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Biomedical subjects

M Ia Ruda

Publications and source records attributed to M Ia Ruda.

At least 19 recordsLinked to original sources
PubMed2006

[Glycoprotein IIb/IIIa antagonist eptifibatide in acute coronary syndrome without elevation of ST segment].

Clinical effects of glycoprotein (GP) IIb-IIIa antagonist eptifibatide (Integrilin) and its inhibitory effects on platelet aggregation were studied upon administration of eptifibatide for the treatment of acute coronary syndrome (ACS) without ST segment elevation. Eptifibatide was introduced to 25 patients with unstable angina and non-Q-wave myocardial infarction (MI) according to the following scheme: two boluses with 10 min interval at the dose of 180 mg/kg followed by supporting infusion of 2 mg/kg per min for the first 24 hours and of 1.3 mg/kg for the next 48 hours. Comparative group in which GP IIb-IIIa antagonists were not used upon therapeutic treatment also included 25 patients. All patients received standard basic therapy. 11 patients from the control group and 13 patients from the group with administration of eptifibatide underwent coronary angioplasty during in hospital period. Eptifibatide completely inhibited ADP-induced platelet aggregation within the whole infusion period but after that platelet aggregating activity was quickly recovered--for more than 50% within 6 hours, and completely within 12 hours after the end of infusion. Eptifibatide administration in none of patients was accompanied with the development of dangerous side effects. Thrombocytopenia (50,000 platelets per mm3) was registered in one, and minor bleeding events--in 3 patients. The rate of unfavourable outcomes (MI, refractory or recurrent angina) within first 30 days was almost the same in eptifibatide and control group--32% (8 out of 25) and 36% (9 out of 25) respectively. Thus, despite the complete inhibition of platelet aggregation for 72 hours, eptifibatide administration failed to decrease the amount of adverse events upon treatment of patients with ACS without ST segment elevation.

Acute Disease↗
PubMed2005

[Results of clinical trials of a novel glycoprotein IIb-IIIa antagonist framon in high-risk coronary angioplasty].

New glycoprotein (GP) IIb-IIIa antagonist preparation framon (Monafram), is the F(ab')(2) fragment of a monoclonal antibody FRaMon directed against GP IIb-IIIa. This preparation blocks GP IIb-IIIa binding with fibrinogen and inhibits platelet aggregation both in vitro and upon intravenous administration. Safety and ability of framon to prevent thrombotic complications in high risk coronary angioplasty (CA) was evaluated in the present study. FRAMON was injected intravenously into 153 patients just before the start of procedure as a single bolus at the dose of 0.25 mg/kg. Control group was formed of 126 patients who underwent angioplasty without GP IIb-IIIa blockers. After framon administration there were no allergic reactions or major bleedings, deep thrombocytopenia (< 50000/microl) developed in 1 patient (< 1%), and antibodies against framon were detected in less than 5% of patients. Number of unfavorable outcomes (cardiovascular death, myocardial infarction, angina recurrence) within 1 month after CA was 3 times higher in control group than in the group of patients treated with framon (11.4% and 3.3%, respectively, p = 0.018). The effect of framon was most strongly pronounced within the first day after procedure -- administration of the drug reduced number of acute thromboses from 6.5% to 0.7% (p = 0.013). Significant differences between numbers of end points was still preserved at 6 months after procedure (25.7 and 14.2% in control and framon groups, respectively, p = 0.023). The data obtained proved safety and clinical efficacy of framon administration in coronary angioplasty with high risk of thrombotic complications.

Angioplasty, Balloon, Coronary↗
PubMed2004

[Anticholinergic Effect of a New Antiarrhythmic Class III Drug RG-2].

In experiments on isolated rat and rabbit right atrium, a new class III antiarrhythmic drug RG-2 (0,01-1 microM) was shown to have anticholinergic action competing with 0.2-1 mM carbachol. RG-2 (0.1-1 microM) produced dose-dependent increase of APD90% in rat and rabbit atrial cells and had no effects on other action potential parameters. In presence of carbachol RG-2 produced significantly greater increase of APD90% and caused significant increase of APD50%. Thus RG-2 exerts anticholinergic action, which can take important part in RG-2 antiarrhythmic activity.

Action Potentials↗
PubMed2004

[Antiplatelet effects of glycoproteins IIb-IIIa antagonist monafram].

First Russian glycoprotein (GP) IIb-IIIa antagonist, preparation Monafram, is the F(ab')2 fragment of anti-GP IIb-IIIa monoclonal antibody FRaMon. In in vitro experiments it was shown that Monafram blocked platelet aggregation induced by ADP and thrombin; reduced secretion from platelet granules; and due to simultaneous interaction with two GP IIb-IIIa molecules almost irreversibly bound to platelet surface. Monafram clinical trials were performed in healthy volunteers (n = 10) and in patients with ischemic heart disease undergoing high risk coronary angioplasty (n = 153). Monafram intravenous bolus administration at 0.25 mg/kg decreased ADP-induced platelet aggregation by more than 90, 80, 60 and 30% at 1, 12, 24 and 72 h after injection, respectively. No significant differences were detected between antiaggregatory effects of Monafram and ReoPro introduced at 0.25 mg/kg bolus + 12 h infusion at 0.125 microg/kg per min. Durable inhibition of aggregation after Monafram administration was mediated by platelet-bound preparation--free Monafram was cleared from plasma within 12 h, while platelet-bound preparation occupied more than 90, 70-80 and 40-50% of GP IIb-IIIa at 1, 12-24 and 72 h after injection, respectively. Major bleedings and allergic reactions were detected in none of patients, deep thrombocytopenia--in one patient and antibodies against Monafram--in 5% of patients. Within one month after coronary angioplasty Monafram decreased the number of end points (fatal and nonfatal myocardial infarction and angina recurrence) from 11.4 to 3.3%.

Antibodies, Monoclonal↗
PubMed2004

[Antiarrhythmic Efficacy of a New Class III Antiarrhythmic Drug RG-2.].

We studied effects of a new class III antiarrhythmic drug RG-2 in a canine model of vagally-mediated atrial fibrillation (AF). RG-2 was intravenously infused to anesthetized open-chest dogs in progressive doses (5, 10, 20 and 40 mg/kg, n=6) during vagally-induced AF. RG-2 significantly dose-dependently increased atrial effective refractory period (AERP) with and without vagal stimulation, but did not change conduction velocity. Five mg/kg terminated vagally-induced AF in 4 of 6 dogs but did not prevent AF reinduction. However, additional doses of drug 20 and 40 mg/kg successfully terminated AF in 100% as well as prevented AF reinduction in 50% and 72% of cases, respectively. Activation mapping (224 epicardial electrodes) showed that under drug influence there was gradual reduction of wavelet number until termination of the reentrant excitation. AF cycle length increased before AF termination from 91+/-4 to 140+/-8 ms (p<0.01). These changes correlated with drug-induced increasing of AERP. In conclusion, the ability of RG-2 to terminate and prevent reinduction of experimental AF appears to be associated with a significant prolongation of the AERP.

Animals↗
PubMed2003

[Effect of restoration of coronary blood flow on dynamics of myocardial perfusion and function in patients with acute myocardial infarction. Data of gated technetium-99m-sestamibi SPECT].

Effects of coronary blood flow restoration on dynamics of myocardial perfusion and function were studied in 50 patients with acute myocardial infarction during 6-month follow-up. Gated SPECT with 99mTc-MIBI (G-SPECT) was performed before onset of reperfusion procedures, in 24 hours, 10 days, 1 and 6 months. In patients with successful reperfusion (n=36) perfusion defect (PD) size decreased by 6.78+/-0.97% (p<0.001) and its severity by 221.3+/-85 std (p<0.001) in 24 hours. In 10 days PD size decreased by 3.9+/-0.88% (r<0.05) and severity by 149+/-39 std (p<0.05), whereas in 1 month PD size decreased by 2,18+/-1,4% (p<0.05), PD severity by 146.3+/-67 std (p<0.05). Successful reperfusion was associated with improvement of contractility: left ventricular ejection fraction increased by 3% (p<0.05) on day 10 of the disease. In patients with failed reperfusion PD size and severity decreased in 10 days by 4.8+/-4.2%, p<0.05, and 276+/-75 std, p<0.05, respectively, in 6 months PD size decreased by 3.1+/-0.9%, p<0.05, left ventricular ejection fraction did not change during follow-up. We conclude that successful reperfusion therapy promotes restoration of myocardial perfusion and improvement of its contractility.

Angioplasty, Balloon, Coronary↗
PubMed2003

[Ionic mechanisms of cardiotropic action of a new class III antiarrhythmic drug RG-2].

A perforated patch-clamp analysis of the effect of a novel class III antiarrhythmic agent RG-2, on voltage-dependent currents was made in rat ventricular myocytes. In these cells, RG-2 decreased delayed rectifier outward K(+) current, I(k), in concentration dependent manner with threshold concentration 0.1 microM/l. In contrast, the drug did not have significant effects on the transient outward and inward rectifier K(+) current. RG-2 in concentration dependent manner decreased Ca(2+) current (I(Ca,L)) with threshold concentration 1 microM/l, tenfold higher than threshold concentration for I(k). We can conclude that decreasing of I(k) may explain prolongation of cardiac repolarization induced by RG-2, and contribute to its antiarrhythmic action.

Animals↗
PubMed2003

[Electrophysiological experimental study of a novel class III antiarrhythmic drug RG-2].

The electrophysiologic effects of a new drug, RG-2 were studied on anesthetized open-chest dogs and on rabbit right atrial tissue. RG-2 was manufactured in Chemical-Pharmaceutical Institute in Moscow. Dogs (n=12) were anesthetized with sodium pentobarbital (30 mg/kg, i.v.). An ECG lead II, arterial blood pressure, His bundle electrogram, atrial and ventricular bipolar electrograms were continuously monitored, recorded and then analyzed by a computerized complex for electrophysiological study. Electrophysiological variables, ECG parameters, atrioventricular conduction (His electrogram) and blood pressure were determined after sequential i.v. administration of 1, 5, 10, 20, 40 and 80 ug/kg of RG-2. Interval between injections was 60 min. RG-2 had no significant effect on PQ, QRS, S-A, A-H and H-V intervals, but the drug caused dose-dependent increase of R-R and QT intervals. Moreover, RG-2 dose-dependently increased the atrial and ventricular effective refractory periods (AERP and VERP). Maximal increases of AERP and VERP registered at 5 min after administration of RG-2 (40 microg/kg) were 46+/-2% (p<0.001 vs control) and 23+/-6% (p<0.05 vs control), respectively. In the isolated rabbit right atrial tissue RG-2 (0.01 to 1 microM) had no effects on maximal diastolic potential, action potential amplitude and Vmax, but revealed concentration-dependent increase of action potential duration at 90% repolarization level (APD90%). The maximal effects on APD90% obtained after RG superfusion at 1 microM were 26+/-7% (p<0.001 vs control). We conclude that RG-2 has significant effects of class III antiarrhythmic drugs in vivo and in vitro.

Animals↗
PubMed2003

[Role of Chlamydia, mycoplasma and cytomegalovirus infection in the development of coronary artery disease].

AIM: To assess relationship between some infection factors and presence of coronary heart disease. MATERIAL: Patients with myocardial infarction (n=56), unstable angina (n=50), stable angina (n=50) and age - matched controls (n=49). METHODS: Levels of IgG, IgM, IgA antibodies to Chlamydia pneumonia, Chlamydia trachomatis, Chlamydia psittaci, IgG, IgM antibodies to Cytomegalovirus, and also of antibodies and antigen to Mycoplasma pneumoniae were measured in blood serum. RESULTS: Compared with controls patients with coronary heart disease had higher frequency of seropositivity to Chlamydia pneumonia, Mycoplasma pneumonia and Cytomegalovirus (p< 0.05 ) and similar levels of seropositivity to Chlamydia trachomatis and Chlamydia psittaci. Infectious burden (quantity of antibodies per one patient) was significantly higher in patients with myocardial infarction, unstable and stable angina than in controls (1.58, 1.42, 1.41 and 0.95, respectively). CONCLUSION: Our results confirm presence of association between infection and coronary heart disease.

Adult↗
PubMed2002

[Pharmacodynamics, safety, and clinical effects of a novel glycoprotein IIb/IIIa antagonist framon during high risk coronary angioplasty].

Preparation framon [F(ab')2 fragments of the anti-glycoprotein (GP) IIb/IIIa monoclonal antibody (FRaMon)] blocks fibrinogen binding to GP IIb/IIIa and platelet aggregation. Dynamics of platelet aggregation inhibition, safety, and clinical effects of framon were studied in high-risk coronary angioplasty. Twenty seven patients underwent angioplasty with framon, 29 - with abciximab and 28 - with no GP IIb/IIIa antagonists. Framon at 0.2 mg/kg (n=16) and 0.25 mg/kg (n=11) bolus administration inhibited platelet aggregation induced by 20 mcM ADP by more than 90%, 80%, 60% and 30% in comparison with the predrug level 1, 12, 24 and 72 h after injection, respectively. Almost the same dynamics of aggregation inhibition was observed upon abciximab administration at 0.25 mg/kg bolus + 0.125 mcg/kg/min infusion for 12 h. No signs of individual intolerance and side effects including allergic reactions and bleedings were detected in patients treated with framon. Slight decrease of platelet count (15-20%) was observed on the first day after framon administration. Antibodies against framon were detected in 1 out of 22 tested patients. Free (nonbound to platelets) framon was completely removed from the circulation 12 h after injection. The number of endpoints (death, myocardial infarction and indications for repeat revascularization) within 1 year after angioplasty was approximately the same in the groups with framon and abciximab - 7 of 25 (28%) and 7 of 28 (25%), respectively, and more than 1.5 fold higher in the group without GP IIb/IIIa blockers - 12 of 27 (44,4%).

Angioplasty, Balloon, Coronary↗
PubMed2001

[Inhibition of thrombocyte aggregation by F(ab')2-fragments of monoclonal antibodies FraMon (CRC64) to glycoproteins IIb-IIIa].

AIM: To study the effects of F(ab')2 fragments of the monoclonal antibody (monAB) FRaMon against glycoproteins (GP) IIb-IIIa on platelet aggregating activity in vitro and after injection to healthy volunteers. MATERIAL AND METHODS: In vitro experiments were performed to study effects of F(ab')2 and Fab fragments of FRaMon on platelet aggregation (PA) and 14C-serotonin secretion and characteristics of 125I-labelled F(ab')2 and Fab FRaMon binding to platelets. In vivo effects of F(ab')2 FRaMon (preparation FRAMON) were studied upon its bolus i.v. injection to 10 healthy volunteers at the doses of 0.025-0.2 mg/kg. PA was registered before and 1, 6, 12, 24 hours and 3 and 12-15 days after FRAMON injection. FRAMON binding to platelets in the vascular bed was evaluated by inhibition of 125I-FRAMON in vitro binding to platelets obtained from volunteers. Development of antibodies against FRAMON was evaluated by ELISA two weeks after FRAMON injection. RESULTS: In vitro F(ab')2 FRaMon completely blocked PA induced by ADP and thrombin at the concentrations < 4 and < 7.5 mcg/ml, respectively, and revealed higher inhibitory capacity than Fab FRaMon. F(ab')2 FRamon also inhibited 14C-serotonin secretion from ADP-activated platelets. F(ab')2 FRamon interacted with two GP IIb-IIIa molecules on one platelet and bound to platelets more tightly than Fab FRaMon. F(ab')2 FRaMon (preparation FRAMON) bolus i.v. injection to healthy volunteers at the doses of 0.025-0.2 mg/kg did not induce any signs of individual intolerance, including allergic reactions, bleeding and thrombocytopenia. FRAMON at 0.2 mg/kg almost completely inhibited ADP-induced PA of volunteer's platelets 1 h after injection and by more than 70% at 12 h and by more than 50% at 24 h after injection. PA ability recovered to normal 3 days after injection. Antibodies against FRAMON were detected in 1 out of 10 volunteers. CONCLUSION: F(ab')2 fragments of monAB FRaMon effectively inhibited aggregating ability both in vitro and after injection to healthy volunteers and could be suggested as a basis for development of a new GP IIb-IIIa antagonist.

Animals↗
PubMed2000

[Soluble P-selectin - a marker of platelet activation and vessel wall injury: increase of soluble P-selectin in plasma of patients with myocardial infarction, massive atherosclerosis and primary pulmonary hypertension].

AIM: A comparative analysis of the content of the soluble form of cell adhesion protein P-selectin in the blood plasma of patients with acute myocardial infarction (AMI), massive atherosclerosis (MA) and primary pulmonary hypertension (PPH), investigation of the relationship between plasma content of P-selectin and known markers of platelets and endothelial cells activation, preliminary assessment of the prognostic value of P-selectin determination. MATERIALS AND METHODS: This study included 16 patients with AMI, 20 patients with MA, 21 patients with PPH and 18 healthy donors. The follow-up was 1-5 years. End-points in the group of patients with AMI were recurrent acute coronary syndrome and coronary artery by-pass operation, in the group with MA--thrombotic complications (acute coronary syndrome, ischemic stroke) and in the group with PPH--death. P-selectin was measured by ELISA and platelet factor 4 (PF4), thromboxane B2 (TXB2), endothelin-I and stable prostacyclin metabolite 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) by means of commercial ELISA kits. RESULTS: Mean level of P-selectin in blood plasma of patients with AMI (1 day) (361 +/- 18 ng/ml), MA (410 +/- 31 ng/ml) and PPH (627 +/- 83 ng/ml) was increased in comparison with the group of healthy donors (269 +/- 12 ng/ml) (everywhere p < 0.001). In AMI, P-selectin was increased on day 1 only, on days 2, 3 and 10-14 of the disease the level of P-selectin was significantly lower than on day 1 and did not differ from the control level in the group of donors. In patients with MA a significant correlation was detected between plasma content of P-selectin and platelet activation marker PF4 (r = 0.606, P = 0.007) and in patients with PPH between the content of P-selectin and another platelet activation marker TXB2 (r = 0.622, p = 0.013). However, no correlation was found in PPH patients between the content of P-selectin and markers of endothelial activation and/or damage (endothelin-1 and 6-keto-PGF1 alpha). Difference in the concentration of P-selectin in patients with or without end-points during the follow-up period was detected in patients with AMI (353 +/- 14 ng/ml and 451 +/- 24 ng/ml, p = 0.009) and PPH (477 +/- 58 ng/ml and 927 +/- 184 ng/ml, p = 0.017) but not with MA (426 +/- 37 ng/ml and 361 +/- 24 ng/ml, p = 0.295). CONCLUSION: The level of P-selectin in plasma was increased in patients with acute thrombosis (AMI, 1 day) as well as in patients without clinical signs of thrombosis but with a massive injury of the vasculature (MA and PPH). The increase of P-selectin was, presumably, caused by its secretion from activated platelets since its concentration in plasma correlated with platelet concentration but not endothelial activation markers. Preliminary data indicate that blood plasma soluble P-selectin may be considered as a potential prognostic marker in AMI and PPH.

6-Ketoprostaglandin F1 alpha↗
PubMed1998

[The first original Russian class-III antiarrhythmic nibentan].

The paper presents experimental and clinical findings of the new antiarrhythmic drug nibentan. The agent was found to be a class-III antiarrhythmic agent in terms of its electrophysiological effects and an inhibitor of the delayed rectifier potassium current in terms of its effects on the ionic channels of cardiomyocytes. The clinical trial of nibentan shows that the drug is highly effective (in 70-100% of cases) in patients with atrial flutter and fibrillation and in those with supraventricular tachycardia and it is less effective in suppressing ventricular premature contractions and tachycardia. The rate of arrhythmogenic effects produced by the drug was inversely related to its antiarrhythmic action. Nibentan has been approved for clinical use.

Animals↗
PubMed1993

[Dynamic signal-averaged ECG during spontaneous stenocardia attacks in patients with ischemic heart disease].

The dynamics of signal-averaged ECG and late potentials was studied in 19 patients with coronary heart disease during spontaneous anginal episodes. Baseline late potentials were observed in 9 (45%) patients, they remaining in all during and after anginal episodes. The occurrence of new late potentials was recorded in none of them. There were no significant differences in some parameters of signal-averaged ECG before, during, and after an anginal episode, though the duration of low-amplitude signals tended to increase at the end of the QRS complex and the mean square amplitude of late 40 msec of QRS complex decreased during transient myocardial ischemia. The differences did not achieve their statistical significance. It was concluded that transient myocardial ischemia during spontaneous anginal episodes failed to lead to the appearance of a substrate for the occurrence of late potentials.

Angina Pectoris↗
PubMed1993

[The clinical aspects of using thrombolytic therapy in myocardial infarct at the prehospital stage].

The examination of 80 patients with acute myocardial infarction has revealed that prehospital thrombolytic therapy (TT) allows it to be initiated significantly earlier by 2.9 hours, resulting in coronary reperfusion and ensuring more complete blood flow recovery than hospital therapy. The natural history of the disease is also more favourable when TT is used in the prehospital period. It is concluded that with strict observance of indications and contraindications, TT used by an emergency team in the prehospital period is no more dangerous than in the hospital period.

Aged↗