Biomedical subjects

V L Lakomkin

Publications and source records attributed to V L Lakomkin.

At least 19 recordsLinked to original sources

PubMed2006

[Variability of hemodynamic parameters and resistance to stress damage in rats of different strains].

Total power of heart rate variability and baroreflex sensitivity were significantly smaller in the August rats than in the Wistar rats, but adrenal and plasma catecholamine contents were considerably higher in the former ones. 1 hour after stress (30 min in cold water), plasma catecholamine was increased 2-fold in Wistar rats, while in August rats the adrenaline concentration increased only by 58% and the were no changes in noradrenaline content. At the same time, activation of catecholamine metabolism in the adrenal glands was similar in both groups. The oxidative stress induced by hydrogen peroxide depressed the contractile function of isolated heart in the August rats to a smaller extent as compared to Wistar rats, control ones and after the cold-water stress. This effect correlated with more pronounced stability ofantioxidant enzymes in the August rats. It seems that the greater resistance to stress damage in the August rats is mediated by enhanced power of defense mechanisms both at systemic and cellular levels.

Adrenal Cortex↗

PubMed2006

[Effect of ubiquinone on contractile function and antioxidant status of the myocardium in spontaneously hypertensive rats].

During the period of aging of spontaneously hypertensive rats (SHR) between 6 and 13 weeks the systolic arterial pressure increased from 131+/-2 up to 176+/-3 mm Hg while in the control group of WKY rats it reached 122+/-2 mmHg. The hypertension was combined with myocardial hypertrophy -- the relative weight of SHR heart was 24% higher. The contractile myocardial function of the isolated isovolumic heart of SHR group did not differ from WKY group in a wide range of coronary perfusion rates. During oxidative stress induced by 40-min intracoronary introduction of H(2)O(2) function of hypertrophied SHR hearts fell significantly deeper. This coincided with decreased myocardial activity of superoxide dismutase and glutathione peroxidase by 29-30%, and increased catalase activity by 18%. The rate of generation of active forms of oxygen (hydroxyl radicals HO(.-)) in mitochondria from SHR hearts was higher as compared with WKY. Thus, the development of hypertension was combined with decreased antioxidant protection of the myocardium. The addition of ubiquinone to drinking water (approximately 10 mg/kg/day) for 6 weeks did not affect arterial pressure level, but was associated with two times lesser degree of myocardial hypertrophy. The hearts of SHR that received ubiquinone differed from those not treated with ubiquinone by increased maximal level of myocardial contractile function, and by improved myocardial relaxability and distensibility. After administration of H(2)O(2), myocardial function of SHR was kept on higher level. That was combined with less myocardial oedema, better preservation of antioxidant enzymes and reduced rate of succinate-dependent generation of superoxide radicals in mitochondria from hearts of ubiquinone treated SHR. The results have shown, that administration of ubiquinone to rats with hereditary hypertension reduces degree of myocardial hypertrophy, improves functional properties of the myocardium, promotes effective protection of antioxidant enzymes and increases the resistance of the cardiac muscle to oxidative stress.

Animals↗

PubMed2005

Changes in antioxidant status of myocardium during oxidative stress under the influence of coenzyme Q10.

Changes in myocardium were studied during oxidative stress induced by infusion of hydrogen peroxide in the coronary vessels of isolated rat heart. Moderate concentrations of H2O2 increased the heart rate but decreased the contractile force, whereas higher concentrations of H2O2 decreased both parameters and increased the end diastolic pressure. The effect of H2O2 was stable, cumulative, and was associated with disturbance in respiration of mitochondria, increased production of ROS in them, and decrease in activities of antioxidant enzymes in the myocardium. Changes in the antioxidant status of the myocardium induced by long-term addition of coenzyme Q(10) into food was accompanied by decrease in the negative inotropic effect of H2O2, whereas the levels of superoxide dismutase and glutathione peroxidase after oxidative stress were virtually unchanged. The activities of these enzymes displayed a high positive correlation with the cardiac function. The findings suggest that coenzyme Q(10) should increase resistance of the myocardium to oxidative stress not only by a direct antioxidant mechanism but also indirectly, due to increased protection of antioxidant enzymes.

Animals↗

PubMed2005

[Effect of granulocyte-macrophage colony stimulating factor on the function and regeneration of myocardium in rats with experimental infarction].

To test the reparative capacity of stromal cells in myocardial infarction, rats were injected with granulocyte-monocyte-colony stimulating factor (GM-CSF) (leukomax), a cytokine known by its ability to raise a level of stromal cells in the blood, during first three days after coronary artery ligation. Only 10 of 17 rats (59%) survived 4 weeks in this group compared with 16 of 24 (67%) among rats not treated with leukomax. Echocardiographic and electromanometric studies showed that in both groups ventricular (LV) dilatation which developed during first hours after surgery persisted throughout 6-8 weeks and was combined with decreased ejection fraction and elevated LV end diastolic pressure. These alterations correlated with infarct size which varied from 0 to 28% of left ventricular weight in both groups. There were no statistically significant differences in functional and morphometric measurements between groups receiving and not receiving GM-CSF. However this result may be inconclusive due to small number of investigated animals and broad variation of ischemic zone size in each group.

Animals↗

PubMed2004

Heart resistance to oxidative stress in rats of different genetic strains.

In August rats reperfusion after regional myocardial ischemia in situ or intracoronary administration of hydrogen peroxide less significantly suppressed contractile activity of the heart compared to Wistar rats. Activities of catalase and superoxide dismutase in the myocardium during reperfusion remained unchanged in August rats. In Wistar rats a profound inhibition of cardiac function was accompanied by a decrease in enzyme activity.

Animals↗

PubMed2004

Protection of rat myocardium by coenzyme Q during oxidative stress induced by hydrogen peroxide.

Ubiquinone Q(10) (coenzyme Q) is an important component of the mitochondrial electron transport chain and an antioxidant. The purpose of this work was to find out whether an increase in the level of coenzyme Q in the heart changes its maximal working capacity and resistance to oxidative stress. Male Wistar rats were treated with coenzyme Q (10 mg/kg body weight per day) for six weeks, and this increased its content in the myocardium by 63%. The myocardial content of malonic dialdehyde and activities of key antioxidant enzymes were unchanged, except nearly 2.5-fold decrease in the activity of superoxide dismutase. The maximal working capacity of the isolated isovolumic heart did not change, but under conditions of oxidative stress induced by 45-min infusion of hydrogen peroxide (70 micro M) into coronary vessels the contractile function of these hearts decreased significantly more slowly. This was associated with less pronounced lesions in the ultrastructure of cardiomyocytes and lesser disorders in the oxidative metabolism of mitochondria that suggested increased antioxidant protection of the myocardium.

Animals↗

PubMed2004

[Protective effect of hydrophilic ubiquinone on cardiac muscle during oxidative stress].

AIM: To assess effects of long term administration of a natural antioxidant ubiquinone on isoproterenol induced myocardial injury. METHODS: Rats were given hydrophilic ubiquinone with water for 8 weeks. RESULTS: Long term use of ubiquinone did not affect myocardial ultrastructure and relative myocardial weight. The dose of isoproterenol used in this study exerted moderate damaging action evidenced by disappearance of glycogen from sarcoplasm, development of edema, and partial destruction of mitochondrial cristae. These effects were associated with lowering of maximal magnitude of contractile function of the isolated heart and augmentation of superoxide radicals release in perfusate. These changes (except disappearance of glycogen) were not present in hearts of ubiquinone fed rats. Compared with controls mitochondria isolated from hearts of ubiquinone fed rats had higher respiratory control and more than twice lower rate of superoxide generation. CONCLUSION: As damaging effects of isoproterenol are mediated by augmented generation of active forms of oxygen the results obtained allow to suggest that myocardium of ubiquinone fed animals is characterized by elevated power of the antioxidant system.

Animals↗

PubMed2002

[The protective action of ubiquinone at ischemia and reperfusion].

Effects of prolonged consumption of ubiquinone on myocardial injury caused by ischemia and reperfusion were studied in reperfused rat hearts. Wistar rats received lipophylic or hydrophilic forms of ubiquinone for 6-8 weeks with chow or water, respectively. Isolated isovolumic hearts with a constant volume latex balloon in the left ventricular cavity were subjected to total normothermic ischemia (25 min) and subsequent reperfusion (50 min). Time course of ischemic contracture and its level in both groups of ubiquinone treated animals were similar to those in controls. However recovery of left ventricular developed pressure after reperfusion was significantly better in both ubiquinone groups (54-/+9, 65-/+7, and 24-/+4 mm Hg in animals treated with lipophylic and hydrophylic ubiquinone and controls, respectively, p<0.01). As a result the developed pressure and heart rate product reflecting maximal aerobic capacity of the heart was also better restored. Both ubiquinone groups demonstrated absence of increased coronary tone that was characteristic for control animals. Mitochondria isolated from reperfused hearts of ubiquinone treated rats showed better preservation of structure and respiratory control. Rate of succinate-dependent generation of superoxide radicals determined with a spin trap TIRON in mitochondria from hearts of rats treated with hydrophylic ubiquinone (35-/+8 mmol O(2) /min/g) was approximately twice lower (p<0.05) than in control group (74-/+12 mmol O(2) /min/g) while the value in lipophylic ubiquinone group (48-/+9 mmol O(2) /min/g) did not differ significantly from the control. The results evidence that prolonged consumption of water-soluble ubiquinone increases resistance of rat myocardium to injuring action of reperfusion.

Animals↗

PubMed2002

[Isoproterenol induced changes of protein expression and myocardial ultrastructure].

AIM: To elucidate alterations in myocardial ultrastructure and protein expression caused by isoproterenol. METHODS: Biochemical, immunohistochemical and electron microscopic studies of rat myocardium were carried out 2 hours and 3 weeks after single injections of isoproterenol (50 and 10 mg/kg). Relative content of myospecific proteins (KRP - kinase-related protein, desmin), cytoskeletal proteins (tubulin, vinculin, and myosin light chain kinase - MLCK) and extracellular matrix protein, fibronectin, was determined by immunoblotting. RESULTS: In 2 hours after injection of 50 mg/kg of isoproterenol destruction of some cardiomyocytes, contracture of myofibrils, and mild edema of intercellular space occurred; the content of KRP decreased by l6%, and that of tubulin, vinculin and fibronectin - by 27-29%. Reduced level of these proteins and also of MLCK persisted until 3 weeks after injection and was associated with altered cardiomyocyte ultrastructure. Glycogen granules were sparse, mitochondria contained arrow-like inclusions characteristic for calcium overload, huge mitochondria connected by specialized intermitochondrial contacts were present. Enlarged intercellular space contained areas of fibrosis with increased amount of type I and II collagens and fibronectin. Lower dose of isoproterenol (10 mg/kg) did not cause noticeable damaging action in the acute period, but in 3 weeks thickening of extracellular matrix occurred accompanied by increases of KRP and tubulin contents (by 26-32% compared with control level). Similar rise in expression of these proteins, and also of MLCK was observed after addition of isoproterenol to culture of chicken cardiomyocytes. CONCLUSION: These results indicate that even single injection of isoproterenol causes long lasting structural alterations in cardiac muscle accompanied by increased expression of extracellular matrix proteins as well as sarcoplasmic proteins apparently involved in the hypertrophic response of the cardiomyocytes.

Adrenergic beta-Agonists↗

PubMed2002

[Effect of adriamycin on expression and content of myocardial structural and regulatory proteins].

The biochemical and morphological study of the cytoskeleton and extracellular matrix of rat heart was carried out after single injection of adriamycin (2.2 or 0.44 mg/kg). Hearts were taken for the study after 2 hours and 3 weeks after injection. The light and electronic microscopy, immunohistochemical determination of type I, III and IV collagens and fibronectin using specific antibodies were implied for morphological study; electrophoresis and immunoblotting were implied for the determination of the content of some proteins of cardiomyocytes (KRP or telokin, desmin, tubulin and vinculin), and extracellular matrix (fibronectin) and vascular smooth muscle cells (MLCK, myosin light chain kinase). Adriamycin injection in the dose 2.2 mg/kg which is close to therapeutic and known to alter intracellular membranes approximately in the half of cardiomyocytes, did not influence the relative volume and structure of collagen network but distinctly reduced the density of fibronectin-distribution. The content of tubulin, fibronectin, MLCK and KRP was significantly decreased by 18-24%, while contents of desmin and vinculin were changed insignificantly. After 3 weeks, an increased density and extension of collagen network indicating the development of diffuse fibrosis were observed. Contents of tubulin and KRP were increased above control level by 50 and 20%, respectively. Similar hyperrestitution of tubulin, fibronectin and KRP content by 15-25% was determined after smaller dose of adriamycin (0.44 mg/kg). Only content of MLCK out of proteins studied remained at lower level in both groups by 25-34%. Isolated chick embryo cardiomyocytes subjected to adriamycin responded by increased level of KRP expression by 20% in 4 days while the level of tubulin expression remained unchanged. Results showed that damage of cardiomyocytes and extracellular matrix after single injection of adriamycin in the dose close to therapeutic was followed by increased expression of some proteins of cytoskeleton and extracellular matrix. KRP seems to play active role in this reparative response while the steadily reduced level of MLCK expression may disturb the control of coronary vessels.

Animals↗

PubMed2000

Effects of preconditioning on myocardial interstitial levels of ATP and its catabolites during regional ischemia and reperfusion in the rat.

The interstitial accumulation of adenine nucleotide breakdown products (ANBP) in the myocardium during ischemia has been shown to provide a useful index of the ischemic injury, whereas reperfusion ANBP washout rate has been regarded as an index of reperfusion damage. The purpose of this study was, using cardiac microdialysis, to examine in the rat model of regional ischemia/reperfusion the relationship between the duration of ischemia and these indices and to assess the profile of interstitial ATP concentrations and the beneficial effects of ischemic preconditioning (IP). The rats underwent 10, 20, 30 or 40 min of coronary artery occlusion and 50 min of reperfusion. Regional ischemia, with its duration, provoked a progressive increase in dialysate ANBP in the ischemic zone. The rate of purine washout during reperfusion exponentially declined with an increase in duration of the ischemic period. IP, induced by three 5-min episodes of ischemia, each separated by 5 min of reperfusion, significantly reduced the accumulation of ANBP during the 30-min period of sustained ischemia and resulted in a marked acceleration of reperfusion ANBP washout, indicating the improvement of postischemic microcirculation. These effects were suggested to be, at least in part, responsible for the infarct size limitation observed. Using the relationship between the duration of ischemia and ANBP washout rate, it could be demonstrated that IP produced similar facilitation of purine washout as shortening of the ischemic period in nonpreconditioned rats from 30 to approximately 7 min. Regional 20-min ischemia induced an early peak increase in interstitial fluid ATP which correlated with the maximal incidence of ventricular arrhythmias, whereas IP abolished both ATP release and arrhythmias during the sustained ischemia. These findings suggest that ATP may be an important mediator of ischemia-induced ventricular arrhythmias.

Adenosine Triphosphate↗

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↗

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↗

PubMed1998

Interstitial ATP level and degradation in control and postmyocardial infarcted rats.

With the aim of estimating interstitial levels and the breakdown process of ATP, cardiac microdialysis was performed in the left ventricular wall of in situ control and postinfarcted as well as of isolated, Langendorff-perfused rat hearts. With the use of a bioluminescence technique for dialysate ATP measurement, the baseline interstitial fluid ATP concentration in in situ hearts was estimated to be 38 +/- 8 nM. Regional ischemia induced an early peak increase in interstitial fluid ATP to 373 +/- 73 nM that correlates with the maximal incidence of ventricular arrhythmias. During continuous infusion of individual adenine nucleotides (50 microM ATP, ADP, or AMP), the dialysate samples were analyzed for adenine nucleotides, nucleosides, and bases using HPLC with ultraviolet detection. The patterns of catabolites were consistent with the major pathway of metabolism, that is, sequential dephosphorylation catalyzed by a chain of separate ecto-nucleotidases. In in situ postinfarcted hearts as well as in perfused hearts, a reduced catabolism rate of extracellular adenine nucleotides was observed. In conclusion, in in situ rat hearts, ATP can be released in substantial amounts in the interstitium where it readily undergoes enzymatic degradation. Dephosphorylation occurs sequentially and faster in in situ control hearts than in in situ postinfarcted or in perfused hearts.

Adenosine↗

PubMed1997

The redox state of coenzyme Q10 in mitochondrial respiratory chain and oxygen-derived free radical generation in cardiac cells.

The aim of this study was to relate changes in the redox state of mitocondrial electron carriers to the 'burst' of oxyradicals in postischemic myocardium. The free radical EPR signals of control and re-oxygenated rat hearts were mainly due to coenzyme Q10, the line width was 0.81 +/- 0.02 mT, and the intensities (1.58 +/- 0.12) x 10(16) and (1.41 +/- 0.13) x 10(16) spins/g. The low-temperature spectra of oxygenated myocardium contained a predominant signal from a S3 Fe-S center and weak signals from N1b, N2, N3, N4 and S1 centers. Global ischemia caused cardinal changes in the redox state of the mitochondrial respiratory chain. The low-temperature EPR spectrum now contained intensive signals from most Fe-S centers. The amount of coenzyme Q10 semiquinones decreased during global ischemia, but the content of flavosemiquinones increased. The line width of the signal of the ischemic heart was 1.28 +/- 0.03 mT, and its intensity corresponded (3.16 +/- 0.94) x 10(16) spins/g. The spin-trapping experiments with TEMPONE-H showed that the rate of oxyradical generation in isolated cardiomyocytes essentially increased after hypoxia or on adding rotenone and antimycin A. It became equal to 4.2 +/- 0.3, 8.2 +/- 0.6 and 7.1 +/- 0.5 nmol/min mg-1 mitochondrial protein, respectively. The maximal stimulatory effect was observed in the presence of both inhibitors. The addition of superoxide dismutase, but not catalase, suppressed the formation of oxyradicals.

Animals↗

PubMed1994

Allopurinol-enhanced postischemic recovery in the isolated rat heart involves repletion of high-energy phosphates.

The effects of allopurinol (AP) on functional and metabolic recovery of the isolated rat heart after global ischemia were studied. Hearts were subjected to aerobic perfusion (30 min), cardioplegic infusion (5 min), normothermic ischemia (37 min), and reperfusion (50 min) which was started with secondary cardioplegic infusion (10 min). AP was injected into rats (44 mg/kg body wt ip 2 h before heart excision) and added to cardioplegic solution (2 mM) prior and after ischemia. AP treatment significantly improved postischemic recovery of the function and reduced the leakage of lactate dehydrogenase from reperfused hearts. These beneficial effects were accompanied by a better preservation of tissue content of ATP, the total adenine nucleotides, phosphocreatine, and the total creatine at the end of reperfusion. Inhibition of xanthine oxidase by AP substantially decreased pre- and postischemic release of xanthine and uric acid and increased postischemic release of hypoxanthine into the coronary effluent. Despite this, AP-treated hearts did not exhibit a reduction in hydroxyl radical adduct formation in the effluents at reperfusion assessed by the spin-trap measurements. The results suggest that AP may protect the heart from ischemia/reperfusion injury due to enhanced energy provision rather than by prevention of oxygen-derived free radical formation.

Adenosine Diphosphate↗

PubMed1994

Human recombinant extracellular-superoxide dismutase type C improves cardioplegic protection against ischemia/reperfusion injury in isolated rat heart.

The cardioprotective effects of human recombinant extracellular-superoxide dismutase type C (hr-EC-SOD C) were compared with those of bovine Cu,Zn-SOD in isolated working rat heart subjected to 35-min global normothermic ischemia followed by 55-min reperfusion. hr-EC-SOD C or bovine Cu,Zn-SOD (3 x 10(4) and 6 x 10(4) IU/L, respectively) was added to St. Thomas' Hospital (STH) cardioplegic solution infused 5 min before and 10 min after the ischemic period. Control hearts were treated with STH cardioplegic solution without SOD. By the end of reperfusion, hr-EC-SOD C-treated hearts recovered left ventricular systolic pressure (LVSP), aortic flow (AF) and cardiac output (CO) to 95 +/- 4, 60 +/- 4, 69 +/- 6% of preischemic value, respectively, as compared with 86 +/- 3, 44 +/- 5, and 52 +/- 6% in the control (p < 0.05). Cardioplegia with hr-EC-SOD C significantly reduced lactate dehydrogenase (LDH) release into myocardial effluent during reperfusion (p < 0.05) and increased ATP, AMP, and total creatine (Cr) tissue contents in reperfused hearts (by 21 +/- 3, 42 +/- 4, and 34 +/- 3%, respectively, as compared with control hearts, p < 0.05). The effects of bovine SOD on functional and biochemical indexes were similar but not statistically significant as compared with control. Treatment with hr-EC-SOD C, but not with bovine SOD, resulted in reduction in hydroxyl radical formation assessed by 5-5-dimethy-1-pyrroline-N-oxide spin trap (DMPO) in coronary effluent at early reperfusion with electron spin resonance (ESR) technique. The results suggest that enhanced myocardial protection against ischemia/reperfusion injury afforded by hr-EC-SOD C is related to scavenging of oxygen-derived free radicals.

Animals↗

PubMed1993

Regulation of cardiac energy turnover by coronary flow: a 31P-NMR study.

The response of cytosolic phosphates ([ATP], [PCr], [Pi] and [ADP]) in rat hearts retrogradely perfused with different oxidizable substrates to increased workload induced by elevated coronary flow (CF) or by addition of inotropic agents has been investigated. Hearts were perfused with glucose (11 mM), pyruvate (5 mM), lactate (3 mM) or a combination of glucose (5.5 mM) and acetate (5 mM), octanoate (0.1 mM) or beta-hydroxybutyrate (5 mM). The initial [ATP]/[ADP] ratio was highest in pyruvate and lactate perfused hearts. Increasing the coronary flow 1.7-fold (from c. 56 to 96 ml/min x g dry wt) resulted in an increase in pressure-rate product (PRP) by 36-52% without significant changes in cytosolic phosphates. Dichloroacetate (1 mM), ruthenium red (2.5 micrograms/ml), or pre-treatment with theophylline (1 mM, 30 min) had no effect either functional or metabolic response to elevated CF in glucose-perfused hearts. Isoproterenol (Iso, 0.1 microM) infusion at maximal coronary flows lead to further elevation of PRP value by 36-88% and the ratio of the maximal rate of relaxation to LV developed pressure ((-dP/dt)m/LVDP) increased two-fold. Simultaneously, [PCr] decreased by 18-30%, [Pi] increased two-fold and ADP increased by 20-90% resulting in reduction of [ATP]/[ADP] by half and ATP affinity (A(ATP) = -delta G(ATP)) by 2.4-3.8 kJ/mol. In hearts perfused with acetate, octanoate and hydroxybutyrate in the presence of glucose, Iso addition resulted in intracellular pH decrease by 0.03-0.07 U and increase in lactate extrusion 1.5-2 times. In hearts perfused with glucose alone, decrease in PRP induced by perfusate Ca2+ reduction was associated with increase in PCr and decrease in Pi levels. These data show that coordinated regulation of energy supply and demand exerted by coronary flow/perfusion pressure does not depend on the availability of reducing equivalents but is rather controlled by oxygen supply and stretch-activated factors.

Animals↗