Interstitial Lactate Concentrations Research Articles

Glucose metabolism in chronic diabetic foot ulcers measured in vivo using microdialysis.

Ten subjects with diabetes mellitus and unilateral chronic foot ulcer were investigated. Local tissue concentrations of glucose and lactate were measured using the microdialysis method at a distance of 0.5-1 cm from the edge of the ulcer and in normal skin in the contralateral foot. Subcutaneous blood flow in the area investigated was measured using the 133Xewashout technique. The interstitial glucose concentration in the ulcer was found to be lower than in intact skin (8.0 +/- 1.0 mmol l-1 vs. 8.5 +/- 1.1 mmol l-1) (P < 0.02), and the interstitial lactate concentration was higher in the ulcer than in intact skin (3.2 +/- 0.2 mmol l-1 vs. 2.1 +/- 0.3 mmol l-1) (P < 0.01). The subcutaneous blood flow was on average 40% higher in the ulcer than in the intact skin. The calculated local glucose uptake and lactate outputs were twofold higher in the ulcer than in the intact skin. However, the molar ratio between lactate output and glucose uptake was approximately two, both in the ulcer and in the intact skin, indicating that the glucose metabolism was qualitatively the same in the two regions.

Inhibition of paracrine angiotensin-converting enzyme in vivo: effects on interstitial glucose and lactate concentrations in human skeletal muscle.

Microdialysis was used to selectively assess the effect of the paracrine renin-angiotensin system (RAS) on interstitial glucose and lactate concentration profiles in skeletal muscle of healthy volunteers (n = 8) during basal and insulin-stimulated conditions. Paracrine RAS was selectively inhibited by local retrodialysis with enalaprilate. Under basal conditions, local administration of enalaprilate (2 micrograms mL-1) increased interstitial dialysate glucose concentration from 0.71 +/- 0.14 mmol L-1 to 0.84 +/- 0.14 mmol L-1 and decreased the serum interstitial gradient (SIGglu) compared with baseline (P < 0.02). Under clamp conditions, enalaprilate, even at the lowest concentration (0.02 microgram mL-1), increased interstitial dialysate glucose concentration from 0.77 +/- 0.11 mmol L-1 to 1.02 +/- 0.09 mmol L-1 and decreased SIGglu compared with baseline (P < 0.01). Interstitial lactate concentrations slightly increased during basal as well as during clamp conditions (P < 0.05 vs. baseline). Selective inhibition of paracrine muscle angiotensin-converting enzyme (ACE) increases interstitial glucose and lactate concentrations and decreases SIGglu in muscle by facilitating transcapillary glucose transport. This effect is more pronounced during hyperinsulinaemia and may be of clinical relevance in diabetic patients treated with therapeutic doses of enalapril.

Absolute concentrations of glycerol and lactate in human skeletal muscle, adipose tissue, and blood.

The absolute concentrations of glycerol and lactate were studied with microdialysis of adipose tissue and skeletal muscle in normal-weight subjects. The basal interstitial glycerol concentration was 232 +/- 33, 96 +/- 8, and 59 +/- 6 mumol/l in fat, muscle, and arterialized plasma, respectively (P = 0.0002). This relationship was maintained during both euglycemic hyperinsulinemia, when glycerol decreased in all three compartments, and hypoglycemia, when glycerol first decreased and then increased in fat, muscle, and blood (P = 0.0001 for both). Basal interstitial lactate concentrations were similar in adipose tissue (1.1 +/- 0.2 mmol/l) and skeletal muscle (1.9 +/- 0.4 mmol/l) and higher than in arterialized blood (0.6 +/- 0.1 mmol/l, P = 0.002). During hyperinsulinemia and hypoglycemia, lactate increased (P = 0.0001) and the tissue-blood relationship was maintained (P = 0.04). In conclusion, adipose tissue and skeletal muscle mobilize glycerol and lactate at rest. Glycerol and lactate production are influenced by hyperinsulinemia and hypoglycemia in both tissues. Adipose tissue appears to be the major site of glycerol production, whereas skeletal muscle and fat may be equally important for lactate production.

Effects of hyperinsulinemia and hyperglycemia on lactate release and local blood flow in subcutaneous adipose tissue of healthy humans.

To determine the effects of hyperglycemia and hyperinsulinemia on lactate production by adipocytes, healthy volunteers were studied during three experimental protocols. In protocol 1, the changes in interstitial lactate concentrations were measured by microdialysis (sc tissue) after oral glucose administration. The plasma lactate concentration increased by 39.4 +/- 6.0%, and the dialysate lactate concentration increased by 117.9 +/- 16.3%. In protocol 2, a 2.5-h hyperinsulinemic euglycemic clamp and somatostatin infusion were performed. The plasma and dialysate lactate concentrations increased by 27.1 +/- 5.5% and 146.8 +/- 44.5%, respectively. In addition, [U-13C]glucose was infused through the probe, and dialysate lactate was enriched in 13C at 2.5 +/- 0.3 molar percent excess basally and at 3.4 +/- 0.3 molar percent excess during the clamp (P < 0.05 vs. basal). [13C]Urea was also infused through the probe, and the outflow to inflow ratio of [13C]urea was used as an index of local blood flow. It decreased by 10.2 +/- 3.6% (P < 0.001) at the end of the hyperinsulinemic euglycemic clamp, indicating an increase in blood flow. In protocol 3, a hyperglycemic clamp (10.0 mmol/L) at the basal insulin concentration was performed. It increased the dialysate lactate concentration by 43.5 +/- 15.9% and did not alter the plasma lactate concentration or local blood flow. It is concluded that hyperinsulinemia and, to a lesser extent, hyperglycemia stimulate glucose conversion into lactate in adipocytes. Hyperinsulinemia, but not hyperglycemia, also increases adipose tissue blood flow.

Microdialysis methodology for the measurement of dermal interstitial fluid in humans

In this study we aimed to validate the microdialysis technique for metabolic measurements in the dermal interstitial fluid. The abdominal and forearm skin was used for microdialysis in 15 healthy normal weight volunteers. The depth of the microdialysis catheter was assessed by ultrasound measurement. Structural impairment and blood flow were judged from biopsies and from laser Doppler measurements taken adjacent to the catheters. Dermal interstitial lactate and pyruvate concentrations were measured, under steady state fasting conditions, after equilibrium calibration of each catheter in situ. The dermal interstitial glucose concentration was estimated by means of the retrodialysis calibration method, which has previously not been evaluated for skin microdialysis. The mean catheter depth (+/- standard deviation) was 0.8 +/- 0.3 mm. Small areas of localized bleeding, but no inflammatory reaction, was found surrounding the catheters. The perfusion in the microdialysis region was slightly increased (15-25%). The lactate/pyruvate ratio (12 +/- 0.7) showed non-ischaemic values. The dermal interstitial lactate concentration was significantly higher (1171 +/- 228 mumol/l) than the plasma lactate (781 +/- 180 mumol/l), indicating an ongoing nonoxidative glucose metabolism. Retrodialysis calibration correctly estimated the dermal glucose level to be similar to that in plasma, which may indicate the usefulness of this calibration method for microdialysis studies of endogenous substrates in the dermal interstitial fluid.

Microdialysis assessment of adipose tissue metabolism in post-absorptive obese NIDDM subjects.

Lactate and glycerol turnover is enhanced in obesity and NIDDM. To evaluate the influence of NIDDM on subcutaneous adipose tissue metabolism microdialysis combined with 133Xe clearance and measurements in arterialized plasma were carried out using samples of subcutaneous abdominal fat from nine obese NIDDM subjects (glucose, 7.9 +/- 0.7 mmol L-1) (mean +/- SEM) and nine obese non-diabetic subjects (glucose, 4.9 +/- 0.1) matched for age, BMI and body fat. After an overnight fast arterialized plasma levels were 1145 +/- 110 vs. 876 +/- 59 mumol L-1 (P < 0.05) for lactate and 75 +/- 10 vs. 66 +/- 8 mumol L-1 for glycerol in the diabetic and control group, respectively. The corresponding abdominal subcutaneous interstitial lactate and glycerol concentrations were 1278 +/- 63 vs 1107 +/- 64 mumol L-1 and 314 +/- 28 vs. 311 +/- 17 mumol L-1, respectively. However, adipose tissue blood flow in the same region was lower in NIDDM subjects (1.5 +/- 0.2 vs 2.4 +/- 0.3 mL 100 g-1 min-1) (P < 0.05). Consequently, apparent subcutaneous lactate and glycerol release, estimated according to Fick, were not statistically different in the two groups (1.8 +/- 0.4 vs 2.4 +/- 0.8 and 2.1 +/- 0.4 vs 3.1 +/- 0.5 mumol kg-1 min-1 in NIDDM and control subjects, respectively). Thus, in the post-absorptive state apparent lactate and glycerol release by the abdominal subcutaneous tissue in obese NIDDM subjects was similar to that in a matched group of obese non-diabetic controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Interstitial lactate and glucose concentrations of the isolated perfused rat heart before, during and after anoxia.

In isolated rat hearts perfused according to the Langendorff technique lactate and glucose concentrations were determined in the interstitial transudate and the venous effluent before, during and after periods of 15 or 30 min anoxia. The interstitial transudate emerged at the surface of the heart as a result of albumin-free perfusion. During normoxic perfusion the interstitial lactate concentration was 0.144 +/- 0.025 mmol/l (n = 6); the venous lactate concentration was 0.033 +/- 0.005 mmol/l. From the interstitial and the mean vascular concentration, together with the lactate release and the glucose uptake, the apparent permeability surface area products (P.S product) were calculated using Fick's law. The apparent P.S products for lactate and glucose were 4.6 and 3.9 ml/(min x g), respectively. During anoxia we measured a four- to sixfold increase of the interstitial lactate concentration. At the end of the anoxic periods the apparent P.S product was two- to threefold higher than during normoxia; the apparent glucose P.S product increased about fourfold. After 15 min anoxia the increases of permeability were completely reversed in the reoxygenation period. However, after a period of 30 min anoxia the apparent P.S products for lactate and glucose remained raised, which means that there was a prolonged or even irreversible increase of capillary permeability. Besides the marked transcapillary concentration difference for lactate, these data show prolonged functional alteration of the capillary wall after 30 min anoxia.

Lactate in rat skeletal muscle after hemorrhage measured by microdialysis probe calibrated in situ

The interstitial lactate concentration in rat skeletal muscle was measured in the normal state and after hemorrhage using a microdialysis probe, and the values calculated by in vitro and in vivo calibration were compared. After withdrawal of 30% of the estimated total blood volume, the lactate concentration in the dialysate gradually increased and then maintained an almost constant level. It was found that interstitial lactate levels of skeletal muscle calculated by the in vitro calibration method were not significantly different from those calculated by in vivo calibration in both the normal state and after hemorrhage. These data indicate that the absolute lactate concentration in the muscle interstitium in the normal state and after acute hemorrhage can be practically measured by a microdialysis probe calibrated in vitro. From the comparison of lactate concentrations in blood and in the muscle interstitium, it was suggested that rat skeletal muscle functions as a lactate consumer, rather than as a lactate producer, after acute hemorrhage.

Interstitial fluid of isolated perfused rat hearts: Glucose and lactate concentration

Interstitial fluid (IF) emerging at the ventricular surface of isolated perfused rat hearts was collected and assayed for rate of production, protein content, glucose and lactate concentration. The influence of four perfusion media was investigated during an experimental period of 150 min: Krebs-Henseleit solution (KH) containing glucose (5.5 mM); KH containing glucose and pyruvate (2 mM); Hypoxic KH (20% O2), substrates as 2; KH containing isoprenaline (8 X 10(-9) M), substrates as 2. Interstitial fluid was produced at a rate of 20 to 100 microliters/min/gww and contained proteins (0.5 to 3 g/l). Interstitial glucose concentration was lower than venous concentration by up to 50%. Interstitial lactate concentration was higher by up to 600%. Permeability X surface area products of glucose calculated from transcapillary concentration differences and transfer rates were different depending on experimental conditions, but were within the rather large range of P X S values for molecules of similar size obtained by other authors. Those of lactate were higher by a factor of 3 to 9 and can be interpreted to be influenced by the metabolic activity of the endothelium. The results demonstrate that interstitial substrate concentration can differ very markedly from intravascular concentration and cannot be estimated reliably without assay of the interstitial fluid. Capillary permeability seems to be variable under the experimental conditions of this study.