Microdialysis of insulin-like growth factor-I in human muscle.

The determination of the insulin like growth factor I (IGF-I) concentration in the interstitial milieu is of outstanding importance to explore its autocrine/paracrine function. We previously reported a method to calibrate microdialysis probes for lactate and glucose (slope method). In the present study, we investigated the ability of our method to determine the concentration of larger molecules, such as IGF-I. We observed in vitro a close linear relationship (r = 0.86, P < 0.0005) between the recoveries of lactate (RecLac) and of IGF-I (RecIGF-I), giving access to the measurement of IGF-I with the same accuracy as the one previously found for lactate and glucose. In seven human volunteers, we calibrated each probe with the slope method: we first determined in vivo for every probe the specific RecLac/loss ethanol relationship and thereafter, using that relationship, we deduced RecLac from the loss ethanol value measured in every dialysate. This allowed calculation of RecIGF-I from the calculated RecLac value and the in vitro RecLac/RecIGF-I relationship, and finally free IGF-I concentration in muscle interstitial fluid. The mean free IGF-I interstitial concentration was 6.8 +/- 3.2 ng/ml while the mean plasma concentration was 0.4 +/- 0.2 ng/ml. This large gradient from interstitium to plasma for free IGF-I could be related to the local action of this growth factor.

Validation of a new calibration method for human muscle microdialysis at rest and during exercise.

Microdialysis presents the unique possibility to measure metabolite concentrations in human interstitial fluid. During exercise, the recovery of these metabolites should be precisely monitored since it is known to increase greatly with muscle blood flow. The loss of ethanol, perfused at low concentration, can be accurately measured and reflects the changes in dialysis conditions. We evaluated whether using the relationship determined in resting metabolic conditions between the loss of ethanol, as reference substance, and the recovery for lactate or glucose would allow us to calculate precisely the concentration of these substances and their variations during exercise. Using the new catheter calibration method (slope method), the error of estimation of lactate and glucose in vitro was limited to -0.6 (5.8)% and -0.7 (6.2)%, respectively. In resting human muscle, the slope method proved to be as accurate as an established calibration technique ("no net flux method") to evaluate interstitial lactate concentration [1.82 (0.58) vs 1.83 (0.47) mM, respectively]. During dynamic knee-extension exercise or light neuromuscular electrical stimulation, the estimated interstitial lactate and glucose concentrations varied differently, but their time course changes remained consistent with their respective plasma values. We conclude that, after an initial calibration step, the slope method allows accurate measurement of interstitial muscle metabolites and it could be used to monitor rapid metabolic changes during exercise.