Key metabolite kinetics in human skeletal muscle during ischaemia and reperfusion: measurement by microdialysis

Abstract

The tissue kinetics of key metabolites of ischaemic and postischaemic tissue damage were studied in the intercellular space of human skeletal muscle by microdialysis. In vivo microdialysis calibration experiments (n = 5) yielded the basal intercellular concentration of glucose in human skeletal muscle (3.6 +/- 0.6 mM; mean +/- SD). The corresponding mean plasma glucose concentration was 4.3 +/- 0.2 mM which was significantly higher. The time vs. concentration profiles of intercellular glucose (n = 7), lactate (n = 5), TxB2 (n = 6) and urea (n = 8) were characterized during a 20 min period of leg constriction. TxB2 increased exclusively during reperfusion in comparison to baseline (n = 6). Administration of 500 mg acetylsalicylic acid, 5-10 min after onset of ischaemia blunted TxB2-response to reperfusion (n = 4). It is concluded that intercellular muscle glucose concentration is less than that in plasma. Glucose uptake in skeletal muscle is rapid even under ischaemic conditions. Synthesis and release of TxB2 is not evident during ischaemia. TxB2 mediated reperfusion injury might be reduced by acetylsalicylic acid, even if administered after onset of ischaemia.

Induction of rat muscle insulin resistance by epinephrine is accompanied by increased interstitial glucose and lactate concentrations

“…This study confirms previous findings that glucose [9] and insulin [10] concentrations are lower in the muscle interstitial fluid than in arterial plasma. The data show for the first time that muscle insulin resistance induced by b-adrenergic stimulation leads to increased interstitial fluid concentrations of glucose and lactate and vasodilatation without altering the interstitial concentration of insulin.…”

“…Moreover, recent research has emphasized the importance of the capillary wall as a major determinant of the transendothelial delivery of glucose [9] and insulin [10] in skeletal muscle since the interstitial concentrations of glucose and insulin are lower than those in the arterial plasma [9,10]. This is further supported by the findings that the insulin-[11] and glucose-[12] stimulated increase in muscle blood flow correlates with glucose uptake in normal as well as in insulin resistant muscles [13].…”

“…By combining microdialysis measurements in muscle interstitial fluid and recordings of muscle blood flow, the interaction between the microcirculation and the extraction of nutrients and hormones from the capillaries could be studied [20]. This approach allowed us to study the regulation of the interstitial fluid concentration of glucose and insulin and thus is probably more informative than the arterio-venous technique in describing the concentration-dependent extraction of these substances [9,10]. Since their interstitial concentration is lower than in arterial plasma but higher than in the cells, two steps which limit the rate of muscle uptake of glucose and insulin should be considered; the plasma membrane and the capillaries.…”

Muscle glucose uptake is effectively activated by ischemia in type 2 diabetic subjects.

“…Under such conditions, the capillary wall is no longer ratelimiting for glucose uptake from the blood. Subsequently, the elimination rate of glucose from the interstitial fluid is proportional to the glucose uptake rate (30). During ischemia, the glucose uptake rate in muscle tissue could be estimated by means of the formula for calculating the rate of glucose disappearance:…”

“…where R d is the rate of disappearance, C 0 is the basal concentration, and C t is the concentration at time t (30). During ischemia, the application of the above formula, with the assumption that the extracellular volume is 11 ml · 100 g -1 · muscle -1 (31), estimated the muscle glucose uptake rate to bẽ 7 and ~14 µmol · 100 g -1 · min -1 in control and type 2 diabetic subjects, respectively.…”