The effects of running stress on plasma vitamin A levels in rats.

The plasma concentrations of vitamin A, zinc and proteins and the hepatic level of vitamin A were determined in rats subjected to running as a model for stress and which were receiving standard or vitamin-A free diets. All rats showed a decrease in plasma vitamin A with running compared with non-running control animals. Hepatic levels of vitamin A were higher in these two test groups than in their weight- and age-matched non-running controls. The data support that running, like other forms of stress, decreases plasma vitamin A, consistent with the retention of vitamin A in the liver.

Physiology course for secondary school biology teachers.

The Department of Physiology at the Medical College of Virginia/Virginia Commonwealth University offered a human physiology course to middle school and high school science teachers in the Richmond, VA, area. It was a three-credit course, team taught, and given at a location convenient to many area teachers. This course served the community by contributing to the continuing education efforts of teachers and concurrently enhanced our recruitment program by advertising "physiology" to teachers who will influence college-bound students for years to come. In addition, we established ties between teachers and physiology faculty such that continuing interactions (e.g., collaborative research during the summer) should be facilitated. The success of the course suggests that this is an effective way to serve local communities, enhance efforts to recruit graduate students into the basic sciences, and at the same time help reverse the educational crisis in the US by bolstering the backgrounds of secondary school teachers.

Contribution of the ryanodine-sensitive fraction to capabilities of cardiac SR.

The contribution of the ryanodine-sensitive fraction of canine cardiac sarcoplasmic reticulum to the total issue calcium uptake was estimated by the oxalate-supported calcium uptake rate in canine whole heart homogenates. Ryanodine stimulated this uptake rate nearly three-fold. Ryanodine stimulated this same activity in isolated SR vesicles only two-fold. An analysis of the yield of calcium uptake activity throughout the isolation procedure showed that the largest discrimination between ryanodine-sensitive and ryanodine-insensitive activity occurs at the first centrifugation step. In isolated vesicles, the initial rate of uptake in the absence of oxalate correlated well with the sustained oxalate-support calcium uptake rate, suggesting that oxalate-supported calcium uptake is a good indicator of in vivo SR function. The similarity between the effects of ryanodine on the rate and capacity of calcium uptake in the presence or absence of oxalate is consistent with earlier observations that ryanodine adds effective volume by closing a calcium release channel in a subpopulation of SR. The data also suggest that the ratio of calcium pumping activity to volume in these two populations is not greatly different.

The rate and capacity of calcium uptake by sarcoplasmic reticulum in fast, slow, and cardiac muscle: effects of ryanodine and ruthenium red.

The rate and capacity of oxalate-supported calcium uptake was measured in homogenates of rat fast, slow, and cardiac muscle. The contribution of the releasing fraction of the sarcoplasmic reticulum (SR) to the calcium uptake abilities was estimated using ruthenium red or ryanodine to block the release channel. A relatively small fraction (12-20%) of the calcium pumping activity was associated with the release channel in skeletal muscle compared to 50% or more in cardiac muscle. The total capacity of the SR in the muscle types was in the ratio 1:0.75:1.5 for cardiac, slow, and fast muscle, respectively, while the rates of uptake were in the ratio 1:3.8:14.4. The major difference in the muscle types appears to be the density of pumping activity in the SR rather than the volume of the SR. The difference in the density of pumping activity is due to intrinsic differences in the kinetics of the calcium pump units and in their surface density.

Glucocorticoid-induced glycogen increases in extensor digitorum longus and soleus grafts in the rat.

The purpose of the present study was to compare dexamethasone-induced glycogen increases in normal EDL and SOL muscles with that in free muscle grafts. Glycogen in mature EDL and SOL grafts in the rat equalled control concentrations irrespective of whether the graft was a nerve-intact (NI), nerve-crushed (NC), reimplanted, or cross-transplanted graft. The grafts also possessed the glycogen-regulatory mechanisms to respond to the glucocorticoid dexamethasone (DEX), which increases muscle glycogen. The increase in glycogen induced by DEX in the EDL and SOL grafts resembled that of the EDL and SOL muscles, respectively, whether the grafted muscle was originally an EDL or SOL. DEX induced an approximate twofold increase in glycogen concentration in control muscles and nerve-intact SOL grafts, and a smaller but significant increase in all other free grafts. Nerve crushing prior to grafting resulted in no significant change in muscle weight, glycogen concentration, or DEX-induced glycogen increase in these grafts. The data suggest that skeletal muscle grafts are qualitatively similar to normal muscles in terms of metabolic responsiveness to hormones. Leaving the nerve intact during grafting quantitatively enhances the graft's hormonal sensitivity but the technique of nerve crushing prior to grafting has no such effect.

Histochemical fiber type distribution and epinephrine sensitivity in normal and cross-transplanted rat muscles.

The metabolic integrity of fully regenerated transplants was investigated by measuring induced changes in glycogen concentration. The extensor digitorum longus and the soleus muscles were cross transplanted: the extensor digitorum longus into the soleus muscle bed (SOLT) and the soleus muscle into the extensor digitorum longus bed (EDLT). The histochemical fiber type distribution of the regenerated muscles was determined and was found to transform in cross-transplanted EDLT and SOLT. After transplantation and regeneration, both muscles had initially low glycogen concentrations. However, the EDLT glycogen concentration was not significantly different from that of the contralateral extensor digitorum longus control muscle after 60 days. In the SOLT, glycogen gradually increased but remained less than in the contralateral soleus control muscle. SOLT and control soleus muscles responded with a significant glycogen depletion to an epinephrine dose two orders of magnitude less than the lowest dose affecting glycogen levels in EDLT and extensor digitorum longus muscles. These results indicate that transplanted muscles are capable of regenerating normal glycogenolytic responses and that the sensitivity of the response observed depends on the site of transplantation and is related to the type of innervation and histochemical fiber type.

Exercise or overloading: effect on skeletal muscle grafts of rats.

The effects of increased usage on regenerated muscle grafts was studied in rats. Soleus muscles were grafted orthotopically, either without neuromuscular anastomoses (standard grafts), or with their original nerves undamaged (nerve-intact grafts). The rats were either run on a treadmill or their soleus grafts were overloaded by extirpation of approximately 50% of the gastrocnemius muscles. Twitch and tetanic contractions, glycogen concentration, and histological features of the grafts were evaluated 60 days after grafting. The results showed that exercise enhanced glycogen levels in nerve-intact grafts as in normal muscle. Overloading had no effect on glycogen. The nonexercised standard grafts had the lowest values for the mechanical parameters studied. However, this was apparently due to the smaller degree of innervation rather than from the lack of exercise. Within the population of nerve-intact grafts, neither exercise nor overloading significantly improved the twitch and tetanic tensions. It is concluded that exercise, but not overloading, is likely to have positive effects on muscle graft metabolism.

Calcium uptake by sarcoplasmic reticulum from nerve-intact and standard skeletal muscle grafts.

A freely grafted rat soleus muscle exhibits a decrease in velocity and capacity of SR calcium uptake. This deficit is not prevented by maintaining neural connections (nerve-intact graft) during grafting. Thus the greater mechanical capability of nerve-intact grafts, relative to standard grafts, is not accompanied by any enhancement of the SR tubules.

Calcium uptake by sarcoplasmic reticulum of muscle grafts in rats.

Cross transplantations were carried out in which the soleus (SOL) and extensor digitorum longus (EDL) muscles were switched to each other's muscle bed. Sixty days later, oxalate-supported calcium uptake was measured in homogenates of these grafts and compared with calcium uptake by homogenates of the contralateral control EDL and SOL muscles. With the incubation conditions used, calcium uptake was essentially limited to sarcoplasmic reticulum (SR) vesicles. The velocities of the initial rapid calcium uptake were compared in the grafts and control muscles. Subsequently calcium uptake slowed and the 30-min accumulation of calcium indicated the loading capacity of the SR. In control muscles, the EDL had a faster velocity (0.234 +/- 0.011 mumol/mg/min) of calcium uptake and higher capacity (0.527 +/- 0.017 mumol/mg) for calcium loading than the SOL (0.089 +/- 0.008 mumol/mg/min and 0.26 +/- 0.014 mumol/mg, respectively). The EDL grafts (originally SOL muscles) had faster calcium uptakes than the control SOL muscles or SOL grafts (0.196 +/- 0.013 versus 0.089 +/- 0.008 or 0.126 +/- 0.024 mumol/mg/min). Also, the calcium uptake capacities were higher in EDL grafts than in control SOL muscles (0.400 +/- 0.017 versus 0.261 +/- 0.014 mumol/mg), but not statistically higher than in SOL grafts (0.360 +/- 0.033 mumol/mg). In contrast, SOL grafts (originally EDL muscles) had slower calcium uptakes (0.126 +/- 0.024 mumol/mg/min) than did the control EDL muscles or EDL grafts and the calcium uptake capacities (0.360 +/- 0.033 mumol/mg) were lower in SOL grafts than in control EDL muscles, but not statistically lower than in EDL grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Differential response of rat cardiac and skeletal muscle glycogen to glucocorticoids.

Though glucocorticoids were previously implicated in the support of myocardial glycogen supercompensation after exercise, it was unclear why skeletal muscle glycogen did not simultaneously supercompensate since it was also exposed to the exercise-induced glucocorticoid increases. The current study shows that glucocorticoids differentially affect cardiac and skeletal muscle glycogen. Following dexamethasone administration (400 micrograms i.p.) myocardial glycogen peaked at 6 h while glycogen in the soleus, red vastus lateralis, and white vastus lateralis increased more slowly and reached the highest values 17 h postinjection. Concurrently, blood glucose, insulin, and glucagon remained at control levels. Liver glycogen increased within 2 h and continued to rise with a peak value at 17 h. Plasma free fatty acid (FFA) levels increased and remained high throughout the 26-h experimental period. High FFA levels inhibit glycogenolysis and thus could be partially responsible for glucocorticoid-induced glycogen increases. It is postulated that glycogen supercompensation does not readily occur in skeletal muscles after exercise because of the brevity of the corticosterone and FFA increases and the slowness of the skeletal muscle glycogen response to glucocorticoids.

Glycogen and histological changes in muscle grafts of rats during fasting or exercise.

The metabolic integrity of skeletal muscle grafts must be restored, along with histological regeneration, if muscle transplants are to be clinically acceptable. The purpose of the present study was to contrast glycogen changes in muscle grafts after exercise or fasting with those in normal muscles. The extensor digitorum longus (EDL) and soleus (SOL) muscles were switched to each other's muscle bed in one leg of male Sprague-Dawley rats. Fifty days later, some of the rats were fasted for 48 h and sacrificed either immediately or after 4 h of refeeding. Other rats were run on a treadmill for 30 min ( 1 mi/h (0.447 m/s)) and sacrificed either immediately or after 4 h of resting. Muscle grafts and contralateral normal muscles of these experimental, as well as control animals (neither exercised nor fasted), were removed for determination of glycogen concentration. The results show that glycogen in muscle grafts, as in normal muscles, decreases with exercise or fasting. After 4 h of rest or refeeding, glycogen is restored in both grafts and normal muscles. It is concluded, therefore, that muscle grafts are metabolically active and that their pattern of utilization and restoration of glycogen in response to physiological events, such as exercise or fasting, is similar to that of normal muscle.U

Substrate changes during fasting and refeeding contrasted in old and young rats.

Carbohydrate and lipid substrate changes associated with fasting were similar in aged (over 24 months), 1-year-old and young (about 4 months old) rats. In all three age-groups fasting reduced liver and skeletal muscle glycogen, elevated myocardial glycogen and plasm free fatty acid (FFA) levels, but did not significantly affect blood glucose. With refeeding, the myocardium from aged and 1-year-old rats lacked the glycogenesis observed in young rats. Less glycogenesis was also observed in aged soleus muscles during refeeding than in soleus muscles from young or 1-year-old rats. This depressed glycogenesis in the old rats could not be attributed to any change in the tissue triglyceride or plasma FFA response to refeeding, but was accompanied by a slightly greater elevation of glucagon in the aged rats. Though its etiology is unclear, the depressed glycogenesis indicates that aging affects aspects of carbohydrate metabolism in addition to the known decrease in glucose tolerance.

Substrate repletion in rat myocardium, liver, and skeletal muscles after exercise.

Carbohydrate and lipid substrates were measured in rats during recovery following exercise or a 24-h fast and compared with values from time-matched control (rested, fed) rats. After exercise muscle glycogen recovered at the expense of liver glycogen repletion. Myocardial glycogen supercompensated whereas soleus, red vastus lateralis (RVL) and white vastus lateralis glycogen merely returned to control levels. A similar recovery pattern occurred after fasting with refeeding promoting glycogen synthesis in the liver, skeletal muscles, and even in the myocardium, where glycogen had already been elevated by the fast. Both soleus and RVL muscles, along with the myocardium, exhibited glycogen supercompensation. Both exercise and fasting increased plasma free fatty acid (FFA) levels which favor myocardial glycogen synthesis. Unchanged tissue triglycerides and relatively stable blood glucose levels suggest that these are unlikely influences on glycogen recovery. It is concluded that exercise per se is unlikely to induce glycogen supercompensation in skeletal muscles though myocardial glycogen supercompensation readily occurs, that food restriction prior to exercise quantitatively affects substrate recovery though its impact could go unnoticed because of the qualitative similarities between substrate recovery following exercise or fasting, and that FFA is the only major energy substrate concurrently changing with glycogen after exercise or fasting which could facilitate glycogen synthesis.

Relative capabilities of sarcoplasmic reticulum in fast and slow mammalian skeletal muscles.

1. The calcium uptake capabilities of the sarcoplasmic reticulum (SR) of the fat-twitch muscles extensor digitorum longus (EDL) and tibialis anterior (TA) of the rat and the extensor digitorum longus of the cat have been compared with the same capabilities of the slow-twitch soleus muscles of the rat and cat. 2. For the ra the Vmax values of sarcoplasmic reticulum from tibialis anterior, extensor digitorum longus and from soleus muscles were 50, 51, and 10 micronmole Ca2+/g per minute, respectively. 3. For the extensor digitorum longus and soleus muscles of the cat the Vmax values were 34 and 5-6 micronmole Ca2+/g per minute, respectively. 4. These data were compared with mechanical data as reported in the literature for the same muscles. The relative calcium uptake capabilities of sarcoplasmic reticulum from slow and fast muscles corresponded closely to the relative rates of relaxation of these muscles.

Anatomy, biochemistry, and physiology laboratory programs in the education of physicians.

The amount of laboratory time devoted to anatomy, biochemistry, and physiology has decreased substantially while lecture time has remained essentially unchanged. Most laboratories consist of student conduction of assigned exercises with a sprinkling of demonstrations, conferences, and seminars. Various objectives for laboratory programs are discussed. A great percentage of the student's final anatomy grade (approximately 40%) still depends on his laboratory performance, while in biochemistry and physiology, lab work contributes only 12% and 10%, respectively, toward his final grade. There is great reluctance to abandon the laboratory program, however, because of the significant role it is thought to play in medical education.