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O I Pisarenko

Publications and source records attributed to O I Pisarenko.

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↗
PubMed2006

Efficiency of cardioplegic solutions containing L-arginine and L-aspartic acid.

In experiments on rats we studied the effects of cardioplegic solutions with L-aspartic acid or L-arginine on functional recovery and metabolism of isolated working heart after 40-min normothermal global ischemia and 30-min reperfusion. After reperfusion of the hearts preventively protected with cardioplegic solution containing L-aspartic acid or L-arginine, coronary flow decreased in comparison with the initial values. As a component of cardioplegic solution, L-arginine was less efficient in recovery of contractility and cardiac output of the hearts in comparison with L-aspartic acid. In hearts protected with L-aspartic acid, the postischemic levels of ATP and phosphocreatine were significantly higher, and the level of lactate was significantly lower than in hearts protected with L-arginine. In comparison with L-arginine, L-aspartic acid is a more efficient component of cardioplegic solution in protection of the heart from metabolic and functional damages caused by global ischemia and reperfusion.

Adenosine Triphosphate↗
PubMed2006

[Controlled reperfusion improves the metabolic and functional recovery of the isolated heart in rats after total ischemia].

Metabolic and functional effects of a hypocalcium reperfusion solution (RS) with low oxygen content containing d-glucose, trisamine, d-mannitol and I-aspartic acid have been studied in isolated rat hearts. The hearts were initially perfused for 20 min with the Krebs solution under constant left atrial filling pressure of 15 mm Hg and aortic perfusion pressure of 60 mm Hg. Then they were subjected to 30-min total normothermic ischemia followed by 30-min of reperfusion. The Krebs solution (control, n=16) or RS (n=11) were infused in retrograde mode with a rate of 4 ml/min during first 5 min of reperfusion. After that the hearts of both groups were reperfused in antegrade mode with the Krebs solution for 25 min under initial conditions. Short-term infusion of RS markedly improved postischemic functional recovery of cardiac function. After 30-min reperfusion coronary flow, an index of contractile function intensity, expressed as the left ventricle developed pressure-heart rate product, and cardiac work, calculated as the minute volume-aortic perfusion pressure product, recovered up to 92+/-1%, 77+/-1% and 61+/-1% of baseline values, respectively. In the control group the same indices were significantly lower and were 74+/-3%, 48+/-5% and 33+/-2%, respectively (p<0.001). At the end of reperfusion hearts treated with RS compared with the control hearts showed higher myocardial levels of ATP, phosphocreatine (PCr) and total creatine (SCr). These metabolic findings indicate better recovery of energy state and lesser sarcolemmal damage of postischemic cardiomyocytes after RS infusion. Thus, optimization of administration mode and composition of reperfusion solutions is a promising tool to attenuate functional and metabolic disturbances of the postischemic heart.

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↗
PubMed2005

[Improvement of restoration of heart function after ischemia by modified reperfusion solution].

AIM: To elucidate effect of saline reperfusion solution (RS) containing aspartic acid, glucose, mannit, and trisamine (pH 7.5+/-0.1 at 22 degrees C) on restoration of isolated perfused rat heart function. METHODS: After 20 minutes of initial perfusion hearts were sequentially subjected to 5 min of cardioplegia, 40 min of normothermic total ischemia and 30-min reperfusion. Hearts of groups 1 and 2 were stopped by hyper-potassium cardioplegic solution and after ischemia reperfused retrogradely for 5 min at 22 degrees C with Krebs solution and RS, respectively. This was followed by antegrade reperfusion with Krebs solution for 25 min at 37 degrees C. In groups 3 and 4 cardioplegia was instituted by perfusol while reperfusion was carried out in the same way as in groups 1 and 2. RESULTS: RS significantly improved restoration of contractile and pump functions. Action of RS was more effective when it was used concomitantly with Perfusol. Thus by the end of reperfusion product of heart rate and left ventricular developed pressure was 76+/-7 and 56+/-2% of initial value in groups 4 and 3, respectively (p<0.05). External heart work calculated as product of cardiac output and mean aortic pressure was restored up to 72+/-4 and 35+/-3% of initial value in groups 4 and 3, respectively (p<0.001). CONCLUSION: RS containing anaerobically utilizable substrates (aspartic acid, glucose), cellular membrane protectors, and antioxidants (mannit and trisamine), as well as optimal mixture of inorganic salts, significantly reduced damaging action of early reperfusion caused by activation of lipid peroxidation, Ca2+ overload and derangements of oxidative phosphorylation.

Animals↗
PubMed2005

[Ischemic preconditioning: from theory to practice].

Brief periods of ischemia and reperfusion are able to protect the heart from irreversible injury induced by consequent prolonged ischemia and reperfusion stress. This phenomenon called ischemic preconditioning (IP) may limit infarct size, enhance postischemic recovery of cardiac function, reduce reperfusion arrhythmias and vascular dysfunction. Mechanisms of IP are tightly related to alterations of efficiency of metabolic pathways and maintenance of ion homeostasis in ischemic cardiac myocytes. They may be initiated by formation of various triggers (adenosine, bradykinin, NO, free oxygen radicals etc.) that interact with receptors of cardiomyocytes and vascular endothelium or directly alter activity of enzymes. These interactions lead to activation of different pathways of intracellular signal conduction involving contribution of mediators and complex of the secondary messengers of IP. The most typical of them are e-isoform of protein kinase C and the ATP-dependent potassium channels. Biochemical pathways of molecular signaling in the preconditioned myocardium may be different, but always have same final effectors -- intracellular metabolism and ion homeostasis. As a rule, successfully preconditioned myocardium exhibits improved energy state of ischemic cardiomyocytes, reduced Ca(+) overload and attenuated damage of the sarcolemma and mitochondrial membranes. These beneficial changes provide myocardial salvage under conditions of deficient supply of cardiomyocytes with energy substrates and oxygen. Stimulation of adaptative mechanisms of IP is possible with specific receptor agonists or activation of secondary messenger pathways without causing ischemia. At present study of such pharmacological approaches to treating ischemia is a high priority task. In clinical practice selective openers of ATP-dependent potassium channels, A(1) and A(2) adenosine receptor agonists and Na(+)/H(+) exchange inhibitors are used to affect the final effectors of signaling pathways. These pharmacological agents are explored in transluminal coronary angioplasty, cardiac surgery and organ transplantation.

Adenosine↗
PubMed2004

[Aspartic Acid and mannitol enhance protective efficiency of asanquineous cardioplegic solution].

The aim of this work was to assess effects of a novel asanquineous cardioplegic solution (CP-5), buffered with trisamine (pH 7.6+/-0.1 at 22 degrees C) and containing 21.5 mM aspartic acid and 20.0 mM mannitol, on postischemic functional and metabolic recovery of isolated rat heart. A modified Ringer solution with 25 mM KCl (pH 7.6+/-0.1 at 22 degrees C) and the St. Thomas' cardioplegic solution (pH 7.8+/-0.1 at 22 degrees C) were used as controls. Osmolarity of all cardioplegic solutions were 340+/-5. After 20-min initial perfusion according to Neely (steady state) the hearts were subjected to 40-min normothermal total ischemia followed by 30-min antegrade reperfusion. Cardioplegic solutions were infused prior to ischemia at rate of the initial coronary flow for 5 min at room temperature. During reperfusion the hearts of CP-5 group completely recovered coronary flow and significantly enhanced restoration of the majority functional indices compared to the hearts in both control groups. This effect was combined with less lactate accumulation and preservation of higher ATP and phosphocreatine (PCr) levels in the heart tissue by the end of ischemia and, probably was induced by inclusion of aspartic acid into composition of CP-5. By the end of reperfusion the hearts treated with CP-5 completely recovered PCr content and restored ATP level up to 65.2+/-4.6% of initial one. A better energy state of reperfused hearts in CP-5 group was accompanied by reduction of myocardial lactate tissue to the preischemic value. Restoration of ATP, PCr and lactate content was significantly poor in both control groups during reperfusion. The least formation of a spin adduct of the short life oxygen radicals was found in the myocardial effluent of the hearts of CP-5 group at the early reperfusion using EPR technique. These data suggest a reduced release of oxygen radical generating systems from postischemic myocardium into perfusate due to antioxidant effect of mannitol. The obtained results substantiate addition of aspartic acid and mannitol to the asanquineous cardioplegic solution, buffered with trisamine, to enhance efficacy of myocardial protection against ischemia and reperfusion injury.

Animals↗
PubMed2004

[Na+/H+ exchange inhibitors: a new class of cardioprotectors].

The Na+/H+ exchanger (NHE) extrudes intracellular H+ in exchange for Na+ in an electroneutral process. Of the 6 mammalian exchanger isoforms identified to date, the NHE-1 is believed to be the molecular homologue of the sarcolemma Na+/H+ transporter. The exchanger is activated primarily by a reduction in intracellular pH, although such activation is subject to modulation by a variety of endogenous mediators (catecholamines, thrombin, endothelin) through receptor-mediated mechanisms. A large body of animal studies using both in vitro and in vivo models indicates that the inhibition of the sarcolemma NHE-1 attenuates myocardial injury in ischemia and reperfusion. Cardioprotective effects of NHE-1 inhibition involve a reduced susceptibility to severe ventricular arrhythmia, augmentation of contractile function recovery, and limitation of infarction size during reperfusion. Such protection is likely to arise partly from attenuation of "Ca2+ overload" in ischemic cardiomyocytes, which has been causally linked with all these pathologic phenomena. A marked benefit that has been observed with cariporide (HOE-642) and its structurally related congener HOE-694 in patients with acute myocardial infarction and in cardiac surgery demonstrates that selective NHE-1 inhibitors represent a novel and effective class of cardioprotectors.

Animals↗
PubMed2003

[Effects of metabolic substrates and mannitol on efficiency of cardioplegic protection in isolated rat heart].

The aim of this work was to study rationality of addition of aspartic acid, phosphocreatine, mannitol and tris(bydroxymethyl) aminomethane (trisamine) to a sanguineous cardioplegic solution. Isolated perfused rat hearts were subjected to 40-min normothermic total ischemia and 30-min reperfusion. Cardioplegic solutions were infused for 5 min prior to ischemia. A modified Ringer solution with 25 mM KCI was used as control. Osmolarity and pH of cardioplegic solutions were 340+/-5 mOms and 7.6+/-0.1 at 22 degreesC, respectively. Efficiency of myocardial protection was evaluated by recovery of contractile and pump function during reperfusion. The optimal solution contained aspartic acid (21.5 mM), mannitol (20.0 mM) and trisamine (5 mM). By the end of reperfusion the heart protected by this solution showed almost complete recovery of coronary flow (98+/-3% of the initial value vs. 77+/-3% in the control), and 2.6-fold higher recovery of stroke volume compared to the control. As a result, recovery of external cardiac work index, calculated as cardiac output-mean perfusion pressure, was 64+/-1% of the initial value vs. 24+/-5% in the control. Increase in buffer capacity of this cardioplegic solution by trisamine (up to 20.0 mM) as well as addition of phosphocreatine (10.0 mM) did not result in further augmentation of cardiac function recovery. The results suggest promising perspectives for development of medicinal form of this solution.

Animals↗
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↗
PubMed2001

Inhibitor of beta-hydroxy-beta-methylglutaryl coenzyme A reductase decreases energy supply to the myocardium in rats.

Hypocholesterolemic preparations, inhibitors of the key enzyme of cholesterol biosynthesis beta-hydroxy-beta-methylglutaryl coenzyme A reductase (statins), block the synthesis of ubiquinone Q10, intermediate electron carrier in the mitochondrial respiratory chain. This should decrease energy supply to tissues. Daily peroral administration of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitor simvastatin (24 mg/kg perorally) for 30 days had no effect on the contents of macroergic phosphates (ATP and creatine phosphate) in the liver, but decreased these parameters in the myocardium.

Adenosine Diphosphate↗
PubMed2000

Effects of prolonged caffeine consumption on cardiac contractile function in rats.

The purpose of the study was to explore effects of prolonged caffeine administration on the contractile function and myocardial energy metabolites of the isolated rat heart. Caffeine treatment for 1 week (10 mg/kg, i.p., twice a day) was followed by unchanged pump function of the isolated heart, but reduced maximal left ventricular (LV) systolic pressure by 14% (p < 0.05). Caffeine consumption during 8-9 weeks (0.1% water solution) was also followed by unchanged maximal pump function but increased maximal double product (LV developed pressure multiplied by heart rate) by 23% (p < 0.05). The hearts of caffeine-consumed rats also maintained a higher level of the pump function at a high rate of atrial electrostimulation. The myocardial content of adenosine triphosphate (ATP), creatine phosphate, as well as creatine was slightly but insignificantly increased after caffeine consumption. Results show that in the course of prolonged caffeine treatment, the maximal myocardial contractile function first decreases and then increases, showing adaptation of the heart.

Adenosine Triphosphate↗
PubMed1999

Metabolic and functional effects of carbachol and ischaemic preconditioning in rat isolated heart.

1. Metabolic and functional effects of ischaemic preconditioning (IP), pretreatment with carbachol (Ch) and combined interventions were studied in rat isolated working hearts subjected to 20 min global ischaemia (37 degrees C) and 40 min reperfusion. Prior to the ischaemic period, hearts were either perfused according to Langendorff (control group), ischaemically preconditioned by 5 min global ischaemia and 5 min reperfusion (IP group), perfused with 0.1 mumol/L Ch for 5 min and then with Ch-free Krebs'-Henseleit buffer for 5 min (Ch group) or perfused with 0.1 mumol/L Ch for 5 min and then subjected to IP (Ch + IP group). 2. Although Ch exerted slight negative chronotropic and inotropic effects during pre-ischaemic Langendorff perfusion, it did not affect myocardial contents of ATP and phosphocreatine (PCr) prior to sustained ischaemia. At the end of final reperfusion, the IP and Ch groups showed similar recovery of aortic output (67.5 +/- 5.0 and 56.8 +/- 5.4%, respectively), cardiac output (65.4 +/- 5.4 and 63.5 +/- 5.7%, respectively) and stroke volume (73.4 +/- 7.5 and 67.0 +/- 6.7%, respectively) expressed as a percentage of steady state values. These indices were higher than those in the control group (42.8 +/- 4.7, 53.8 +/- 4.3 and 56.1 +/- 5.6%, respectively; P < 0.05). The Ch + IP group exhibited complete recovery of all indices of pump function, including cardiac work, expressed as the cardiac output-mean aortic pressure (CO-MAP) product. 3. There were no differences in ATP recovery between the groups after reperfusion: the ATP content was, on average, 73.1 +/- 3.5% of the initial ATP content. However, all treated groups had enhanced PCr recovery and better preservation of total creatine (sigma Cr = PCr + Cr), an index of cell membrane integrity, than control. Metabolic efficacy of the pre-ischaemic interventions can be ranked as follows: IP < or = Ch < Ch + IP. In all groups, myocardial content of sigma Cr was positively correlated with percentage recovery of the CO-MAP product at the end of reperfusion (r = 0.79, P < 0.05). 4. The results demonstrate that Ch treatment combined with IP provides significantly greater postischaemic myocardial salvage. The similarity of the metabolic and functional effects of Ch treatment and IP strongly suggests muscarinic M2 acetylcholine receptor involvement in acute adaptation of rat heart to ischaemia/reperfusion stress.

Adenosine Triphosphate↗
PubMed1999

[Changes in the energy state of tissues in spontaneously hypertensive rats].

The contents of adenine nucleotides (ATP, ADP, AMP), phosphocreatine (PCr) and creatine (Cr) in the heart, skeletal muscle, liver and spleen in spontaneously hypertensive (SHR) and normotensive (WKY) rats. The ATP/ADP ratio in cardiac tissue was lower in SHR compared with WKY, while myocardial contents of adenine nucleotides, PCr and Cr did not differ significantly between the groups. A lower ATP/ADP ratio in the skeletal muscle SHR of was accompanied by a reduction of PCr content comparing with these indices in WKY rats. The liver and spleen of SHR exhibited lower ATP contents and higher ADP and AMP levels compared with those ones in WKY rats, despite of the close values of adenine nucleotide pools (sigma AN = ATP + ADP + AMP). This redistribution of tissue adenine nucleotides was corresponded to lower energy charges (EC = (ATP + 0.5 ADP)/sigma AN) and ATP/ADP ratios in SHR group. The reduction of the energy state of tissues in SHR rats increased in the following rank: heart > skeletal muscle > liver > spleen, thus, reflecting progressive decrease of intensity of oxidative metabolism. The results suggest changes in the balance of rates of ATP formation and hydrolysis occur at the system level in primary hypertension. Probably, consequences of such rearrangement in energy metabolism are functional disturbances of plasma membrane and sacroplasmic reticulum well-documented in a number of experimental and clinical studies.

Adenine Nucleotides↗
PubMed1998

Aspartate improves recovery of the recently infarcted rat heart after cardioplegic arrest.

BACKGROUND: We have previously shown that aspartate improves the tolerance of normal hearts to cardioplegia. The aim of this study was to investigate whether aspartate is also beneficial in the recently infarcted heart. METHODS: Myocardial infarction was produced in rats by left coronary artery ligation. Twenty hours later their hearts were perfused on an isolated working rat heart apparatus and underwent cardioplegic arrest for 30 min at 37 degrees C with or without 20 mM aspartate in the cardioplegic solution (n = 11 per group). Functional recovery and myocardial high energy phosphate levels were measured at the end of arrest and after 30 min of reperfusion. RESULTS: There was no difference in pre-arrest pump function between the untreated and aspartate-treated groups. However, after reperfusion the aspartate group generated more power (3.4 +/- 0.2 mJ/s per g) than the untreated group (2.5 +/- 0.3 mJ/s per g; P < 0.05) such that the percentage recovery of pre-arrest power in the aspartate group (67.7 +/- 3.5%) was greater than in the untreated group (53.6 +/- 4.9%; P < 0.05). The aspartate group also showed increases in aortic flow and myocardial oxygen consumption compared to the untreated group (P < 0.05). There were no between-group differences in high energy phosphate levels at the end of arrest or after reperfusion. CONCLUSION: Aspartate improves functional recovery of the recently infarcted heart during cardioplegic arrest, and therefore has potential as a useful adjunct to myocardial protection in patients with recent myocardial infarction undergoing cardiac surgery.

Animals↗
PubMed1998

Association of pre-ischaemic disturbances in energy metabolism with postischaemic dysfunction of the rat isolated working heart.

1. Metabolic and functional effects of two protocols of preconditioning were compared in rat isolated hearts subjected to 20 min global ischaemia (37 degrees C) and reperfusion (30 min Langendorff + 15 min working). Prior to the ischaemic period, hearts were perfused according to Langendorff (control group) or were preconditioned by three 5 min cycles or two 10 min cycles of ischaemia and reperfusion (PC-I and PC-II groups, respectively). 2. There was no difference in the contractile function between the two preconditioned groups at the onset of sustained ischaemia, although the PC-II group showed enhanced release of adenosine (Ado), inosine, hypoxanthine and xanthine into the interstitium accompanied by losses of tissue adenine nucleotides (sigmaAN = ATP + ADP + AMP), total creatine (sigmaCr = phosphocreatine + creatine) and activation of glycolysis following the preconditioning period. During reperfusion, the PC-I group showed enhanced functional recovery, higher contents of sigmaAN and sigmaCr, and the smallest lactate dehydrogenase release compared with these indices in the control and PC-II groups. Postischaemic myocardial dysfunction was similar in the control and PC-II groups. 3. Functional recovery of hearts in both preconditioned groups was positively correlated with myocardial contents of ATP, sigmaAN and sigmaCr at the end of reperfusion, but not with pre-ischaemic Ado release into the interstitium. The results suggest that pre-ischaemic disturbances of energy metabolism, rather than activation of Ado receptors or stunning, may contribute to efficacy of multiple preconditioning in the rat isolated heart.

Animals↗
PubMed1997

Metabolic and antioxidant effects of R(+/-)-N6-(2-phenylisopropyl)-adenosine following regional ischemia and reperfusion in canine myocardium.

Recent studies have indicated that activation of A1/A2-receptors may mediate metabolic adaptation of the heart to ischemia/reperfusion stress. This study tests whether pretreatment with A1-selective agonist R(-)-N6-(2-phenylisopropyl) adenosine (R-PIA) might mimic effects of a brief period of coronary occlusion (ischemic preconditioning, IP) on energy metabolism and hydroxyl radical (OH.) formation in canine myocardium following subsequent prolonged ischemia and reperfusion. Anaesthetized dogs were randomized to a control group subjected to 40-min occlusion of a diagonal branch of left anterior descending coronary artery (LAD) followed by 1-h reperfusion, or a preconditioned group (PC) in which the same period of sustained ischemia and reperfusion was preceded by a single cycle of IP (5-min occlusion of the same LAD branch and 10-min reperfusion), or to PIA group in which R-PIA infusion into the same branch of LAD (0.4 microg/kg per min during 5 min) was followed by 10 min of perfusion prior to sustained ischemia-reperfusion. Pretreatment with R-PIA similarly to IP reduced lactate (Lac), creatine (Cr) and inorganic phosphate (Pi) release from myocytes into the interstitial fluid during sustained ischemia compared to these indices in control. By the end of reperfusion, both IP and R-PIA infusion enhanced recovery of myocardial ATP and phosphocreatine (PCr) and attenuated the total creatine (sigmaCr = PCr + Cr) loss, an index of cell membrane damage. A1-receptor activation by R-PIA, as IP, led to a significant reduction in OH. radical generation following reperfusion assessed by a spin trap 5,5'-dimethyl-1-pyrroline-N-oxide (DMPO) using cardiac microdialysis. R-PIA pretreatment did not affect systemic and cardiac hemodynamic parameters. We conclude that (1) adaptive mechanisms of IP involve A1-receptor activation that contributes to the overall metabolic response and (2) R-PIA acts as a useful preconditioning-mimetic and anti-ischemic agent in dogs.

Adenosine↗