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Biomedical subjects

V Manninen

Publications and source records attributed to V Manninen.

At least 91 records · Page 5Linked to original sources
PubMed1987

Pirmenol in the termination of paroxysmal supraventricular tachycardia.

The effects of pirmenol in terminating paroxysmal supraventricular tachycardia were studied in 25 patients. Pirmenol was administered as 1 or 2 injections of 50 mg to 17 patients during a spontaneous attack, or as a 50-mg bolus followed by steady infusion of 2.5 mg/min in 8 patients during a tachycardia that was induced electrophysiologically. Termination was successful in 11 of 17 patients who had a spontaneous attack and in 3 of 8 patients who had induced tachycardia. Pirmenol was effective in 3 of 5 patients with atrioventricular nodal reentrant mechanism, but in none of 3 patients with a reentrant tachycardia with a retrogradely conducting atrioventricular bypass tract. Conversion to sinus rhythm was achieved in 14 of 25 patients (56%). No hemodynamic adverse effects occurred. Pirmenol increased the atrial effective refractory period, but had little effect on conduction in the atrioventricular node and His-Purkinje system. Reentry was abolished through a block in the retrograde part of the dual atrioventricular nodal pathway, which is typical of class I antiarrhythmic agents.

Adolescent↗
PubMed1987

Conversion of paroxysmal atrial fibrillation to sinus rhythm by intravenous pirmenol.

The acute effects of pirmenol on atrial fibrillation were investigated in 40 patients with paroxysm of atrial fibrillation. Patients were randomized to receive either pirmenol, 50 or 100 mg intravenously, or placebo. Patients with congestive heart failure or a history of sinus node disorder were excluded. Sinus rhythm was achieved in 12 of 20 patients in 2 to 16 minutes after pirmenol administration and in 3 of 20 patients in the control group within 1 hour. A nodal escape rhythm during sinus slowing was observed in 1 patient. No sinus arrest, atrioventricular conduction disturbance or hypotension appeared. Pirmenol has an antifibrillatory effect on the atria. Sinus rhythm is restored rapidly after intravenous administration. Treatment of atrial fibrillation of recent onset was well tolerated in patients accepted for the study.

Adrenergic beta-Antagonists↗
PubMed1987

Clinical and lipid metabolic effects of unopposed oestrogen and two oestrogen-progestogen regimens in post-menopausal women.

No differences in the clinical effects on climacteric complaints of an unopposed oestrogen and two oestrogen-progestogen regimens were observed in a double-blind cross-over study. Only 4 out of 18 women with an intact uterus had withdrawal bleeding during oestradiol valerate (2 mg/day) treatment alone, but 14 out of 18 had regular bleeding during the two oestrogen-progestogen regimens (oestradiol/medroxyprogesterone acetate and oestradiol/levonorgestrel (LNG], each of which prevented the development of endometrial hyperplasia. High-density-lipoprotein cholesterol (HDL-CH) concentration remained 6% above the initial level and the atherogenic index (low-density-lipoprotein (LDL) cholesterol to HDL-CH ratio) improved significantly during the oestradiol/medroxyprogesterone acetate regimen, while the HDL-CH concentration fell by 20% in relation to the initial level and there was a deterioration in the atherogenic index during the oestradiol/LNG regimen. The data suggest that both of these oestradiol/progestogen combinations are clinically as effective and well-tolerated as oestradiol alone, but that combined oestradiol/medroxyprogesterone acetate causes fewer adverse lipid metabolic effects than the oestradiol/LNG combination.

Cholesterol↗
PubMed1987

Minimal doses of digoxin: a new marker for compliance to medication.

A direct and objective method of measuring compliance to medication is presented. Digoxin is used as a marker in capsules of either gemfibrozil or placebo with a minimal dose of 4.4 micrograms twice a day. Compliance is estimated by measuring the ratio of urinary digoxin to creatinine concentration. By choosing two cut-off points of this ratio patients who are taking their capsules regularly and those who have taken no capsules at all could be distinguished from others. Reduced dosage was easily detected in the marker results. During regular intake of three quarters of the dose, 53% of the samples would have classified the patient to the good compliance group. With half of the dose, 24% of samples and with a quarter of the dose, 5% of samples would have classified the subject to good compliance. Since the digoxin marker was planned for compliance measurements in the Helsinki Heart Study, a primary prevention study of coronary heart disease, it was tested under the conditions of a clinical trial. Digoxin concentrations were measured using a routine method normally applied to serum but shown to be valid for urine. The results of the urinary assays were not affected by storage at room temperature, as occurs during postal transport of samples, nor were they affected by freezing, routinely used for the storage of samples in clinical trials. The results therefore suggest that the digoxin marker represents a particularly effective method to study compliance to medication during such long-lasting clinical investigations.

Clinical Trials as Topic↗
PubMed1987

Comparison of the digoxin marker with capsule counting and compliance questionnaire methods for measuring compliance to medication in a clinical trial.

During the last quarter of the third year of follow-up in the Helsinki Heart Study, compliance to medication was measured in 1739 patients with digoxin used as a marker substance, capsule counting and a compliance questionnaire. The estimates for good and poor compliers were found to be highly dependent on the method and the cut-off points chosen for the compliance allocation. The methods studied here were more reliable for the detection of poor rather than good compliance. In the poor compliance group, defined with the use of the digoxin marker, there was 39% of subjects who returned less than 5% of their capsule dosage or reported a deviation less than 5%. In the good compliance group, defined by the digoxin marker, only 11.8% of patients either returned or reported a deviation of at least 25% of their dose. The compliance was better when measured by the questionnaire than by capsule counting. The size of the poor compliance group, defined by the use of the digoxin marker, was as large as a group who had returned at least 27% of their capsule dose and a group who had reported a deviation of 11% or more from their dosing schedule. The size of the group allocated to the good compliance category by the use of the digoxin marker was equivalent in size to a group of patients who had returned less than 15% of their prescribed dose or reported a deviation of less than 6% from their prescription. When the strictest criteria for the combination of all three methods were used, 57% of subjects were classified as good and 31% as poor compliers to medication in the third year of the primary prevention trial designed to reduce the incidence of coronary heart disease.

Capsules↗
PubMed1987

Effects of indomethacin on hormonal and blood pressure responses to captopril in spontaneously hypertensive rats.

The possible role of vasodilatory prostanoids in the antihypertensive action of captopril was investigated in spontaneously hypertensive rats (SHR). Captopril (100 mg/kg/day for 5 days) decreased systolic blood pressure and increased water consumption, urine excretion and plasma renin activity (PRA). It also enhanced the urinary excretion of the prostacyclin metabolite 6-keto-PGF1 alpha, but did not change the excretion of PGE2. Indomethacin (3 mg/kg/day), given both alone and in combination with captopril, reduced markedly the urinary excretions of 6-keto-PGF1 alpha and PGE2 but did not alter PRA, compared with corresponding groups without indomethacin. The suppression of prostanoid synthesis caused by indomethacin did not affect the antihypertensive effect of captopril or the basal blood pressure in SHR. Neither did indomethacin influence drinking or urine excretion in SHR not receiving captopril, but it reduced the dipsogenic and diuretic effects of captopril. The results suggest that captopril augments the production of vasodilatory prostacyclin. Yet prostanoids have no significant role in the antihypertensive mechanism of captopril in SHR.

6-Ketoprostaglandin F1 alpha↗
PubMed1986

Effect of activated charcoal on hypercholesterolaemia.

Seven patients with hypercholesterolaemia were treated for 4 weeks with activated charcoal at a dose of 8 g three times a day. Plasma total cholesterol and LDL-cholesterol decreased by 25% and 41%, respectively, whereas HDL-cholesterol increased by 8%. Side-effects were negligible.

Blood Pressure↗
PubMed1986

A comparison of different formulations and dosage administrations of gemfibrozil.

To assess the lipid-regulating effects of 2 new gemfibrozil formulations, a nonblind parallel group comparison was performed using Finnish industrial workers with types IIA and IIB primary hyperlipoproteinemia. In all, 670 subjects were evaluated; 416 had total low density lipoprotein (LDL) cholesterol (serum total cholesterol--high density lipoprotein [HDL] cholesterol) levels greater than or equal to 200 mg/dl and thus qualified for the screening period of the trial. During this 2-month period, the subjects were placed on an optimal diet according to their Fredrickson phenotype. Those whose total LDL levels remained greater than or equal to 200 mg/dl until the end of the 2-month period (n = 321) were admitted to the active drug phase of the trial and randomized to 1 of 3 treatment groups. Group 1 received the standard gemfibrozil dosage of two 300-mg capsules 2 times a day, for a total daily dosage equal to 1,200 mg. Group 2 also received a 1,200-mg daily dose, given as a 600-mg tablet of gemfibrozil 2 times a day. Group 3 received a once-a-day dose of two 450-mg tablets in the evening. Preliminary results show that the alternate gemfibrozil formulations are thus far equal to the standard gemfibrozil dosage in their effects on blood lipids. Substantial decreases have been noted in serum cholesterol, serum triglycerides, LDL cholesterol and serum apolipoprotein B. The 3 formulations also produced similar increases in HDL cholesterol and its subfractions HDL2 and HDL3, as well as in serum apolipoproteins AI and AII.

Administration, Oral↗
PubMed1986

Acute haemodynamic effects of the antiarrhythmic agent pirmenol in cardiac patients: a comparison with lidocaine.

The acute haemodynamic effects of pirmenol, a new Class 1 antiarrhythmic agent, were investigated in a double-blind comparison with lidocaine and placebo. Three groups of 10 patients each received either pirmenol as a 50 mg intravenous injection followed by a 2.5 mg min-1 infusion, or lidocaine as a 75 mg injection followed by a 3 mg min-1 infusion, or placebo. Mean plasma pirmenol concentrations during the 30 min infusion period were 2.3-2.5 mg l-1, and were considered to be therapeutically effective. Compared to measurements taken during a baseline phase of 15 min duration, pirmenol increased heart rate by 10 beats min-1 (P less than 0.001) and mean arterial pressure (MAP) by 5 mmHg (P less than 0.001). It also increased systemic vascular (P less than 0.05) and pulmonary arterial resistances (P less than 0.01). Left ventricular end-diastolic pressure (LVEDP) was not increased significantly. Cardiac index and left ventricular work index remained unchanged. Lidocaine induced a comparable increase in MAP (6 mmHg; P less than 0.001) and elevated LVEDP (2.8 mmHg; P less than 0.05) and did not affect left ventricular work index. Echocardiographic left ventricular ejection fraction was reduced more by pirmenol (-0.05; P less than 0.001) than by lidocaine (-0.03; P less than 0.05), but the greater reduction may partly be explained by the increase in heart rate. Primenol did not induce excessive circulatory responses or side-effects in any patient. Intravenous administration of pirmenol results in increased heart rate and afterload but has little effect on preload. The myocardial depressant effect is relatively slight, and comparable to that of lidocaine.

Adult↗
PubMed1986

Conversion of paroxysmal atrial fibrillation to sinus rhythm by intravenous pirmenol. A placebo controlled study.

The efficacy of pirmenol (a class I antiarrhythmic agent) as a converter of paroxysmal atrial fibrillation was investigated. Forty patients without congestive heart failure or a history of sinus node disorder were randomly allocated to receive either intravenous pirmenol (50-100 mg) or placebo in a double blind trial. In 12 of 20 patients sinus rhythm was restored 2-16 minutes after pirmenol, and in 3 of 20 patients in the control group it returned within one hour. A nodal escape rhythm was seen during sinus slowing in one patient, but in other patients there was no sinus arrest, atrioventricular conduction disturbance, or hypotension. The ventricular rate was slightly increased in patients in whom sinus rhythm was not restored by pirmenol. The results indicate that pirmenol has an antifibrillatory effect on the atria. Sinus rhythm was restored rapidly after intravenous administration. It was well tolerated in patients with atrial fibrillation of recent onset.

Anti-Arrhythmia Agents↗
PubMed1986

Inhibition of angiotensin-converting enzyme with quinapril (CI-906): investigation of antihypertensive mechanisms in spontaneously hypertensive rats.

Treatment for 8 days with a new nonsulfhydryl angiotensin-converting enzyme inhibitor, quinapril (CI-906), produced a marked and progressive reduction in the blood pressure of spontaneously hypertensive rats. Quinapril was given p.o. in a dose of 20 or 40 mg/kg once daily. Both doses increased plasma renin activity and decreased the urinary excretion of aldosterone. These results, together with a marked decrease in serum angiotensin-converting enzyme activity, indicate that the drug produced a considerable fall in circulating angiotensin II. The urinary excretion of vasopressin was not altered by the smaller dose of quinapril but was reduced by the larger dose, which increased water intake and urine excretion. Quinapril did not affect plasma kininogen or the urinary excretion of kallikrein. The urinary excretion of neither the prostacyclin metabolite 6-keto-prostaglandin F1 alpha nor the thromboxane metabolite thromboxane B2 were altered by the drug. However, quinapril did produce a temporary decrease in the excretion of prostaglandin E2, the effect passing off with the continuation of the treatment. These data indicate that vasodilatory prostanoids do not contribute to the blood pressure lowering effect of quinapril in spontaneously hypertensive rats. The inhibition of the renin-angiotensin system is probably the principal mechanism of the drug's antihypertensive action, but these results do not rule out the possibility that an increase in vasodilatory kinins may also be involved.

Aldosterone↗
PubMed1986

Effects of two structurally different angiotensin-converting enzyme inhibitors, captopril and quinapril (CI-906), in rats with one-kidney deoxycorticosterone-salt hypertension.

Possible non-renin antihypertensive actions of two angiotensin-converting enzyme inhibitors, the sulfhydryl compound captopril and the new nonsulfhydryl inhibitor quinapril (CI-906), were compared in rats with one-kidney deoxycorticosterone-salt hypertension. Plasma renin activity remained low during the 12-day treatments and showed very strong suppression of the renin-angiotensin system. Quinapril did not influence the rapidly increasing blood pressure. Although captopril tended to reduce the development of hypertension (p = 0.08), it did not have any significant effect, either. The results indicate that these ACE inhibitors with different chemical structures lack any significant blood pressure lowering mechanism in severe deoxycorticosterone-salt hypertension, a model in which they cannot act through their established antihypertensive mechanism, the inhibition of the renin-angiotensin system.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1985

Antiarrhythmic efficacy of pirmenol in the treatment of premature ventricular complexes.

We assessed the antiarrhythmic effectiveness, therapeutic plasma concentrations and adverse effects of pirmenol in 16 patients with frequent (mean 933 h-1) premature ventricular complexes (PVC). Progressive increase in dose to a maximum of 200 mg twice daily suppressed PVC in a majority of patients. By preset criteria 11 patients (69%) exhibited an effective suppression of PVCs whereas in 5 patients (31%) the suppression was inadequate despite therapeutic plasma concentrations. The responders exhibited an 87% mean reduction of PVCs and a 97% reduction in repetitive PVC. This therapeutic effectiveness was verified against placebo by repetitive 24-hour ECG monitorings recorded in a double-blind cross-over fashion. The plasma trough concentration during the effective dose averaged 1.31 +/- 0.67 mg-1 (SD). The efficacy was maintained with the twice daily regimen despite an elimination half life of 6.3 +/- 1.7 h (SD) but a slight decrease in PVC suppression was observed towards the end of the administration interval. Pirmenol was well tolerated but aggravation of the arrhythmia occurred in one patient who shared an associated excessive prolongation of the Q-T interval, a feature observed with quinidine-like class I agents.

Anti-Arrhythmia Agents↗
PubMed1985

The Gemfibrozil Study.

In clinical studies in dyslipidaemic patients gemfibrozil has produced falls in LDL and VLDL of 10-20% and 30-50%, respectively, but a rise in HDL of 15-25%. Gemfibrozil also produces increases in both Apo AI and AII, and in kininogen and prekallikrein. Side-effects are not a major problem. The Helsinki Heart Study has compared the effects of gemfibrozil with those of placebo in a group of 4080 dyslipidaemic Finnish men aged 40-55. The results are not yet available but there is reason to believe that the probable level of coronary risk reduction will be at least as great as that reported by the Lipid Research Clinics Study Coronary Primary Prevention Trial (LRC-CPPT).

Adult↗
PubMed1984

Interaction between propranolol and electron donors in altering the calcium ion-dependent potassium ion-permeability of the human red blood cell membrane.

Both propranolol and the electron donors ascorbate plus phenazine methosulfate increase the K+-permeability of the red blood cell membrane. The present investigation examined whether these effects were additive. Contrary to expectations, propranolol added after electron donors sharply inhibited the K+ (86Rb) efflux induced by such donors, without forming new K4 channels analogous to those induced by propranolol in intact red blood cells. The inhibitory effect of propranolol may be due to generalized disturbances of membrane structures necessary for the functioning of the K+ channels organized in the presence of reducing agents. In contrast, the electron donors added after propranolol caused a further stimulation of the 86Rb loss from the propranolol-treated red cells. The combined effect of these drugs therefore depends on the order of their addition. The possible mechanism of their interaction is briefly discussed.

Ascorbic Acid↗
PubMed1984

Differing effects of two angiotensin converting enzyme inhibitors, captopril and CI-906, on diuresis and the urinary excretion of kallikrein and prostaglandins in spontaneously hypertensive rats.

The effects of two angiotensin I converting enzyme inhibitors on the kallikrein-kinin system and prostanoids were studied in spontaneously hypertensive rats. The doses of captopril were 20, 50 and 100 mg/kg X day given twice daily, and those of CI-906 20 and 40 mg/kg once daily. Both drugs were equally effective in reducing the systolic blood pressure. Captopril increased urine volume dose-dependently (up to 3-fold with the largest dose). Only the larger dose of CI-906 was slightly diuretic. Captopril decreased the 24-h urinary excretion of kallikrein, while the excretion of the prostacyclin metabolite 6-keto-PGF1 alpha was increased markedly and that of T X B2 to a lesser extent. CI-906 had no effect on the 24-h urinary excretion of kallikrein, 6-keto-PGF1 alpha and T X B2. Both drugs tended to reduce PGE2 excretion. Captopril and CI-906 did not alter plasma kininogen levels. The marked renal effects of captopril may be caused by a strong local inhibition of converting enzyme in the kidneys. Captopril is mainly excreted unchanged in urine, and it is secreted actively by the proximal tubular cells. CI-906 is eliminated predominantly by biliary excretion. It is also possible that direct stimulation of prostacyclin formation by captopril may be involved in the diuretic action of the drug. However, as it was shown with CI-906, the increase in urine flow and the associated changes in urinary kallikrein and prostanoids are not necessary for the antihypertensive effect caused by the inhibition of converting enzyme.

6-Ketoprostaglandin F1 alpha↗