PubMed Health⌕ Search

Biomedical subjects

O V Tskitishvili

Publications and source records attributed to O V Tskitishvili.

At least 19 recordsLinked to original sources
PubMed2006

Metabolic correction reduces the area of acute ischemic myocardial infarction in rats.

The possibility of decreasing the degree of irreversible alterations in cardiomyocytes with original saline reperfusion solution enriched with L-aspartic acid, D-glucose, and Dmannitol was studied on experimental rats with regional ischemia and reperfusion. Infusion of the test solution into the left ventricle during the early reperfusion stage significantly reduced the area of myocardial infraction. This effect was accompanied by improvement of energy metabolism and decrease in damage to cell membranes in the risk zone. Our results indicate that metabolic protection during reperfusion increases myocardial resistance to ischemic and reperfusion stress.

Animals↗
PubMed2005

[Protection of rat heart myocardium with a selective Na(+)/H(+) exchange inhibitor and ischemic preconditioning].

Aim of this study was to compare effects of BIIB-722, a novel Na(+)/H(+) exchanger-1 inhibitor, and ischemic preconditioning (IP) on infarct size and metabolism of area at risk in rats. Regional ischemia was induced by 40-min occlusion of a diagonal branch of left anterior descending coronary artery (LAD); it was followed by 60-min reperfusion. Intravenous bolus injection of BIIB-722 (3 mg/kg) dissolved in 280 mM xylitol was performed before regional ischemia or during the first minute of reperfusion. In the control group 280 mM xylitol was infused before ischemia or at the beginning of reperfusion at the same mode. IP was initiated by two cycles of 5-min LAD occlusion followed by 5-min reperfusion prior to sustained regional ischemia. Microdialysis technique was used to monitor pH and inorganic phosphate (P(i)) in the interstitial fluid of the area at risk. Metabolic state of the area at risk was assessed by ATP, phosphocreatine (PCr) and lactate levels; cellular membrane damage was evaluated by total creatine (SigmaCr=PCr+Cr) tissue content. Myocardial infarct size was determined by computer planimetry after staining of left ventricular slices with 2,3,5-triphenyltetrazolium chloride. BIIB-722 administration before or after ischemia, as well as IP, had no effect on cardiac hemodynamics and acid-base indices of arterial blood throughout the experiments. The infarct size/area at risk ratio was 43.5+/-5.2% in control and was reduced to 11.4+/-3.1% with IP, and to 17.0+/-3.6% and 25.8+/-2.6% with BIIB-722 infused on early reperfusion and before ischemia, respectively. BIIB-722 administration during the first minute of reperfusion as well as IP significantly augmented ATP and PCr contents, reduced lactate level and decreased ECr loss at the area at risk by the end of reperfusion as compared with values in control. Additionally significantly higher rates of pH recovery and reduction of P(i) concentration in the interstitial fluid were observed during reperfusion compared with these indices in control. BIIB-722 administration before ischemia had much effects on contents of energy and carbohydrate metabolites at area at risk. The results obtained indicate that ability of BIIB-722 to limit infarct size and improve metabolism in the area at risk is comparable to cardioprotective effects of IP. Therefore this study substantiates a possibility of application of a novel Na(+)/H(+) exchange inhibitor for clinical investigations.

Adenosine Triphosphate↗
PubMed2003

[Effects of Na(+)/H(+)-exchanger inhibition on metabolism of area at risk and myocardial infarct size in dogs].

The aim of this work was to study cardioprotective effects of BIIB 722, a novel Na(+)/H(+) exchanger-1 inhibitor, during regional ischemia and reperfusion in canine myocardium. The experiments were carried out on anaesthetized dogs intubated and artificially ventilated with room air enriched with oxygen. Regional ischemia was induced by 30-min occlusion of a diagonal branch of left anterior descending coronary artery (LAD), which was followed by 60-min reperfusion. BIIB 722, dissolved in 280 mM xylitol, was infused intracoronary for 10 min prior to LAD occlusion and at the beginning of reperfusion at the rate of 1 ml/min (30 microg/g myocardial tissue). In the control group, 280 mM xylitol was used for intracoronary administration with the same regimen. Microdialysis probes were implanted in the region of LAD occlusion to monitor interstitial pH, inorganic phosphate (Pi) and hydroxyl radical adduct. Energy state of the area at risk was evaluated by ATP and phosphocreatine (PCr) contents, cell membrane damage was assessed by total creatine (SigmaCr=PCr+Cr) tissue content. Myocardial infarct size was determined by staining with Evans Blue dye and further incubation of left ventricular slices in 2,3,5-triphenyltetrazolium chloride. The percentage ratio of infarct size to area at risk was calculated by computer planimetry. BIIB 722 administration had no effect on cardiac hemodynamics and acid-base indices of arterial blood throughout the experiments but induced 1.8-fold reduction of myocardial infarct size comparing with control. Treatment with BIIB 722 decreased acidification of the interstitial fluid following ischemia and facilitated recovery of pH to initial value on reperfusion. This effect was combined with significantly less Pi formation in the area at risk during LAD occlusion and reduction of this index to the initial value during reperfusion. At the end of reperfusion, the treated group showed augmented recovery of ATP and PCr tissue levels and higher content of SigmaCr comparing with the control. Additionally, BIIB 722 treatment markedly decreased generation of free oxygen radicals following LAD occlusion and completely avoided their formation on early reperfusion. The results indicate that BIIB 722 ability to limit myocardial infarct size in dogs is tightly connected with its influence on energy metabolism and oxygen radical generation.

Animals↗
PubMed1995

Allopurinol: kinetics, inhibition of xanthine oxidase activity, and protective effect in ischemic-reperfused canine heart as studied by cardiac microdialysis.

With microdialysis, we monitored cardiac interstitial fluid (ISF) levels of allopurinol, its metabolites, and the adenine nucleotide breakdown products (ANBP), inosine, hypoxanthine (HYP), xanthine (Xa), uric acid (UA) in dogs that received 1 and 10 mg/kg allopurinol intravenously (i.v.). Half-life (t1/2) of drug penetration into the heart was dose independent (1.8 min), whereas for the 10-mg/kg dose terminal elimination t1/2 (96 min) was much prolonged and ISF clearance (9.6 l/min kg) was reduced as compared with that induced by 1 mg/kg (28 min and 30.4 l/min kg) probably due to capacity limitation of allopurinol conversion to oxypurinol by Xa dehydrogenase/oxydase (Xa D/O). Inhibition of Xa D/O activity by allopurinol resulted in a dose-dependent increase in ISF HYP and Xa levels and a decrease in UA level. For a 10-mg/kg dose, maximal effect was attained approximately 40 min after drug injection. Allopurinol (1 mg/kg) given 30 min after the start of 40-min coronary artery occlusion during ischemia entered the ischemic zone ISF very slowly as compared with that of the control zone; the no-reflow phenomenon was evident because the levels became similar in both zones only 15 min after initiation of reperfusion. To examine cardioprotective efficiency, we administered allopurinol (10 mg/kg) 40 min before 40-min occlusion; it had little effect on total ANBP release during ischemia but facilitated washout of ANBP from the ischemic zone during reperfusion, thus manifesting protective efficacy against reperfusion injury and no-reflow. As shown by the lack of ischemia-induced increase in ISF Xa, myocardial Xa D/O activity was completely blocked by allopurinol.

Adenine Nucleotides↗
PubMed1994

Microdialysis study of ischemia-induced hydroxyl radicals in the canine heart.

A new experimental approach for spin-trapping of oxygen radicals in a selected region of the heart in situ is described. This approach is based on microdialysis, and it permits the detection of oxygen radicals in conditions of local ischemia and restoration of normal blood flow. Increased hydroxyl radical generation in an ischemic area of canine myocardium, as a result of 40 min local occlusion, has been studied.

Animals↗
PubMed1992

Cardiac microdialysis measurement of extracellular adenine nucleotide breakdown products during regional ischemia and reperfusion in canine heart: protective effect of propranolol against reperfusion injury.

Using cardiac microdialysis, we studied release of the adenine nucleotide breakdown products (ANBP) adenosine (ADS), inosine (INS), and hypoxanthine (HYP) into the interstitium of canine myocardium during 20- and 40-min occlusion of the anterior descending coronary artery and reperfusion. Dialysate ANBP concentrations reached maximum values not at the end of ischemia but in the first 10 min of reperfusion. The effect was more pronounced after 20-min ischemia. Further reperfusion led to an ANBP decrease that was more prolonged after 40-min ischemia. Pretreatment with DL-propranolol (0.5 mg/kg, intravenously, i.v.) given 40 min before coronary occlusion had no effect on adenine nucleotide catabolism rate during 20- and 40-min ischemia, but it facilitated washout of ANBP from ischemic zone immediately after the start of reperfusion. A similar effect was elicited by a D-stereoisomer of propranolol with no beta-adrenoceptor blocking activity. Results suggest that the reperfusion injury and probably the no-reflow phenomenon were the cause of enhanced adenine nucleotide catabolism at the beginning of reperfusion and prolonged ANBP washout from the ischemic zone. Reduction of reperfusion injury by propranolol could be related to the membrane stabilizing and antioxidant activity of this agent. Examination of DL-propranolol kinetics in arterial and coronary venous blood plasma showed that drug accumulation in the myocardium was almost maximum at the start of ischemia; therefore, the efficiency of cardio-protection with DL-propranolol was not limited by pharmacokinetic causes. Insertion of an additional microdialysis probe in the myocardium allowed monitoring of extracellular propranolol concentrations.

Adenine Nucleotides↗
PubMed1991

[Effect of echinochrom on experimental myocardial reperfusion injury].

Echinochrom, a new antioxidant of the polyhydroxynaphthaquinone class, was tested for its cardioprotective activity in a model of occlusive reperfusion myocardial infarction (90-min occlusion and 4-hour reperfusion) in the acute experiments with open-chest dogs. The bolus intravenous injection of echinochrom in a dose of 1 mg/kg 5 min before reperfusion caused a significant (over 40%) reduction in the size of a necrotic focus. A supplementary administration of echinochrom 5 min after the onset of ischemia failed to contribute to a significant enhancement of its protective effect, suggesting that there is no substantial effect of the agent on ischemic lesion. The efficacy of echinochrom given after prolonged ischemia, low effective doses, and no adverse effects create prerequisites for using the drug in the clinical setting.

Animals↗
PubMed1990

[A method of modeling of occlusion-reperfusion induced myocardial infarction and quantitative evaluation of the effectiveness of limitation of its size].

An experimental mathematical model was proposed to assess the efficiency of experimental myocardial infarction (MI) size limitation. A canine model of occlusion-reperfusion myocardial lesion was used in an acute experiment with an open chest. 90-minute occlusion and 4-hour reperfusion were performed by carotid coronary bypass surgery. The necrotic zone and the risk area were visualized by double perfusion with tetrazolium staining. Retrograde coronary blood flow was used as a measure of collateral blood flow. The multiple linear regression equation with values of the risk zone and retrograde blood flow/risk area ratio used as independent variables enabled the size of myocardial infarction to be highly accurately predicted. Comparison of the true size of MI with the "expected" one provided methods for quantitative assessment of pharmacological limitation of MI sizes. Calculating an individual value for each animal made it possible to examine its relation to coronary circulation parameters and facilitated comparison of benefits from various agents.

Animals↗
PubMed1988

[Effect of a decrease in perfusion pressure on the alpha-adrenergic reactions of the coronary vessels].

Acute dog experiments involving the perfusion of donor coronary arteries demonstrated that alpha-adrenoreceptor stimulation in the presence of a beta-adrenergic block resulted in a 30% drop of coronary flow. This response is maintained at low perfusion coronary blood pressure values (up to 25 +/- 13 mmHg, p less than 0.02), whereas coronary dilatation reserve is already fully depleted at 60 +/- 8 mmHg, suggesting that the degree of coronary arterial stenosis associated with coronary insufficiency may be a decisive factor shaping coronary response to alpha-adrenoreceptor stimulation.

Animals↗
PubMed1985

Function and metabolism of dog heart in ischemia and in subsequent reperfusion: effect of exogenous glutamic acid.

The effect of intravenous infusion of glutamic acid on cardiac contractile function during short-term ischemia and subsequent reperfusion was studied in anaesthetized dogs. Left ventricular ischemia was induced by underperfusion of the anterior descending and circumflex coronary arteries. Infusion of glutamic acid at 3 mg/kg/min resulted in less depression of cardiac function when given after a 2 min period of 60% coronary blood flow reduction: left ventricular systolic pressure decreased by 9% vs. 22%, dP/dt decreased by 16% vs. 29%, the double product (left ventricular systolic pressure by heart rate) was reduced by 16% vs. 31%. When reperfusion was carried out during glutamic acid infusion there was a significantly enhanced recovery in cardiac function. The augmentation of cardiac performance in ischemia and reperfusion caused by glutamic acid was not accompanied by changes in myocardial oxygen consumption. Glutamic acid uptake by the ischemic myocardium increased 2-fold during infusion. This led to cessation of ammonia release from the heart due to stimulation of glutamine synthesis, and an enhancement of alanine formation coupled with pyruvate uptake but it did not effect lactate production. However, glutamic acid infusion did not influence cardiac performance and metabolism under conditions of normal coronary flow. The results suggest that elevation of glutamate arterial concentration exerts a beneficial effect on ischemic heart. The mechanisms of the protective action are discussed.

Alanine↗
PubMed1985

[Correction of contractile function and metabolism in canine ischemic myocardium due to exogenous glutamic acid].

The effect of intravenous glutamic acid infusion (3 mg/kg/min) was studied during myocardial ischemia and reperfusion in anesthetized dogs. Left ventricular ischemia was induced by underperfusion of the anterior descending and circumflex coronary arteries. Glutamic acid reduced the ischemic contractile depression 2 min after a 60%-reduction of the coronary blood flow. The left ventricular systolic pressure was decreased by 9% versus 22%, dP/dt by 16% versus 29%, left ventricular systolic pressure heart rate product by 16% versus 31%. Reperfusion with glutamic acid improved the recovery of cardiac performance without any increase in myocardial oxygen consumption. Glutamic acid infusion resulted in a 2-fold augmentation of glutamate uptake by the ischemic myocardium. It led to cessation of ammonia release by the heart due to activation of glutamine synthesis, enhancement of alanine formation coupled with pyruvate utilization and did not change lactate production. The mechanisms of the protective action of glutamic acid are discussed.

Alanine↗
PubMed1983

Changes in coronary blood flow produced by the coronary artery occlusion.

The influence of the occlusion of one coronary artery on coronary blood flow in an intact myocardium was investigated in narcotised dogs with open chest by using the crossed circulation method. Interruption of blood inflow to one of the branches of the left coronary artery under autoperfusion of the coronary bed led to a drop in the blood flow rate in the intact branch of the same artery, which was caused by decreased perfusion pressure. Stabilization of coronary perfusion pressure made it possible to detect the dilatatory reaction of the intact coronary bed to the occlusion of one of the coronary arteries. On the basis of an analysis of the dilatatory reaction, conclusions are drawn about the reflex nature of the observed phenomenon. The results of experiments with selective pharmacological blockade of both parts of the autonomous nervous system suggest that the afferent and efferent pathways run in the sympathetic nervous system.

Afferent Pathways↗
PubMed1983

[Role of oxygen extraction from coronary blood in the regulation of oxygen transport to the myocardium].

Experiments on anesthetized dogs were made to examine oxygen extraction from coronary blood during increase and decrease in cardiac rhythm frequency under varying conditions of vasomotor regulation. With an initially high tone of the coronary vessels both increase and reduction of myocardial oxygen supply occurred at the expense of vasomotor reactions. Under these conditions the coronary blood flow velocity and systolic rhythm correlated well. At the same time the oxygen level in coronary blood did not experience noticeable changes. As the initial tone of the coronary vessels dropped, vasomotor reactions were attenuated and oxygen extraction from coronary blood underwent alterations which had occurred prior to depletion of the coronary expanding reserves. The data obtained suggest that reduction of the initial tone of the coronary vessels proceeds non-uniformly, leading to a decrease in vascular sensitivity to the tissue oxygen level.

Animals↗
PubMedDate not supplied

[Free radical centers in the dog myocardial tissue in regional ischemia].

The effect of regional ischemia on canine myocardial in situ free radical species was studied by the EPR method. Rapid fixation of heart muscle samples by freezeclamping was performed at the following physiological states: native myocardial blood circulation, regional ischemia with the presence of collateral circulation, total ischemia, and postischemic reperfusion. EPR spectra of the samples at -40 degrees C exhibited two free radical signals from the semireduced forms of ubiquinone and flavine coenzymes. Upon transition from normal blood supply to regional ischemia, an increase in the contribution of the flavine signal was registered, but reperfusion resulted in the recovery of the characteristics of EPR signals. It was found that the increase in the intensity of collateral circulation in the ischemic area led to an increase in the portion of ubisemiquinone in the integral EPR signal, whereas in total ischemia this signal was not registered. It was shown that the changes in spectral characteristics of integral free radical signals are accompanied by changes in their relaxation parameters.

Animals↗
PubMedDate not supplied

[Microdialysis study in vivo of the release of adenine nucleotide degradation products into intercellular space of canine myocardium during regional ischemia and reperfusion].

Intercellular concentrations of adenine nucleotide degradation products (ANDP)--adenosine inosine and hypoxanthine--in ischemic and control regions of the canine myocardium were measured by microdialysis technique during 20- and 40-min coronary artery occlusion and reperfusion. In hearts that fibrillated on reperfusion during the ischemic 40-min period catabolism of adenine nucleotides was more intensive, which could be the min cause of the reperfusion ventricular fibrillation. Reperfusion ventricular fibrillation was accompanied by an increase in the intercellular ANDP level in the control region, that indicated the development of the total myocardial ischemia. During the initial period of reperfusion after 20-min, a sharp increase in the interstitial ANDP level was observed in the ischemic region as compared with the end of the ischemia which could be explained as a result of demasking of reperfusion damage in such a case. The 40-min reperfusion induced slow reduction of the intercellular ANDP level in the ischemic region, while the regional blood flow already 5 min after the reperfusion did not differ from the blood flow in the control region. It is supposed that a slow washout of ANDP could be caused by the "no-reflow" phenomenon.

Adenine Nucleotides↗