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Biomedical subjects

N A Klitgaard

Publications and source records attributed to N A Klitgaard.

At least 73 records · Page 4Linked to original sources
PubMed1986

Sodium homeostasis in lymphocytes and blood pressure alterations before and during salt restriction in normotensives and in essential hypertensives.

Blood pressure, lymphocytic sodium content and sodium efflux were studied in hypertensive and normotensive subjects during salt restriction. Diastolic blood pressure decreased significantly in both groups. In essential hypertension the initial high lymphocyte sodium content decreased during salt depletion with a simultaneous decrease in absolute sodium efflux probably due to primary changes in sodium influx. Conversely intralymphocytic sodium content increased in normotensive subjects, which may be caused by an inhibition of the sodium, potassium pump. Our findings indicate that autoregulatory mechanisms with regard to lymphocyte sodium metabolism differs between hypertensive and normotensive subjects.

Adult↗
PubMed1986

Effect of oral salt loading on blood pressure and lymphocyte sodium metabolism in borderline hypertension.

A randomized double-blind cross-over trial was performed to test the effects of oral salt loading (normal diet + 200 mmol NaCl/day for 4 weeks followed by normal diet + 400 mmol/day for 1 week) against placebo on blood pressure and lymphocyte sodium homeostasis in 10 young borderline hypertensive men, genetically predisposed for essential hypertension. Salt loading caused no significant changes in blood pressure levels, lymphocyte sodium content and efflux. In conclusion, our subjects seem insensitive to a few weeks of excessive salt intake.

Blood Pressure↗
PubMed1986

Non-interaction between nifedipine and digoxin.

In order to evaluate a possible interaction between digoxin and nifedipine, we studied steady state digoxin pharmacokinetics before and during oral coadministration of nifedipine in eight healthy subjects. Mean plasma digoxin concentration was 0.68 +/- 0.15 ng/ml during control conditions versus 0.74 +/- 0.13 ng/ml (NS) after two weeks of nifedipine coadministration. Nifedipine caused no significant changes in either renal digoxin clearance (173.6 +/- 25.9 versus 173.1 +/- 33.2 ml/min) or 24-hour urinary recovery of digoxin (164.7 +/- 25.7 versus 183.8 +/- 29.2 micrograms/24 hrs). Our findings support earlier observations that nifedipine coadministration is not associated with any significant alteration of digoxin pharmacokinetics.

Adult↗
PubMed1985

Rubidium uptake of mononuclear leukocytes from normotensive and borderline hypertensive first degree relatives to patients with essential hypertension.

Uptake of 86Rubidium of mononuclear leukocytes (MNL) was used as a measure of cellular sodium-potassium pump activity. 86Rb-uptake was determined with the pump stimulated mainly from inside the cells by sodium as well as with a combined stimulation from inside by sodium and from outside by Rb. In the first case there was an increased pump activity in MNL from borderline hypertensive offspring of hypertensive patients (BHO), and this may be related to an increased number of pump sites observed previously (10). Estimation of maximal pump activity (Vmax) of MNL suggested that Vmax of each pump site in MNL from BHO may be decreased compared to control value of MNL from healthy normotensive subjects.

Humans↗
PubMed1985

Effect of quinine on plasma digoxin concentration and renal digoxin clearance.

In order to explore the digoxin-quinine interaction, digoxin steady state pharmacokinetics was studied before and during quinine coadministration in seven healthy subjects. Quinine (250 mg/day) increased mean plasma digoxin concentration from 0.64 +/- 0.12 to 0.80 +/- 0.18 ng/ml (p less than 0.05) within one week. Urinary digoxin recovery rose from 154.0 +/- 18.8 to 181.5 +/- 22.6 micrograms/24 h (p less than 0.01), whereas renal digoxin clearance was unaltered in the presence of quinine (181.5 +/- 24.2 vs. 174.1 +/- 26.5 ml/min). An increase in quinine dose (to 750 mg/day) caused further increments in plasma digoxin levels, whereas renal digoxin clearance remained unchanged. Quinine elevates plasma digoxin concentrations in a stepwise fashion probably due to an impairment of extrarenal digoxin clearance.

Adult↗
PubMed1985

Lymphocyte cell membrane handling of sodium and blood pressure control during salt restriction in normotensive subjects.

Intralymphocytic sodium and potassium concentrations, 22Na efflux rate constants (EFRC) and blood pressures (BPs) were studied in nine normotensive young males without a history of essential hypertension before, during and after 5 weeks of severe sodium depletion. Diastolic and median BPs decreased significantly as estimated by both ambulatory and home readings. A slight decrease in intralymphocytic potassium content and a significant increase in sodium content was found. Measurements of 22Na-EFRC were reduced by 15% in the ouabain-sensitive component of the sodium pump, while the absolute sodium efflux stayed constant during sodium depletion. These results are evidence of a primary inhibition of the sodium pump during salt restriction in normotensives.

Adult↗
PubMed1983

Influence of verapamil on the inotropism and pharmacokinetics of digoxin.

Verapamil has been demonstrated to inhibit the elimination of digoxin and to increase its steady state plasma level by 60-80%. Animal studies suggest that verapamil abolishes the intropic action of other drugs such as ouabain and dopamine. The clinical consequences of this drug interaction were investigated by examining the inotropic activity of single doses of digoxin (assessed from systolic time intervals), with and without coadministration of verapamil. Verapamil decreased total-body clearance of digoxin from 4.68 +/- 0.41 to 3.29 +/- 0.26 ml/min/kg (p less than 0.001) and increased the plasma half-life of the drug from 33.50 +/- 2.38 to 41.31 +/- 2.27 h (p less than 0.01). Verapamil had no influence on the base-line values of the systolic time intervals. Both in the absence and presence of verapamil, digoxin caused significant shortening of the total electromechanical systole and the left ventricular ejection time. However, compared to control conditions, the decay of these changes was slower in the presence of verapamil, in parallel with the prolongation of the plasma half-life of digoxin. A linear relationship was established between reductions in the systolic time intervals and the computer-derived concentration of digoxin in the deep compartment. These regression lines, which represent the concentration-effect relationships of the inotropism of digoxin, were not affected by verapamil. Thus, verapamil per se had no measurable effect either on base-line contractile function of the heart or on digoxin-induced inotropism. The elevated plasma digoxin concentration induced by verapamil appears cardioactive in terms of inotropism.

Adult↗
PubMed1983

Influence of quinidine on the binding of [3H]-ouabain and [3H]-digoxin by human lymphocytes.

To explore the molecular basis of the glycoside-quinidine interaction, the in vitro effect of quinidine on the binding of [3H]-ouabain and [3H]-digoxin to Na + K + ATPase receptors on human mononuclear cells was investigated. The maximum [3H]-ouabain binding capacity was 45.7 +/- 9.4 X 10(3) molecules/cell in pure lymphocyte preparations (n = 8) and 75.5 +/- 7.3 X 10(3) molecules/cell in mixtures of mononuclear cells (n = 8). These parameters were not influenced by 10(-5)M quinidine. In eight equilibrium experiments with pure lymphocytes, the dissociation constant of [3H]-ouabain increased from 0.79 +/- 0.26 X 10(-8)M in the absence of 10(-5)M quinidine to 1.56 +/- 0.74 X 10(-8)M in its presence (p less than 0.01), indicating that the affinity of the drug was decreased. Similar findings were observed using mixed mononuclear cells. In five uptake and release experiments, quinidine decreased the association rate constant of [3H]-ouabain from 3.15 +/- 0.36 X 10(4)M-1 X s-1 to 2.01 +/- 0.37 X 10(4)M-1 s-1 (p less than 0.01), whereas the dissociation rate constant was not affected. A therapeutic concentration of quinidine does not affect the number of glycoside receptors on lymphocytes, but it does appear to reduce fractional receptor occupancy by both [3H]-ouabain and [3H]-digoxin at lower tracer concentrations. This finding is compatible with the clinical observation that quinidine reduces the distribution volume of digoxin.

Adult↗
PubMed1983

Effect of quinidine on digoxin bioavailability.

To evaluate the possible effect of quinidine on digoxin bioavailability, the steady state digoxin kinetics was examined with and without concomitant quinidine therapy, in 7 cardiac patients after simultaneous administration of oral digoxin and intravenous [3H]-digoxin. In the presence of quinidine, the absorption rate constant of digoxin (ka) increased from 2.72 +/- 1.04 to 3.53 +/- 1.34 h-1 (p less than 0.05), whereas lag time and peak time decreased from 0.16 +/- 0.10 to 0.05 +/- 0.04 h (p less than 0.05) and from 0.92 +/- 0.27 to 0.69 +/- 0.19 h (p less than 0.02), respectively. Predose plasma digoxin increased from 0.41 +/- 0.25 to 0.70 +/- 0.31 ng/ml (p less than 0.02), while peak plasma digoxin increased from 0.93 +/- 0.34 to 1.63 +/- 0.46 ng/ml (p less than 0.02). The systemic availability of digoxin increased from 68.48 +/- 13.35 to 79.09 +/- 14.89% (p less than 0.05) in the presence of quinidine. Quinidine had no effect on the biotransformation pattern of digoxin, as assessed by thin layer chromatography. Quinidine increases the rate and extent of digoxin absorption, and this interaction contributes significantly to the elevation in plasma digoxin during both its distribution and elimination phases.

Aged↗
PubMed1983

Verapamil-induced changes in digoxin kinetics and intraerythrocytic sodium concentration.

Verapamil increases plasma digoxin concentration by about 60% to 80%. To explore the clinical consequences of this interaction, we evaluated single-dose digoxin kinetics along with repeated measurements of intraerythrocytic sodium concentration in eight healthy subjects before and during verapamil coadministration. Verapamil reduced mean total body clearance of digoxin from 4.68 +/- 0.41 to 3.29 +/- 0.26 ml/min/kg and prolonged digoxin biologic t1/2 from 33.5 +/- 2.4 to 41.4 +/- 2.3 hr. These kinetic changes were associated with a greater elevation of intraerythrocytic sodium concentration than controls. Verapamil had no effect on intraerythrocytic sodium content. In vitro experiments revealed no influence of verapamil on the number of glycoside receptors on human lymphocytes. Since intracellular sodium concentration has proved to correlate closely with clinical signs of digoxin toxicity, our indicate that verapamil is likely to increase the risk of digoxin-induced arrhythmias.

Adult↗
PubMed1983

Effects of physical activity and immobilization on plasma digoxin concentration and renal digoxin clearance.

Plasma digoxin concentration and renal digoxin clearance were determined during 2 hr of normal physical activity and during 2 hr of complete immobilization in eight healthy subjects on steady-state digoxin dosing. Mean plasma digoxin concentration rose from 0.64 +/- 0.13 ng/ml during physical activity to 1.04 +/- 0.19 ng/ml (63%) after 2 hr of rest. Resumption of physical activity resulted in gradual decline of plasma digoxin, and subsequent strenuous exercise reduced the value to preimmobilization level. Mean renal digoxin clearance was reduced from 168.4 +/- 18.7 ml/min during physical activity to 137.2 +/- 32.7 ml/min during rest whereas creatinine clearance was unchanged. The rise in plasma digoxin during rest is presumed to be due to changes in the binding of the drug to tissues such as skeletal muscles. Our findings indicate that attention should be given to the state of physical activity when kinetic studies are performed or when digoxin therapy is monitored by means of plasma digoxin analysis.

Adult↗
PubMed1983

Ouabain-binding and 86rubidium-uptake in lymphocytes of normal and borderline hypertensive subjects.

In borderline hypertensives cellular sodium concentration seems to be increased, indicating that cellular abnormalities are present in the early course of essential hypertension. In order to study the mechanisms underlying this finding the number of sodium/potassium pump sites and the cation pump activity were studied in lymphocytes of nine borderline hypertensives (27 (20-36) years) and nine controls (28 (20-36) years). Maximum 3H-ouabain binding and 86Rb-uptake were taken as measures of the number of pump sites and cation pump activity, respectively. The median number of sodium/potassium pump sites was 49.6 X 10(3) molecules/cell in the BH group compared to 32.4 X 10(3) in the control group (P less than 0.01). Median 90 min 86Rb-uptakes were 54.0 pmol/10(6) cells in BH subjects and 39.4 in controls (P less than 0.10). The increased number of sodium/potassium pump sites and the tendency to increased cation pump activity in lymphocytes of BH subjects in vitro may be interpreted as an adaptive change possibly induced by a circulating natriuretic substance.

Adult↗