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1.
Bull Exp Biol Med ; 176(4): 447-451, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38491254

ABSTRACT

The effect of a new JNK inhibitor IQ-1 (11H-indeno[1,2-b]quinoxalin-11-one oxime) was studied in male Wistar rats in a model of acute myocardial ischemia/reperfusion. Area at risk and myocardial infarct zones were studied in two series of experiments: 16 h after a single dose of IQ-1 (25 mg/kg intraperitoneally during cardiac ischemia) and on day 5 after its course administration (25 mg/kg intraperitoneally during cardiac ischemia and daily over 4 days). On day 5 after ischemia/reperfusion, cardiodynamic indicators were also studied: systolic, end-diastolic, and minimum pressure in the left ventricle, stress-time index, as well as the maximum rates of pressure rise and fall in the left ventricle (+dP/dtmax and -dP/dtmax). In 16 h after ischemia/reperfusion, the infarct area in the control was 24±2% of the total area of the sections, while after administration of IQ-1 this parameter was 14±1% (p<0.05). On day 5, the infarct area in the control group was 25±1% of the total area of myocardial sections. A course of IQ-1 administration led to a significant reduction in the infarct area to 10±2% of the total area of myocardial slices. Course administration of IQ-1 led to improvement in contractile function and weakening of the diastolic dysfunction of the left ventricle: systolic pressure in the left ventricle increased by 20%, +dP/dtmax by 23%, voltage-time index by 12%, -dP/dtmax by 43%, and the minimum pressure in the left ventricle decreased by 3.4 times.


Subject(s)
Coronary Artery Disease , Myocardial Infarction , Myocardial Reperfusion Injury , Rats , Male , Animals , Myocardial Reperfusion Injury/drug therapy , Rats, Wistar , Myocardial Infarction/drug therapy , Reperfusion
2.
Bull Exp Biol Med ; 173(1): 17-20, 2022 May.
Article in English | MEDLINE | ID: mdl-35624349

ABSTRACT

The effect of p-tyrosol on the main hemodynamic parameters and contractile function of the heart was studied and a morphometric assessment of left-ventricular remodeling was performed in Wistar rats 2 months after acute 1-h myocardial ischemia followed by reperfusion. p-Tyrosol in a dose of 20 mg/kg was injected intraperitoneally 5 times: 20 min before the start of reperfusion, 4 h after the start of reperfusion, and then once a day over the next 3 days. Administration of p-tyrosol to animals in the acute period of myocardial infarction slowed down the formation of systolic and diastolic myocardial dysfunction, improved the pumping function of the heart, maintained the hemodynamic parameters at a significantly higher level, and reduced left-ventricular remodeling in the late period of myocardial infarction. In 2 months after acute myocardial ischemia modeling, the dimensions of the left-ventricular cavity, the area of the postinfarction focus, and the area of connective tissue in rats treated with p-tyrosol were significantly lower than in the control group. In the group treated with p-tyrosol, no anterior left-ventricular wall aneurysms were found.


Subject(s)
Myocardial Infarction , Ventricular Remodeling , Animals , Myocardial Infarction/drug therapy , Phenylethyl Alcohol/analogs & derivatives , Rats , Rats, Wistar , Ventricular Function, Left
3.
Bull Exp Biol Med ; 169(3): 310-313, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32748134

ABSTRACT

2,6-Diisobornyl-4-methylphenol (Dibornol, 10 mg/kg intragastrically daily for 5 days after myocardial ischemia/reperfusion) 1.5-fold increased rat survival during the acute post-infarction period in comparison with the control group. In survivors, Dibornol reliably prevented post-ischemic progression of heart failure in the delayed post-infarction period (30 days after ischemia/reperfusion), which was seen from an increase in the left-ventricular developed pressure by 22%, left-ventricular contractility index by 19%, and +dP/dt by 34%. Left-ventricular end-diastolic pressure was by 39% lower than in control animals. Morphological study of heart sections from control group animals showed that Dibornol reduced the area of post-ischemic myocardial damage in the delayed period after ischemia/reperfusion to 3±1% (vs 18±2% in the control group).


Subject(s)
Cresols/therapeutic use , Heart Ventricles/drug effects , Myocardial Reperfusion Injury/drug therapy , Animals , Blood Pressure/drug effects , Cresols/chemistry , Heart/drug effects , Heart Ventricles/metabolism , Male , Myocardial Reperfusion , Myocardial Reperfusion Injury/metabolism , Rats
4.
Bull Exp Biol Med ; 165(5): 625-628, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30225710

ABSTRACT

We studied anti-ischemic activity of n-tyrozol under conditions of repeated transient myocardial ischemia in rats caused by repeated (5×3 min) occlusion of the left coronary artery. n-Tyrozol administered intraperitoneally in a dose of 20 mg/kg daily over 4 days before the ischemia modeling (the last injection 15 min prior to the start of the experiment) produced a clear-cut anti-ischemic effect: it reduced ST elevation and promoted more complete recovery of ECG during reperfusion. During reperfusion periods, n-tyrozol significantly decreased the risk of ventricular fibrillation and shortened the duration of tachyarrhythmia episodes (ventricular tachycardia and fibrillation).


Subject(s)
Arrhythmias, Cardiac/drug therapy , Cardiotonic Agents/pharmacology , Coronary Occlusion/drug therapy , Myocardial Ischemia/drug therapy , Myocardial Reperfusion Injury/drug therapy , Phenylethyl Alcohol/analogs & derivatives , Ventricular Fibrillation/drug therapy , Animals , Arrhythmias, Cardiac/physiopathology , Coronary Occlusion/physiopathology , Coronary Vessels/surgery , Drug Administration Schedule , Injections, Intraperitoneal , Myocardial Ischemia/physiopathology , Myocardial Reperfusion Injury/physiopathology , Phenylethyl Alcohol/pharmacology , Rats , Rats, Wistar , Treatment Outcome , Ventricular Fibrillation/physiopathology
5.
Bull Exp Biol Med ; 165(5): 657-659, 2018 Sep.
Article in English | MEDLINE | ID: mdl-30225716

ABSTRACT

We studied the cardioprotective effect of 2,6-diisobornyl-4-methylphenol under conditions of myocardial ischemia/reperfusion in rats. Daily administration of 2,6-diisobornyl-4-methylphenol (100 mg/kg intragastrically) over 3 days before and 5 days after modeling of myocardial ischemia/reperfusion prevented the increase in the infarction area by almost 2 times in comparison with the control by day 5 after recirculation. The type and severity of pathological changes in ECG parameters reflecting necrotic changes in the myocardium under the action of the compound significantly decreased by day 35 of the experiment. Animal survival rate during the first 24 h after ischemia/reperfusion modeling in the experimental group was by 29% higher than in the control group.


Subject(s)
Anti-Arrhythmia Agents/pharmacology , Antioxidants/pharmacology , Boron Compounds/pharmacology , Cardiotonic Agents/pharmacology , Cresols/pharmacology , Myocardial Infarction/drug therapy , Myocardial Reperfusion Injury/drug therapy , Animals , Anti-Arrhythmia Agents/chemical synthesis , Antioxidants/chemical synthesis , Boron Compounds/chemical synthesis , Cardiotonic Agents/chemical synthesis , Coronary Occlusion/drug therapy , Coronary Occlusion/mortality , Coronary Occlusion/physiopathology , Coronary Vessels/surgery , Cresols/chemical synthesis , Drug Administration Schedule , Gastric Absorption , Heart Rate/drug effects , Male , Myocardial Infarction/mortality , Myocardial Infarction/physiopathology , Myocardial Reperfusion Injury/mortality , Myocardial Reperfusion Injury/physiopathology , Rats , Rats, Wistar , Survival Analysis
6.
Bull Exp Biol Med ; 157(2): 211-4, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24952488

ABSTRACT

We studied the effects of novel sterically hindered phenol, 4-methyl-2,6-diisobornyl phenol (dibornol) on the rheological properties of the blood in the model of myocardial ischemia/reperfusion. Dibornol (100 mg/kg intraperitoneally for 3 days before and 5 days after ischemia/reperfusion) decreased blood viscosity by 9-25% in comparison with that in sham-operatedanimals by modulating cellular (erythrocyte deformability and aggregation) and plasma (plasma viscosity) rheological parameters. Normalization of blood rheology under the influence of dibornol increased the availability of oxygen to tissues at high shear rates by 9-18% after acute ischemia/reperfusion in rats.


Subject(s)
Camphanes/pharmacology , Camphanes/therapeutic use , Cresols/pharmacology , Cresols/therapeutic use , Myocardial Ischemia/drug therapy , Animals , Blood Viscosity/drug effects , Erythrocyte Deformability/drug effects , Male , Rats , Rats, Wistar
7.
Eksp Klin Farmakol ; 74(7): 19-21, 2011.
Article in Russian | MEDLINE | ID: mdl-21894763

ABSTRACT

The effect of flaxseed extract (FSE) containing 42% secoisolariciresinol diglucoside on the blood plasma estradiol level and theological properties of blood in female Wistar rats after ovariectomy was investigated by measuring hematocrit, fibrinogen concentration, platelet aggregation and deformability, and the whole blood and plasma viscosity. Bilateral ovariectomy in rats led (in comparison to sham-operated animals) to a decrease in the estrogen level to 59% and produced a 5-9% increase in the whole blood viscosity, which was caused by impairment of the erythrocyte deformability and aggregation. The efficacy of oxygen transport to tissues was decreased by 4-7%. The treatment of ovariectomized rats with FSE (peroral administration at a daily dose of 40 mg/kg for 14 days) reduced the whole blood viscosity by 4-11% and increased the coefficient of oxygen transport to tissues by 5-11%, but did not restore the estrogen level. Thus, the hemorheological effect of FSE reduces to the improvement of microrheological parameters (decrease in erythrocyte aggregation and increase in their deformability) without the modification ofmacrorheological parameters (hematocrit, plasma viscosity and fibrinogen level).


Subject(s)
Butylene Glycols/pharmacology , Estradiol/blood , Flax/chemistry , Glucosides/pharmacology , Ovariectomy/adverse effects , Plant Extracts/pharmacology , Animals , Blood Viscosity/drug effects , Erythrocyte Aggregation/drug effects , Erythrocyte Deformability/drug effects , Female , Fibrinogen/analysis , Hematocrit , Plant Extracts/chemistry , Plants/chemistry , Platelet Aggregation/drug effects , Rats , Rats, Wistar
8.
Eksp Klin Farmakol ; 74(12): 36-9, 2011.
Article in Russian | MEDLINE | ID: mdl-22379881

ABSTRACT

Optimum design of preclinical research for pharmacological agents influencing the rheological properties of blood is presented. Models of hyperviscosity syndrome and approaches to studying the hemorheological activity mechanisms are described.


Subject(s)
Blood Viscosity/drug effects , Drug Evaluation, Preclinical , Hemorheology/drug effects , Research Design , Algorithms , Animals , Humans
9.
Bull Exp Biol Med ; 147(2): 204-7, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19513422

ABSTRACT

Antithrombogenic and antiplatelet effects of a new drug, containing isoflavonoids (extract from the wood of Maackia amyrensis, a Far Eastern plant), were studied. A course (200 mg/kg intragastrically during 14 days) of Maackia amyrensis extract prevented intravascular clotting, initiated by application of 10% iron chloride solution on the vessel. The drug increased antiaggregant activity of the vascular wall and potentiated endothelium-dependent vasodilatation in ovariectomied rats. The reference drug ethinylestradiol (25 mug/kg intragastrically during 14 days) potentiated the antiaggregant effect of the endothelium, but was inferior to Maackia amyrensis extract in the capacity to induce endothelium-dependent vasodilatation in ovariectomied rats.


Subject(s)
Blood Coagulation/drug effects , Fibrinolytic Agents/pharmacology , Maackia/chemistry , Plant Extracts/pharmacology , Platelet Aggregation Inhibitors/pharmacology , Vasodilation/drug effects , Animals , Ethinyl Estradiol/pharmacology , Female , Isoflavones/pharmacology , Ovariectomy , Rats , Rats, Wistar , Vasodilator Agents/pharmacology
10.
Bull Exp Biol Med ; 146(1): 92-5, 2008 Jul.
Article in English | MEDLINE | ID: mdl-19145361

ABSTRACT

Ovariectomy reduces blood levels of sex hormones and considerably increases blood viscosity due to an increase in hematocrit and plasma fibrinogen content, disorders in viscoelastic characteristics of erythrocytes, and increase of their aggregation activity. Changes in the macrorheology are mainly responsible for the development of the hyperviscosity syndrome.


Subject(s)
Blood Flow Velocity , Blood Viscosity , Ovariectomy , Animals , Erythrocyte Aggregation , Estrogens/blood , Female , Fibrinogen/metabolism , Hematocrit , Hemodynamics , Humans , Progesterone/blood , Rats , Rheology , Syndrome
11.
Eksp Klin Farmakol ; 71(6): 28-30, 2008.
Article in Russian | MEDLINE | ID: mdl-19140512

ABSTRACT

Ovariectomy in rats induces the activation of lipid peroxidation processes, reduces total lipid content, and decreases the accumulation of lysophospholipids in erythrocyte membranes. The administration of Maackia amurensis extract (200 mg/kg, p.o., during 14 days) reduces the level of lipid peroxidation, prevents a decrease in the total lipid content, normalizes the proportion of lipids and proteins, and eliminates the accumulation of lysophospholipids in erythrocyte membranes in ovariectomized rats.


Subject(s)
Antioxidants/pharmacology , Erythrocyte Membrane/drug effects , Lipid Peroxidation/drug effects , Lipids/analysis , Maackia/chemistry , Animals , Erythrocyte Membrane/metabolism , Estradiol/blood , Ethinyl Estradiol/pharmacology , Female , Lipid Metabolism/drug effects , Lipid Peroxides/blood , Ovariectomy , Plant Extracts/pharmacology , Rats , Rats, Wistar
13.
Eksp Klin Farmakol ; 58(2): 27-9, 1995.
Article in Russian | MEDLINE | ID: mdl-7773083

ABSTRACT

In experiments on rats with cerebral ischemia (30-min occlusion of carotid arteries), the novel calcium antagonist Cerebrocrast (0.4 microgram.kg-1.min-1 i.v. for 15 min) was found to provide the functional maintenance of the parietal cerebral bed in the postischemic period by improving cerebral hemodynamics, reducing the number of highly narrowed capillaries. The agent prevented the erythrocytic accumulation of lipid peroxidation (LPO) products (diene conjugates and Schiff bases) in the intra- and postischemic periods, promoted the maintenance of viscoelastic properties during LPO activation.


Subject(s)
Calcium Channel Blockers/pharmacology , Cerebrovascular Circulation/drug effects , Dihydropyridines/pharmacology , Ischemic Attack, Transient/prevention & control , Vasodilator Agents/pharmacology , Acute Disease , Animals , Calcium Channel Blockers/therapeutic use , Cerebrovascular Circulation/physiology , Dihydropyridines/therapeutic use , Drug Evaluation, Preclinical , Ischemic Attack, Transient/metabolism , Ischemic Attack, Transient/physiopathology , Lipid Peroxidation/drug effects , Male , Microcirculation/drug effects , Microcirculation/physiology , Rats , Vasodilator Agents/therapeutic use
15.
Eksp Klin Farmakol ; 57(1): 25-7, 1994.
Article in Russian | MEDLINE | ID: mdl-8142857

ABSTRACT

The effects of ethomersole (50 mg/kg orally during 10 days) on local cerebral blood flow and cerebral tissue impedance were investigated in rats after left carotid artery ligation and right carotid artery narrowing (blood flow was decreased to 50%). Under these conditions, ethomersole accelerated the blood flow recovery, levelled blood flow asymmetry between the hemispheres, decreased the development of brain edema. In in vitro experiments ethomersole demonstrated a pronounced limitation of cerebral lipid peroxidation.


Subject(s)
Benzimidazoles/therapeutic use , Brain Edema/drug therapy , Brain Ischemia/drug therapy , Cerebrovascular Circulation/drug effects , Vasodilator Agents/therapeutic use , Animals , Benzimidazoles/pharmacology , Brain/drug effects , Brain/physiopathology , Brain Edema/etiology , Brain Edema/physiopathology , Brain Ischemia/complications , Brain Ischemia/physiopathology , Chronic Disease , Drug Evaluation, Preclinical , Electric Impedance , Male , Rats , Rats, Wistar , Time Factors , Vasodilator Agents/pharmacology
16.
Eksp Klin Farmakol ; 56(3): 35-7, 1993.
Article in Russian | MEDLINE | ID: mdl-8219988

ABSTRACT

The new calcium antagonist cerebrocrast intravenously infused in a dose of 0.4 micrograms.kg-1.min-1 during 15 min prevented erythrocyte deformability disturbances at the end of cerebral ischemia in rats, which was induced by carotid artery occlusion during 30 min. The agents also prevented the deformability 1 hour after the onset of recirculation. Cerebrocrast reduced spontaneous erythrocyte aggregation, the strength of erythrocytic aggregates, and hemoglobin affinity for oxygen. The latter effect was associated with the drug-induced increase in erythrocytic 2,3-diphosphoglycerate levels.


Subject(s)
Calcium Channel Blockers/pharmacology , Dihydropyridines/pharmacology , Erythrocytes/drug effects , Animals , Calcium Channel Blockers/therapeutic use , Dihydropyridines/therapeutic use , Drug Evaluation, Preclinical , Erythrocyte Aggregation/drug effects , Erythrocyte Deformability/drug effects , Erythrocytes/physiology , Hydrogen-Ion Concentration , Ischemic Attack, Transient/blood , Ischemic Attack, Transient/drug therapy , Male , Oxyhemoglobins/drug effects , Oxyhemoglobins/metabolism , Rats , Time Factors
17.
Biull Eksp Biol Med ; 114(10): 378-80, 1992 Oct.
Article in Russian | MEDLINE | ID: mdl-1288692

ABSTRACT

Acute cerebral ischemia in cats (both carotid arteries occlusion during 30 min after permanent occlusion of both vertebral arteries) was accompanied by postischemic hypoperfusion and hypo-oxygenation of the cerebral tissue. Intravenous infusion of cerebrocrast (1 micrograms.kg-1.min-1 during 60 min) prevented manifestation of the postischemic phenomena. Antihypoxic effect of cerebrocrast involved the cerebral blood flow increase, brain oxygen consumption lowering and Hb-O2-affinity decrease.


Subject(s)
Calcium Channel Blockers/therapeutic use , Dihydropyridines/therapeutic use , Ischemic Attack, Transient/drug therapy , Vasodilator Agents/therapeutic use , Acute Disease , Animals , Brain/drug effects , Brain/metabolism , Cats , Drug Evaluation, Preclinical , Female , Hemodynamics/drug effects , Ischemic Attack, Transient/physiopathology , Male , Oxygen Consumption/drug effects , Time Factors
18.
Eksp Klin Farmakol ; 55(4): 11-3, 1992.
Article in Russian | MEDLINE | ID: mdl-1458175

ABSTRACT

In rat experiments during brain ischemia (30-min carotid artery occlusion), ethomersol administered intraperitoneally in a dose of 50 mg/kg before occlusion or at the end of ischemia eliminated postischemic hypoperfusion. The effect of the drug was due to its spasmolytic and antiaggregatory activities. An analysis of the vasodilating action of ethomersol revealed its capacity to block potential-dependent calcium channels and partially intracellular calcium mobilization when the adrenergic and serotoninergic receptors were activated. The antiaggregatory activity of the drug appeared as inhibited platelet aggregation, which was induced by ADP, serotonin, arachidonic acid, thrombin, and as enhanced antiaggregatory activity of the vascular wall.


Subject(s)
Benzimidazoles/therapeutic use , Calcium Channel Blockers/therapeutic use , Ischemic Attack, Transient/drug therapy , Platelet Aggregation Inhibitors/therapeutic use , Vasodilator Agents/therapeutic use , Animals , Drug Evaluation, Preclinical , Drug Interactions , Ischemic Attack, Transient/complications , Ischemic Attack, Transient/prevention & control , Platelet Aggregation/drug effects , Rabbits , Rats , Time Factors
20.
Biull Eksp Biol Med ; 113(5): 504-6, 1992 May.
Article in Russian | MEDLINE | ID: mdl-1421270

ABSTRACT

Cerebral ischemia in rats (both carotid arteries occlusion) during 30 min, 3 hours and recirculation (1 hour) after ischemia (30 min) stimulated diene conjugates and fluorescent products accumulation in brain tissue. Intraperitoneal injection of sodium hydroxybutyrate (100 mg/kg), bemitil (50 mg/kg), ethomersol (50 mg/kg) reduced brain lipid peroxidation and did not yield in this respect to emoxypin (5 mg/kg). In contrast to emoxypin, sodium hydroxybutyrate, bemitil and ethomersol had no antiradical activity.


Subject(s)
Antioxidants , Benzimidazoles/therapeutic use , Brain Ischemia/drug therapy , Picolines/therapeutic use , Sodium Oxybate/therapeutic use , Animals , Arterial Occlusive Diseases/drug therapy , Carotid Artery Diseases/drug therapy , Rats , Rats, Wistar
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