Biomedical subjects

R Lassila

Publications and source records attributed to R Lassila.

63 records · Page 4Linked to original sources

PubMed1988

Vasoactive and atherogenic effects of cigarette smoking: a study of monozygotic twins discordant for smoking.

The mechanism by which atherosclerotic disease is induced by cigarette smoking has not yet been identified unequivocally. Chronic cigarette smoking and the generation of vasoactive prostanoids and the size of carotid atherosclerotic plaques were studied in nine pairs of identical male twins discordant for smoking for over 20 years. The urinary excretion of 2,3-dinor-thromboxane B2 (thromboxane B2 metabolite) of the smoking twin was significantly higher (on average 1.8 times higher) in every pair and that of 2,3-dinor-6-keto-prostaglandin F1 alpha (prostacyclin metabolite) was significantly higher (on average 1.3 times higher) in eight of the nine pairs. The ratio of excretion of these metabolites was significantly higher, being 4.0 (95% confidence interval 2.7 to 5.4) among the smokers compared with 2.9 (2.1 to 3.8) among the non-smokers, thus favouring a mechanism of vasoconstriction. Excretion of the thromboxane B2 metabolite was related to the urinary concentrations of nicotine metabolites. Atherosclerotic plaques detected by ultrasonography in the carotid arteries were significantly larger among smokers but did not correlate with the urinary excretion of prostacyclin and thromboxane B2 metabolites or intensity of smoking. Smoking was concluded to induce activation of platelets by an effect mediated by nicotine. The increased prostacyclin production, on the other hand, suggested a compensatory mechanism for the general vasoconstrictive properties of cigarette smoking.

6-Ketoprostaglandin F1 alpha↗

PubMed1988

Physical exercise provokes platelet desensitization in men who smoke cigarettes--involvement of sympathoadrenergic mechanisms--a study of monozygotic twin pairs discordant for smoking.

Since chronic smoking is known to be a dominant risk factor for morbidity and mortality in cardiovascular diseases related to enhanced atherogenesis and arterial thrombogenesis, the mechanisms causing these effects are of interest. The present study aims to assess the basic biochemical and haemorheological parameters among male monozygotic twinpairs, who have been discordant for smoking in average for over 20 years. Because smoking is known to cause enhanced sympathoadrenergic activation, the study was designed to further stimulate this by means of physical exercise. The platelet aggregation in vitro and serum-thromboxane B2 (S-TxB2) did not differ at rest, but after exercise smokers' platelets were desensitized to all doses of adrenaline and low doses of ADP as well as collagen and the levels of S-TxB2 were lower than among nonsmokers. This finding was supported by the decreased release of serotonin and TxB2 during aggregation induced with adrenaline. The leucocyte counts were significantly higher among smokers at rest and haematocrit as well as platelet counts showed the same tendency. Fibrinogen tended to be be elevated among smokers after exercise and together with haematocrit levels implicated increased blood viscosity. FVIII, vWF and beta-thromboglobulin did not differ. In conclusion we suggest that in smokers the significant exhaustion of platelets to in vitro stimulation might be a consequence of continuous platelet activation during physical stress. This phenomenon together with our other findings implies that the sympathoadrenergic system has a multiple role in vivo, which needs further research to elucidate the mechanisms involved in the effects of smoking on cardiovascular diseases.

Adult↗

PubMed1988

Enhanced activation of the renin-angiotensin-aldosterone system in chronic cigarette smokers: a study of monozygotic twin pairs discordant for smoking.

Plasma renin activity (PRA) and aldosterone concentration were measured before and during submaximal exercise in 10 male monozygotic twin pairs who were discordant for smoking. In nine twin pairs PRA was higher in the smoker both at rest and during exercise. The mean PRA was 99% higher at rest and 84% higher during exercise than in nonsmokers. Plasma aldosterone levels were higher at rest in seven smokers and during exercise in eight smokers compared with the respective nonsmokers. The mean aldosterone level at rest was 23% and during exercise 40% higher in the smokers than in the nonsmokers. Chronic smoking induces increased PRA, which results in increased aldosterone formation, presumably via enhanced generation of angiotensin II. This may partly explain the greater vasoconstrictive reactivity typical of the arteries of chronic smokers.

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

Decreased beta-adrenergic receptor density and catecholamine response in male cigarette smokers. A study of monozygotic twin pairs discordant for smoking.

The effect of long-term cigarette smoking on beta-adrenoceptor density and catecholamine response was studied in 10 monozygotic male twin-pairs discordant for smoking, with an average discordance time for smoking of 23 years (range, 12-35 years). The density of beta-adrenergic receptors was 40% lower in the lymphocytes of smoking twins compared with their nonsmoking cotwins (beta-receptor density, 6.7 +/- 1.2 and 11.1 +/- 1.8 fmol/10(6) cells, respectively; p less than 0.05). The corresponding apparent Kd values were 31.7 +/- 5.5 and 26.7 +/- 5.4 pM, respectively. Stimulation of the lymphocyte beta-receptors resulted in significantly lower levels of cyclic adenosine monophosphate in the smokers compared with the nonsmokers (16.2 +/- 3.3 vs. 29.2 +/- 6.5 pmol/10(6) cells, p less than 0.05). When subjected to submaximal exercise, the smokers had a lower level of cyclic adenosine monophosphate in plasma (25.9 +/- 1.2 vs. 28.6 +/- 1.0, p less than 0.05) and a net decrease was seen in plasma free fatty acids in the smokers compared with a net increase in the nonsmokers (-15% vs. +19%, p less than 0.01). The total plasma catecholamine level was, in the basal state, significantly higher in smokers compared with nonsmokers (74.8%, p less than 0.05). The intrapair difference in plasma norepinephrine predicted well the intrapair difference in beta-receptor density (r = -0.84, p less than 0.001). We conclude that the autonomic neurohumoral response evoked by cigarette smoking results in downregulation of beta-adrenergic receptors in long-term smokers.

Adult↗

PubMed1986

Peripheral arterial disease--natural outcome.

Three hundred and twelve patients with peripheral arterial disease were followed up for 8 3/4 years or more (maximum 11 3/4 years) to assess the natural history of the disease and factors determining its outcome. Of the 312 patients, 188 (69%) died during the follow-up, 68% of the deaths having cardiovascular causes. The 10-year relative cumulative survival rate was 0.61 for males and 0.48 for females. The role of smoking as a risk factor could not be analysed without bias. In addition to known risk factors diabetes mellitus, cerebrovascular disease and coronary heart disease, the degree of peripheral arterial disease itself also proved to be a risk factor among men. The expected life lost for men with intermittent claudication was 20%, but 44.3% for men with advanced lower limb ischaemia (p less than 0.01). This difference could not be explained by the well-known association of advanced ischaemia and diabetes mellitus. The present results therefore suggest that the state of advanced ischaemia indicates larger involvement of the whole of the arterial tree and predicts fatal cardiovascular events among these patients.

Aged↗

PubMedDate not supplied

The effect of acetylsalicylic acid on the outcome after lower limb arterial surgery with special reference to cigarette smoking.

A prospective controlled study of 144 patients with peripheral obstructive arterial disease was undertaken to evaluate the efficacy of acetylsalicylic acid (ASA) treatment (250 mg daily) on the outcome after lower limb arterial surgery which mainly involved endarterectomy. By random enrollment, 2 groups of 72 patients were formed after the surgery. Patients with ASA treatment for 3 months, starting from the seventh postoperative day, were compared with patients who were not treated with ASA. The patients in both groups had similar characteristics as to sex ratio, age, concomitant diseases, preoperative arm-ankle systolic blood pressure index, and type and primary success of the reconstruction. Forty-seven of the ASA-treated and 48 of the untreated patients reported to continue cigarette smoking. Postoperative ASA-treatment protected against local adverse events which occurred in 15 patients (21%) of the ASA-treated group compared with 31 patients (43%) of the untreated group (p less than 0.01). Among heavy smokers (greater than 15 cigarettes/day) the efficacy of antiplatelet treatment was not detectable. These results imply that, in patients with peripheral arterial disease, ASA prevents platelet interaction to endarterectomized and atherosclerotic lower limb arteries thereby affecting the subsequent risk of occlusion; however, heavy cigarette smoking, which is very common among patients with peripheral arterial disease, counteracts the local antithrombotic potency of ASA.

Adult↗

PubMedDate not supplied

Dynamic monitoring of platelet deposition on severely damaged vessel wall in flowing blood. Effects of different stenoses on thrombus growth.

The formation of an arterial thrombus is a dynamic process that depends upon the characteristics of blood flow, the triggering substrate, and the blood components. We have developed and characterized a sensitive and specific computer-assisted nuclear scintigraphic method to study the dynamics of platelet deposition on severely damaged vessels both in vitro and in vivo in nonstenotic and stenotic flow conditions. Heparinized pig blood with Indium-111-labeled platelets was perfused for 50 minutes. Method variability in both static and flowing conditions was evaluated by Indium-111-labeled transferrin and Indium-111-labeled platelets. Positive scintigrams were obtained mainly in the presence of severe high grade stenoses on a thrombogenic substrate. Since the method is highly sensitive, computer-assisted axial dependence analysis was performed on the scintigraphic images to locate the thrombotic accumulation with respect to the area of the stenosis and to monitor the dynamic changes in platelet accumulation over time. Both in vitro and in vivo the highest level of platelet deposition occurred at the apex of the 80% stenosis, where embolization could be usually detected after 30 minutes of perfusion. This study is the first to assess the dynamics of thrombus growth in nonparallel flow streamlines such as are encountered in stenotic vessels. This method provides a new experimental tool with which to study factors affecting thrombus formation and stability.

Analysis of Variance↗

PubMedDate not supplied

Cigarette smoking and the outcome after lower limb arterial surgery.

After reconstructive arterial surgery 190 patients with peripheral arterial disease of lower limbs (PAD) were followed up for three years in a prospective manner to assess the effects of smoking habits on the outcome. 173 patients (91%) were smokers at presentation. 48 patients reported to have given up smoking during the study. Exsmokers could not be included in the analysis, however, due to differences in the severity of PAD, age, sex ratio, type of operation and other risk factors. Current moderate (MS) (less than 15 cigarettes/day, N = 45) and heavy smokers (HS) (greater than or equal to 15, N = 80) were comparable groups. The three-year relative cumulative survival rates among male HS and MS were 0.40 and 0.65 (p less than 0.05), respectively. HS died mostly of cardiovascular causes. Major amputation was needed in 21% of HS compared to only 2% in MS (p less than 0.001). The present results show a strong association with heavy smoking, cardiovascular mortality and severe local adverse events. Thus, arterial thrombogenity appears to be enhanced by continued heavy smoking in patients with peripheral atherosclerosis.

Adult↗