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Biomedical subjects

R Lassila

Publications and source records attributed to R Lassila.

At least 55 records · Page 3Linked to original sources
PubMed1996

Association of chronic stress with plasminogen activator inhibitor-1 in healthy middle-aged men.

The effect of chronic stress on tissue-type plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1) antigens was studied in 69 healthy middle-aged men. Chronic stress, defined as feelings of fatigue, lack of energy, increased irritability, and demoralization, was positively associated with plasma concentrations of PAI-1 antigen but was unrelated to TPA. The association remained unaltered after controlling for age, smoking, alcohol consumption, and physical activity but became nonsignificant after further controlling for abdominal obesity, BMI, and serum insulin and triglyceride levels. This attenuated association implies that the relationship between vital exhaustion and PAI-1 may be secondary to the effects of the metabolic variables. Thus, the present study shows that long-term stress affects the fibrinolytic system and suggests that obesity and insulin and triglyceride concentrations, which are closely correlated with the fibrinolytic parameters, may mediate the association. These findings are consistent with the hypothesis that chronic stress causes increased synthesis of PAI-1, thus promoting the risk for atherothrombotic disease by decreasing the likelihood of spontaneous fibrinolysis and increasing the likelihood of fibrin deposition.

Adult↗
PubMed1996

Epinephrine augments platelet recruitment to immobilized collagen in flowing blood--evidence for a von Willebrand factor-mediated mechanism.

Although elevated plasma epinephrine (epi) levels are associated with clinical atherothrombosis, the role of epi in platelet-vessel wall interaction has not been established. Our aim was to study the effect of high physiological epi (10 nM) in an experimental model which tests the interaction between platelets and immobilized collagen in whole blood. Shear forces and anticoagulation were modulated. Epi significantly enhanced platelet deposition, but only at high shear rate (1,600 s-1). In PPACK- or LMWH-anticoagulated blood, the increase in platelet deposition was 32 to 85% (p < 0.02-0.05). Furthermore, platelet aggregation was cotriggered with subthreshold concentrations of epi and ristocetin, and monoclonal antibodies against glycoprotein (GP) Ib (AN 51 and SZ 2) attenuated epi-induced aggregation. We conclude that epi is capable of augmenting platelet functions, which are dependent on the interaction of vWF with GP Ib and GP IIb/IIIa. Via this mechanism epi may promote arterial thrombosis in vivo.

Adult↗
PubMed1995

Blood coagulation and fibrinolysis activation during sudden arterial occlusion of lower extremities--an association with ischemia and patient outcome.

We compared hemostatic and fibrinolytic plasma markers in 41 patients having acute or subacute occlusion of lower limb arteries with 20 patients suffering stable peripheral arterial occlusive disease (PAOD). During occlusion, the amount of thrombin-antithrombin III (TAT) complex was five-fold higher compared with stable PAOD, being 16 micrograms/l [95% confidence interval (CI) 11-21 micrograms/l] vs 3 micrograms/l (95% CI 2-4 micrograms/l), p < 0.003. Similarly, D-dimer was over four-fold (p = 0.0001), while tissue plasminogen activator and plasminogen activator inhibitor-1 (PAI-1) antigens were about two-fold (p = 0.02 and p < 0.003, respectively) higher than in PAOD. Coagulation and fibrinolysis markers were increased most in patients with recent symptom onset, which mainly represented embolus rather than thrombosis. The marker levels assessing coagulation and fibrinolysis were related with myoglobin and CK, indicators of skeletal muscle damage. Finally, increased TAT, PAI-1 antigen, and myoglobin concentrations associated with poor outcome.

Aged↗
PubMed1994

Ability to work after arterial surgery for chronic incapacitating ischaemia of the lower limb in middle-aged patients.

OBJECTIVE: To assess the efficacy of arterial surgery in restoring ability to walk and working capacity. DESIGN: Retrospective follow up study. SETTING: Fourth Department of Surgery, Helsinki University Central Hospital. SUBJECTS: 67 middle-aged patients (mean age 53 years) with chronic incapacitating ischaemia of the lower limb. INTERVENTIONS: Arterial reconstruction. MAIN OUTCOME MEASURES: Clinical outcome, vascular laboratory assessments, mortality, morbidity, return to work, and retirement. RESULTS: According to objective vascular laboratory criteria a primary positive effect was achieved in 63/67 (94%). Fourty-eight of the 65 surviving patients (74%) were free of symptoms on treadmill testing three months after the operation. Working capacity was restored in 41/50 of the patients not yet retired (82%). Three years postoperatively 77% of the surviving patients still fared objectively better than before operation. The 10-year survival rate was 67%. Fourteen of the 22 patients who died did so of cardiovascular diseases (64%). Advanced distal ischaemia (indicated by a preoperative ankle-brachial index of 0.5 or less) was associated with increased risk of death. Altogether 251 working years were achieved of the 435 that could have potentially been gained. The most common reason for retirement during follow up was progression of peripheral arterial disease in the lower limbs in 13/41 patients (32%). At the end of the study there were nine patients still working with potentially 73 working years left. CONCLUSION: These results indicate that arterial surgery can restore working capacity in middle aged patients with threatening or temporary invalidity. Long term outcome, especially mortality, is mostly affected by other signs of cardiovascular disease, whereas working capacity is dependent on a wider variety of factors.

Adult↗
PubMed1993

Severity of peripheral atherosclerosis is associated with fibrinogen and degradation of cross-linked fibrin.

Immunohistochemical studies of human atherosclerotic lesions have demonstrated the occurrence of fibrin deposition and its degradation in the arterial wall. We studied fibrinogen, the generation of thrombin, and the degradation of fibrin in 40 patients with stable peripheral arterial occlusive disease of varying severity, as assessed by the ankle/brachial pressure index and duplex ultrasonography and/or angiography. Circulating fibrinogen (functional and immunological), fibrinopeptide A, thrombin-antithrombin III complex, and D-dimer were measured. The severity of atherosclerosis was associated with both fibrinogen (both functional and immunological) and D-dimer (r = .57, P < .0002, and r = .57, P < .0001, respectively). Fibrinogen and D-dimer showed a significant positive correlation (r = .50, P < .001). Generation of thrombin was detected in 24 patients (60%) by fibrinopeptide A and levels of thrombin-antithrombin III complex. As a sign of coagulation activation and fibrinolysis, we found that thrombin-antithrombin III complex and the degradation of cross-linked fibrin were progressively associated with the extent of vascular disease. The plasmin-mediated fibrin breakdown contributed to increased levels of circulating fibrinogen, an established risk factor for thrombotic complications. The significant correlations between fibrinogen/D-dimer and the severity of atherosclerosis support previous pathological studies and imply that local degradation of cross-linked fibrin is involved in the progression of atherosclerosis.

Adult↗
PubMed1993

Atherogenesis and inflammation.

Following endothelial injury, monocytes attach to the subendothelium and penetrate into the vessel wall, forming macrophage/foam cells by accumulating lipids. Macrophages release various products such as interleukins, complement factor fragments, tumour necrosis factors, oxidized cholesterol, and oxygen free radicals, leading to further endothelial injury and cytolysis. Platelets at the site of vascular injury, monocytes, endothelial cells, and smooth muscle cells release mitogenic factors which stimulate smooth muscle cell proliferation and migration. This smooth muscle cell proliferation, together with organization of thrombus and extracellular matrix synthesis, leads to the development of atheromatous plaques. Macrophages, by releasing proteases such as collagenase and elastase, form an abscess in the plaque which is covered by a thin fibrous cap. When this cap ruptures, a local thrombus is formed and depending upon the degree and duration of thrombus, and the degree of collateral development the fate of this thrombotic process is determined.

Arteriosclerosis↗
PubMed1993

Inflammation in atheroma: implications for plaque rupture and platelet-collagen interaction.

Atherosclerosis is an inflammatory reaction to accumulated extracellular lipid in the arterial intima. Evidence from pathological studies indicate that there is constant deposition and lysis of fibrin within the atherosclerotic arterial wall. In patients with stable peripheral atherosclerosis, the functional severity of the disease is associated with circulating fibrinogen and degradation of cross-linked fibrin reflecting procoagulant activity in the blood-vessel wall interface, or in the wall itself. In atheromas the fibrinolytic activity is connected to macrophages, which can assemble in the plasminogen-plasmin system and generate plasmin-mediated pericellular proteolysis in tissues with inflammation. Plasmin capable of activating collagenase may therefore be a candidate for plaque rupture. The nature of the exposed vascular tissue, the inflammatory state, tissue-factor dependent thrombin generation and the degree of matrix degradation regulate platelet reactivity. Little is yet known about platelet adhesive functions in proteolyzed collagens that are the underlying substrate where platelets deposit during plaque rupture, the triggering event for thrombosis. Research in these areas is likely to improve the understanding of the thrombogenicity of atheromas when the tissue is suddenly exposed to blood.

Arteriosclerosis↗
PubMed1991

Thrombin regulation of platelet interaction with damaged vessel wall and isolated collagen type I at arterial flow conditions in a porcine model: effects of hirudins, heparin, and calcium chelation.

The role of thrombin inhibition in platelet vessel wall interaction and thrombus growth was studied under controlled flow conditions. Natural hirudin and recombinant hirudin (r-hirudin), which are specific thrombin inhibitors, were compared with heparinized blood (1.8 +/- 0.2 U/mL) and Ca(2+)-chelated blood in their potential to inhibit platelet interaction and thrombus growth on two biologic vascular surfaces and one immobilized vessel wall component. The substrates were perfused by flowing blood at shear rates typical of patent and stenosed arteries (212 to 1,690/s) for 5 minutes. Platelet deposition was measured by In-111-labeled platelets. We found that both natural and r-hirudin have similar effects on platelet-substrate interaction. As compared with heparin, platelet deposition to mildly damaged vessel wall and digested collagen type I was not reduced by hirudin or citrate. However, hirudin and citrate significantly reduced platelet deposition to severely damaged vessel wall (platelets x 10(6)/cm2: 93 +/- 10 in heparinized blood v 50 +/- 7 in blood treated with 100 U/mL r-hirudin). Therefore, thrombus growth on areas of severe wall damage is in part dependent on local thrombin production at the site of vascular damage. We also found that hirudin added to heparinized blood reduced platelet deposition to severely injured wall but not to subendothelium or collagen-coated slides. Hirudin added to citrated blood did not affect platelet deposition. Our study indicates that local thrombin generation at the site of severe injury will induce platelet activation and deposition even in the presence of average therapeutic heparin levels that inhibit blood coagulation.

Adenosine Diphosphate↗
PubMed1991

Cigarette smoking alters sympathoadrenal regulation by decreasing the density of beta 2-adrenoceptors. A study of monitored smoking cessation.

We report the effects of monitored smoking cessation on adrenergic regulation in chronic smokers. The beta 2 adrenoceptor density of mononuclear leukocytes (MNLs) and plasma catecholamines was analyzed before cessation and 2, 3, and 8 weeks after cessation. We found a progressive increase in beta-adrenoceptor density after smoking cessation. During smoking the beta-adrenoceptor density was 1.456 +/- 83 (mean +/- SEM) binding sites per cell (n = 10), whereas 3 weeks after cessation the density was 1,774 +/- 157 sites per cell (n = 10; p less than 0.05), and at 8 weeks, 1,900 +/- 227 sites per cell (n = 8; p less than 0.05), representing an overall increase of 23%. Smoking cessation had no effect on binding affinity nor on lymphocyte subgroup distribution. The density of MNL cell beta-adrenoceptors in age-matched nonsmoking men was higher, at 1,896 +/- 271 sites per cell, than that of the chronic smokers before cessation, 1,419 +/- 117 sites per cell (n = 14; p less than 0.01). Plasma epinephrine decreased as a result of cessation from 0.36 pmol/ml (0.26-0.44, 95% confidence interval; baseline) to 0.26 pmol/ml (0.20-0.32) at 8 weeks (p less than 0.05), and norepinephrine decreased from 2.09 pmol/ml (1.38-2.80) to 1.69 pmol/ml (1.14-2.24; p = 0.06). We conclude that stopping smoking progressively increases beta 2-adrenoceptor density on MNL cells. Eight weeks after cessation the adrenoceptor density reaches the corresponding level of nonsmokers. These reversible changes in adrenergic regulation after smoking cessation may be associated with the relatively rapid reduction in cardiovascular disease risk among ex-smokers.

Adrenergic Fibers↗
PubMed1991

Smoking and occlusive peripheral arterial disease. Clinical review.

Cigarette smoking is a strong but avoidable risk factor for development of cardiovascular disease and its acute complications. Intermittent claudication is most strikingly associated with smoking. The link between smoking and occlusive peripheral arterial disease is dose-dependent and can be broken by cessation of smoking. The risk of chronic as well as acute limb ischemia is then decreased in conservatively treated patients and also in those with reconstructive arterial surgery. Heavy smoking seems to abolish the positive effect of adjuvant antiplatelet medication. Cessation of smoking is a cornerstone in the management of occlusive peripheral arterial disease at any stage.

Aged↗
PubMed1991

[Interaction between the arterial wall and thrombocytes in smokers].

Smoking is per se a major risk factor in cardio-vascular diseases. It causes atherosclerosis and blockage particularly in the aorta and the leg arteries. The components of tobacco smoke damage the endothelium, increase arterial contractility, and accelerate the formation of plaque therein. The mechanisms of the effect of smoking on the genesis of atherothrombotic diseases have been studied in inter alios identical twins where the one smokes and the other does not. Smoking activates the sympathetic nerves and affects their regulation. Tobacco smokers show signs of activated thrombocyte function and increased sensitivity to vasoconstriction, which provokes a counter-reaction in the arterial walls. The observations emphasize the importance of vaso-active agents for the development and complications of atherosclerosis.

Arteriosclerosis↗
PubMed1989

The platelet alpha 2-adrenoceptor and prostacyclin sensitivity are not altered by cigarette smoking--a study of monozygotic twin pairs discordant for smoking.

A study with ten identical twin pairs discordant for cigarette smoking for over 20 years was undertaken to evaluate the effect of smoking on platelet alpha 2-adrenoceptor binding ([3H]-yohimbine) and prostacyclin (IloprostR) sensitivity. Since plasma catecholamines, adrenaline and noradrenaline were increased in smokers (3.95 +/- 0.7 vs 2.26 +/- 0.1 pmol/ml, p less than 0.05) at rest, the objective of an acute additional adrenergic discharge by physical exercise was to uncover possible tachyphylaxis. Aggregation of adrenaline-stimulated platelets was significantly reduced in smokers after exercise and the refractoriness appeared to be maintained for 15 and 30 min afterwards. However, the densities of binding sites for the radioligand were not markedly different between the study groups at rest or after exercise. The binding affinity decreased after exercise in both groups. Adrenaline-stimulated platelets responded to prostacyclin by inhibiting aggregation and activating cAMP production equally in smokers and nonsmokers implying a preserved sensitivity to prostacyclin. Although smoking introduces long-term sympathoadrenergic effects, it does not alter alpha 2-adrenoceptor binding in platelets. Thus, the present data support a theory that smoking mediates its effects by platelet to vessel wall interaction and vasoactivity, rather than directly changing the properties of adrenoceptor in platelet or the coupling to adenylate cyclase.

Blood Platelets↗