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Biomedical subjects

E Mikkelsen

Publications and source records attributed to E Mikkelsen.

At least 55 records · Page 3Linked to original sources
PubMed1979

Effects of digoxin on islated human mesenteric vessels.

Digoxin had contractant effects on isolated, human mesenteric arteries and veins. Veins were more sensitive to this action of the glycoside than arteries. The contractions were not affected by phentolamine or by washing with a digoxin-free solution. However, they were abolished by the calcium antagonist nifedipine, and by washing with a calcium-free medium. In the presence of digoxin, the maximum response to noradrenaline (1.8 x 10(-5) M) increased markedly in both arteries and veins, and the concentration-response curve for the amine was displaced to the left. Immersion of vein preparations in calcium-free solution for 30 min. abolished the digoxin contracture; an increase in extracellular calcium restored the response. Changes in extracellular potassium concentration caused changes in tension in tension of the mesenteric veins similar to those previously demonstrated in peripheral veins--both in the presence and in the absence of digoxin. It is concluded that digoxin contracts mesenteric vessels by a direct action on the muscle cells, and potentiates the contractant effects of noradrenaline. These effects are dependent on the availability of extracellular calcium. Mesenteric vascular reactions caused by changes in extracellular potassium are influenced by digoxin.

Aged↗
PubMed1979

Effects of digoxin in isolated human pulmonary vessels.

In isoalted human pulmonary arteries and veins the contractile response to noradrenaline (1.8 X 10(-5)M) was 33 +/- 7.4% and 20 +/- 4.5% (Mean +/- S.E.M.) of that induced by potassium (127 mM). A variable degree of spontaneous contractile activity was recorded in the vein preparations. This activity was abolished by nifedipine (2.9 X 10(-6)M). Digoxin (10(-6)M) induced contractions in pulmonary vessels. In the arteries, the digoxin contraction developed slowly and reached a maximum amplitude of 90 +/- 4% (Mean +/- S.E.M.) of the potassium evoked contraction. In the veins, the amplitude of the digoxin contraction was 32 +/- 5% of that induced by potassium. Digoxin (10(-6)M) also increased the maximum response to noradrenaline and potassium in both arteries and veins. In the arteries, the noradrenaline and potassium contractions increased to 211 +/- 6.8% and 145 +/- 8.9 of control, and in the veins to 169 +/- 13.5% and 163 +/- 9.9%, respectively. Nifedipine in concentrations which completely relaxes arterial and venous preparations contracted by potassium, had only a slight relaxing effect on digoxin induced contraction. It is concluded that digoxin increases the tension in pulmonary arteries and veins, and increases the maximum response to noradrenaline and potassium in both types of vessels. The digoxin induced contraction is highly resistant to blockade of extracellular calcium influx.

Adult↗
PubMed1979

Effects of digoxin on isolated human peripheral arteries and veins.

In isolated human crural arteries and veins, digoxin induced slowly developing, long-lasting contractions. These contractions were not diminished by alpha-adrenoceptor blockade or by washing, but were abolished by the calcium antagonist nifedipine. In the presence of digoxin, the maximum contractile responses to noradrenaline (18 microM) and potassium (127 mM) markedly increased, and the glycoside shifted the noradrenaline concentration-response curve to the left. Immersion of vein preparations in calcium-free medium for 30 min. abolished the digoxin contraction, whereas responses could still be elicited by potassium and noradrenaline. A change of the extracellular potassium concentration from 4.6 to 6.9 and 9.2 mM caused relaxation, and a further increase to 13.8 mM contracted the preparations. After pretreatment with digoxin (1 micronM), a potassium change from 4.6 to 1.15 mM caused relaxation and all concentrations exceeding 4.6 mM produced contraction. It is concluded that digoxin has a direct contractile effect on isolated human crural vessels, and that this effect is dependent on the extracellular calcium concentration. In the presence of the glycoside, the responses to noradrenaline and potassium are potentiated. Vascular responses to changes in extracellular potassium concentration are influenced by digoxin.

Adolescent↗
PubMed1979

Comparison of the in vitro effects of prazosin, nifedipine, and dihydralazine in isolated human mesenteric and crural vessels.

The inhibitory and relaxing effects of prazosin, nifedipine, and dihydralazine on contractions induced by noradrenaline (NA), or potassium (K+), were investigated in isolated human crural and mesenteric arteries and veins. Vascular ring preparations were suspended in organ baths and isometric tension was recorded. Prazosin was the most potent of the drugs in counteracting NA-induced contractions in all types of vessels except crural veins, in which the effect of nifedipine was the more pronounced. On K+-induced contractions prazosin was completely devoid of relaxing or inhibitory effects, whereas nifedipine was by far the most effective of the investigated drugs. Nifedipine had a more marked effect in venous than in arterial preparations from the peripheral circulation, but no such difference was seen in mesenteric vessels. Dihydralazine was found to have a very low potency in all types of vessels, and no difference between the effects on arterial and venous preparations was found. The results suggest that the in vitro effects of prazosin, nifedpine, and dihydralazine are different from those observed in vivo. Thus, the balance between the effects on arteries and veins in vitro was quite different from those reported in clinical studies on the three vasodilatators. The results give no support to the hypothesis of an unspecific vasodilatating effect of prazosin. The clinical usefulness of dihydralazine cannot be explained from the poor in vitro effects of the unmetabolized drug.

Adolescent↗
PubMed1978

Pharmacokinetics of furosemide in anephric patients and in normal subjects.

The pharmacokinetics of furosemide 40 mg i.v. were compared in 7 anephric patients and in 7 normal subjects. The average serum clearance was 66 ml/min in the patients and 219 ml/min in the normal subjects, and the corresponding weight corrected clearances were 1.33 ml/min . kg and 2.96 ml/min . kg. Binding to serum proteins was significantly decreased in the anephric subjects, in whom a significant negative correlation was found between the percentage binding and the volume of distribution VDSS. In the patients, but not in the normal subjects, there was a significant positive correlation between VDSS and serum clearance. Both in normal and anephric individuals 4-chlor-5-sulphamoyl-anthranilic-acid (CSA) was found, but there was no evidence of special accumulation either of CSA or anthranilic acid in the anephric patients. In the patients the initial increase in serum concentration of sodium and protein followed by a more conspicuous decrease were more pronounced, but none of the changes were statistically significant.

Adolescent↗
PubMed1978

Effects of verapamil and nitroglycerin on contractile responses to potassium and noradrenaline in isolated human peripheral veins.

Isolated ring preparations of human vein were contracted by potassium (127 mM) and noradrenaline (1.8 X 10(-5) M). The potassium-induced contracture developed more rapidly and had a higher maximum amplitude than that produced by noradrenaline. Addition of phentolamine (10(-5) M) reduced the amplitude of the potassium contracture by 22% and abolished the noradrenaline response. Verapamil and nitroglycerin relaxed preparations contracted by potassium and noradrenaline, and, when added prior to stimulation, reduced the contractile responses to these agents. Both verapamil and nitroglycerin inhibited the contractile effect of noradrenaline more strongly than that of potassium. After immersion of the preparations for 30 min. in a calcium-free medium, the responses to potassium and noradrenaline were reduced to 21.3 +/- 2.5% and 7.1 +/- 0.8%, respectively, of the control. Addition of verapamil caused a further reduction of the response to potassium, but not of that to noradrenaline. Nitroglycerin caused a further reduction of the contractions induced by both agents. When the calcium concentration in the extracellular medium was increased from 0 to 4 mM, the contractile responses to potassium and noradrenaline returned to the control level. Both verapmil and nitroglycerin inhibited the contractile responses to calcium; the inhibiting effects of verapamil were significantly more marked than those of nitroglycerin. Tachyphylaxis to nitroglycerin was demonstrated on contractions induced by potassium, but not on noradrenaline-produced responses.

Adult↗
PubMed1978

Effects of extracellular calcium on potassium and noradrenaline induced contractions in the aorta of spontaneously hypertensive rats--increased sensitivity to nifedipine.

Isolated preparations of the thoracic aorta from spontaneously hypertensive rats (SHR) and normotensive Wistar rats (NWR) were contracted by noradrenaline (NA) 1.8 X 10(-5)M, and potassium (K+) 127 mM, after 30 min. pretreatment in a Ca++-free medium. In both SHR and NWR aortae, the contractions were markedly reduced; no significant differences were found between the two types of vessels in Ca++-free medium. On addition of Ca++, the contractions were restored to a significantly greater extent in the NWR than in the SHR aortae. In the presence of nifedipine 7.2 X 10(-9)M, the response to Ca++ was significantly more reduced in the SHR than in the NWR preparations. Relaxation of NA and K+ contracted preparations was induced by wash-out of the contractile agents, by addition of nifedipine 2.9 X 10(-8)M, and by introduction of a Ca++-free medium. After wash-out of NA, relaxation was slower in SHR than in NWR vessels. Relaxation induced by nifedipine and Ca++-free medium was more complete in SHR than in NWR preparations. After wash-out of K+, relaxation was more rapid in NWR than in SHR aortae. Nifedipine and Ca++-free medium induced relaxation was more complete in SHR than in NWR preparations. The results suggest that in the SHR aortae contraction induced by NA and K+ is more dependent on extracellular Ca++ than is the response in the NWR preparations; the SHR vessels are also more sensitive to the relaxing effects of nifedipine.

Animals↗
PubMed1978

The effect of nifedipine on isolated human peripheral vessels.

Isometric tension was recorded in ring preparations of human peripherial arteries and veins contracted by potassium (127mM) and noradrenaline (1.8 X 10(-5)M). In the veins, nifedipine had a marked relaxing effect on contractions induced by both agents, and also reduced the contractile amplitude when added prior to stimulation. The inhibiting effect of nifedipine was more marked on the potassium than on the noradrenaline-evoked responses. This was in contrast to verapamil, which inhibited the noradrenaline-induced contractions significantly more, than those produced by potassium. After immersion of the vein preparations in calcium-free medium for 30 min., the potassium contracture decreased to 26+/2.0% (mean +/ S.E.M.) of the response in normal Krebs solution, and the noradrenaline-evoked to 7.1+/0.8%. The responses to both agents were completely restored when the calcium concentration was increased from 0 to 4 mM. Nifedipine (1.5X10(-7)M) depressed the potassium contracture in calcium-free solution to 7.3+/1.6%, and the noradrenaline response to 5.5+/1.6%; on addition of calcium, the response elicited by potassium increased to 16+/1.7%, and that by noradrenaline to 56+/8.6%. Compared with its actions on the veins, the effect of nifedipine on the arterial preparations was less pronounced. In the arteries, too, the inhibiting effect of nifedipine was significantly more pronounced on the potassium than on the noradrenaline-induced contraction. Immersion for 30 min. in calcium-free medium reduced the response to potassium to 61+/6.0% and that to noradrenaline to 68+/5.6% of the control in normal Krebs. Nifedipine (2.9X10(-7)M) further reduced the potassium contraction to 20+/4.0%; the response to noradrenaline was unaffected, being 74+/6.4% of the control.

Adolescent↗
PubMed1978

Contractile effects of prostaglandin F2alpha on isolated human peripheral arteries and veins.

The effects of prostaglandin F2alpha (PGF2alpha 2.8 X 10(-7) --2.8 X 10(-5) M) on isolated segments of human peripheral arteries and veins were investigated. In both types of vessel, PGF2alpha had a concentration-dependent contracting effect. The contraction developed more slowly and had a longer relaxation time after washing than responses induced by noradrenaline or potassium. In the veins, the maximum response to the prostaglandin was 128 +/- 3.6% of that to potassium (P less than 0.01); in the arteries, the maximum amplitudes of PGF2alpha and potassium induced contractions were of similar magnitude. The arterial preparations were less responsive to PGF2alpha than to noradrenaline. On a molar basis, noradrenaline was approximately 10 times more potent than PGF2alpha. Veins, maximally contracted by noradrenaline or potassium, increased their tension further on addition of PGF2alpha. Similarly, preparations maximally contracted by PGF2alpha also showed a further increase in tension after addition of noradrenaline or potassium. The PGF2alpha induced contractions were not affected by alpha-adrenoceptor blockade (phentolamine, prazosin). The calcium antagonists verapamil and nifedipine relaxed preparations contracted by PGF2alpha, and reduced the responses in a concentration-dependent way when added 15 min. before the prostaglandin. Immersion for 30 min. in a calcium-free medium, reduced the PGF2alpha induced response in both arteries and veins. In the veins, but not in the arteries, the responses to potassium and noradrenaline were more reduced than that to PGF2alpha (P less than 0.01). Contractions induced by all agents were further depressed by verapamil and nifedipine after exposing the preparations to the calcium-free medium. It is suggested that PGF2alpha induces contraction both by enhancing the transmembrane flow of calcium, and by facilitating release of calcium from intracellular stores.

Adult↗
PubMed1977

Distribution, elimination and effect of furosemide in normal subjects and in patients with heart failure.

After furosemide 40 mg i. v. its plasma concentration was significantly higher during an 8-hour period in 6 patients with left sided heart failure than in 8 normal subjects. The plasma clearance was significantly lower in the patients than in the normal subjects--1.23 and 2.34 ml/kg/min, respectively. The apparently smaller volume of distribution in the cardiac patients (0.140 1/kg and 0.181 1/kg, respectively) was not significantly different. In the group of normal subjects, whose ages ranged from 27 to 74 years, no correlation was found between age and either plasma clearance or volume of distribution. In all the patients, the renal clearance of furosemide rose from the first to the second hour after the injection (average +/- SD)--39 +/- 17 and 77 +/- 51 ml/min. In normal subjects, the average values did not change--116 +/- 79 and 117 +/- 54 ml/min. The urinary excretion of furosemide and a metabolite (probably a glucuronide) was measured in 16 individuals. 24-hour urines from all the subjects investigated contained between 20 and 30 mg unchanged furosemide (average 25.2 mg). In addition, between 2.7 and 11.2 mg (average 6.7 mg) furosemide was excreted as the metabolite in five patients who had been treated with furosemide for at least the preceding 6 months. An average of 0.8 +/- 0.8 mg of the metabolite was found in 11 subjects who had not previously been treated with furosemide.

Adult↗
PubMed1977

Simultaneous determination of furosemide and two of its possible metabolites in biological fluids.

By the means of thin-layer chromatography (TLC) prior to fluorometry it was possible to determine furosemide (F) in plasma and urine with improved specificity. Antranilic acid (A) and 4-chlor-5-sulphamoyl-antranilic acid (CSA) could be determined simultaneously with F in plasma. In urine, only F and A could be determined quantitatively by this method. The sensitivity is 0.1 microgram/ml for F and 0.15-0.20 microgram/ml for A and CSA. By means of TLC prior to fluorometry the blank value for F was reduced in normal subjects and in different groups of patients, and its diurnal variation was eliminated. The average values of the plasma concentrations of F after the intravenous injection of 40 mg into 12 normal subjects were at all times found to be lower by the TLC method than by the fluorometric method without TLC. A higher plasma clearance and a lower volume of distribution were found for F when the values obtained by the TLC method were used for the calculation.

Chromatography, Thin Layer↗
PubMed1975

Assessment of verapamil in the treatment of angina pectoris.

A brief review is given of the pharmacological data of verapamil, which chemically shows a certain similarity to papaverine. The effect of the drug (80 mg) 3 times daily, on angina pectoris, as compared with placebo, was evaluated in a double-blind cross-over therapeutic trial with 4-wk periods in 47 patients. The incidence of attacks and the nitroglycerine consumption decreased in the second fortnight of the verapamil period by approximately 25% compared with the placebo period. An ergometer test showed a prolongation of the exerice time of 20%. The mean blood pressure and the heart rate fell under verapamil treatment if the patients had values which were relatively high in the placebo period. The increase in heart rate during exercise from two different resting levels showed a tendency to become more pronounced under treatment with verapamil than under placebo. The length of the P-Q intervals were not affected by verapamil. The mechanism of action in angina pectoris is discussed, but it is concluded that it is still not possible to explain it. Twelve Danish medical departments took part in the trial.

Aged↗