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Biomedical subjects

S Munkvad

Publications and source records attributed to S Munkvad.

31 records · Page 2Linked to original sources
PubMed1991

Possible role of vascular intima for generation of coagulant activity in patients undergoing coronary thrombolysis with recombinant tissue-type plasminogen activator. A randomized, placebo-controlled study.

In our present placebo-controlled study on recombinant tissue-type plasminogen activator (rt-PA) and heparin treatment of patients with acute ischaemic heart disease (IHD), we studied the extent of fibrin resolution and generation of coagulant activity. In rt-PA treated patients the lysis of fibrin in vivo (median 60 nmol of fibrin--estimated as fibrinogen equivalents) was significantly higher (p less than 0.02) than can be accounted for solely by lysis of a coronary thrombus (approximately 2 nmol) and circulating soluble fibrin (median 15 nmol). We observed a 200% increase of plasma concentrations of both prothrombin fragment 1 + 2 (p less than 0.001) and thrombin-antithrombin III complexes (p less than 0.001) as a consequence of rt-PA treatment, indicating that the coagulant activity is primarily caused by a physiological activation of the coagulation system. We conclude that an important contribution to the activation of coagulation in patients undergoing coronary thrombolysis is lysis of fibrin deposited widespread on the vascular intima, and that this process causes an intimal-dependent activation of the coagulation system.

Adolescent↗
PubMed1991

Early thrombolytic treatment reduces analgesic requirement in patients with myocardial infarction.

The duration and amount of analgesics required were investigated in 67 patients with myocardial infarction treated with intravenous recombinant tissue-type plasminogen activator (rtPA) or placebo in a randomized double-blind trial. Infusion of rtPA (100 mg)/placebo was started within 5 h after the onset of symptoms, and the requirement for analgesics during the following 48 h was recorded. Sixty-seven per cent of the 30 rtPA-treated patients required analgesic treatment for less than 6 h, compared to 38% of the 37 patients in the placebo group (P = 0.04). During the study period, patients in the rtPA group used the equivalent of 5.3 mg (median value) intravenous morphine, which was significantly less than the 11.2 mg used in the placebo group (P = 0.04). In conclusion, the present study suggests that early thrombolysis with intravenous rtPA reduces the amount and duration of analgesic treatment required by patients with myocardial infarction.

Adult↗
PubMed1991

Interleukin-1 and tumor necrosis factor-alpha in plasma of patients with acute ischemic heart disease who undergo thrombolytic therapy: a randomized, placebo-controlled study.

In patients with acute ischemic heart disease who undergo thrombolytic therapy we have previously observed a marked endothelium-dependent activation of the coagulation system. Concomitantly the concentrations of the fast acting plasminogen activator inhibitor type 1 (PAI-1) in plasma increased. The results of recent in vitro studies would suggest that these in vivo phenomena could be associated with the procoagulant effects of the cytokines interleukin-1 (IL-1) and/or tumor necrosis factor-alpha (TNF). In the present placebo-controlled study on patients with acute ischemic heart disease treated with thrombolytic agents we observe low or undetectable concentrations, and insignificant deviations during the study periods, of IL-1 and TNF in plasma. We conclude that IL-1 and TNF play a minor role for generation of coagulant activity and systemic deviations of PAI-1 in patients who undergo coronary thrombolysis.

Acute Disease↗
PubMed1990

Enhanced generation and resolution of fibrin in women above the age of 30 years using oral contraceptives low in estrogen.

Epidemiologic studies have suggested a relationship between the use of oral contraceptives and mortality from cardiovascular diseases in older women. Therefore we studied generation and resolution of fibrin in 28 healthy women above age 30 years, using oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol. Thirty healthy nonusers served as control subjects. The oral contraceptive group had increased plasma concentration of thrombin-antithrombin III complexes (p less than 0.01), which indicated an enhanced generation of thrombin, increased plasma activity of tissue-type plasminogen activator (p less than 0.01), decreased plasma activity of plasminogen activator inhibition (p less than 0.01), and increased plasma concentration of fibrin degradation products (p less than 0.04). Interestingly, the ratio of thrombin-antithrombin III complexes/fibrin degradation products did not deviate significantly between groups. Twelve of the 28 women using oral contraceptives were light smokers, that is, less than 15 cigarettes per day. There were no differences in the determined variables between smokers and nonsmokers. Our study suggests that healthy women older than 30 years who use oral contraceptives containing 30 to 50 micrograms of ethinyl estradiol have an enhanced generation and resolution of fibrin, while the hemostatic balance is unaltered. These findings are unaffected by moderate cigarette smoking.

Adult↗
PubMed1990

A depression of active tissue plasminogen activator in plasma characterizes patients with unstable angina pectoris who develop myocardial infarction.

The balance between the coagulation system generating fibrin and its subsequent removal by the fibrinolytic system determines the fate of fibrin deposited in the vascular system. In a prospective study, selected haemostatic variables assessing this balance were determined in plasma samples from 20 consecutive patients admitted with unstable angina pectoris. Over a follow-up period of 6 years, eight patients developed myocardial infarction, whereas 12 patients did not. There was no significant difference between the two groups in the median plasma concentrations of thrombin-antithrombin III complexes reflecting the coagulant activity. The infarction group was characterized by a significantly lower median activity of tissue plasminogen activator in plasma euglobulins (P less than 0.05), a higher median concentration of tissue plasminogen activator antigen in plasma (P less than 0.05) and a tendency to higher plasma levels of antigenic and functional plasminogen activator inhibition. In all patients, the activities of tissue plasminogen activator inhibitor and of tissue plasminogen activator were significantly associated (rs = -0.4811, P less than 0.05). We conclude that a depressed fibrinolytic capacity attributable to a low tissue plasminogen activator activity is of pathogenetic importance for the development of myocardial infarction in patients with unstable angina pectoris.

Aged↗
PubMed1990

Interrelationship between coagulant activity and tissue-type plasminogen activator (t-PA) system in acute ischaemic heart disease. Possible role of the endothelium.

Patients with unstable angina pectoris (UAP; n = 20) and acute myocardial infarction (AMI; n = 34) were studied in the acute phase of ischaemic heart disease. We found significantly higher levels of thrombin-antithrombin-III (TAT) complexes, lower levels of systemic tissue plasminogen activator (t-PA) activity, and higher levels of plasminogen activator inhibitor (PAI) activity in the AMI patients compared to the UAP patients. In contrast to these specific changes, general acute phase reactants such as C-reactive protein, fibrinogen and von Willebrand factor did not differ significantly between the two groups. Studies of the relationship between coagulation (TAT-complexes) and fibrinolysis data revealed a significant positive correlation between plasma antigen concentrations of TAT-complexes and t-PA (P less than 0.02), and between TAT-complexes and PAI-I (P less than 0.002). These observations indicate a common pathophysiological mechanism underlying the changes in coagulation and fibrinolysis, suggesting that coagulation activity and t-PA-related fibrinolysis are interrelated processes in vivo, and probably take place at the level of the endothelial cell.

Acute-Phase Proteins↗
PubMed1990

Plasma HMW fibrinogen in patients with ischaemic heart disease.

Fibrinogen has been reported to be a risk factor for development of myocardial infarction in patients with ischaemic heart disease. The functional properties of plasma high molecular weight (HMW) fibrinogen would suggest that this fibrinogen species is responsible for the association. In a prospective study with a follow-up period of 6 years the plasma concentrations of clottable fibrinogen and of HMW fibrinogen were related to the subsequent development of myocardial infarction in 53 patients admitted with ischaemic heart disease. Neither the concentrations of clottable fibrinogen nor of HMW fibrinogen in the 25 patients developing myocardial infarction deviated from the concentrations in the 28 patients with an uncomplicated course. A significant positive correlation between the concentrations of clottable fibrinogen and of HMW fibrinogen (rs = 0.58, p less than 0.001) suggests that HMW fibrinogen represents a major fraction of the clottable fibrinogen concentration in patients with ischaemic heart disease.

Aged↗
PubMed1990

Effects of methylamine and heparin on a rapid chromogenic assay of C1-esterase inhibitor in plasma.

We describe a rapid assay of C1-esterase inhibitor (C1-inh) activity in plasma. After adding purified C1s serine protease (EC 3.4.21.42) in excess to plasma, we determine the residual C1s activity towards a new chromogenic tripeptide, CH3CO-Lys(CbO)-Gly-Arg-pNA. Optimal conditions include the addition of methylamine (final concentration 0.12 mol/L) to reduce the potential inhibitory capacity of alpha 2-macroglobulin towards C1s and the addition of heparin (final concentration 3000 int. units/L) to enhance the reaction of C1s with C1-inh. The correlation with C1-inh antigen concentrations in plasma was excellent. The estimated interassay CV was 4.3%, whereas the intra-assay CV was 2.0% for activity concentrations within the range of normal individuals (means +/- 2 SD: 70-124%), 1.3% at lower concentrations. The method is more convenient, rapid, and precise than previous methods, and C1-inh activity in plasma can be assessed within 30 min. We found that concentrations of C1-inh in plasma were low during open-heart bypass surgery.

Antigens↗
PubMed1990

Specific, sensitive, precise, and rapid functional chromogenic assay of activated first complement component (C1) in plasma.

We present a new functional assay for the first complement component (C1) in plasma, based on its activation by inhibition of the C1-esterase inhibitor (C1-inh) when monospecific antiserum to C1-inh is added to the plasma. After maximal activation, we can determine the concentration of activated C1 by using an amidolytic rate assay with a chromogenic substrate. We have optimized the assay conditions with respect to incubation time, concentration of antiserum to C1-inh, ionic strength, and pH. Our method determines specifically the concentration in plasma of free activated C1, not complexes of activated C1 with C1-inh, and is not influenced by the concentration of C1-inh in the test sample. Concentrations of C1 correlated significantly with activities determined by a hemolytic assay (r = 0.55, t = 4.09, P less than 0.001). The estimated interassay CV was 5% and the intra-assay CV was 1%. The sensitivity, imprecision, and practical test performance of our assay are superior to those of conventionally used hemolytic assays.

Adult↗
PubMed1989

Depressed plasma fibrinolytic activity in a group of patients with connective tissue diseases.

In various connective tissue disorders, a depressed fibrinolytic activity of the blood, attributed a contributory role in the development of disease, has been reported. We have determined selected fibrinolysis variables of the blood in 16 patients (7 patients with mixed connective tissue disease, 4 with systemic lupus erythematosus, 3 with rheumatoid arthritis and 2 with systemic sclerosis) and in 16 apparently healthy, age- and sex-matched controls. A significantly reduced mean activity of the intrinsic derived, urokinase-like plasminogen activator was found in the patient group. None of the other variables, including the extrinsic plasminogen activator (t-PA), differed from the control group. Possible implications of our findings in relation to the patho-physiology of these connective tissue diseases are discussed.

Adolescent↗