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Biomedical subjects

O M Sejersted

Publications and source records attributed to O M Sejersted.

At least 109 records · Page 6Linked to original sources
PubMed1984

Ouabain inhibits renin release by a direct renal haemodynamic effect.

The effect of intrarenal infusion of ouabain (90 micrograms/kg) on renin release was examined in the anaesthetized dog. Ouabain reduced cortical Na-K-ATPase activity to 23% and outer medullary activity to 18% of the control level. During renal arterial constriction to a perfusion pressure below the autoregulatory range, renin release rose from 1.2 +/- 0.4 to 47.4 +/- 6.9 micrograms/min (P less than 0.001). This response was abolished by ouabain. When superimposed on renal arterial constriction, beta-adrenergic stimulation enhanced renin release from 25.6 +/- 10.7 to 56.9 +/- 9.5 micrograms/min (P = 0.02) at a urinary sodium excretion of 2 +/- 1 mumol/min. After ouabain, the corresponding increment substantially decreased since release rose from 5.6 +/- 2.0 to 19.9 +/- 5.3 micrograms/min only (P = 0.02), at a urinary sodium excretion of 140 +/- 67 mumol/min. When glomerular filtration was reduced to zero by ureteral occlusion in one series, renin release increased to 22.6 +/- 5.1 but was reduced (P less than 0.05) by ouabain to 13.5 +/- 5.5 micrograms/min and superimposed isoproterenol had no effect. According to these observations, ouabain inhibits renin release by a direct effect on the afferent arteriole through constriction of the autoregulating renin-secreting segment.

Adrenergic beta-Agonists↗
PubMed1984

Inhibition of transcellular NaCl reabsorption in dog kidneys during hypercalcemia.

Reduced concentrating and diluting capacity of the kidney in acute and chronic hypercalcemia may partly be due to inhibition of transcellular sodium reabsorption (RNa) in the thick ascending limb of Henle's loop. To examine this hypothesis, local heat production and RNa were measured during normo- and hypercalcemia at comparable glomerular filtration rate (GFR) in volume expanded, anesthetized dogs. Changes in proximal RNa which might occur during CaCl2 infusion, were minimized by infusing acetazolamide (75 mg/kg body wt iv). When ultrafiltrable calcium was increased from 1.12 +/- 0.09 to 2.95 +/- 0.10 mmol/l, cortical heat production was unchanged, whereas outer medullary heat production fell by 32 +/- 4%. RNa was reduced by 32 +/- 6%. Bicarbonate reabsorption did not change but calcium reabsorption and potassium excretion increased significantly. The potassium content of cortex and outer medulla increased during hypercalcemia, whereas ouabain, an inhibitor of Na+, K+-ATPase reduces the potassium content. We conclude that hypercalcemia does not inhibit transcellular RNa in the diluting segment by a direct effect on the Na+, K+-ATPase or the mitochondria, but by interfering with the coupled NaCl transport across the luminal cell membrane.

Animals↗
PubMed1984

Renal venous and urinary PGE2 output during intrarenal arachidonic acid infusion in dogs.

Inferences about total renal (venous and urinary) PGE2 output from determinations of urinary excretion rates (U PGE2 V) cannot be made unless the distribution of PGE2 between renal venous plasma and urine is known. Therefore, in the present study on intact kidneys of anesthetized dogs both urinary excretion of PGE2 and the renal venous output (the product of plasma flow and venous concentration of PGE2) was determined during low and high rates of renal PGE2 synthesis. PGE2 was measured in urine and arterial and renal venous plasma by radioimmunoassay during the following conditions: (1) Hydropenia. In the control condition U PGE2 V averaged 0.041 +/- 0.012 pmol/g . min and varied between 4 and 70% of the total PGE2 output. With infusion of arachidonic acid (AA, 160 micrograms/kg . min) into the renal artery total PGE2 output increased from 0.18 +/- 0.03 to 3.23 +/- 0.51 pmol/g . min, whereas arterial concentrations of PGE2 were unchanged. The urinary fraction still varied between 6 and 46% of total renal PGE2 output. (2) High urine flows caused by mannitol, saline or saline and ethacrynic acid (ECA) infusion. These procedures did not stimulate total renal PGE2 output and the urinary fraction varied between 4 and 49%. ECA combined with saline infusion increased the urinary fraction significantly to 34.7 +/- 4.0%. AA increased the total PGE2 output as during hydropenia, but the urinary fraction fell to 13% in 13 dogs and was unchanged at about 8% in six dogs. On average the urinary fraction of total PGE2 output was significantly lower than in hydropenia. Thus, the urinary fraction of total renal PGE2 output is not constant, and urinary excretion of PGE2 does not give reliable information about renal synthetic rates of prostaglandins.

Animals↗
PubMed1984

Relationship between PGE2 and renin release in dog kidneys. Effects of afferent arteriolar dilation and adrenergic stimulation.

To study the relationship between PGE2 and renin release from the kidney, examinations were performed on anesthetized dogs during afferent arteriolar dilation. This condition is known to increase renin release and enhance the stimulatory effects on renin release of beta-adrenergic agonists, such as isoproterenol. Afferent arteriolar dilation induced by constricting the renal artery or occluding the ureter increased PGE2 and renin release before, but not after, indomethacin administration. Isoproterenol infusion during afferent arteriolar dilation increased renin release but not PGE2 release both before and after indomethacin administration. Phenylephrine, an alpha-adrenergic agonist, which also induces afferent arteriolar dilation, increased PGE2 and renin release at control blood pressure but not when the afferent arterioles already were dilated by ureteral occlusion. We conclude that afferent arteriolar dilation caused by renal arterial constriction, ureteral occlusion or infusion of phenylephrine increases prostaglandin synthesis which stimulates renin release. The effect of isoproterenol on renin release is independent of prostaglandin synthesis.

Animals↗
PubMed1984

Intramuscular fluid pressure during isometric contraction of human skeletal muscle.

Intramuscular fluid pressures were recorded in the vastus medialis of seven healthy male volunteers. Pressures were measured simultaneously at three different sites in the muscle by a catheter-tip transducer with extremely low volume-displacement characteristics and by two extracorporeal transducers connected to slit catheters. All three recording systems gave qualitatively similar results provided the catheters had inner diameters exceeding 0.53 mm and allowed measurement of pressures lasting as short as 1 s. Wick catheters yielded slower responses than slit catheters. At any position intramuscular fluid pressure increased linearly with force up to maximal voluntary contraction (MVC). However, slopes of these curves varied greatly mainly because the pressure was also a linear function of the distance from the fascia. The highest recorded pressure was 570 Torr. At prolonged submaximal contractions intramuscular fluid pressure oscillated independent of contraction force. The linearity of both the pressure-force relationship and the pressure-depth relationship is compatible with a simple model based on the law of Laplace because the muscle fibers are curved during contraction in this muscle. It is hypothesized that blood flow is first compromised deep in the muscle where pressure is highest and in general at lower stress or tension in short bulging muscles with great curvature of the fibers compared with long slender ones.

Adolescent↗
PubMed1984

Glycolate causes the acidosis in ethylene glycol poisoning and is effectively removed by hemodialysis.

Six male patients with severe ethylene glycol poisoning were studied with respect to the origin of the metabolic acidosis. The plasma concentrations of ethylene glycol were 4-41 mmol/l and treatment included alkali, ethanol and hemodialysis. Plasma analysis by isotachophoresis and whole blood lactate determinations showed that glycolate (17.0-29.3 mmol/l), lactate (1.4-6.2 mmol/l) and beta-hydroxybutyrate (less than or equal to 1.8 mmol/l) were present in elevated concentrations contributing to the acidosis. Oxalate (less than or equal to 0.33 mmol/l), glyoxylate (less than 0.2 mmol/l) and formate (less than 0.4 mmol/l) concentrations were negligible and did not contribute to any significant degree to the acidosis. The elevated plasma glycolate concentration was highly correlated to the anion gap (r = 0.923) and the glycolate made up for 96.1% (n = 6, range 84.7-108.8) of the increased anion gap. We conclude that glycolate accumulation is the main reason for the metabolic acidosis in ethylene glycol poisoning. The mean dialysator (1.6 m2) clearances of glycolate at a blood flow of 200 ml/min in two patients were 137 ml/min (n = 9, SD +/- 8, range 125-149) and 144 ml/min (n = 11, SD +/- 8, range 133-158). By applying first order kinetics during hemodialysis a volume of distribution of glycolate of 0.55 l/kg was found, assuming that the dialysator clearance equals the total body clearance of glycolate. Thus glycolate, the probable main metabolite of ethylene glycol, is efficiently removed by hemodialysis.

Acidosis↗
PubMed1983

Formate concentrations in plasma from patients poisoned with methanol.

Formate and methanol were quantified in blood samples from 11 untreated methanol-poisoned subjects. The range for whole blood methanol concentrations was 0-137 mmol/l and for plasma formate concentrations 0.4-17.1 mmol/l. Simultaneously determined acid-base status and serum electrolyte concentrations allowed assessment of the relative importance of formate accumulation for the acidosis. The plasma formate concentration was highly correlated to both the calculated anion gap (r = 0.833), the bicarbonate concentration (r = 0.852) and the negative base excess (r = 0.865). The accumulation of formate fully accounted for the increase in the anion gap and the fall in plasma bicarbonate, whereas the negative base excess values were about 22% higher than the plasma formate concentration. We conclude that formate accumulation is the main or only reason for acidosis in the early, uncomplicated stages of methanol poisoning. Lactate may appear at more advanced stages.

Acid-Base Imbalance↗
PubMed1983

Toxicokinetics of formate during hemodialysis.

During hemodialysis in a methanol poisoned patient, formate elimination followed first order kinetics with a plasma half-life of formate of 165 min. The mean dialysator (1.6 m2) clearance of formate was 148 ml/min (n = 8, SD +/- 11, range 128-161) at a blood flow of 215 ml/min. By applying first order kinetics, a volume of distribution of 0.5 l/kg was found, assuming that the dialysator clearance equals the total body clearance of formate. Formate, the main toxic agent in methanol poisoning, is thus probably more effectively removed by hemodialysis than methanol. This fact, and the very slow endogenous methanol elimination during appropriate ethanol treatment, should be considered when deciding on the treatment of a methanol poisoned patient presenting with metabolic acidosis.

Adult↗
PubMed1983

A model for quantitative sampling of myocardial venous blood in the pig.

A lack of good models for studies of myocardial metabolism prompted us to develop a model which allows the continuous measurement of myocardial blood flow and sampling of adequate amounts of coronary sinus (c.s.) blood without admixture of blood from the right atrium, with the working heart in situ. In the pig the left azygos vein drains into the c.s. and can easily be cannulated after thoracotomy. Thus, a shunt to the right atrium can be established by closing the entrance of the c.s. into the right atrium by a stitch ligature. More than 90% of shunt flow originates from the left ventricular myocardium. It is presently shown that establishing the shunt does not compromise myocardial flow, and there are no observable changes in left ventricular pressure, flow or dimensions. Myocardial flow in the drained and adjacent regions, as determined by injections of microspheres, and flow determined by electromagnetic flowmetry on the shunt are all identical. The model is stable during aortic constriction and isoproterenol infusion which induce expected changes in myocardial flow- and oxygen consumption. Thus, the model described is suitable for hemodynamic and metabolic studies of the left ventricular myocardium with the working heart in situ.

Animals↗
PubMed1982

Lack of stimulation of renal (Na+ +K+)-ATPase by thyroid hormones in the rabbit.

The effect of 1-3,5,3'-triiodothyronine (T3) and thyroxine (T4) on (Na+ +K+)-ATPase activities was examined in rabbit kidneys because in this tissue almost 80% of the metabolism is connected to active sodium transport. T3-receptor concentrations were estimated as 0.62 and 0.80 pmol/mg per DNA in the cortex and outer medulla, respectively. A dose of 0.5 mg T3/kg body weight for 3 days increased basal metabolic rate by almost 60%, and the mitochondrial 1-alpha-glycerophosphate dehydrogenase activity was increased by 50% in both the cortex and medulla. (Na+ +K+)-ATPase activity in the liver was raised by almost 50%. However, no changes in (Na+ +K+)-ATPase activities or binding sites for [3H]ouabain in either the kidney cortex or medulla could be observed. T4 at 16 mg/kg daily for 14 days was also without effect on renal (Na+ +K+)-ATPase activities. Furthermore, the response to T3 was absent at high sodium excretion rates induced by unilateral nephrectomy and extracellular volume expansion. Thus, despite stimulation of basal metabolic rate and renal 1-alpha-glycerophosphate dehydrogenase activity by T3 and T4, the (Na+ +K+)-ATPase activity in the rabbit kidney is identical in euthyroid and hyperthyroid states. However, thyroid hormones prevent the normal natriuretic response to extracellular volume expansion.

Animals↗
PubMed1982

Metabolic acidosis and changes in water and electrolyte balance after maximal exercise.

The purpose of this investigation was to study lactate production and the consequent changes in acid-base status, and in water and electrolyte balance, in response to 1 min of maximal exercise in sprint- and endurance-trained subjects. So far, the results from only two subjects (one sprinter and one marathon runner) have been analysed. The rate of lactate production was higher in the sprinter than in the marathon runner, as shown by peak blood lactate concentrations of 20.8 and 13.3 mM for the two subjects, respectively. Arterial blood pH fell from 7.43 to 7.14 in the sprinter and from 7.44 to 7.23 for the marathon runner. The metabolic acidosis was partly compensated for by a lowering of arterial CO2 tension by 0.0775 kPa per 1 mM drop in base excess. In each subject large changes in water and electrolyte balance occurred. Haematocrit increased dramatically in both subjects, and the calculated decrease in plasma volume was 20% for the marathon runner and 30% for the sprinter. In each subject sodium was removed from the circulation in amounts sufficient to keep the plasma sodium concentration constant. Plasma potassium concentration was unrelated to the state of acidosis, being 2.5 mM above the resting concentration immediately after maximal exercise, and dropping by 3 mM in the subsequent 2-3 min of recovery during prevailing acidosis. The degree of lactic acidosis was large in both subjects, although more severe in the sprinter than in the endurance runner. However, buffer capacity and compensatory mechanisms were largely similar in both subjects.

Acidosis↗
PubMed1982

Energetics of tubular sodium reabsorption sensitive to ethacrynic acid and ouabain.

Ouabain reduces renal oxygen consumption more extensively than ethacrynic acid despite similar natriuretic effects. Therefore, ethacrynic acid, which does not inhibit Na-K-ATPase, might stimulate energy metabolism unrelated to net sodium reabsorption. Experiments were performed on anesthetized dogs that had received isotonic saline intravenously corresponding to 10% of body wt and acetazolamide (100 mg.kg-1 i.v.). Subsequent infusion of ouabain in nine dogs (120 nmol.kg-1 intrarenally) reduced sodium reabsorption and oxygen consumption in parallel, giving a delta Na/delta O2 ratio of 18.0 +/- 1.1. With ethacrynic acid (3 mg.kg-1 i.v.) in six other dogs the delta Na/delta O2 ratio averaged 24.5 +/- 1.4. In a third group of five dogs, ouabain administered after ethacrynic acid reduced sodium reabsorption and oxygen consumption to the same levels as when ouabain was given alone. Thus, the high oxygen consumption remaining after ethacrynic acid can be inhibited by ouabain. We propose that ethacrynic acid generates a futile cycling of sodium by Na-K-ATPase across the basolateral cell membrane that is not apparent as net sodium reabsorption and is stopped by ouabain.U

Absorption↗
PubMed1981

Transcellular and intercellular transport of anions in the kidney tubules of dogs.

Fractional reabsorption of 4 anions was measured in anesthetized dogs either during inhibition of bicarbonate-dependent intercellular NaCl transport by acetazolamide or mannitol, or during inhibition of transcellular NaCl reabsorption in the diluting segment by ethacrynic acid or ouabain. When administered subsequent to ethacrynic acid, acetazolamide reduced fractional reabsorption of SCN, Br, Cl and I by 0.28 +/- 0.03, 0.28 +/- 0.02, 0.27 +/- 0.03 and 0.31 +/- 0.03. Mannitol given after ethacrynic acid reduced fractional reabsorptions by 0.23 +/- 0.04, 0.20 +/- 0.04, 0.20 +/- 0.05 and 0.20 +/- 0.05, respectively. Thus, the bicarbonate-dependent reabsorption system does not discriminate between these anions. Ethacrynic acid reduced fractional reabsorption of SCN, Br and Cl by 0.28 +/- 0.05, 0.24 +/- 0.03, 0.22 +/- 0.03 in one group, by 0.32 /+- 0.04, 0.34 +/- 0.03, 0.31 +/- 0.04 in another group, with significantly smaller reductions for I, 0.07 +/- 0.03, in both groups. Ouabain reduced fractional reabsorption of Br, Cl and I by 0.48 +/- 0.04, 0.46 +/- 0.04 and 0.24 +/- 0.03, respectively. Thus, anion permeability or transport affinity for bromide, chloride and iodide are equal both for inter- and transcellular transport, while iodide transport is slow along the transcellular route. No specific transport mechanism for chloride was detected.

Absorption↗