase)activities of type I, IIx, and IIb fibers in denervated andtetrodotoxin-treated Dia_m werereduced by ~20, 45, and 60%, respectively, and actomyosin ATPasevariability among fibers was ~60% lower. In contrast, onlyactomyosin ATPase activity of type IIb fibers was reduced (~20%) inST Dia_m. These results suggestthat disruption of neurotrophic influence has a greater impact onmuscle fiber metabolic properties than inactivity per se.