D. A. MacLean

1. This study was performed to test the hypothesis that the exercise-induced increase in circulating cytokine levels is associated with muscle damage. Nine healthy young male subjects performed two high-intensity bicycle exercise trials separated by two weeks. The first trial consisted of 30 min of normal bicycle exercise (concentric exercise), whereas the second consisted of 30 min of braking with reversed revolution (eccentric exercise). The work loads were chosen to give the same increases in heart rate and catecholamine levels in the blood during each trial. 2. Significant increases (P < 0.05) in plasma concentration of creatine kinase (CK), aspartate aminotransferase and alanine aminotransferase were observed only after the eccentric exercise. Furthermore, the level of interleukin-6 (IL-6) in serum increased significantly after the eccentric exercise and was significantly correlated to CK concentration in the following days, whereas no significant changes were found after the concentric exercise. 3. The total concentration of lymphocytes increased significantly (P < 0.05) as a result of eccentric compared with concentric exercise. This was mainly due to a significantly more pronounced recruitment of natural killer (NK) cells and CD8 positive cells (CD8+ cells) during the eccentric trial. However, no significant differences between the two types of work were found in regard to the circulating concentration of monocytes. The concentration of neutrophils was only significantly increased 2 h after the concentric exercise. 4. The finding that high-intensity eccentric exercise caused a more pronounced increase in the plasma level of IL-6, compared with concentric exercise, supports the hypothesis that the post-exercise cytokine production is related to skeletal muscle damage. The fact that no differences between eccentric and concentric exercise were found in the recruitment of most blood mononuclear cell subsets to the blood supports the hypothesis that the exercise-induced increase in plasma catecholamines is a major determinant of the mobilization of these cells into the blood. However, as eccentric exercise caused a more pronounced increase in the concentration of NK cells and CD8+ cells, factors involved in muscle damage may also contribute to the recruitment of these cells.

We examined the effects of a high-caffeine dose on endurance performance and muscle acetyl group metabolism during prolonged exercise. Eight subjects cycled to exhaustion at approximately 80% maximal oxygen uptake (VO2max) 1 h after ingestion of 9 mg/kg body wt dextrose (Pl) or caffeine (Caf). In the Pl trial, muscle biopsies were taken at rest (1 h postingestion) and at 15 min and exhaustion during exercise. The Caf trial followed the same protocol 1 wk later, with an additional biopsy at the time corresponding to Pl exhaustion. The subjects cycled significantly longer during the Caf trial (96.2 +/- 8.8 min) than in the Pl trial (75.8 +/- 4.8 min). Net glycogenolysis during the initial 15 min of cycling was reduced in the Caf vs. Pl trial (4.7 +/- 1.5 vs. 10.6 +/- 1.3 mmol.kg dry muscle-1.min-1; P less than 0.05). Muscle citrate concentration was increased at rest with Caf (0.59 +/- 0.07 vs. 0.37 +/- 0.05 mmol/kg dry muscle; P less than 0.05) but increased to similar values in both trials during cycling. Caf elevated the acetyl-CoA/CoA-SH ratio at rest (0.316 +/- 0.046 vs. 0.201 +/- 0.023; P less than 0.05) but had no effect on the increases in muscle acetyl-CoA and acetylcarnitine during exercise. The results indicate that Caf before exercise decreased muscle glycogenolysis by approximately 55% over the first 15 min of exercise at approximately 80% VO2max. This "spared glycogen" was available late in exercise and coincided with a prolonged time to exhaustion. Increased utilization of intramuscular triacylglycerol and/or extramuscular free fatty acids after caffeine ingestion may inhibit carbohydrate use at rest and early during exercise via elevations in muscle citrate and the acetyl-CoA/CoA-SH ratio. Muscle acetyl-CoA and acetylcarnitine were maintained above resting contents even at exhaustion when muscle glycogen was depleted.

1. This study examined the effects of caloric content (caloric density and the nature of calories) on the rate of gastric emptying using the double-sampling gastric aspiration technique. Four test meals of 600 ml (glucose, 0.1 kcal ml-1; pea and whey peptide hydrolysates, both 0.2 kcal ml-1; milk protein, 0.7 kcal ml-1) were tested in six healthy subjects in random order on four separate occasions. 2. The glucose solution was emptied the fastest with a half-time of 9.4 +/- 1.2 min (P < 0.05) and the milk protein the slowest with a half-time of 26.4 +/- 10.0 min (P < 0.05); the pea peptide hydrolysate and whey peptide hydrolysate solutions had half-times of emptying of 16.3 +/- 5.4 and 17.2 +/- 6.1 min, respectively. The rates of gastric emptying for the peptide hydrolysate solutions derived from different protein sources were not different. 3. Despite the lower rate of gastric emptying for the milk protein solution, the rate of caloric delivery to the duodenum during the early phase of the gastric emptying process was higher than that for the other three solutions (46.3 +/- 6, 63.5 +/- 22, 62.5 +/- 19 and 113.8 +/- 25 cal min-1 kg-1 for the glucose, pea peptide hydrolysate, whey peptide hydrolysate and milk protein meals, respectively; P < 0.05). The caloric density of the test solutions was linearly related to the half-time of gastric emptying (r = 0.96, P < 0.05) as well as to the rate at which calories were delivered to the duodenum (r = 0.99, P < 0.001). 4. This study demonstrates that the rate of gastric emptying is a function of the caloric density of the ingested meal and that a linear relationship exists between these variables. Furthermore, the nature of the calories seems to play a minor role in determining the rate of gastric emptying in humans.

BACKGROUND: Adenosine has been proposed to be a locally produced regulator of blood flow in skeletal muscle. However, the fundamental questions of to what extent adenosine is formed in skeletal muscle tissue of humans, whether it is present in the interstitium, and where it exerts its vasodilatory effect remain unanswered. METHODS AND RESULTS: The interstitial adenosine concentration was determined in the vastus lateralis muscle of healthy humans via dialysis probes inserted in the muscle. The probes were perfused with buffer, and the dialysate samples were collected at rest and during graded knee extensor exercise. At rest, the interstitial concentration of adenosine was 220+/-100 nmol/L and femoral arterial blood flow (FaBF) was 0.19+/-0.02 L/min. When the subjects exercised lightly, at a work rate of 10 W, there was a markedly higher (1140+/-540 nmol/L; P<0.05) interstitial adenosine concentration and a higher FaBF (2.22+/-0.18 L/min; P<0.05) compared with at rest. When exercise was performed at 20, 30, 40, or 50 W, the concentration of adenosine was moderately greater for each increment, as was the level of leg blood flow. The interstitial concentrations of ATP, ADP, and AMP increased from rest (0.13+/-0.03, 0.07+/-0.03, and 0.07+/-0.02 micromol/L, respectively) to exercise (10 W; 2.00+/-1.32, 2.08+/-1.23, and 1.65+/-0.50 micromol/L, respectively; P<0.05). CONCLUSIONS: The present study provides, for the first time, interstitial adenosine concentrations in human skeletal muscle and demonstrates that adenosine and its precursors increase in the exercising muscle interstitium, at a rate associated with intensity of muscle contraction and the magnitude of muscle blood flow.