Biomedical subjects

K Winther

Publications and source records attributed to K Winther.

At least 73 records · Page 4Linked to original sources

PubMed1991

Beta 1-blockade and acute coronary ischemia. Possible role of platelets.

Although the benefit of beta-adrenergic blocking agents in acute coronary ischemia has been well documented, it is unclear whether the responsible mechanisms include the modification of platelet function. In recent studies, metoprolol appeared to reduce the total number and duration of episodes of silent ischemia in patients with stable coronary artery disease throughout the day. This effect was not associated with a change in baseline or circadian variability of the platelet aggregability. Since the treatment caused significant decreases in heart rate and blood pressure, the drug effect is more likely to be based on reduction of myocardial oxygen demand. Metoprolol, however, prevented a platelet aggregability increase and intracellular cAMP decrease during exercise stress testing in patients with stable angina pectoris. We speculate that this effect of beta 1-adrenergic blockade may be due to hemodynamic and neurohormonal changes, or possibly also to an increase in synthesis or release of platelet inhibiting substances.

Acute Disease↗

PubMed1990

Dose-dependent effects of verapamil and nifedipine on in vivo platelet function in normal volunteers.

The effects of 1 week of treatment with low and moderate doses of verapamil or nifedipine upon platelet function has been studied in 12 healthy volunteers. The ex vivo platelet aggregation threshold for ADP or adrenaline was not altered by verapamil or nifedipine. The plasma concentrations of beta-thromboglobulin and platelet factor 4 were significantly reduced by low but not by moderate doses of verapamil and nifedipine. Low doses of verapamil and nifedipine inhibit in vivo platelet activity in healthy volunteers.

Adenosine Diphosphate↗

PubMed1990

Exercise-induced platelet aggregation in angina and its possible prevention by beta 1-selective blockade.

Moderate exercise increased platelet aggregability of 12 middle-aged men with stable angina pectoris: the mean ADP threshold fell from 4.58 +/- 0.63 to 3.18 +/- 0.41 microM, P less than 0.01. Exercise did not, however, alter platelet aggregability in 12 healthy matched controls. Physical effort approximately doubled the plasma levels of adrenaline and noradrenaline in patients as well as in controls. Under the same conditions the cAMP content of platelets fell in the angina group from 20.86 +/- 1.86 to 17.78 +/- 1.71 pmol 10(-9) platelets, P less than 0.01, while there was no change in control levels. The fall of cAMP could account for the observed increase in platelet aggregability. We speculate that the increased aggregability of platelets in the exercising anginal subjects represents an imbalance between prostacyclin release and haemodynamic changes. The beta 1-selective blocker metoprolol, in usual therapeutic dosages, prevented the observed platelet changes probably by minimizing the haemodynamic disturbances and stimulating release of prostacyclin.

Adrenergic beta-Antagonists↗

PubMed1990

Platelet P1, P4-Di (adenosine-51) tetraphosphate (AP4A) in migraine patients before and during beta-adrenoceptor blockade.

P1,P4-Di(adenosine-51) tetraphosphate (AP4A) is a metabolically inactive nucleotide which can be released from platelet dense granules. This study was designed firstly, to investigate whether platelet content of AP4A was decreased in patients with classical migraine and secondly, whether the content of AP4A was changed by beta-adrenoceptor blockade. No significant difference in platelet dense granule content of AP4A, was observed between 10 migraine patients and 10 normal controls. Both metoprolol, a beta 1-selective blocker and propranolol, a non-selective beta-blocker significantly decreased the migraine attack rate. However, while propranolol significantly reduced the platelet content of AP4A, metoprolol did not. Therefore, the present data suggest that platelet dense granule release, as estimated by the content of AP4A is not of major importance in migraine.

Adenosine Triphosphate↗

PubMed1990

High urinary cAMP in hypertensives despite careful drug treatment--an epidemiological study from the Dalby population.

The correlation between serum calcium (S-Ca), plasma parathyroid hormone (P-PTH) and hypertension was determined in a population-based, cross-sectional study of carefully treated hypertensives (n = 391; diastolic blood pressure 90.2 mmHg; 57 years) compared with normotensive controls (n = 328; diastolic blood pressure 82.1 mmHg; 57 years). Levels of urinary cyclic-adenosinemonophosphate (U-cAMP), but not of plasma cAMP (P-cAMP), were higher (P less than 0.001) in hypertensives than in controls. This was the case regardless of the type of drug treatment and the blood pressure level that was reached. U-cAMP correlated with adrenaline in multivariate analyses. S-Ca levels were higher (P less than 0.001) and S-Mg levels were lower (P less than 0.001) in hypertensives than in controls. This was not explained by thiazide treatment. Thus, despite 'adequate' blood pressure reduction, substantial differences in S-Ca, S-Mg and U-cAMP still exist between hypertensives and normotensive controls.

Antihypertensive Agents↗

PubMed1990

LongoVital in the prevention of recurrent aphthous ulceration.

LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal based tablet enriched with recommended doses of vitamins. The present study was undertaken to investigate prevention of recurrent aphthous ulceration (RAU) during 6 months' daily intake of LV as compared with placebo in a double-blind, randomized clinical, cross-over 1-yr study. The population comprised 29 otherwise healthy minor RAU patients (18 F, 11 M), mean age 36 (18-67), with an estimated average number of recurrences the previous year of 12.8 (3-30). The number of recurrences was significantly reduced on LV the latter 4 of the 6 months (P less than 0.01) where 31% were totally free of recurrences. Subjective all-over evaluation of treatment period was significantly in favor of LV. LV induced no adverse reactions and is the first harmless systemic treatment which has proved better than placebo in the prevention of RAU.

Adolescent↗

PubMed1990

Immunomodulation by LongoVital in patients with recurrent aphthous ulceration.

LongoVital (LV) (DK. Reg. No. 5178/75) is a herbal based tablet enriched with recommended doses of vitamins. Peripheral lymphocyte subsets: T-helper/CD4 (OKT4+) and T-suppressor/cytotoxic/CD8 (OKT8+) were studied quantitatively in 31 otherwise healthy patients with minor recurrent aphthous ulceration (RAU) during 6 months' daily LV intake in a double-blind, randomized, crossover 1-year study. Fourteen had had LV during the first 6 months (GrA) and 17 LV during the latter 6 months (GrB). OKT4+ percentages increased significantly during the LV period in both groups (P less than 0.05). OKT8+ percentages increased in both groups, however, only significantly in GrA (P less than 0.05). It is concluded that LV acts as an immunostimulator in patients with RAU and that the increase in T-lymphocyte subsets may account for the previously reported benefit of LV in RAU prevention.

Adult↗

PubMed1990

Effect of disulfiram on the platelet function and fibrinolysis in healthy volunteers.

Disulfiram was studied for platelet and fibrinolytic activity in 12 healthy volunteers of both sexes (age 23-75 years). Placebo was given for 7 days, followed by disulfiram, 800 mg for 2 days and 400 mg for an additional 12 days. Finally, there was another placebo period of 14 days. With the exception of an initial platelet activation on day 2, no significant effects were found on the platelet variables studied: platelet aggregation with collagen, ADP and adrenaline, beta-thromboglobulin and platelet factor 4. Treatment for 14 days with disulfiram resulted in a decreased euglobulin clot lysis time: from 421 +/- 82 to 246 +/- 41 min (p less than 0.01). After an initial increase, plasminogen activator inhibitor activity was slightly decreased on disulfiram, from 8.4 +/- 1.6 on placebo to 6.0 +/- 1.2 U/ml (p less than 0.05) after 14 days of treatment. Plasminogen, fibrinogen and alpha 2-antiplasmin were unchanged. It is concluded that disulfiram can increase fibrinolytic activity in healthy subjects.

Adult↗

PubMed1989

Differential effects of non-specific beta-blockade and calcium antagonism on blood-clotting mechanisms.

The effects of non-selective beta-blockade (timolol, 5 mg twice daily) and calcium antagonism (isradipine, 2.5 mg twice daily) on heart rate, blood pressure, platelet aggregation, fibrinolytic activity, and platelet cyclic adenosine monophosphate content were investigated in 10 patients with mild hypertension in a randomized, placebo-controlled, double-blind study. Each patient served as his or her own control, taking each drug in turn for two weeks. Both drugs lowered blood pressure to the same degree. During timolol treatment, however, platelet aggregation increased whereas isradipine resulted in a shortening of the euglobulin clot lysis time (p less than 0.05), indicating increased fibrinolytic activity. Platelet aggregation and fibrinolytic activity are modified by cyclic adenosine monophosphate. Since beta-adrenoceptors are present on platelets and endothelial cells, the differences in platelet behavior and fibrinolytic activity may reflect a decreased cyclic adenosine monophosphate production caused by non-selective beta-adrenoceptor blockade.

Adult↗

PubMed1989

Effect of felodipine, a new calcium channel antagonist, on platelet function and fibrinolytic activity at rest and after exercise.

Fourteen healthy male volunteers (age 21-29 years, mean 23.7 years) were given placebo for 14 days followed immediately by felodipine 5 mg b.d. for a further 14 days. After each period of treatment blood for analysis was taken at rest and after exercise on a cycle ergometer. Platelet aggregation, plasma beta-thromboglobulin (B-TG), platelet factor 4 (PF-4), adrenaline and noradrenaline, and serum thromboxane B2 (TXB2), 6-keto-prostaglandin (F1 alpha (6-keto-PGF1 alpha), and euglobulin clot lysis time (ECLT), were measured on each occasion. The ECG, heart rate and blood pressure were monitored during the exercise tests. After felodipine therapy there was a significant decrease in the plasma level of PF-4 and B-TG at rest. This effect was maintained during exercise. There was no significant change in platelet aggregation, ECLT, TXB2 or 6-keto-PGF1 alpha at rest or during exercise. Irrespective of therapy, the plasma levels of adrenaline and noradrenaline were increased and the ECLT was decreased when measured immediately after exercise. Thus, felodipine in modest therapeutic dosage decreases the plasma levels of B-TG and PF-4, indicating an inhibitory effect on platelet on release. The effect also occurred during exercise. Felodipine did not change fibrinolytic activity or the production of TXB2 or 6-keto-PGF1 alpha.

Adult↗

PubMed1988

Differential effects of timolol and metoprolol on platelet function at rest and during exercise.

Ten male patients suffering from stable angina pectoris were studied at rest and immediately after exercise during treatment either with timolol (a non-selective beta-blocker) or with metoprolol (a beta 1-selective blocker). Timolol induced a significant increase in platelet aggregation and a reduction in platelet cyclic AMP, and it also raised the plasma adrenaline at rest and during exercise as compared to the pre-treatment level. Metoprolol had none of these effects. Prior to medication and during metoprolol treatment, exercise led to an increase in the peripheral platelet count, whereas timolol was associated with a reduction of platelets during physical effort. Neither drug affected platelet thromboxane B2 at rest. During exercise, its level was not affected in the pre-treatment period or during metoprolol treatment but it was sharply increased by timolol therapy.

Adrenergic beta-Antagonists↗

PubMed1988

Effects of three beta-blockers with different pharmacodynamic properties on platelet aggregation and platelet and plasma cyclic AMP.

The effects of three different types of beta-adrenoceptor blocking agents on platelet aggregation and on platelet and plasma cyclic AMP content have been studied in 14 patients with mild hypertension given each drug in turn for two weeks. The drugs were a non-selective blocking agent with high intrinsic sympathomimetic activity, pindolol, the nonspecific blocking agent propranolol, and the beta 1-selective metoprolol. The threshold values of ADP and adrenaline for irreversible platelet aggregation were significantly higher for pindolol and metoprolol than for propranolol. The cyclic AMP content of platelets was higher during pindolol and metoprolol than during propranolol treatment. Pindolol produced a substantial increase in plasma cyclic AMP relative to the other two drugs. Thus, platelet aggregation and cyclic AMP formation are influenced by beta-adrenoceptor blockade in proportion to intrinsic sympathomimetic activity and affinity for different beta-adrenoceptor subtypes.

Adenosine Diphosphate↗

PubMed1988

Effect of auranofin on human platelet aggregation, release of serotonin, and cyclic-AMP formation.

Auranofin (Aur), a new oral gold compound valuable in treatment of patients with rheumatoid arthritis, is known to have an inhibitory effect on ADP- and epinephrine-induced platelet aggregation in vitro. This may be of clinical importance as platelets participate in thrombus formation and are believed to act as proinflammatory cells in the diseased synovial tissue of rheumatoid arthritis. In the present in vitro study it was confirmed that Aur inhibits both ADP- and adrenaline-induced platelet aggregation in a dose- and time-dependent manner. In addition, a time- and dose-dependent decrease in platelet release of serotonin as well as a pronounced increase in the production of cyclic-AMP was found to result from Aur incubation. Aur's inhibitory effect on platelets is probably mediated through cyclic-AMP stimulation. Future studies of Aur's platelet inhibitory effect should investigate the mechanisms by which cyclic-AMP formation is increased, since this may be of importance also for Aur's action on other cell types.

Adenosine Diphosphate↗

PubMed1988

The effect of nifedipine and captopril on platelet activation and prostanoid production in essential hypertension.

Sixteen patients with mild to moderate essential hypertension were randomly allocated to 6 weeks of treatment with nifedipine and captopril in a crossover trial. Nifedipine and captopril lowered blood pressure significantly both 2 and 12 h after the last dose. Apart from an increased heart rate 2 h after the last dose of nifedipine, the heart rate did not change. Platelet factor 4, thromboxane B2, 6-keto prostaglandin F1 alpha (6-keto PGF1 alpha) and cyclic (c)AMP did not change during either therapy. There was no correlation between the plasma concentration of nifedipine measured 2 and 12 h after the last dose and the platelet variables described above. The findings show that nifedipine and captopril in therapeutic doses do not affect platelet activity in patients with mild to moderate essential hypertension.

Adult↗

PubMed1988

The effect of ageing on human platelet sensitivity to serotonin.

Twelve healthy young volunteers (mean age 21, range 18-27 years) and 12 elderly people (mean age 77, range 72-86 years) were tested regarding platelet aggregation induced by adrenaline, ADP and serotonin. The serum levels of thromboxane B2 (TXB2) and serum 6-keto-PGF1 alpha and the plasma level of adrenaline and cyclic AMP (cAMP) were also measured. Platelet aggregation induced by adrenaline and ADP increased significantly in the elderly compared with the young group (P less than 0.05 and P less than 0.02, respectively). There was a substantial and highly significant increase in the response of platelets from elderly people to serotonin (P less than 0.01). No alteration was observed in the serum level of TXB2 or 6-keto-PGF1 alpha. Plasma adrenaline increased in the old group, but plasma cAMP was unaffected. As serotonin is known to amplify adrenaline- and ADR-induced platelet aggregation, the considerable increase in platelet sensitivity to serotonin could be an important factor in the increased adrenaline and ADP-induced platelet aggregability of elderly people.

Adenosine Diphosphate↗

PubMed1988

The effect of exercise on platelet beta-adrenoceptor function and platelet aggregation in healthy human volunteers.

UNLABELLED: Plasma levels of adrenaline and noradrenaline, platelet cyclic-AMP (cAMP) content, platelet aggregation, platelet release of beta-thromboglobulin, and platelet factor 4 and serum content of thromboxane B2(TXB2) and 6-keto-PGF1 alpha were measured in 12 healthy male volunteers (age 38-72, mean 54.2 years) who were tested at rest and immediately after five min light cycle exercise. The plasma levels of adrenaline and noradrenaline increased significantly after exercise (P less than 0.01). The platelet cAMP level was not changed by exercise. The functional capacity of platelet beta-adrenoceptors, determined as cAMP production after beta-adrenoceptor stimulation in vitro, decreased highly significantly after exercise in all 12 volunteers (P less than 0.01). No alteration was observed in platelet aggregation induced by adrenaline or in platelet release of beta-thromboglobulin or platelet factor 4. No change was observed in the serum levels of TXB2 and 6-keto-PGF1 alpha. IN CONCLUSION: light cycle exercise results in a decreased functional capacity of platelet beta-adrenoceptors, but has no effect on platelet aggregation or platelet release. This might indicate a concomitant and equal decreased functional capacity of platelet alpha-adrenoceptors.

Adult↗

PubMed1988

Platelet function in classic migraine during attack-free periods.

It has been reported that migraine sufferers have an enhanced platelet activity, as well as an enhanced thromboembolic risk. In this study, 12 subjects with classic migraine were compared with 12 age- and sex-matched controls. The following parameters were tested: platelet aggregation; platelet content of ADP, ATP and cyclic-AMP (cAMP); plasma levels of cAMP, 6-keto-PGF1 alpha and thromboxane B2, serum levels of TxB2 and lipids. ADP- and adrenaline-induced platelet aggregation, platelet content of ADP, ATP and cAMP did not differ significantly between the groups. Platelets from migraine subjects, however, showed a decreased beta-adrenoceptor response to stimulation with isoprenaline when determined as platelet cAMP production in vitro. The prostacyclin metabolite 6-keto-PGF 1 alpha was significantly decreased in the migraine group. No difference were observed in TxB2. Plasma lipids were similar, except that the migraine cases had higher levels of LDL-cholesterol. These data do not confirm a general platelet malfunction in migraine patients, but suggest a decreased functional capacity of platelet beta-adrenoceptors and an altered metabolism of prostacyclin and LDL-cholesterol.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Are there reasons to believe that the antihypertensive effects of serotonin (S2) antagonists are age-related?

The potential age-dependent antihypertensive responses to serotonin antagonists are critically reviewed with regard to the following considerations: Are they beneficial to the patient? Are they related to age-dependent changes in pharmacokinetics or pharmacodynamics? Are they necessarily true? The paper is focused on ketanserin, which is the only major serotonin (S2) antagonist that has yet been used to any extent in patients. Based on the available data in the literature, we conclude that the age-related antihypertensive effect of ketanserin is a beneficial phenomenon since it does not seem to be paralleled by a corresponding increase in side effects. Furthermore, the mechanism seems to be due to changes in the pharmacodynamics of the drug on the platelet or vascular smooth muscle since there is only negligible alteration in pharmacokinetics occurring with advanced age. Although multiple independent trials or pooled data strongly indicate that the efficacy of ketanserin increases with age, not all investigators agree. In our opinion, the interindividual variation in drug response is more characteristic to the drug than the relationship to age. Therefore, the selection of patients for ketanserin therapy should be based on individual testing in addition to age grouping.

Aged↗