Nine African and eight Caucasian 10-km runners resident at sea level volunteered. Maximal O2 consumption and peak treadmill velocity (PTV) were measured by using a progressive test, and fatigue resistance [time to fatigue (TTF)] was measured by using a newly developed high-intensity running test: 5 min at 72, 80, and 88% of individual PTV followed by 92% PTV to exhaustion. Skeletal muscle enzyme activities were determined in 12 runners and 12 sedentary control subjects. In a comparison of African and Caucasian runners, mean 10-km race time, maximal O2 consumption, and PTV were similar. In African runners, TTF was 21% longer (P < 0.01), plasma lactate accumulation after 5 min at 88% PTV was 38% lower (P < 0.05), and citrate synthase activity was 50% higher (27.9 +/- 7.5 vs. 18.6 +/- 2.1 micromol. g wet wt-1. min-1, P = 0.02). Africans accumulated lactate at a slower rate with increasing exercise intensity (P < 0.05). Among the entire group of runners, a higher citrate synthase activity was associated with a longer TTF (r = 0.70, P < 0.05), a lower plasma lactate accumulation (r = -0.73, P = 0.01), and a lower respiratory exchange ratio (r = -0.63, P < 0.05). We conclude that the African and Caucasian runners in the present study differed with respect to oxidative enzyme activity, rate of lactate accumulation, and their ability to sustain high-intensity endurance exercise. (+info)
Pyruvate dehydrogenase activation in inactive muscle during and after maximal exercise in men.
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Pyruvate dehydrogenase activity (PDHa) and acetyl-group accumulation were examined in the inactive deltoid muscle in response to maximal leg exercise in men. Seven subjects completed three consecutive 30-s bouts of maximal isokinetic cycling, with 4-min rest intervals between bouts. Biopsies of the deltoid were obtained before exercise, after bouts 1 and 3, and after 15 min of rest recovery. Inactive muscle lactate (LA) and pyruvate (PYR) contents increased more than twofold (P < 0.05) after exercise (bout 3) and remained elevated after 15 min of recovery (P < 0.05). Increased PYR accumulation secondary to LA uptake by the inactive deltoid was associated with greater PDHa, which progressively increased from 0.71 +/- 0.23 mmol. min-1. kg wet wt-1 at rest to a maximum of 1.83 +/- 0.30 mmol. min-1. kg wet wt-1 after bout 3 (P < 0.05) and remained elevated after 15 min of recovery (1.63 +/- 0.24 mmol. min-1. kg wet wt-1; P < 0.05). Acetyl-CoA and acetylcarnitine accumulations were unaltered. Increased PDHa allowed and did not limit the oxidation of LA and PYR in inactive human skeletal muscle after maximal exercise. (+info)
Effect of fast duration on disposition of an intraduodenal glucose load in the conscious dog.
(11/5450)
The effects of prior fast duration (18 h, n = 8; 42 h, n = 8) on the glycemic and tissue-specific responses to an intraduodenal glucose load were studied in chronically catheterized conscious dogs. [3-3H]glucose was infused throughout the study. After basal measurements, glucose spiked with [U-14C]glucose was infused for 150 min intraduodenally. Arterial insulin and glucagon were similar in the two groups. Arterial glucose (mg/dl) rose approximately 70% more during glucose infusion after 42 h than after an 18-h fast. The net hepatic glucose balance (mg. kg-1. min-1) was similar in the two groups (basal: 1.8 +/- 0.2 and 2.0 +/- 0.3; glucose infusion: -2.2 +/- 0.5 and -2.2 +/- 0.7). The intrahepatic fate of glucose was 79% glycogen, 13% oxidized, and 8% lactate release after a 42-h fast; it was 23% glycogen, 21% oxidized, and 56% lactate release after an 18-h fast. Net hindlimb glucose uptake was similar between groups. The appearance of intraduodenal glucose during glucose infusion (mg/kg) was 900 +/- 50 and 1,120 +/- 40 after 18- and 42-h fasts (P < 0.01). CONCLUSION: glucose administration after prolonged fasting induces higher circulating glucose than a shorter fast (increased appearance of intraduodenal glucose); liver and hindlimb glucose uptakes and the hormonal response, however, are unchanged; finally, an intrahepatic redistribution of carbons favors glycogen deposition. (+info)
Evaluation of the microdialysis technique in the dog fat pad.
(12/5450)
In the present study the microdialysis technique was evaluated in an isolated autoperfused dog fat pad. Concentrations of glucose, lactate, and glycerol were measured in interstitial fluid by microdialysis and simultaneously in arterial and adipose venous plasma. Adipose tissue blood flow was measured by both 133Xe washout and timed weighing of venous blood. Metabolite concentrations in adipose venous plasma calculated from interstitial and arterial metabolite concentrations and 133Xe washout were positively correlated with measured venous concentrations (glucose: r = 0.95, lactate: r = 0.92, glycerol: r = 0.81). Calculated and measured venous plasma concentrations did not differ for either glucose or lactate, but for glycerol, calculated concentration was on average 76% of measured concentration. Metabolite exchanges (Fick's principle) calculated from interstitial metabolite concentrations were positively correlated with measured exchanges only for lactate (r = 0.69). In conclusion, metabolite concentrations in adipose venous plasma can be calculated from microdialysis measurements with greater accuracy for glucose and lactate than for glycerol. The precision, however, is too low to allow calculation of metabolite exchange when arteriovenous metabolite differences are low. (+info)
Transforming growth factor-beta1 is a potent inhibitor of interleukin-1beta action in whole ovarian dispersates.
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Transforming growth factor beta1 (TGFbeta1) acts as an inhibitor of the actions of interleukin-1beta (IL-1beta) in various organ systems. In order better to understand the inter|P-actions between these polypeptides in the ovary, we evaluated the effect of TGFbeta1 co-treatment on various IL-1beta-mediated actions in cultures of whole ovarian dispersates. Treatment with IL-1beta enhanced media accumulation of nitrites (4.8-fold), prostaglandin E2 (PGE2, 3. 9-fold) and lactate (2.0-fold), and enhanced glucose consumption (2. 1-fold). Treatment with TGFbeta1 alone did not significantly affect any of these parameters. However, the addition of TGFbeta1 inhibited IL-1beta-stimulated nitrite (100%), PGE2 (44%) and lactate (78%) accumulation and inhibited IL-1beta-stimulated glucose consumption (74%) in a dose-dependent manner. The addition of TGFbeta1 also suppressed the steady-state levels of IL-1beta-stimulated IL-1beta, type I IL-1 receptor and IL-1 receptor antagonist transcripts (98, 67 and 83% inhibition respectively). These data suggest that TGFbeta1 is capable of inhibiting several IL-1beta-stimulated endpoints. Since IL-1 has been identified as a possible proinflammatory mediator of ovulation and TGFbeta has been implicated as a promotor of fibrosis and healing, we speculate that IL-1 and TGFbeta might play antagonistic roles in the normal ovulatory sequence. (+info)
Differential effects of defibrillation on systemic and cardiac sympathetic activity.
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OBJECTIVE: To assess the effect of defibrillation shocks on cardiac and circulating catecholamines. DESIGN: Prospective examination of myocardial catecholamine balance during dc shock by simultaneous determination of arterial and coronary sinus plasma concentrations. Internal countershocks (10-34 J) were applied in 30 patients after initiation of ventricular fibrillation for a routine implantable cardioverter defibrillator test. Another 10 patients were externally cardioverted (50-360 J) for atrial fibrillation. MAIN OUTCOME MEASURES: Transcardiac noradrenaline, adrenaline, and lactate gradients immediately after the shock. RESULTS: After internal shock, arterial noradrenaline increased from a mean (SD) of 263 (128) pg/ml at baseline to 370 (148) pg/ml (p = 0.001), while coronary sinus noradrenaline fell from 448 (292) to 363 (216) pg/ml (p = 0.01), reflecting a shift from cardiac net release to net uptake. After external shock delivery, there was a similar increase in arterial noradrenaline, from 260 (112) to 459 (200) pg/ml (p = 0.03), while coronary sinus noradrenaline remained unchanged. Systemic adrenaline increased 11-fold after external shock (p = 0.01), outlasting the threefold rise following internal shock (p = 0.001). In both groups, a negative transmyocardial adrenaline gradient at baseline decreased further, indicating enhanced myocardial uptake. Cardiac lactate production occurred after ventricular fibrillation and internal shock, but not after external cardioversion, so the neurohumoral changes resulted from the defibrillation process and not from alterations in oxidative metabolism. CONCLUSIONS: A dc shock induces marked systemic sympathoadrenal and sympathoneuronal activation, but attenuates cardiac sympathetic activity. This might promote the transient myocardial depression observed after electrical discharge to the heart. (+info)
Kinetics of lactate and pyruvate transport in cultured rat myotubes.
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Skeletal muscle transport of lactate and pyruvate was studied in primary cultures of rat myotubes, applying the pH-sensitive fluorescent indicator 2', 7'-bis(carboxyethyl)-5(6)-carboxyfluorescein. The initial rate of decrease in intracellular pH (pHi) upon lactate or pyruvate incubation was used to determine total transport (carrier mediated and diffusion). Both lactate and pyruvate transport could be inhibited by a combination of 0.5 mM 4,4'-diisothiocyanostilbene-2, 2'-disulfonic acid, 5 mM mersalyl and 10 mM alpha-cyano-4-hydroxycinnamate. The kinetic parameters, Km and Vmax, for carrier-mediated transport of lactate were 9.9+/-1.1 mM and 0. 69+/-0.02 mmol l-1 s-1, respectively. For pyruvate, Km and Vmax were 4.4+/-1.3 mM and 0.30+/-0.05 mmol l-1 s-1, respectively. The diffusion component of the total transport was 0.0040+/-0.0005[S] (n=4) and 0.0048+/-0.0003[S] (n=4) for lactate and pyruvate, respectively. Furthermore, it was observed that the two monocarboxylate transporter isoforms present in mature skeletal muscles, MCT1 and MCT4 (formerly called MCT3 (M.C. Wilson, V.N. Jackson, C. Heddle, N.T. Price, H. Pilegaard, C. Juel, A. Bonen, I. Montgomery, O.F. Hutter, A.P. Halestrap, Lactic acid efflux from white skeletal muscle is catalyzed by the monocarboxylate transporter isoform MCT3, J. Biol. Chem. 273 (1998) 15920-15926)), were also expressed in primary culture of myotubes. (+info)
Myocardial metabolism of 123I-BMIPP in a canine model with ischemia: implications of perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease.
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123I-(rho-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) is a fatty acid analog for SPECT imaging. This radiopharmaceutical possesses the unique property, that is, perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease. However, the reason of this mechanism remains unclear. METHODS: Using open-chest dogs under anesthesia, we made a system to release all the blood of the great cardiac vein outside without recirculation, if necessary. Left anterior descending artery (LAD) was occluded for 30 min after reperfusion. After the injection of BMIPP into LAD, blood samplings from the cardiac vein and abdominal aorta (6 dogs) or serial biopsy specimens from the LAD region (5 dogs) were performed, and then compared with the normal control. The catabolites of BMIPP, including backdiffusion of nonmetabolized BMIPP, were evaluated with high-performance liquid chromatography (HPLC) in the efflux study. Thin-layer chromatography (TLC) technique was introduced in the tissue analytical study. RESULTS: Although the rapid extraction of BMIPP from the plasma into the myocardium and the subsequent retention were unchanged, the early washout (8 min) of radioactivity significantly increased (51% +/- 12% to 65% +/- 7%; P < 0.05) with ischemia. The metabolites from the myocardium consisted of backdiffusion of nonmetabolized BMIPP, alpha, intermediate, and full oxidation metabolites. Among these metabolites, backdiffusion of nonmetabolized BMIPP in blood significantly increased (27.9% +/- 7.7% to 42.3% +/- 8.1%; P < 0.05), especially in the early phase with ischemia. In tissue, the radioactivity was concentrated in the triglyceride pool even in the early phase, and in addition, BMIPP and alpha-oxidized metabolite significantly decreased in the early phase with ischemia (t = 1 min after BMIPP injection, 25.9% +/- 8.6% to 14.5% +/- 2.1%, P < 0.01; t = 2 min, 8.9% +/- 5.0% to 4.5% +/- 1.7%, P < 0.05). CONCLUSION: These results show that backdiffusion of nonmetabolized BMIPP from the myocardium increased and BMIPP (long-chain fatty acids) in tissue decreased with ischemia, suggesting backdiffusion of nonmetabolized BMIPP might play an important role in myocardial perfusion-metabolism mismatch on SPECT images in patients with ischemic heart disease. (+info)