Biomedical subjects

V Manninen

Publications and source records attributed to V Manninen.

At least 73 records · Page 4Linked to original sources

PubMed1990

Effects of single doses of quinapril and atenolol on autonomic nervous function and exercise capacity in healthy volunteers.

The effects of single oral doses of the angiotensin converting enzyme (ACE) inhibitor quinapril (CI-906) 40 mg and the cardioselective beta-adrenoceptor blocker atenolol 100 mg on sympathetic and parasympathetic function and on exercise capacity have been studied in 8 healthy young men. The trial followed a double-blind, placebo controlled, randomized cross-over design, with at least one week between treatments. Blood pressure (BP) and heart rate (HR) at rest were slightly reduced by atenolol but were not affected by quinapril. Atenolol impaired the sympathetically mediated increases in HR and BP caused by standing, immersion of the hand into melting ice, the Valsalva manoeuvre and isometric forearm exercise. Quinapril did not influence those responses nor the vagally mediated bradycardia of the diving reflex. Atenolol, however, augmented the vagal bradycardia, presumably by sympathetic inhibition. In a dynamic bicycle ergometer test with a stepwise increasing work load, exercise performance was decreased by atenolol but not by quinapril. Inhibition of the renin-angiotensin system by quinapril was shown by a marked decrease in serum ACE activity and a several-fold increase in plasma renin activity (PRA). Atenolol produced a moderate reduction in PRA. Before or during exercise, plasma noradrenaline and adrenaline were not influenced by either drug. The results indicate that, unlike the atenolol-induced beta-adrenoceptor blockade, ACE inhibition by a single dose of quinapril had no clear effect on autonomic nervous function or exercise capacity.

Adult↗

PubMed1990

Effect of gemfibrozil on the concentration and composition of serum lipoproteins. A controlled study with special reference to initial triglyceride levels.

We investigated the modulating effect of serum total triglycerides on the lipid composition of various lipoproteins, and on the response to gemfibrozil treatment. This placebo controlled study was conducted blind in 60 participants of the Helsinki Heart Study. An inverse relationship was observed between cholesterol content in all lipoprotein fractions and serum total triglyceride level. Gemfibrozil, in addition to changing the absolute amounts of lipoprotein lipids, also normalized the qualitative abnormalities associated with hypertriglyceridemia. Gemfibrozil increased the level of HDL-cholesterol with the main effect on HDL3-subfraction. The observed reduction in LDL-cholesterol was dependent on the initial triglyceride level.

Cholesterol, HDL↗

PubMed1990

Reduction in Q wave myocardial infarctions with gemfibrozil in the Helsinki Heart Study.

The Helsinki Heart Study demonstrated a 34% (p less than 0.02) reduction in the incidence of cardiac end points (myocardial infarction and cardiac death) with the use of gemfibrozil compared with the use of a placebo in dyslipidemic middle-aged men. The major effect was confined to nonfatal myocardial infarctions. In this study we analyzed the effect of gemfibrozil therapy on the incidences of Q wave and non-Q wave infarctions, since the long-term prognoses of these two types of myocardial infarction may be different. The analyses indicated a 45% reduction (P less than 0.02, log-rank test) in the cumulative incidence of Q wave infarctions in the gemfibrozil group without a statistically significant effect on either the rate of non-Q wave infarctions or of coronary deaths. The reduction in the incidence of Q wave infarctions became evident during the second half of the 5-year study period.

Creatine Kinase↗

PubMed1990

Lipoproteins and coronary heart disease in the Helsinki Heart Study.

The changes in serum lipids in men treated with gemfibrozil in the Helsinki Heart Study, a controlled primary prevention trial of coronary heart disease, varied according to baseline lipid levels, type of dyslipidaemia, and treatment compliance. In subjects with the best treatment compliance, gemfibrozil induced mean decreases of 14% in total cholesterol, 15% in low density lipoprotein (LDL)-cholesterol, and 45% in triglycerides, and a mean increase of 14% in high density lipoprotein (HDL)-cholesterol, compared with placebo. These changes were significantly greater than those observed in the entire cohort. There was a strong association between baseline levels and the response to treatment (expressed as the difference in mmol l-1 between the gemfibrozil- and placebo-treated groups) for LDL-cholesterol and triglycerides. In contrast, the corresponding change in HDL-cholesterol was not dependent on the baseline level. Ultracentrifuge analysis in a subsample of the cohort revealed that gemfibrozil raised the level of HDL3-cholesterol but had little effect on HDL2-cholesterol. The gemfibrozil-associated reduction in the incidence of definite coronary events varied according to lipid values at baseline and their changes during treatment. The greatest reductions were seen in subjects with low initial HDL-cholesterol and high initial triglycerides. In the gemfibrozil group, the increase in HDL-cholesterol and decrease in LDL-cholesterol were associated with significantly lower risk of coronary events.

Coronary Disease↗

PubMed1990

HDL-cholesterol as a risk factor in coronary heart disease. An update of the Helsinki Heart Study.

The aim of the Helsinki Heart Study, a 5-year primary prevention placebo-controlled study involving 4081 dyslipidaemic men (aged 40 to 55 years), was to investigate if increasing high density lipoprotein (HDL)-cholesterol plasma levels and decreasing low density lipoprotein (LDL)-cholesterol levels would reduce the incidence of coronary heart disease. Gemfibrozil 600mg twice daily was administered to induce these changes in lipoprotein levels. Baseline HDL-cholesterol levels in the study group were similar to those in the general population. Data from patients treated with placebo were analysed to investigate the influence of HDL-cholesterol levels on the incidence of coronary heart disease. Using the number of cardiac end-points per 1000 person-years to indicate the risk of coronary heart disease, it was clear that elevated HDL-cholesterol levels reduced the risk of coronary heart disease while the incidence increased at low HDL-cholesterol levels. This relationship was not altered when the effect of HDL-cholesterol levels was analysed jointly with other coronary risk factors (age, smoking or blood pressure). A weaker association was seen between LDL-cholesterol and risk of coronary heart disease, and triglycerides appeared to have no significant effect on the incidence of the disease. The data clearly suggest that HDL-cholesterol is a strong predictor of the incidence of coronary heart disease in the placebo group of the Helsinki Heart Study.

Cholesterol↗

PubMed1990

Thallium and rubidium permeability of human and rat erythrocyte membrane.

Transport of Tl+ and Rb+ in human and rat erythrocytes was investigated in the presence of ouabain. The chloride-dependent cotransport of Tl+, Rb+ and Na+ was precluded by replacement of Cl- by NO3-. The inward and outward rate constants for the residual fluxes of the cations were determined by measuring the transport of 204Tl and 86Rb in double label experiments. The rate of passive transport of Tl+ exceeded that of Rb+ by one-two orders of magnitude in human as well as rat erythrocytes. The membrane barrier which contributes to the maintenance of ion gradients was shown not to be a barrier for Tl+ which easily penetrates the membrane by an unknown mechanism. In rat erythrocytes the barrier for Rb+ was 10-15 times weaker than that in human red blood cells, while the corresponding ratio of rat/human Tl+ permeabilities was about 1.8-2.0. It follows that Tl+ permeability is only slightly affected by factors modifying the permeability to alkali cations. The increase of temperature from 20 degrees to 37 degrees C resulted in a three-fourfold stimulation of the passive transport of Tl+ both in human and rat erythrocytes. The movement of Tl+ and Rb+ through the erythrocyte membrane differed substantially from their diffusion along the excitable membrane channels characterized both by poor Tl+/K+ selectivity and weak temperature dependence.

Animals↗

PubMed1989

Relation between baseline lipid and lipoprotein values and the incidence of coronary heart disease in the Helsinki Heart Study.

A 34% reduction in the incidence of definite coronary heart disease events was observed in dyslipidemic men treated with gemfibrozil in the Helsinki Heart Study, a controlled 5-year, double-blind primary prevention trial for coronary heart disease. Over the entire study period, gemfibrozil therapy induced mean decreases of 10% in serum total cholesterol levels, 11% in low-density lipoprotein (LDL) cholesterol, 35% in triglyceride levels, and a mean increase of 11% in high-density lipoprotein (HDL) cholesterol level, compared with placebo. The differences in percentage changes in LDL cholesterol between gemfibrozil- and placebo-treated men varied among Fredrickson hyperlipoproteinemia types; after 1 year of treatment the difference was greatest for type IIA hyperlipoproteinemia (14 percentage units) and smallest for IIB hyperlipoproteinemia (3 percentage units). The treatment-associated changes in HDL cholesterol and triglycerides did not differ materially between the 3 hyperlipoproteinemia types, when calculated in the same way. The gemfibrozil-associated reduction in incidence of definite coronary events varied among Fredrickson types and among tertiles of baseline HDL cholesterol and triglycerides. The greatest rate reductions were seen in subjects with type IIB hyperlipoproteinemia, low initial HDL level or high initial triglycerides. These results suggest that subjects with low HDL cholesterol and type IIB hyperlipoproteinemia (and possibly type IV hyperlipoproteinemia) would benefit from treatment with gemfibrozil.

Adult↗

PubMed1989

Activated charcoal in the treatment of hypercholesterolaemia: dose-response relationships and comparison with cholestyramine.

The dose-response relationship of activated charcoal in reducing serum cholesterol was determined and the effects of charcoal and cholestyramine were compared in patients with hypercholesterolaemia. In a cross-over study 7 patients ingested charcoal 4, 8, 16 or 32 g/day, and finally bran, each phase lasting for 3 weeks. Serum total and LDL-cholesterol were decreased (maximum 29% and 41%, respectively) and the ratio of HDL/LDL-cholesterol was increased (maximum 121%) by charcoal in a dose dependent manner. Ten further patients with severe hypercholesterolaemia ingested daily for 3 weeks, in random order, activated charcoal 16 g, cholestyramine 16 g, activated charcoal 8 g + cholestyramine 8 g, or bran. The concentrations of total and LDL-cholesterol were reduced by charcoal (23% and 29%, respectively), cholestyramine (31% and 39%) and their combination (30% and 38%). The ratio of HDL/LDL-cholesterol was increased from 0.13 to 0.23 by charcoal, to 0.29 by cholestyramine, and to 0.25 by their combination. Serum triglycerides were increased by cholestyramine but not by charcoal. Other parameters, including the serum concentrations of vitamin A, E and 25(OH)D3 remained unaffected. The changes in lipids only partly subsided during the 3-week bran phase. In general, the acceptability by the patients and the efficacy of activated charcoal, cholestyramine and their combination were about equal, but there were individual preferences for particular treatments.

Adult↗

PubMed1989

Guar gum and gemfibrozil--an effective combination in the treatment of hypercholesterolaemia.

Twenty-nine hypercholesterolaemic patients, treated for one year with gemfibrozil but being still hypercholesterolaemic (serum total cholesterol greater than or equal to 6.25 mmol/l) were included in a double-blind trial to evaluate the hypocholesterolaemic effects of gemfibrozil-guar gum combination (GE + GU) vs. gemfibrozil-placebo combination (GE + PL) using a cross-over study design. The patients were treated with gemfibrozil on a constant dosage (range 900-1200 mg/day) during the entire trial. After a 4-week run-in period on GE + PL treatment the patients were randomly allocated to 2 groups: one received GE + GU 15 g/day, and the other GE + PL for 3 months and after that groups were crossed over. Guar gum and placebo were administered as granules taken 3 times a day during meals. Serum total cholesterol was 8.61 +/- 0.17 mmol/l before gemfibrozil therapy, and 7.29 +/- 0.15 mmol/l at the end of the run-in period on GE + PL (P less than 0.01). During the double-blind phase serum total cholesterol values were 6.28 +/- 0.19 mmol/l at the end of the GE + GU treatment period and 7.21 +/- 0.16 mmol/l at the end of the GE + PL treatment period (P less than 0.01). At the end of the GE + GU treatment period serum total cholesterol was 27% lower and LDL-cholesterol 39% lower than before gemfibrozil treatment. A marked improvement (23%) was found in HDL/LDL ratio during GE + GU treatment compared with GE + PL treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1989

The mechanism of the hypocholesterolaemic effect of activated charcoal.

The hypocholesterolaemic mechanism of activated charcoal was studied in seven patients with primary hypercholesterolaemia. The reduction of serum cholesterol was correlated with the serum concentrations of cholesterol precursors and of two plant sterols. Activated charcoal, 8 g t.i.d. for 4 weeks, reduced serum concentration of total cholesterol by 27% (P less than 0.01). The effect was accompanied by a moderate elevation (P less than 0.05) in serum squalene and desmosterol concentrations and by a marked increase (up to 300-700%) in serum lathosterol and delta 8 lathosterol concentrations. The levels of two plant sterols, campesterol and beta-sitosterol, were unchanged or only slightly decreased by the use of activated charcoal. The decrease of serum cholesterol concentration had significant negative correlations with serum lathosterol and delta 8 lathosterol, and significant positive correlations with serum cholestanol and beta-sitosterol. These observations suggest an increased cholesterol synthesis upon treatment with activated charcoal, probably caused by the interference with the enterohepatic circulation of bile acids.

Anticholesteremic Agents↗

PubMed1989

Blood pressure responses to enalapril in rats with one- and two-kidney DOC-NaCl hypertension.

Blood pressure responses to the angiotensin-converting enzyme (ACE) inhibitor enalapril were investigated in rats with salt-dependent hypertension. In both one- and two-kidney deoxycorticosterone (DOC)-NaCl hypertension, enalapril (50 mg/kg p.o.) caused a similar, slight blood pressure fall, which passed off with continuation of the treatment. Changes in the salt concentration of the drinking fluid (from 1% NaCl to 0.2% NaCl in the one-kidney rats and from 1% NaCl to 2% NaCl in those with intact kidneys) did not alter the depressor effect of enalapril. Plasma renin activity in all DOC-NaCl hypertensive groups was negligible. Our results indicate that in DOC-NaCl hypertensive rats, the presence of intact kidneys vs. one kidney has no influence on the blood pressure response to ACE inhibition. The blood pressure-lowering effect of enalapril may result from local converting enzyme inhibition in tissues.

Animals↗

PubMed1988

Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study.

In the Helsinki Heart Study, a randomized five-year, double-blind trial, a 34% reduction in the incidence of coronary heart disease (CHD) was observed in dyslipidemic men treated with gemfibrozil. Averaged over the five years of the trial, gemfibrozil therapy produced, compared with placebo, mean decreases of 10% in serum total cholesterol level, 14% in non-high-density lipoprotein (HDL) cholesterol level, 11% in low-density lipoprotein (LDL) cholesterol level, 35% in triglyceride level, and a mean increase of 11% in HDL cholesterol level from baseline levels measured prior to treatment. While changes in HDL cholesterol level were similar in all Fredrickson types, the effect on concentrations of total cholesterol and LDL cholesterol was largest in type IIA and on LDL minimal in type IV. The reduction of CHD incidence over placebo was largest in type IIB and smallest in type IIA. The lipid changes were dependent on lipid levels prior to treatment and on compliance with the medication regimen. When risk factors for CHD, including age, blood pressure, smoking and drinking habits, baseline lipid levels, and exercise and relative weight, were controlled by applying the Cox proportional hazards model, the changes in serum HDL and LDL cholesterol levels were both statistically significantly associated with the decline in CHD incidence within the gemfibrozil-treated group. The large decrease in serum triglyceride levels had relatively small effect on CHD incidence. Thus, the results of this study, together with earlier observations, suggest that both elevating HDL and lowering LDL cholesterol levels are effective in the primary prevention of CHD.

Adult↗

PubMed1988

Gemfibrozil decreases platelet reactivity in patients with hypercholesterolemia during physical stress.

The effects of the lipid-lowering drug gemfibrozil on platelet reactivity at rest and during submaximal exercise were investigated in 10 patients with serum cholesterol levels greater than 270 mg/dl. No significant changes were observed in platelet reactivity at rest after gemfibrozil treatment. However, a marked decrease in platelet reactivity was seen in almost all patients treated with gemfibrozil during exercise. The adrenaline concentration necessary to induce secondary aggregation increased in eight patients during exercise after gemfibrozil and in two after placebo treatment. When adenosine diphosphatase (2 to 4 mumol/L) was used to induce aggregation, 5-hydroxytryptamine (serotonin) and thromboxane B2 secretion by platelets decreased by 35% and 67%, respectively, during exercise in patients treated with gemfibrozil. The area under the aggregation curve decreased by 28% during exercise after gemfibrozil. No significant changes occurred in these variables during exercise after placebo. Thus, gemfibrozil seems to have antiplatelet effects that might have importance in the prevention of acute complications of atherosclerosis in patients with hypercholesterolemia.

Adult↗

PubMed1988

Effects of the converting enzyme inhibitor quinapril (CI-906) on blood pressure, renin-angiotensin system, and prostanoids in essential hypertension.

Fourteen patients with mild to moderate essential hypertension were randomized, after a baseline placebo period of 4 weeks, to receive the angiotensin converting enzyme (ACE) inhibitor quinapril or a placebo. During a 12 week, double-blind phase, the dosage of quinapril was increased from 10 to 40 mg twice daily being doubled every 4 weeks. At the end of the baseline period and of each month of the double-blind phase, 12 h overnight urine collections were made and morning blood samples were taken about 12 h after the last dose of medication. During the double-blind phase, blood pressure in the quinapril group (n = 7) decreased from 159 +/- 3/105 +/- 1 to 141 +/- 6/94 +/- 2 mm Hg (mean +/- SEM). Serum ACE activity and plasma angiotensin II concentration were reduced to 4 +/- 1% and 14 +/- 1% of the pretreatment values, respectively. Neither the plasma concentrations nor the urinary excretions of prostaglandin E2, 6-keto-prostaglandin F1 alpha (a prostacyclin metabolite), or thromboxane B2 (a metabolite of thromboxane A2) were affected by quinapril. In the placebo group, blood pressure tended to decline but the biochemical variables remained essentially unchanged. These results indicate that prostanoids are not involved in the antihypertensive action of quinapril, the principal effect of which seems to be inhibition of the renin-angiotensin system.

Adult↗

PubMed1988

Quinapril and blood lipids.

To assess the effects of angiotensin-converting enzyme inhibition with quinapril on blood lipid profile, serum total cholesterol and triglycerides, together with high-density and low-density lipoprotein cholesterol were analysed in 23 hypertensive patients receiving either placebo (7 patients) or quinapril hydrochloride (16 patients). After 12 weeks of therapy there were no significant changes in blood lipids in either group. No unfavourable changes in blood lipid profile were observed even after 1 year of therapy with quinapril hydrochloride in 13 patients.

Adult↗

PubMed1988

Helsinki Heart Study. New perspectives in the prevention of coronary heart disease.

The Helsinki Heart Study tested the effect of modifying plasma low density lipoprotein (LDL)- and high density lipoprotein (HDL)-cholesterol on the primary prevention of coronary heart disease in middle-aged men with non-HDL-cholesterol greater than or equal to 5.2 mmol/L (200 mg/dl). One group (2046 men) received 600mg of gemfibrozil twice daily, and the other (2035 men) received placebo. Averaged over the 5-year trial period, gemfibrozil induced mean decreases of 11% in LDL-cholesterol and 35% in triglycerides and a mean increase of 11% in HDL-cholesterol compared with placebo. These changes were accompanied by a 34% reduction (number of end-points; 56 vs 84) in the incidence of coronary heart disease. The reduction was largest in subjects with type IIB hyperlipoproteinaemia and smallest in subjects with type IIA hyperlipoproteinaemia. The changes in serum HDL- and LDL-cholesterol during the trial were associated (p less than 0.02 and p less than 0.05, respectively) with the risk of coronary heart disease in the gemfibrozil group, but not in the placebo group.

Adult↗

PubMed1987

Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease.

In a randomized, double-blind five-year trial, we tested the efficacy of simultaneously elevating serum levels of high-density lipoprotein (HDL) cholesterol and lowering levels of non-HDL cholesterol with gemfibrozil in reducing the risk of coronary heart disease in 4081 asymptomatic middle-aged men (40 to 55 years of age) with primary dyslipidemia (non-HDL cholesterol greater than or equal to 200 mg per deciliter [5.2 mmol per liter] in two consecutive pretreatment measurements). One group (2051 men) received 600 mg of gemfibrozil twice daily, and the other (2030 men) received placebo. Gemfibrozil caused a marked increase in HDL cholesterol and persistent reductions in serum levels of total, low-density lipoprotein (LDL), and non-HDL cholesterol and triglycerides. There were minimal changes in serum lipid levels in the placebo group. The cumulative rate of cardiac end points at five years was 27.3 per 1,000 in the gemfibrozil group and 41.4 per 1,000 in the placebo group--a reduction of 34.0 percent in the incidence of coronary heart disease (95 percent confidence interval, 8.2 to 52.6; P less than 0.02; two-tailed test). The decline in incidence in the gemfibrozil group became evident in the second year and continued throughout the study. There was no difference between the groups in the total death rate, nor did the treatment influence the cancer rates. The results are in accord with two previous trials with different pharmacologic agents and indicate that modification of lipoprotein levels with gemfibrozil reduces the incidence of coronary heart disease in men with dyslipidemia.

Adult↗

PubMed1987

Hemodynamic effects of pirmenol and lidocaine: a placebo-controlled, double-blind, comparative study.

The acute hemodynamic effects of pirmenol and lidocaine were studied in a double-blind, placebo-controlled investigation. Thirty patients undergoing catheterization received one of the following: pirmenol as a 50-mg intravenous bolus injection followed by a 2.5 mg/min infusion, lidocaine as a 75-mg intravenous bolus injection followed by a 3 mg/min infusion or placebo administered in a similar fashion. Mean plasma pirmenol concentrations during steady infusion were 2.3 to 2.4 mg/liter, and mean plasma lidocaine concentrations were 16 to 24 mumol/liter. Pirmenol increased heart rate from baseline by 10 beats/min (p less than 0.001) and mean arterial pressure by 5 mm Hg (p less than 0.001), with similar increases in systemic (p less than 0.05) and pulmonary vascular resistance (p less than 0.01). Lidocaine induced a comparable increase in mean arterial pressure (6 mm Hg, p less than 0.001), but unlike pirmenol, it increased left ventricular and diastolic pressure by 2.8 mm Hg (p less than 0.05). Indexes of left ventricular work were not affected by either drug. Echocardiographic ejection fraction was reduced more by pirmenol (-0.05, p less than 0.0001) than by lidocaine (-0.03, p less than 0.05), a difference that may be related to the changes in heart rate. Side effects were not observed in any patient. The myocardial depressant effect of pirmenol is relatively slight and comparable to that of lidocaine.

Adult↗