Browsing by Author "Spangenburg, Espen E."

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    The effects of congestive heart failure and functional overload on rat skeletal muscle
    Spangenburg, Espen E. (Virginia Tech, 2000-06-23)
    Numerous references have suggested that alterations in exercise capacity during congestive heart failure (CHF) are not simply due to changes in myocardial function. In fact, recent evidence has indicated that reductions in skeletal muscle strength and endurance during CHF significantly impact exercise capacity of the CHF patient. Currently, it is believed that alterations in skeletal muscle phenotype, or more specifically a slow to fast transformation in phenotypic protein isoforms contribute to the reductions in muscle function. However, currently there are few data which directly document this slow to fast transformation of the skeletal muscle. Interestingly, it is well established that exercise training can cause changes in skeletal muscle phenotype, more specifically in the fast to slow direction. This is in direct contrast to what is known to occur during CHF. However, it is unclear if similar adaptations will result from training in a CHF patient. Also, it is not clear if the adaptations are due to alterations in the myocardium or changes directly imposed upon the muscle by the exercise training. Therefore, the purpose of this study was two-fold: 1) to clarify the changes in skeletal muscle myosin heavy chain (MHC) during CHF and 2) to determine if skeletal muscle can adapt to increased activity levels, utilizing functional overload (FO) without significantly improving cardiac function. In the first study the mixed plantaris muscles from rats afflicted with severe CHF demonstrated a significant (p<0.05) increase in fast MHC (e.g. IIb expression at the expense of IIx expression) compared to the control animal (SHAM). The mixed red gastrocnemius, regardless of the severity of CHF, exhibited significant (p<0.05) changes in all of the MHC isoforms. The slow soleus and fast white gastrocnemius did not display any significant changes in MHC expression. The changes in MHC isoform significantly correlated with indicators of disease severity, suggesting there may be an existing relationship between skeletal muscle MHC expression and alterations in myocardial function. In the second study, there were no differences exhibited between CHF and SHAM absolute or specific plantaris mass. There was a significant (p<0.05) 30% increase in both absolute and specific mass of the plantaris in the CHF-FO and SHAM-FO groups compared to the CHF and SHAM groups. There was a significant (p<0.05) 3.5% increase in slow MHC I expression and a significant (p<0.05) 6.5% decrease in fast MHC IIb expression in the CHF-FO group compared to the CHF group. In the SHAM-FO group, there was a significant (p<0.05) 4% increase in MHC I expression and a subsequent 8% decrease in fast MHC IIx+IIb in the SHAM-FO compared to the SHAM groups. There were no differences detected in the rates of Ca²⁺ uptake between the CHF-FO, SHAM, and SHAM-FO. However, Ca²⁺ uptake rates were significantly (p<0.05) elevated by 44% in the CHF group when compared to the other three groups. There were very few changes in plantaris SERCA 1 or 2 protein expression between the four groups. These data suggest that during CHF there are alterations in skeletal muscle isoform expression. However, at least some of the data suggest that changes in function are not always associated with changes in phenotype. Instead, it seems that the changes in Ca²⁺ handling may be due to an alteration in a regulatory mechanism. Also, the data indicate that skeletal muscle is adaptable to increases in activity levels without significantly altering myocardial morphology.
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    The Effects of Lactate on Whole Muscle Function and Sarcoplasmic Reticulum Function
    Spangenburg, Espen E. (Virginia Tech, 1997-04-24)
    Numerous studies have attributed the decrease in force production of skeletal muscle during exercise to a increase in lactate concentration ([lactate]). This notion is based on the high negative correlation between plasma lactate and force during fatigue and recovery. These experiments attempted to determine if lactate directly effects force production in skeletal muscle. Mouse extensor digitorum longus muscles (EDL) were isolated and incubated in a buffered Ringers solution at a pH 7.2 and exposed at three minute intervals to a final concentration of 10, 20, 30, 50mM lactate. At 21° C, tetanic force production (Po, 250ms, 110Hz) decreased to 99.3 ± 1.0, 97.1 ± 1.2, 94.9 ± 1.1* and 93.1 ± 1.3*% of initial and the rate of force development (+dP/dt) was reduced to 99.4 ± 0.7, 96.8 ± 0.5, 93.5 ± 0.6*, and 89.3 ± 1.2*% of initial (*p<0.05 vs untreated muscles). At 37° C the effects of lactate were augmented. Po was reduced to 89.7 ± 1.1, 81.0 ± 2.4, 73 ± 3.9*, and 61.6 ± 5.4*% and +dP/dt was reduced to 79.4 ± 1.8*, 65.9 ± 2.8*, 55.4 ± 4.0*, and 44.3 ± 5.0*% of initial (*p<0.05 vs control muscles). The next phase was to determine if the changes in Po and +dP/dt were due to alterations in the sacroplasmic reticulum (SR) Ca2+ exchange. The SR of EDL homogenates were actively loaded with Ca2+ and release was initiated by 25 mM AgNO3. The rate of Ca2+ release was significantly reduced by 31% (2.48 ± 1.21 vs 1.72 ± 0.24 mmol·mg-1·min-1) in the presence of 25 mM lactate. These results indicate that exposure to increased [lactate], independent of the H+, decreases force production of whole muscle, effects that are greater at 37° C than 21° C. Also increased lactate reduces the rate of SR Ca2+ release. These results suggest that lactate depresses whole muscle force production by altering Ca2+ release of the SR. They also support the idea that increased lactate concentrations disrupt normal muscle function leading to the development of fatigue.