David A. MacLean

Caffeine ingestion does not alter carbohydrate or fat metabolism in human skeletal muscle during exercise

1 This study examined the effect of ingesting caffeine (6 mg kg−1) on muscle carbohydrate and fat metabolism during steady‐state exercise in humans. Young male subjects (n= 10) performed 1 h of exercise (70 % maximal oxygen consumption (V̇O2,max)) on two occasions (after ingestion of placebo and caffeine) and leg metabolism was quantified by the combination of direct Fick measures and muscle biopsies. 2 Following caffeine ingestion serum fatty acid and glycerol concentration increased (P≤ 0.05) at rest, suggesting enhanced adipose tissue lipolysis. 3 In addition circulating adrenaline concentration was increased (P≤ 0.05) at rest following caffeine ingestion and this, as well as leg noradrenaline spillover, was elevated (P≤ 0.05) above placebo values during exercise. 4 Caffeine resulted in a modest increase (P≤ 0.05) in leg vascular resistance, but no difference was found in leg blood flow. 5 Arterial lactate and glucose concentrations were increased (P≤ 0.05) by caffeine, while the rise in plasma potassium was dampened (P≤ 0.05). 6 There were no differences in respiratory exchange ratio or in leg glucose uptake, net muscle glycogenolysis, leg lactate release or muscle lactate, or glucose 6‐phosphate concentration. Similarly there were no differences between treatments in leg fatty acid uptake, glycerol release or muscle acetyl CoA concentration. 7 These findings indicate that caffeine ingestion stimulated the sympathetic nervous system but did not alter the carbohydrate or fat metabolism in the monitored leg. Other tissues must have been involved in the changes in circulating potassium, fatty acids, glucose and lactate.

The exercise metaboreflex is maintained in the absence of muscle acidosis: insights from muscle microdialysis in humans with McArdle's disease

1 In McArdles disease, muscle glycogenolysis is blocked, which results in absent lactate and enhanced ammonia production in working muscle. Using McArdle patients as an experimental model, we studied whether lactate and ammonia could be mediators of the exercise pressor reflex. 2 Changes in muscle interstitial ammonia and lactate were compared with changes in blood pressure and muscle sympathetic nerve activity (MSNA) during static arm flexor exercise at 30 % of maximal contraction force. Muscle interstitial changes in lactate and ammonia were assessed by microdialysis of the biceps muscle, and MSNA by peroneal nerve microneurography, in six McArdle patients and 11 healthy, matched controls. One McArdle patient also had myoadenylate deaminase deficiency, a condition associated with abolished ammonia production in exercise. 3 Exercise‐induced increases were higher in McArdle patients vs. controls for MSNA (change of 164 ± 71 vs. 59 ± 19 %) and blood pressure (change of 47 ± 7 vs. 38 ± 4 mmHg). Interstitial lactate increased in controls (peak change 1.3 ± 0.2 mmol l−1) and decreased in McArdle patients (peak change ‐0.5 ± 0.1 mmol l−1) during and after exercise. Interstitial ammonia did not change during exercise in either group, but was higher post‐exercise in McArdle patients, except in the patient with myoadenylate deaminase deficiency who had a flat ammonia response. This patient had an increase in MSNA and blood pressure comparable to other patients. MSNA and blood pressure responses were maintained during post‐exercise ischaemia in both groups, indicating that sympathetic activation was caused, at least partly, by a metaboreflex. 4 In conclusion, changes in muscle interstitial lactate and ammonia concentrations during and after exercise are temporally dissociated from changes in MSNA and blood pressure in both patients with McArdles disease and healthy control subjects. This suggests that muscle acidification and changes in interstitial ammonia concentration are not mediators of sympathetic activation during exercise.

Muscle Interstitial Calcium During Head-Up Tilt in Humans

Background—During head-up tilt (HUT), peripheral vasoconstriction occurs. This response requires appropriate communication between the sympathetic nerve terminal and vascular smooth muscle cell in the neurovascular space. Both of these cell types require extracellular calcium ([Ca2+]o) for proper activation and function. We hypothesize that [Ca2+]o rises with tilt and in the process contributes to vasoconstriction. Methods and Results—We used microdialysis techniques in the lower-limb skeletal muscle to measure [Ca2+]o changes in this space with HUT. [Ca2+]o was measured in 10 healthy subjects during HUT. We found a 62% increase in the dialysate [Ca2+] (0.223±0.018 to 0.353±0.028 mmol/L) with HUT. Conclusions—This result implies a significant increase in [Ca2+]o in the neurovascular space during HUT. This represents the first report of such in situ [Ca2+]o measurements in humans. This rise in [Ca2+]o may provide a mechanism for proper cell-cell interaction, helping to promote peripheral vasoconstriction during HUT. How this [Ca2+]o transient affects the nerve terminal, vascular smooth muscle cells, or both remains to be determined.