Reduced aldosterone and sodium excretion in endurance-trained athletes before and during immersion.

Aldosterone excretion (AE) and plasma renin activity (PRA) were measured in eight untrained (UT) and eight endurance-trained (TR) male subjects before and during 4 h head-out immersion to study the mechanism of reduced renal sodium excretion in athletes. AE was significantly lower before immersion, and decreased less during immersion, in TR than in UT. Fractional sodium excretion, too, was lower and increased less during immersion in TR than in UT. PRA decreased in the water bath in all subjects (p less than 0.001) with no significant difference between the groups. During immersion, plasma sodium concentration oscillated whereas potassium concentration showed a temporary rise in TR (p less than 0.001). The attenuated response of AE in TR may be due partly to this increase of plasma potassium concentration. The generally reduced aldosterone release in TR might be caused by a training induced adaptation of the adrenals to corticotropin. The lowered renal sodium excretion of TR in spite of the decreased AE suggests an intensified aldosterone effect in these subjects, diminishing the salt loss during exercise.     

Effect of somatostatin on renal function.

Somatostatin has profound effects on both splanchnic and portal vascular beds. The effects of intravenous somatostatin (100 micrograms/h) on urinary volume, effective renal plasma flow, and glomerular filtration rate were compared with the effects of a control infusion of physiological saline in six normal subjects. Renal plasma flow and glomerular filtration rate were measured by primed constant isotope infusions of iodine-125 iodohippurate and chromium-51 edetic acid. Urinary volume, renal plasma flow, and glomerular filtration rate were measured during 20 minute clearance periods. During the control infusion urinary volume, renal plasma flow, and glomerular filtration rate remained essentially unchanged at 254 (SEM 3) ml/20 min, 568 (5) ml/min/1.73 m2, and 110 (2) ml/min/1.73 m2 respectively. From similar basal values the infusion of somatostatin led to a rapid decrease in all three variables. After 120 minutes of infusion of somatostatin urinary volume, renal plasma flow, and glomerular filtration rate were reduced to 148 (17) ml/20 min (p less than 0.01), 422 (7) ml/min/1.73 m2 (p less than 0.001), and 93 (3) ml/min/1.73 m2 (p less than 0.05) respectively. This effect on renal function should be borne in mind whenever somatostatin is used.     

Lithium clearance in water immersion-induced natriuresis in humans

Lithium clearance (CLi) has been advanced as a measure of sodium delivery from the proximal tubules. Because information on the intrarenal effects of water immersion is only limited, and available data are conflicting with respect to the effects on the proximal tubule, we examined the effects of 3 h of water immersion on renal functional parameters, including CLi, in eight healthy subjects. Studies were carried out during maximal water diuresis. Water immersion resulted in a significant increase in sodium excretion, from preimmersion values of 74.0 +/- 9.6 to 155.4 +/- 12.0 mumol/min at the third immersion hour (P less than 0.01). This natriuresis was accompanied by an increase in CLi from 26.3 +/- 1.9 (preimmersion) to 37.0 +/- 3.1 ml/min (P less than 0.01). Fractional lithium reabsorption (FRLi) decreased from 76.4 +/- 1.0 to 69.6 +/- 1.3% (P less than 0.01). None of these changes was found in eight healthy subjects undergoing a time-control study without water immersion. The large fall in FRLi found during immersion is compatible with a major resetting of the proximal glomerulotubular balance. In this regard the renal response to water immersion resembles saline expansion rather than mere intravascular expansion. The lithium data suggested a large rise in distal delivery accompanied by an almost as large rise in distal reabsorption. The free water clearance data were in agreement with this interpretation. However, no changes were found in fractional excretion of phosphate and uric acid. Therefore such a major resetting of proximal glomerulotubular balance can be doubted.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mild endotoxemia, NF-kappaB translocation, and cytokine increase during exertional heat stress in trained and untrained individuals

This study examined endotoxin-mediated cytokinemia during exertional heat stress (EHS). Subjects were divided into trained [TR; n=12, peak aerobic power (VO2peak)=70+/-2 ml.kg lean body mass(-1).min(-1)] and untrained (UT; n=11, VO2peak=50+/-1 ml.kg lean body mass(-1).min(-1)) groups before walking at 4.5 km/h with 2% elevation in a climatic chamber (40 degrees C, 30% relative humidity) wearing protective clothing until exhaustion (Exh). Venous blood samples at baseline and 0.5 degrees C rectal temperature increments (38.0, 38.5, 39.0, 39.5, and 40.0 degrees C/Exh) were analyzed for endotoxin, lipopolysaccharide binding protein, circulating cytokines, and intranuclear NF-kappaB translocation. Baseline and Exh samples were also stimulated with LPS (100 ng/ml) and cultured in vitro in a 37 degrees C water bath for 30 min. Phenotypic determination of natural killer cell frequency was also determined. Enhanced blood (104+/-6 vs. 84+/-3 ml/kg) and plasma volumes (64+/-4 vs. 51+/-2 ml/kg) were observed in TR compared with UT subjects. EHS produced an increased concentration of circulating endotoxin in both TR (8+/-2 pg/ml) and UT subjects (15+/-3 pg/ml) (range: not detected to 32 pg/ml), corresponding with NF-kappaB translocation and cytokine increases in both groups. In addition, circulating levels of tumor necrosis factor-alpha and IL-6 were also elevated combined with concomitant increases in IL-1 receptor antagonist in both groups and IL-10 in TR subjects only. Findings suggest that the threshold for endotoxin leakage and inflammatory activation during EHS occurs at a lower temperature in UT compared with TR subjects and support the endotoxin translocation hypothesis of exertional heat stroke, linking endotoxin tolerance and heat tolerance.     

Red cell hemoglobin, hydrogen ion and electrolyte concentrations during exercise in trained and untrained subjects

Red cell concentrations of hemoglobin (MCHC), H+, Na+, K+, Mg++, cl- were measured in femoral venous blood of six untrained (UT), six endurance trained (TR) and three semitrained (ST) subjects during graded increasing work (4, 8, 12, 18 and 24 mkp/s, 10-15 min on each step) on a bicycle ergometer. Before exercise no significant differences were detected for the measured variables when comparing UT and TR. During exercise MCHC, [Na+], [K+] and [Mg++] remained constant indicating lack of water shift into the erythrocytes in spite of a marked acidosis (lowest pH Blood value 7.225). This lack resulted from an elevated extracellular osmolality. [H+]Ery and [Cl-]Ery maximally increased by 2.0 X 10(-8) eq/kg H2O and 10 meq/l, respectively. The change was markedly greater in UT than in TR at equal load. However, if [H+] Ery and [Cl-] Ery were related to pH of whole blood, differences between groups, almost disappeared and the ions were distributed as predictable from in vitro experiments (Fitzsimmons and Sendroy, 1961). Behaviour of H+ and Cl- may be of importance for oxygen dissociation under in vivo conditions.     

Suppression of ADH during water immersion in normal man.

Since previous studies from this laboratory have demonstrated that the redistribution of blood volume and concomitant relative central hypervolemia induced by water immersion to the neck causes a profound natriuresis and a suppression of the renin-aldosterone system, it was of interest to assess whether the diuresis induced by immersion was mediated by an analogous inhibition of ADH. The effects of water immersion on renal water handling and urinary ADH excretion were assessed in 10 normal male subjects studied following 14 h of overnight dehydration on two occasions, control and immersion. The conditions of seated posture and time of day were identical. During control ADH persisted at or above prestudy values. Immersion resulted in a progressive decrease in ADH excretion from 80.1 plus or minus 7 (SEM) to 37.3 plus or minus 6.3 muU/min (P smaller than 0.025). Cessation of immersion was associated with a marked increase in ADH from 37.3 +/- 6.3 muU/min to 176.6 +/- 72.6 muU/min during the recovery hour (P smaller than 0.05). Concomitant with these changes urine osmolality decreased significantly beginning as early as the initial hour of immersion from 1044 +/- 36 to 542 +/- 66 mosmol/kg H2O during the final hour of immersion (P smaller than 0.001). Recovery was associated with a significant mean increase in Uosm of 190 +/- 40 mosmol/kg H2O over the final hour of immersion (P smaller than 0.001). The suppression of ADH occurred without concomitant changes in plasma tonicity. These studies are consistent with the suggestion that in hydrated subjects undergoing immersion suppression of ADH release contributes to the enhanced free water clearance, which has been previously documented.     

Effect of training on the dose-response relationship for insulin action in men

Seven endurance-trained subjects [maximal O2 consumption (VO2max) 64 +/- 1 (SE) ml.min-1.kg-1] were subjected to three sequential hyperinsulinemic euglycemic clamps 15 h after having performed their last training session (T). Results were compared with findings in seven untrained subjects (VO2max 44 +/- 2 ml.min-1.kg-1) studied both at rest (UT) and after 60 min of bicycle exercise at 150 W (UT-ex). In T and UT-ex compared with UT, sensitivity for insulin-mediated whole-body glucose uptake was higher [insulin concentrations eliciting half-maximal glucose uptake being 44 +/- 2 (T) and 43 +/- 4 (UT-ex) vs. 52 +/- 3 microU/ml (UT), P less than 0.05] and responsiveness was higher [13.4 +/- 1.2 (T) and 10.9 +/- 0.7 (UT-ex) vs. 9.5 +/- 0.7 mg.min-1.kg-1 (UT), P less than 0.05]. Furthermore, responsiveness was higher (P less than 0.05) in T than in UT-ex. Insulin-stimulated O2 uptake and maximal glucose oxidation rate were higher in T than in UT and UT-ex. Insulin-stimulated conversion or glucose to glycogen and muscle glycogen synthase was higher in T than in UT and UT-ex. However, glycogen storage in vastus lateralis muscle was found only in UT-ex. No change in any glucoregulatory hormone or metabolite could explain the increased insulin action in trained subjects. It is concluded that physical training induces an adaptive increase in insulin responsiveness of whole-body glucose uptake, which does not reflect increased glycogen deposition in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen dissociation curves in trained and untrained subjects.

Oxygen dissociation curves (ODC) in whole blood and organic phosphate concentrations in red cells were determined in 10 highly trained male athletes (TR), 6 semitrained subjects (ST) who played sports regularly at low intensities and 8 untrained people (UT). In all groups standard ODCs (37 degrees C, pH 7.40, PCO2 approximately 43 Torr) at rest and after a short exhaustive exercise were nearly identical, but PO2 values measured immediately after blood sampling and corrected to standard conditions tended to fall to the right of the in vitro ODC. Elevated P50 in the physically active [28.65 +/- 1.4 Torr (3.81 +/- 0.18 kPa) in ST, 28.0 +/- 1.1 Torr (3.73 +/- 0.15 kPa) in TR, but 26.5 +/- 1.1 Torr (3.53 +/- 0.15 kPa) in UT] were partly caused by different [DPG] (11.9 +/- 1.3 mumol/GHb in UT, 13.3 +/- 1.5 mumol/GHb in TR, 13.8 +/- 2.2 mumol/gHb in ST). There were remarkable differences in the shape of the curves between the groups. The slope "n" in the Hill plot amounted to 2.65 +/- 0.12 in UT, 2.74 +/- in ST and 2.90 +/- 0.11 in the TR (2 p against UT less than 0.001), leading to an elevated oxygen pressure of about 2 Torr (0.27 kPa) at 20% saturation and an augmented oxygen extraction of 5--7 SO2 at a PO2 of about 15 Torr (2kPa), which might be favorable at high workloads. The reason for the phenomenon could be an increased amount of young red cells in the blood of TR, caused by exercise induced hemolysis.     

Effect of head-out immersion on plasma atrial natriuretic factor in man

This study was conducted to examine the role of atrial natriuretic factor (ANF) in the development of diuresis and natriuresis in response to the head-out immersion in 35 degrees C water. Six male subjects were hydrated (0.5% body wt), sat for 1 hr in air (preimmersion), were immersed in water to the neck for 3 hr, and then sat for 1 hr in air (postimmersion). In another series they were similarly hydrated and then sat for 5 hr in air for the time control. Urine and venous blood samples were collected hourly for creatinine and electrolyte measurements. In addition, the concentration of ANF was determined in unextracted plasma by a radioimmunoassay. The pattern of electrolyte excretion was evaluated on the basis of fractional excretion of filtered load. In the time control series, urine flow and fractional excretion of Na and K remained low throughout the 5-hr experimental period. On the other hand, urine flow increased significantly from the preimmersion level of approximately 2 to approximately 7 ml/min during the first hour of immersion (P less than 0.05), after which it decreased to approximately 5 ml/min during the second hour of immersion (P less than 0.05) and to approximately 2 ml/min during the third hour of immersion. Fractional excretion of Na increased continuously from preimmersion level of approximately 1.0 to approximately 1.8% during the second and third hours of immersion (P less than 0.05) and then decreased to 1.2% during the 1-hr postimmersion period. The plasma ANF remained low (approximately 75 pg/ml) during the 5-hr time control period. In the immersion series, plasma ANF increased significantly from the preimmersion level of approximately 80 to approximately 120 pg/ml during the entire 3-hr immersion period and then returned to the preimmersion level during 1 hr postimmersion. These results indicate that the immersion diuresis and natriuresis are indeed associated with the increased ANF release. However, it can not be ascertained from the present study if the increased ANF contributes directly to these renal responses to immersion or in concert with other mediators.     

Effects of beta-blockade on exercise capacity of trained and untrained men: a hemodynamic comparison

To study the effects of cardiovascular fitness on hemodynamic responses to exercise during beta-adrenergic blockade (BAB), submaximal [60% of maximum O2 uptake (VO2max)] and maximal treadmill exercise data were collected in 11 trained (T, VO2max 63.3 ml X kg-1 X min-1, 26.8 yr) and 11 untrained (UT, VO2max 44.5 ml X kg-1 X min-1, 25.0 yr) male subjects. Subjects completed two maximal control tests followed by a randomized, double-blind series of maximal tests after 1-wk treatments with placebo (PLAC), propranolol (PROP, 160 mg/day, beta 1- and beta 2-blockade), and atenolol (ATEN, 100 mg/day, beta 1-blockade). Treatments were separated by 1-wk washout periods. At 60% of control VO2max T and UT subjects experienced no reductions in O2 uptake (VO2) with either drug. Submaximal heart rate (HR, beats/min) was 134.8 PLAC, 107.0 PROP, 107.9 ATEN (P less than 0.05 both drugs vs. PLAC) in T subjects and 141.1 PLAC, 106.1 PROP, and 105.0 ATEN (P less than 0.05 both drugs vs. PLAC) in UT subjects. Cardiac output (1/min) for T was 17.3 PLAC, 16.9 PROP, 16.5 ATEN (P less than 0.05 ATEN vs. PLAC in T only) and for UT it was 12.2 (PLAC), 11.7 (PROP), 11.5 (ATEN) (P less than 0.05 both drugs vs. PLAC in UT). Stroke volume increased from 129.8 ml (PLAC) to 158.6 (PROP) and 156.2 (ATEN) in T (P less than 0.05 both drugs vs. PLAC) and from 86.8 (PLAC) to 110.0 (PROP) and 109.8 (ATEN) (P less than 0.05 both drugs vs. PLAC) in UT. The increases in stroke volume (SV) were similar in both groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cardiorenal-endocrine responses to head-out immersion at night

Cardiorenal-endocrine responses to 3-h head-out immersion (HOI) (water temperature = 34.5 +/- 0.5 degrees C) were studied during day (0900-1400 h) and night (2300-0400 h) in six hydropenic male human subjects. Although HOI induced a reversible increase in urine flow in all subjects, the response was faster and greater in magnitude during the day compared with night (P less than 0.05). Na excretion and osmolal clearance (Cosm) also followed the identical response pattern as urine flow, and in fact, the HOI-induced diuresis was entirely accounted for by the increased Cosm. Endogenous creatinine clearance was not different between the day and the night and remained unchanged during HOI. Both plasma renin activity and aldosterone concentration and urinary aldosterone excretion were nearly twofold greater during the day compared with night before HOI but decreased to the same level during HOI in both daytime and the nighttime series (P less than 0.05). There was no correlation between the Na excretion rate and renin-aldosterone levels either before or during HOI. Plasma antidiuretic hormone (ADH) level was comparable between day and night before HOI and decreased to a similar level during HOI in both daytime and nighttime series (P less than 0.05 for nighttime HOI). Cardiac output increased from 3.3 1/min before HOI to 5-6 1/min during HOI without showing any significant circadian difference. Hematocrit, hemoglobin, and plasma concentrations remained unchanged under all conditions. It is concluded that the renal response to HOI is subject to nocturnal inhibition, which cannot be attributed to circadian differences in the degree of HOI-induced central blood pooling, renin-aldosterone, or ADH responses.     

The relationship between lactic acid and work load: a measure for endurance capacity or an indicator of carbohydrate deficiency?

The influence of low and high carbohydrate diets on the relationship between blood lactate concentration ([Lac]) and work load (WL) in incremental exercise tests (cycle ergometer) and endurance tests was evaluated in trained subjects. The relationship between relative work load (WLrel) and [Lac] in arterialized blood was compared in untrained subjects (UT) and trained male athletes (TR) after 2 days without training while consuming a high carbohydrate diet (HCD). In both groups [Lac] of 2 mmol.l-1 was reached at about 60% [(mean +/- SD) UT 57.7% +/- 6%, TR 62.7% +/- 3.8%] and 4 mmol.l-1 at about 75% (UT 75.2% +/- 3.6%, TR 77.8 +/- 2.2) of the maximal work load (WLmax). In eight cyclists the relationship between [Lac] and WL was not influenced by a 13-day training camp; however, heart rate was lower after the training camp. During their normal training programme, trained subjects had high relative work loads at their [Lac] thresholds, but after an HCD combined with an interruption of the training of 3 days, the relationship between [Lac] and WLrel was the same as in UT. In six TR a low carbohydrate diet (LCD) combined with training led to high absolute (WLabs) and WLrel at [Lac] at 2 and 4 mmol.l-1; an HCD combined with 3 days without training led to low WLabs and WLrel at the same [Lac] and to higher WLmax. In spite of the apparently lower endurance capacities TR were able to work significantly longer after HCD than after LCD (23 +/- 10.5 min and 49 +/- 16.2 min, respectively) at 65% of their WLmax. The variability of the relationship between [Lac] and WL following the dietary regimes leads to the conclusion that the "typical" [Lac] versus WL curve of endurance TR may result from a permanent glycogen deficiency.     

Effect of intravenous administration of cimetidine on renal excretion of calcium, phosphates, magnesium and adenosine cyclic monophosphate

An effect of cimetidine on parathyroid glands functioning in healthy subjects was evaluated. Serum calcium, phosphate, and magnesium concentrations together with renal excretion++ of these ions in healthy subjects as well as cAMP excretion++ in selected individuals were determined before and following intravenous administration of cimetidine (Altratmet Lek Ljublijana) in total dose of 500 mg (50 mg injected rapidly as a bolus following with 450 mg in an intravenous infusion during 60 minutes). No significant changes in serum calcium, phosphates, and magnesium concentrations were noted. Renal clearance of calcium and magnesium remained unchanged whereas renal phosphate excretion++ increased from 10.69 +/- 4.9 mL/min to 15.1 +/- 5.41 mL/min (p less than 0.02). Excretion++ of 3.5 cAMP increased from 2.65 +/- 2.19 nM/min to 5.16 +/- 2.0 nM/min (p less than 05). The obtained results do not exclude stimulating effect of intravenous cimetidine on parathyroid glands. Cimetidine given intravenously in the bleeding gastric or duodenal ulcers in the course of the primary hyperparathyroidism+ may decrease serum phosphate levels due to increased exretion of this ion with the urine.     

Effect of training status on fuel selection during submaximal exercise with glucose ingestion.

In this study, an oral glucose load was enriched with a [U-(13)C]glucose tracer to determine differences in substrate utilization between endurance-trained (T) and untrained (UT) subjects during submaximal exercise at the same relative and absolute workload when glucose is ingested. Six highly trained cyclists/triathletes [maximal workload (Wmax), 400 +/- 9 W] and seven UT subjects (Wmax, 296 +/- 8 W) were studied during 120 min of cycling exercise at 50% Wmax ( approximately 55% maximal O(2) consumption). The T subjects performed a second trial at the mean workload of the UT group (148 +/- 4 W). Before exercise, 8.0 ml/kg of a (13)C-enriched glucose solution (80 g/l) was ingested. During exercise, boluses of 2.0 ml/kg of the same solution were administered every 15 min. Measurements were made in the 90- to 120-min period when a steady state was present in breath (13)CO(2) and plasma glucose (13)C enrichment. Energy expenditure was higher in T than in UT subjects (58 vs. 47 kJ/min, respectively; P < 0.001) at the same relative intensity. This was completely accounted for by an increased fat oxidation (0.57 vs. 0.40 g/min; P < 0.01). At the same absolute intensity, fat oxidation contributed more to energy expenditure in the T compared with the UT group (44 vs. 33%, respectively; P < 0.01). The reduction in carbohydrate oxidation in the T group was explained by a diminished oxidation rate of muscle glycogen (indirectly assessed by using tracer methodology at 0.72 +/- 0.1 and 1.03 +/- 0.1 g/min, respectively; P < 0.01) and liver-derived glucose (0.15 +/- 0.03 and 0.22 +/- 0.02 g/min, respectively; P < 0.05). Exogenous glucose oxidation rates were similar during all trials (+/-0.70 g/min).     

Altered cardiovascular responsiveness to adrenoceptor agonists in endurance-trained men

The influence of physical training on responses to intravenous infusions of phenylephrine (Phe) and isoproterenol (Iso) were investigated in 10 well-trained runners (WT) and 10 age-matched untrained controls (UT). The latter were reinvestigated after a 4-mo training period. The venous plasma Iso and Phe concentrations attained during infusions were lower in WT than in UT. Responses were related to the corresponding plasma concentrations. Phe-induced decreases and Iso-induced increases in heart rate were less pronounced (P less than 0.01) in WT than in UT. At venous plasma concentrations of 100 nM Phe and 0.8 nM Iso, the responses were -9 +/- 1 and 30 +/- 2, and -17 +/- 2 and 44 +/- 4 beats/min, respectively. Increases in blood pressures during Phe infusions were greater in WT than in UT (100 nM Phe: systolic 36 +/- 3 vs. 25 +/- 3 mmHg, P less than 0.05). The Iso-induced decrease in diastolic blood pressure was also more pronounced in WT (0.8 nM Iso: -29 +/- 3 vs. -15 +/- 2 mmHg, P less than 0.01). Iso-induced changes in systolic time intervals showed no consistent differences between training states. Increases in plasma adenosine 3',5'-cyclic monophosphate during Iso infusions were smaller (P less than 0.05) in WT than in UT, whereas increases in plasma glycerol were larger (P less than 0.05). Lymphocyte beta 2-adrenoceptor function and binding characteristics did not differ between training states. In summary, the present results indicate that beta-adrenergic vasodilator and alpha-adrenergic vasopressor responses are enhanced in endurance-trained subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of alpha-adrenergic receptors in the vasoconstrictor response induced by indomethacin in the kidney.

The effect of indomethacin, an inhibitor of prostaglandin (PG) synthesis, was studied on the renal circulation, Na+ and water excretion in anaesthesized dogs during alpha-receptor inhibition. Indomethacin decreased cortical blood flow (CBFcontr, 454 +/- 142; CBFindo, 332 +/- 51 ml per min per 100 g; p less than 0.02) as well as medullary blood flow (OMBFcontr, 339 +/- 95; OMBFindo, 183 +/- 46 ml per min per 100 g; p less than 0.001), salt and water excretion, further it caused a shift in the intrarenal blood flow distribution toward the cortex. Alpha-blockade prevented the indomethacin-induced vasoconstriction in the cortex (CBF alpha inhibition + indo, 455 +/- 76 ml per min per 100 g) but not in the medullar (OMBF alpha inhibition + indo, 259 +/- 102 ml per min per 100 g, p less than 0.05). Alpha-blockade failed to prevent the indomethacin-induced antidiuresis, antinatriuresis and the intrarenal blood flow redistribution. GFR remained unaffected in all three series of studies. Our experimental findings are in line with the presumption that alpha-receptors are involved in the renal circulatory changes caused by indomethacin, probably as a result of an enhanced NE release during the inhibition of PG production. A NE--PG feed back mechanism is suggested in the regulation of renal circulation. The reduction of salt and water output induced by indomethacin appears to be independent of the alterations in renal haemodynamics, and seems rather to be the result of enhanced Na+ reabsorption, predominantly at the distal segment of the nephron, in the absence of PG, and/or a direct action of indomethacin.     

Renal response to hemorrhage in dogs with subacute biliary obstruction

In the present study, we tested the hemodynamic and renal response of 15 sham-operated dogs and 15 dogs with subacute (5-9 days) biliary obstruction to either acute or more chronic hemorrhage. All studies were conducted on sedated but unanaesthetized animals. Both groups were comparable before blood withdrawal with respect to central hemodynamics and renal perfusion. Serum bilirubin was 0.70 +/- 0.09 mg/dL for control dogs and 8.25 +/- 0.14 for experimental dogs (P less than 0.05). In the acute protocol, nine control and seven jaundiced dogs were bled over a period of 30-40 min to lower blood pressure by 19.1 and 19.5%, respectively. Blood volumes required to achieve this drop were 21.3 and 20.05 mL/kg, respectively (P greater than 0.05). Cardiac output declined by an equivalent value for each group and glomerular filtration rate and clearance of p-aminohippurate remained unchanged from control values. In six control and eight experimental dogs, 500 mL of blood was withdrawn over 5 days. Although blood pressure and cardiac output declined for each group by an equivalent amount, renal perfusion remained unchanged for each group from control values. We conclude that acute or chronic hemorrhage of modest degree does not predispose to acute renal insufficiency in dogs with subacute biliary obstruction.     

Muscle glycogen utilization during shivering thermogenesis in humans

The purpose of the present study was to clarify the importance of skeletal muscle glycogen as a fuel for shivering thermogenesis in humans during cold-water immersion. Fourteen seminude subjects were immersed to the shoulders in 18 degrees C water for 90 min or until rectal temperature (Tre) decreased to 35.5 degrees C. Biopsies from the vastus lateralis muscle and venous blood samples were obtained before and immediately after the immersion. Metabolic rate increased during the immersion to 3.5 +/- 0.3 (SE) times resting values, whereas Tre decreased by 0.9 degrees C to approximately 35.8 degrees C at the end of the immersion. Intramuscular glycogen concentration in the vastus lateralis decreased from 410 +/- 15 to 332 +/- 18 mmol glucose/kg dry muscle, with each subject showing a decrease (P less than 0.001). Plasma volume decreased (P less than 0.001) markedly during the immersion (-24 +/- 1%). After correcting for this decrease, blood lactate and plasma glycerol levels increased by 60 (P less than 0.05) and 38% (P less than 0.01), respectively, whereas plasma glucose levels were reduced by 20% after the immersion (P less than 0.001). The mean expiratory exchange ratio showed a biphasic pattern, increasing initially during the first 30 min of the immersion from 0.80 +/- 0.06 to 0.85 +/- 0.05 (P less than 0.01) and decreasing thereafter toward basal values. The results demonstrate clearly that intramuscular glycogen reserves are used as a metabolic substrate to fuel intensive thermogenic shivering activity of human skeletal muscle.     

A possible contribution of endogenous atrial natriuretic peptide to proteinuria in patients with chronic renal failure.

Plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) were measured with a specific radioimmunoassay in 19 undialysed patients with chronic renal failure. At the beginning, an extremely high level of plasma hANP (50 fmol/ml) seen in a patient was rejected with Smirnov's test and was excluded from further statistics. The plasma IR-ANP levels in these patients were significantly higher than those of 19 normal subjects matched with age and sex (10.9 +/- 1.6 vs 5.3 +/- 0.6 fmol/ml, mean +/- SEM, p less than 0.01), and positively correlated with mean blood pressure (r = 0.44, p less than 0.05) and the cardiothoracic ratio (r = 0.65, p less than 0.01), but did not correlate with creatinine clearance (r = -0.38, n.s.). Further, a significant correlation was observed between plasma IR-ANP and urinary protein output (r = 0.47, p less than 0.05). On the other hand, urinary protein output did not correlate significantly with variables such as mean blood pressure, the cardiothoracic ratio or creatinine clearance. Since it has been suggested that ANP enhances glomerular capillary permeability, increased ANP responding to volume overload in those patients may play an important role in increasing urinary protein excretion.     

Glucose clearance in aged trained skeletal muscle during maximal insulin with superimposed exercise.

Insulin and muscle contractions are major stimuli for glucose uptake in skeletal muscle and have in young healthy people been shown to be additive. We studied the effect of superimposed exercise during a maximal insulin stimulus on glucose uptake and clearance in trained (T) (1-legged bicycle training, 30 min/day, 6 days/wk for 10 wk at approximately 70% of maximal O(2) uptake) and untrained (UT) legs of healthy men (H) [n = 6, age 60 +/- 2 (SE) yr] and patients with Type 2 diabetes mellitus (DM) (n = 4, age 56 +/- 3 yr) during a hyperinsulinemic ( approximately 16,000 pmol/l), isoglycemic clamp with a final 30 min of superimposed two-legged exercise at 70% of individual maximal heart rate. With superimposed exercise, leg glucose extraction decreased (P < 0.05), and leg blood flow and leg glucose clearance increased (P < 0.05), compared with hyperinsulinemia alone. During exercise, leg blood flow was similar in both groups of subjects and between T and UT legs, whereas glucose extraction was always higher (P < 0.05) in T compared with UT legs (15.8 +/- 1.2 vs. 14.6 +/- 1.8 and 11.9 +/- 0.8 vs. 8.8 +/- 1.8% for H and DM, respectively) and leg glucose clearance was higher in T (H: 73 +/- 8, DM: 70 +/- 10 ml. min(-1). kg leg(-1)) compared with UT (H: 63 +/- 8, DM: 45 +/- 7 ml. min(-1). kg leg(-1)) but not different between groups (P > 0.05). From these results it can be concluded that, in both diabetic and healthy aged muscle, exercise adds to a maximally insulin-stimulated glucose clearance and that glucose extraction and clearance are both enhanced by training.