No abstract

We used 31P magnetic resonance spectroscopy to compare the response of rat skeletal muscle to three kinds of proton load. During exercise (tetanic sciatic nerve stimulation), protons from lactic acid were buffered passively and consumed by net hydrolysis of phosphocreatine (PCr). During recovery from exercise, the pH-dependent efflux of protons produced by PCr resynthesis could be partially inhibited by amiloride or 4,4'-diisothiocyanostilbene-2,2'-disulphonate (DIDS), implicating both sodium/proton and bicarbonate/chloride exchange, but was not inhibited by simultaneous respiratory acidosis. In early recovery, up to 30% of proton efflux was mediated by lactate/proton cotransport. During acute respiratory acidosis at rest, the eventual change in muscle pH was consistent with passive buffering and was unaffected by amiloride or DIDS, implying no significant contribution of proton fluxes.

The correlations can be interpreted in two ways: 1) Our sampling of cerebellar biochemistry reflects a measure of "global" cerebral biochemistry and is unrelated to cerebellar function, or 2) The relations indicate that cerebellar neuronal integrity is a requirement (on a developmental time scale or in real-time) for ability on a variety of cognitive tests.

Objective-To examine the effect of a relatively low dose of creatine on skeletal muscle metabolism and oxygen supply in a group of training athletes. Methods-"P magnetic resonance and near-infrared spectroscopy were used to study calf muscle metabolism in a group of 10 female members of a university swimming team. Studies were performed before and after a six week period of training during which they took either 2 g creatine daily or placebo. Calf muscle metabolism and creatine/choline ratios were studied in resting muscle, during plantar flexion exercise (10-15 min), and during recovery from exercise. Results-There was no effect of creatine on metabolite ratios at rest or on metabolism during exercise and recovery from exercise. Muscle oxygen supply and exercise performance were not improved by creatine if compared to placebo treated subjects.Conclusions-Oral creatine supplementation at 2 g daily has no effect on muscle creatine concentration, muscle oxygen supply or muscle aerobic or anaerobic metabolism during endurance exercise. (BrJ Sports Med 1996;30:222-225) We used 31p and 'H magnetic resonance spectroscopy (MRS) to examine noninvasively the effect of a longer course of a lower dose of creatine on the constituents of the creatine kinase reaction in resting and exercising skeletal muscle in a group of athletes. We coupled the MRS studies with a study of muscle reoxygenation rate using near-infrared spectroscopy (NIRS). The study was conducted in a placebo controlled fashion and the subjects were studied before and after six weeks of either placebo or creatine treatment. Methods SUBJECTSTen non-vegetarian female athletes [lean body mass 45.7 (SEM 1.1) kg] from the university swimming team were studied by 3p MRS and NIRS immediately before an eight week training period leading up to an intervarsity competition. Six weeks after the initial studies, the MRS and NIRS studies were repeated. The performance times of each subject swimming freestyle over 100 m and 400 m were recorded within one week of the MRS study.

Skeletal muscle metabolic abnormalities exist in chronic heart failure. The influence of physical training on muscle metabolism after myocardial infarction was studied in a rat model. 31P magnetic resonance spectroscopy and enzyme assays were performed in Wistar rats 12 weeks after coronary artery ligation. Infarcted rats were allocated randomly to either 6 weeks of training or non-training. Spectra were collected from the calf muscles during sciatic nerve stimulation at 2 Hz. Fibre typing and enzymatic assays were performed on the muscles of the contralateral non stimulated leg. Post-mortem rats were also divided into severe and moderate heart failure according to the lung weight per body weight. At 200 g twitch tension, phosphocreatine and pH were found to be significantly lower in the non-trained severe heart failure group compared with the other groups. Phosphocreatine recovery half-time was significantly longer in the non-trained group with severe heart failure and correlated with the citrate synthase activity in the muscle. The training did not induce a change in the enzyme activities in the infarcted animals with moderate heart failure but did correct the lower citrate synthase activity in the non-trained severe heart failure animals. This normalization of muscle metabolism was achieved by training without any change in calf muscle mass, making atrophy unlikely to be the sole cause of the metabolic changes in heart failure. Training in rats with severe heart failure can reverse the abnormalities of skeletal muscle metabolism, implicating decreased physical activity in the aetiology of these changes.

These results are consistent with one or more of the following: (a) decreased level of activity of these patients; (b) changes in the fibre type of the muscle; (c) decreased oxygen supply to the muscle during exercise but not during recovery. They are not consistent with an intrinsic defect of mitochondrial ATP synthesis in skeletal muscle in respiratory failure.

SUMMARY1. The role of extracellular HCO3-and H+ in the formation of primary saliva and its subsequent modification by the glandular ducts has been investigated in the isolated perfused mandibular salivary gland of the rabbit.2. Variation of extracellular HCO3-concentration between 12-5 and 50-0 mmol/l was without effect on salivary flow rate or on Na+ and K+ excretion, even though salivary HCO3-(and Cl-) content altered with changes in the extracellular concentration of the two anions.3. Complete replacement ofperfusate HCO3-by Cl-reduced fluid secretion by 34 % and almost abolished ductal Na+ absorption. However, when extracellular pH was controlled by replacing HCO3-with the hydrophilic HEPES buffer, fluid secretion but not ductal Na+ absorption was restored to normal.4. Complete replacement ofexogenous HCO3-with acetate increased fluid secretion by 110 % and also stimulated ductal Na+ absorption. This effect did not appear to be related to changes in cell pH and remains unexplained. Acetate entered the saliva in concentrations comparable to those seen for HCO3 in control experiments. 5. Salivary secretion showed an almost linear dependence on extracellular pH, rising from 14 % of control (pH 7 4) levels at pH 6-2 to 130 % at pH 7-8. Ductal Na+ absorption showed a similar pH dependence.6. Carbonic anhydrase inhibitors did not affect fluid secretion rates (except when supramaximal doses of ACh were used to evoke secretion) but they did cause a large reduction in salivary HCO3-output. In glands perfused with acetate rather than HCO3 , carbonic anhydrase inhibitors had no effect on excretion of fluid, acetate or metabolically derived HCO3. Duct perfusion studies suggested that the effect of the inhibitors on HC03-output was at the site of primary secretion rather than at the ductal site of HCO3-transport.

1. An analysis of the recovery kinetics of intracellular pH and phosphocreatine concentration after exercise in skeletal muscle was developed to calculate the rate of proton efflux in vivo. 2. Recovery of rat leg muscle pH after sciatic nerve stimulation was faster in spontaneously hypertensive rats than in Wistar-Kyoto controls (both n = 5). 3. Analysis of these data showed that the rate of proton efflux depends on intracellular pH, being greater at lower pH. 4. The early rate of proton efflux was greater in spontaneously hypertensive rats [measured over the first 0.8 min, 12.5 mmol min-1 kg-1 (SEM 1.8) in spontaneously hypertensive rats compared with 7.6 mmol min-1 kg-1 (SEM 0.4) in Wistar-Kyoto rats, P less than 0.05], even though pH at the start of recovery was higher [6.30 (SEM 0.03) in spontaneously hypertensive rats compared with 6.17 (SEM 0.01) in Wistar-Kyoto rats, P less than 0.01]. 5. This novel analysis provides a quantitative estimate of the rate of proton efflux in vivo, and demonstrates directly that this is increased in spontaneously hypertensive rats, as has previously been inferred from pH changes during exercise and studies of cultured muscle cells in vitro.