Incremental knee extensor (KE) exercise performed at 25, 70, and 100% of single-leg maximal work rate (WR(MAX)) was combined with ex vivo electron paramagnetic resonance (EPR) spectroscopic detection of alpha-phenyl-tert-butylnitrone (PBN) adducts, lipid hydroperoxides (LH), and associated parameters in five males. Blood samples were taken from the femoral arterial and venous circulation that, when combined with measured changes in femoral venous blood flow, permitted a direct examination of oxidant exchange across a functionally isolated contracting muscle bed. KE exercise progressively increased the net outflow of LH and PBN adducts (100% > 70% > 25% WR(MAX), P < 0.05) consistent with the generation of secondary, lipid-derived oxygen (O(2))-centered alkoxyl and carbon-centered alkyl radicals. Radical outflow appeared to be more intimately associated with predicted decreases in intracellular Po(2) (iPo(2)) as opposed to measured increases in leg O(2) uptake, with greater outflow recorded between 25 and 70% WR(MAX) (P < 0.05 vs. 70-100% WR(MAX)). This bias was confirmed when radical venoarterial concentration differences were expressed relative to changes in the convective components of O(2) extraction and flow (25-70% WR(MAX) P < 0.05 vs. 70-100% WR(MAX), P > 0.05). Exercise also resulted in a net outflow of other potentially related redox-reactive parameters, including hydrogen ions, norepinephrine, myoglobin, lactate dehydrogenase, and uric acid, whereas exchange of lipid/lipoproteins, ascorbic acid, and selected lipid-soluble anti-oxidants was unremarkable. These findings provide direct evidence for an exercise intensity-dependent increase in free radical outflow across an active muscle bed that was associated with an increase in sarcolemmal membrane permeability. In addition to increased mitochondrial electron flux subsequent to an increase in O(2) extraction and flow, exercise-induced free radical generation may also be regulated by changes in iPo(2), hydrogen ion generation, norepinephrine autoxidation, peroxidation of damaged tissue, and xanthine oxidase activation.

Growth retardation is a frequent finding in patients after renal transplantation (Tx). Areal bone mineral density (BMD) in these patients has usually been reported to be low for age. We investigated the possible influence of height and weight retardation on the measurement of BMD in lumbar spine (BMD(L2-4)) and total body (BMDbody) using dual-energy X-ray absorptiometry in 44 (13 female) pediatric Tx patients with a median age of 13.1 (range 3.3-23.1) years. Patients were studied at 2.9 (range 1-10) years after Tx. Median body height in female and male patients was -2.10 (-3.6 to -0.3) and -2.35 (-5.3 to +1.0) standard deviation score (SDS), respectively. BMD expressed as grams per square centimeter bone area according to age was below the 5th percentile in 10 of 44 patients, but only 1 patient had low values for BMD(L2-4), and none for BMDbody, when the data were corrected for height or weight. BMDbody was closely correlated with height, weight, and body surface area (r=0.88), whereas the correlation for BMD(L2-4) was less (r=0.76). In 6 patients who achieved final height, height SDS was -2.27 (-4.3-0.4). Z-scores for BMDbody related to age, height, and weight were -1.0 (-2.6 to -2.3), 1.25 (0.1-3.4), and 0.81 (0.0-2.4), respectively. There was no age-dependent change when areal BMD values (g/cm2) were corrected for vertebral size to obtain bone volumetric density (BMDvol, g/cm3). Independent of height, cumulative methylprednisolone dose correlated negatively with BMD(L2-4) only in patients who had received a total dose of more than 6 g/m2 of the drug (r = -0.54, P= 0.045). In conclusion, BMD in pediatric patients after Tx is no longer diminished when the data are corrected for height or weight rather than age, or when the data are expressed as bone volumetric density.

To further explore the limitations to maximal O(2) consumption (.VO(2 max)) in exercise-trained skeletal muscle, six cyclists performed graded knee-extensor exercise to maximum work rate (WR(max)) in hypoxia (12% O(2)), hyperoxia (100% O(2)), and hyperoxia + femoral arterial infusion of adenosine (ADO) at 80% WR(max). Arterial and venous blood sampling and thermodilution blood flow measurements allowed the determination of muscle O(2) delivery and O(2) consumption. At WR(max), O(2) delivery rose progressively from hypoxia (1.0 +/- 0.04 l/min) to hyperoxia (1.20 +/- 0.09 l/min) and hyperoxia + ADO (1.33 +/- 0.05 l/min). Leg .VO(2 max) varied with O(2) availability (0.81 +/- 0.05 and 0.97 +/- 0.07 l/min in hypoxia and hyperoxia, respectively) but did not improve with ADO-mediated vasodilation (0.80 +/- 0.09 l/min in hyperoxia + ADO). Although a vasodilatory reserve in the maximally working quadriceps muscle group may have been evidenced by increased leg vascular conductance after ADO infusion beyond that observed in hyperoxia (increased blood flow but no change in blood pressure), we recognize the possibility that the ADO infusion may have provoked vasodilation in nonexercising tissue of this limb. Together, these findings imply that maximally exercising skeletal muscle may maintain some vasodilatory capacity, but the lack of improvement in leg .VO(2 max) with significantly increased O(2) delivery (hyperoxia + ADO), with a degree of uncertainty as to the site of this dilation, suggests an ADO-induced mismatch between O(2) consumption and blood flow in the exercising limb.

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