Robert A. Herb

Caffeine and exercise performance. An update.

SummaryThree principal cellular mechanisms have been proposed to explain the ergogenic potential of caffeine during exercise: (a) increased myofilament affinity for calcium and/or increased release of calcium from the sarcoplasmic reticulum in skeletal muscle; (b) cellular actions caused by accumulation of cyclic-3′,5′-adenosine monophosphate (cAMP) in various tissues including skeletal muscle and adipocytes; and (c) cellular actions mediated by competitive inhibition of adenosine receptors in the central nervous system and somatic cells. The relative importance of each of the above mechanisms in explaining in vivo physiological effects of caffeine during exercise continues to be debated. However, growing evidence suggests that inhibition of adenosine receptors is one of the most important, if not the most important, mechanism to explain the physiological effects of caffeine at nontoxic plasma concentrations. Numerous animal studies using high caffeine doses have reported increased force development in isolated skeletal muscle in both in vitro and in situ preparations. In contrast, in vivo human studies have not consistently shown caffeine to enhance muscular performance during high intensity, short term exercise. Further, recent evidence supports previous work that shows caffeine does not improve performance during short term incremental exercise. Although controversy exists, the major part of published evidence evaluating performance supports the notion that caffeine is ergogenic during prolonged (>30 min), moderate intensity (≈75 to 80% V̇2max) exercise. The mechanism to explain these findings may be linked to a caffeine-mediated glycogen sparing effect secondary to an increased rate of lipolysis.

Regional training-induced alterations in diaphragmatic oxidative and antioxidant enzymes

We examined the relationship between the intensity and duration of exercise training and the up-regulation of diaphragmatic oxidative and antioxidant enzyme activities. Nine groups of rats exercised for 10 weeks (4 days/week). Groups of animals exercised at three intensities (low, moderate, and high); at each exercise intensity, a group of animals ran at one of three exercise durations (30, 60, and 90 min/day). Sedentary animals served as controls. Muscle oxidative capacity was assessed by citrate synthase (CS) activity while antioxidant capacity was evaluated by total superoxide dismutase (SOD) and total glutathione peroxidase (GPX) activities. All intensities and durations of exercise training promoted significant (P < 0.05) increases in costal diaphragmatic CS, SOD, and GPX activities. Increases in costal CS, SOD, and GPX activity were independent of the exercise intensity and duration. High and moderate intensity exercise of 90 min duration significantly elevated (P < 0.05) crural diaphragm CS activity. Further, high and moderate intensity exercise of durations > or = 60 min promoted significant (P < 0.05) increases in crural diaphragm SOD activities. Exercise did not influence (P > 0.05) crural diaphragm GPX activity. We conclude that the training threshold for up-regulation of oxidative and antioxidant enzyme activities differs between the costal and crural diaphragm.

Clenbuterol-induced fiber type transition in the soleus of adult rats.

This study examined the effects of 6 weeks of treatment with theβ(2)-adrenoceptor agonist, clenbuterol, on the soleus muscle of adult female Sprague-Dawley rats. Animals (4 months old) were divided into two groups: clenbuterol treated (CL,n=7) (2 mg kg−1 body mass injected subcutaneously every other day), and control (CON,n=7) (injected with isotonic saline). Post-treatment body weights were ≈ 5% greater in the CL group compared to CON (P<0.05). Polyacrylamide gel electrophoresis (SDS-PAGE) of soleus myofibrillar protein indicated a clenbuterol-induced decrease (P<0.05) in the relative percentage of type I myosin heavy chain (MHC) with a concomitant increase (P<0.05) in type IIdx MHC, while the proportion of type IIa MHC was unaffected. ATPase fiber typing revealed increases (P<0.05) in the proportion of type II fibers expressed both as a percentage of total fiber number and total cross-sectional area (CSA). Finally, mean type II fiber CSA was ≈25% greater (P<0.05) in the CL groups as compared to the CON group. These data indicate that clenbuterol treatment results in alterations in the MHC phenotype and an increased proportion of type II fiber CSA in the soleus of adult rats. These observations were due to an increase in the total number of type II fibers, as well as hypertrophy of these fibers. Thus, the relative increase in the number of histochemically determined type II fibers and the emergence of the normally unexpressed type IIdx MHC isoform in the soleus suggest a clenbuterol-induced transition of muscle fiber phenotype as well as selective hypertrophy of the type 11 fibers.

Mechanism of specific force deficit in the senescent rat diaphragm

Aging is associated with a decline in the maximal in vitro specific force in the rat costal diaphragm. The purpose of this study was to determine if this force deficit is associated with a decrease in the concentration of myofibrillar protein in diaphragm fibers of senescent rats. Isometric twitch and tetanic contractile properties were measured on diaphragm strips from young adult (9-month-old: n = 12) and senescent (26-month-old: n = 13) male specific pathogen free-barrier protected Fischer 344 rats. Maximal tetanic force (Po) normalized to the cross-sectional area (CSA) of the in vitro diaphragm strips was 16.4% lower in the senescent diaphragms (21.03 +/- 0.4 N/cm2) compared to the young adult (25.16 +/- 0.5 N/cm2) (p < 0.001). Diaphragm water content was significantly higher in the senescent group (75.9% of total wet mass) compared to the young adult (72.1% of total wet mass, p < 0.05). Subtracting the contribution of water from the CSA of the diaphragm strips significantly reduced (p < 0.05) the senescent specific Po deficit (from -16.4 to -6.4%). Further, correcting Po for the contribution of myofibrillar protein to CSA resulted in no age group differences in specific force. These data indicate that the age-related decline in diaphragm in vitro maximal specific Po can be explained by an age-related increase in the water content of the diaphragm muscle. Future experiments are necessary to determine the mechanism(s) responsible for this observation.

The effects of hypothyroidism on single fibers of the rat soleus muscle

Skinned single fibers were used to test the hypothesis that skinned fibers from hypothyroid soleus muscle would have a higher sensitivity to calcium compared with control fibers, as indicated by a leftward shift of the pCa-force curve. Control rats (n = 14) received sham injections, while the hypothyroid group (n = 16) received thyroidectomy and a 6-week injection period of the antithyroid drug 6-n-propyl-2-thiouracil. Hypothyroidism caused the type I fiber number to increase significantly (11%) in the soleus. Hypothyroid fibers produced 16% less absolute tension than control fibers. However, cross-sectional areas of control fibers were significantly greater (25%) than those of hypothyroid fibers, so that when force was normalized to cross-sectional area, no differences between groups existed. Calcium requirement for half-maximal force production (pCa50) did not differ, but the slope of the pCa-force curve was different between groups. These data suggest that hypothyroidism did not alter the intrinsic force-generating capacity of the soleus muscle fibers. Thus, alterations in hypothyroid soleus contractile function seen in vitro may be explained by alterations in excitation-contraction coupling and (or) shifts in muscle fiber types.