共查询到20条相似文献,搜索用时 15 毫秒
1.
A.J. Higgins M. Morville R.A. Burges D.G. Gardiner M.G. Page K.J. Blackburn 《Life sciences》1980,27(11):963-970
In isolated diaphragms from rats fed on a high-fat diet, oxfenicine (S-4-hydroxyphenylglycine) stimulated the depressed rates of pyruvate decarboxylation (2-fold) and glucose oxidation (5-fold). In diaphragms from normal-fed rats, oxfenicine had no effect on pyruvate decarboxylation but doubled the rate of glucose oxidation and inhibited the oxidation of palmitate. Treatment of fat-fed rats with oxfenicine restored the proportion of myocardial pyruvate dehydrogenase in the active form to that observed in normal-fed rats. In rat hearts perfused in the presence of glucose, insulin and palmitate, oxfenicine increased carbohydrate oxidation and stimulated cardiac performance with no increase in oxygen consumption - i.e. improved myocardial efficiency. Working rat hearts perfused with glucose, insulin and palmitate and subjected to 10 min global ischaemia recovered to 81% of their pre-ischaemic cardiac output after 30 min reperfusion, and released large amounts of lactate dehydrogenase into the perfusate. Hearts perfused with oxfenicine had slightly higher pre-ischaemic cardiac outputs and, on reperfusion, recovered more completely (to 96% of the pre-ischaemic value). Oxfenicine reduced the amount of lactate dehydrogenase released by 73%. We conclude that, in rat hearts with high rates of fatty acid oxidation, a relative increase in carbohydrate oxidation will improve myocardial efficiency, and preserve mechanical function and cellular integrity during acute ischaemia. 相似文献
2.
《Cytokine》2014,70(2):255-262
Activin A, a member of the transforming growth factor-β superfamily, is stimulated early in inflammation via the Toll-like receptor (TLR) 4 signalling pathway, which is also activated in myocardial ischaemia–reperfusion. Neutralising activin A by treatment with the activin-binding protein, follistatin, reduces inflammation and mortality in several disease models. This study assesses the regulation of activin A and follistatin in a murine myocardial ischaemia–reperfusion model and determines whether exogenous follistatin treatment is protective against injury. Myocardial activin A and follistatin protein levels were elevated following 30 min of ischaemia and 2 h of reperfusion in wild-type mice. Activin A, but not follistatin, gene expression was also up-regulated. Serum activin A did not change significantly, but serum follistatin decreased. These responses to ischaemia–reperfusion were absent in TLR4−/− mice. Pre-treatment with follistatin significantly reduced ischaemia–reperfusion induced myocardial infarction. In mouse neonatal cardiomyocyte cultures, activin A exacerbated, while follistatin reduced, cellular injury after 3 h of hypoxia and 2 h of re-oxygenation. Neither activin A nor follistatin affected hypoxia-reoxygenation induced reactive oxygen species production by these cells. However, activin A reduced cardiomyocyte mitochondrial membrane potential, and follistatin treatment ameliorated the effect of hypoxia-reoxygenation on cardiomyocyte mitochondrial membrane potential. Taken together, these data indicate that myocardial ischaemia–reperfusion, through activation of TLR4 signalling, stimulates local production of activin A, which damages cardiomyocytes independently of increased reactive oxygen species. Blocking activin action by exogenous follistatin reduces this damage. 相似文献
3.
Chavez PN Stanley WC McElfresh TA Huang H Sterk JP Chandler MP 《American journal of physiology. Heart and circulatory physiology》2003,284(5):H1521-H1527
Metabolic interventions improve performance during demand-induced ischemia by reducing myocardial lactate production and improving regional systolic function. We tested the hypotheses that 1) stimulation of glycolysis would increase lactate production and improve ventricular wall motion, and 2) the addition of fatty acid oxidation inhibition would reduce lactate production and further improve contractile function. Measurements were made in anesthetized open-chest swine hearts. Three groups, hyperglycemia (HG), HG + oxfenicine (HG + Oxf), and control (CTRL), were treated under aerobic conditions and during demand-induced ischemia. During demand-induced ischemia, HG resulted in greater lactate production and tissue lactate content but had no significant effect on glucose oxidation. HG + Oxf significantly lowered lactate production and increased glucose oxidation compared with both the CTRL and HG groups. Myocardial energy efficiency was greater in the HG and HG + Oxf groups under aerobic conditions but did not change during demand-induced ischemia. Thus enhanced glycolysis resulted in increased energy efficiency under aerobic conditions but significantly enhanced lactate production with no further improvement in function during demand-induced ischemia. Partial inhibition of free fatty acid oxidation in the presence of accelerated glycolysis increased energy efficiency under aerobic conditions and significantly reduced lactate production and enhanced glucose oxidation during demand-induced ischemia. 相似文献
4.
The present study is designed to investigate the role of Na+-H+ exchanger in the cardioprotective effect of ischaemic and angiotensin (Ang II) preconditioning. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Left ventricular developed pressure (LVDP) and dp/dt were recorded to evaluate myocardial contractility. Four episodes of ischaemic or Ang II preconditioning markedly reduced LDH and CK release in coronary effluent and decreased myocardial infarct size. 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a Na+-H+ exchange inhibitor, produced no marked effect on ischaemic preconditioning and Ang II preconditioning induced cardioprotection. On the other hand, EIPA administration prior to global ischaemia produced a similar reduction in myocardial injury as was noted with ischaemic preconditioning or Ang II preconditioning. On the basis of these results, it may be concluded that inhibition of Na+-H+ exchanger protects against ischaemia-reperfusion induced myocardial injury whereas activation of Na+-H+ exchanger may not mediate the cardioprotective effect of ischaemic and Ang II preconditioning. 相似文献
5.
Mária Kovács Attila Kiss Márton G?nczi Gottfried Miskolczi Gy?rgy Seprényi József Kaszaki Mark J. Kohr Elizabeth Murphy ágnes Végh 《PloS one》2015,10(4)
Background and Purpose
To provide evidence for the protective role of inorganic nitrite against acute ischaemia and reperfusion-induced ventricular arrhythmias in a large animal model.Experimental Approach
Dogs, anaesthetized with chloralose and urethane, were administered intravenously with sodium nitrite (0.2 µmolkg-1min-1) in two protocols. In protocol 1 nitrite was infused 10 min prior to and during a 25 min occlusion of the left anterior descending (LAD) coronary artery (NaNO2-PO; n = 14), whereas in protocol 2 the infusion was started 10 min prior to reperfusion of the occluded vessel (NaNO2-PR; n = 12). Control dogs (n = 15) were infused with saline and subjected to the same period of ischaemia and reperfusion. Severities of ischaemia and ventricular arrhythmias, as well as changes in plasma nitrate/nitrite (NOx) levels in the coronary sinus blood, were assessed throughout the experiment. Myocardial superoxide and nitrotyrosine (NT) levels were determined during reperfusion. Changes in protein S-nitrosylation (SNO) and S-glutathionylation were also examined.Key Results
Compared with controls, sodium nitrite administered either pre-occlusion or pre-reperfusion markedly suppressed the number and severity of ventricular arrhythmias during occlusion and increased survival (0% vs. 50 and 92%) upon reperfusion. There were also significant decreases in superoxide and NT levels in the nitrite treated dogs. Compared with controls, increased SNO was found only in NaNO2-PR dogs, whereas S-glutathionylation occurred primarily in NaNO2-PO dogs.Conclusions
Intravenous infusion of nitrite profoundly reduced the severity of ventricular arrhythmias resulting from acute ischaemia and reperfusion in anaesthetized dogs. This effect, among several others, may result from an NO-mediated reduction in oxidative stress, perhaps through protein SNO and/or S-glutathionylation. 相似文献6.
Ross A. Breckenridge Izabela Piotrowska Keat-Eng Ng Timothy J. Ragan James A. West Surendra Kotecha Norma Towers Michael Bennett Petra C. Kienesberger Ryszard T. Smolenski Hillary K. Siddall John L. Offer Mihaela M. Mocanu Derek M. Yelon Jason R. B. Dyck Jules L. Griffin Andrey Y. Abramov Alex P. Gould Timothy J. Mohun 《PLoS biology》2013,11(9)
7.
C Mannheimer T Eliasson B Andersson C H Bergh L E Augustinsson H Emanuelsson F Waagstein 《BMJ (Clinical research ed.)》1993,307(6902):477-480
OBJECTIVE--To investigate the effects of spinal cord stimulation on myocardial ischaemia, coronary blood flow, and myocardial oxygen consumption in angina pectoris induced by atrial pacing. DESIGN--The heart was paced to angina during a control phase and treatment with spinal cord stimulation. Blood samples were drawn from a peripheral artery and the coronary sinus. SETTING--Multidisciplinary pain centre, department of medicine, Ostra Hospital, and Wallenberg Research Laboratory, Sahlgrenska Hospital, Gothenburg, Sweden. SUBJECTS--Twenty patients with intractable angina pectoris, all with a spinal cord stimulator implanted before the study. RESULTS--Spinal cord stimulation increased patients'' tolerance to pacing (p < 0.001). At the pacing rate comparable to that producing angina during the control recording, myocardial lactate production during control session turned into extraction (p = 0.003) and, on the electrocardiogram, ST segment depression decreased, time to ST depression increased, and time to recovery from ST depression decreased (p = 0.01; p < 0.05, and p < 0.05, respectively). Spinal cord stimulation also reduced coronary sinus blood flow (p = 0.01) and myocardial oxygen consumption (p = 0.02). At the maximum pacing rate during treatment, all patients experienced anginal pain. Myocardial lactate extraction reverted to production (p < 0.01) and the magnitude and duration of ST segment depression increased to the same values as during control pacing, indicating that myocardial ischaemia during treatment with spinal cord stimulation gives rise to anginal pain. CONCLUSIONS--Spinal cord stimulation has an anti-anginal and anti-ischaemic effect in severe coronary artery disease. These effects seem to be secondary to a decrease in myocardial oxygen consumption. Furthermore, myocardial ischemia during treatment gives rise to anginal pain. Thus, spinal cord stimulation does not deprive the patient of a warning signal. 相似文献
8.
R N Ladi L Hollaar J H Souverijn A van der Laarse 《Clinical physiology and biochemistry》1990,8(5):250-255
In 27 patients with acute myocardial infarction (AMI) we calculated cumulative release of alpha-hydroxybutyrate dehydrogenase (alpha HBDH) per liter plasma which is a routine procedure in our coronary care unit, and compared these values with calculated cumulative release of lactate dehydrogenase isoenzyme-1 (LDH-1) per liter plasma using a LDH-1 test that has become commercially available recently. Theoretically, myocardial (iso)enzyme release is more accurately determined with LDH-1 than with alpha HBDH, due to the higher cardiac specificity of LDH-1 compared to alpha HBDH. The only disadvantage of LDH-1 is its abundance in erythrocytes necessitating a correction by measurement of free hemoglobin (Hb) concentration in plasma. After division of cumulatively released activities (Q72) of alpha HBDH and LDH-1 by the activities per gram of normal myocardium (135 and 81 U/g, respectively), the values of Q72(alpha HBDH)/135 and Q72(LDH-1)/81 were compared per patient. Elevated alpha HBDH levels in the presence of normal creatine kinase levels in plasma samples taken on admission, as well as hemolysis gave rise to overestimation of cumulative release of alpha HBDH as compared to LDH-1, but hepatic congestion occurring secondary to AMI (48-72 h after onset of infarction) did not disturb the equality of Q72 (alpha HBDH)/135 and Q72(LDH-1)/81 values. In 16 patients showing none of the mentioned conditions, the relation between Q72(alpha HBDH)/135 and Q72(LDH-1)/81 coincided with the line of identity (r = 0.97). We conclude that the use of an easy and rapid plasma LDH-1 assay improves the assessment of enzymatic infarct size, provided free Hb levels are measured to correct LDH-1 activities for a contribution by erythrocytes. 相似文献
9.
Inhibition of Rac1 reduces store overload‐induced calcium release and protects against ventricular arrhythmia
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Lili Zhang Xiangru Lu Le Gui Yan Wu Stephen M. Sims Guoping Wang Qingping Feng 《Journal of cellular and molecular medicine》2016,20(8):1513-1522
Rac1 is a small GTPase and plays key roles in multiple cellular processes including the production of reactive oxygen species (ROS). However, whether Rac1 activation during myocardial ischaemia and reperfusion (I/R) contributes to arrhythmogenesis is not fully understood. We aimed to study the effects of Rac1 inhibition on store overload‐induced Ca2+ release (SOICR) and ventricular arrhythmia during myocardial I/R. Adult Rac1f/f and cardiac‐specific Rac1 knockdown (Rac1ckd) mice were subjected to myocardial I/R and their electrocardiograms (ECGs) were monitored for ventricular arrhythmia. Myocardial Rac1 activity was increased and ventricular arrhythmia was induced during I/R in Rac1f/f mice. Remarkably, I/R‐induced ventricular arrhythmia was significantly decreased in Rac1ckd compared to Rac1f/f mice. Furthermore, treatment with Rac1 inhibitor NSC23766 decreased I/R‐induced ventricular arrhythmia. Ca2+ imaging analysis showed that in response to a 6 mM external Ca2+ concentration challenge, SOICR was induced with characteristic spontaneous intracellular Ca2+ waves in Rac1f/f cardiomyocytes. Notably, SOICR was diminished by pharmacological and genetic inhibition of Rac1 in adult cardiomyocytes. Moreover, I/R‐induced ROS production and ryanodine receptor 2 (RyR2) oxidation were significantly inhibited in the myocardium of Rac1ckd mice. We conclude that Rac1 activation induces ventricular arrhythmia during myocardial I/R. Inhibition of Rac1 suppresses SOICR and protects against ventricular arrhythmia. Blockade of Rac1 activation may represent a new paradigm for the treatment of cardiac arrhythmia in ischaemic heart disease. 相似文献
10.
O I Pisarenko E B Novikova L I Serebriakova O V Tskitishvili V E Ivanov 《Biulleten' eksperimental'no? biologii i meditsiny》1985,100(9):280-282
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. 相似文献
11.
Tamara Zaobornyj Tamara Mazo Virginia Perez Anabella Gomez Mario Contin Valeria Tripodi 《Free radical research》2013,47(9-10):993-1004
AbstractSildenafil is a phosphodiesterase type 5 inhibitor which confers cardioprotection against myocardial ischaemia/reperfusion (I/R) injury. The aim of this study was to determine if Trx1 participates in cardioprotection exerted by sildenafil in an acute model of I/R, and to evaluate mitochondrial bioenergetics and cellular redox status. Langendorff-perfused hearts from wild type (WT) mice and a dominant negative (DN-Trx1) mutant of Trx1 were assigned to placebo or sildenafil (0.7?mg/kg i.p.) and subjected to 30?min of ischaemia followed by 120?min of reperfusion. WT?+?S showed a significant reduction of infarct size (51.2?±?3.0% vs. 30?±?3.0%, p < .001), an effect not observed in DN-Trx. After I/R, sildenafil preserved state 3 oxygen consumption from WT, but had a milder effect in DN-Trx1 only partially protecting state 3 values. Treatment restored respiratory control (RC) after I/R, which resulted 8% (WT) and 24% (DN-Trx1) lower than in basal conditions. After I/R, a significant increase in H2O2 production was observed both for WT and DN-Trx (WT: 1.17?±?0.13?nmol/mg protein and DN-Trx: 1.38?±?0.12?nmol/min mg protein). With sildenafil, values were 21% lower only in WT I/R. Treatment decreased GSSG levels both in WT and DN-Trx1. In addition, GSSG/GSH2 ratio was partially restored by sildenafil. Also, an increase in p-eNOS/eNOS even before the myocardial ischaemia was observed with sildenafil, both in WT (14%, p > .05) and in DN-Trx (35%, p < .05). Active Trx1 is required for the onset of the cardioprotective effects of sildenafil on I/R injury, together with the preservation of cellular redox balance and mitochondrial function. 相似文献
12.
Occurrence of oxidative stress during myocardial reperfusion 总被引:1,自引:0,他引:1
Prof. R. Ferrari C. Ceconi S. Curello A. Cargnoni F. De Giuli O. Visioli 《Molecular and cellular biochemistry》1992,111(1-2):61-69
Reperfusion, without doubt, is the most effective way to treat the ischaemic myocardium. Late reperfusion may however cause further damage. Myocardial production of oxygen free radicals above the neutralizing capacity of the myocytes is an important cause of this reperfusion damage. There is evidence that prolonged ischaemia reduces the naturally occurring defence mechanisms of the heart against oxygen free radicals, particularly mitochondrial manganese superoxide dismutase, and intracellular pool of reduced glutathione. Consequently, reperfusion results in a severe oxidative damage, as evidenced by tissue accumulation and release of oxidized glutathione.An oxygen free radical-mediated impairment of mechanical function also occurs during reperfusion of human heart. In fact we observed during surgical reperfusion of coronary artery disease (CAD) patients, a prolonged and sustained release of oxidized glutathione;the degree of oxidative stress was inversely correlated with recovery of mechanical and haemodynamic function. These findings represent the rationale for therapeutic interventions which increase the cellular antioxidant capacities and improve the efficacy of myocardial reperfusion. 相似文献
13.
J J Spitzer 《Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N.Y.)》1976,151(1):28-31
Changes in myocardial substrate utilization were studied in anesthetized dogs following the production of anaphylactic shock. Mean arterial blood pressure, cardiac output, and pH decreased significantly during this form of shock. Myocardial FFA oxidation was greatly diminished especially within the first hour following challenge and lactate uptake more than doubled during the same time. Thus, it is concluded that myocardial substrate utilization shifted away from FFA and towards lactate during anaphylactic shock and these changes resembled those observed following an acute, severe hemorrhage, or the administration of E. coli endotoxin. 相似文献
14.
Stumpe T Schrader J 《American journal of physiology. Heart and circulatory physiology》2001,280(1):H42-H50
The mechanism of myocardial hibernation, the reversible downregulation of contractile activity on reduction of coronary flow with unchanged cardiac energetics, is presently not understood. The oxygen consumption (VO(2)), shortening fraction (DeltaL), energy status [phosphocreatine (PCr), ATP, and adenosine and lactate release], and free intracellular Ca(2+) concentration ([Ca(2+)](i)) were measured in isolated rat cardiomyocytes at precisely controlled ambient PO(2) (Oxystat). When PO(2) was reduced from 25 to 6 mmHg, VO(2) decreased by 50%, while DeltaL was downregulated from 11.2 +/- 4.1 to 7.6 +/- 4.0%, and energy status was unchanged in the steady state (observation time 12 min). Only transiently PCr decreased, and lactate and adenosine release increased. Further reduction of PO(2) (to 3 mmHg) reduced VO(2) by 80%, decreased PCr by 35%, moderately increased adenosine and lactate release, and progressively reduced DeltaL by 50% (to 5.6 +/- 3.3%). All parameters fully recovered during reoxygenation. PO(2)-dependent downregulation of DeltaL was accompanied by a progressive reduction in systolic [Ca(2+)](i) (from 512 +/- 110 to 357 +/- 91 nmol/l at 6 mmHg and to 251 +/- 69 nmol/l at 3 mmHg), whereas diastolic free [Ca(2+)](i) remained unchanged. Therefore, the mechanism of the reversible, PO(2)-dependent downregulation of contractile activity (myocardial hibernation) involves a substantial reduction of systolic calcium. 相似文献
15.
O'Donnell JM Kudej RK LaNoue KF Vatner SF Lewandowski ED 《American journal of physiology. Heart and circulatory physiology》2004,286(6):H2237-H2242
Glycolysis supplements energy synthesis at high cardiac workloads, producing not only ATP but also cytosolic NADH and pyruvate for oxidative ATP synthesis. Despite adequate Po(2), speculation exists that not all cytosolic NADH is oxidized by the mitochondria, leading to lactate production. In this study, we elucidate the mechanism for limited cytosolic NADH oxidation and increased lactate production at high workload despite adequate myocardial blood flow and oxygenation. Reducing equivalents from glycolysis enter mitochondria via exchange of mitochondrial alpha-ketoglutarate (alpha-KG) for cytosolic malate. This exchange was monitored at baseline and at high workloads by comparing (13)C enrichment between the products of alpha-KG oxidation (succinate) and alpha-KG efflux from mitochondria (glutamate). Under general anesthesia, a left thoracotomy was performed on 14 dogs and [2-(13)C]acetate was infused into the left anterior descending artery for 40 min. The rate-pressure product was 9,035 +/- 1,972 and 21,659 +/- 5,266 mmHg.beats.min(-1) (n = 7) at baseline (n = 7) and with dobutamine, respectively. (13)C enrichment of succinate was 57 +/- 10% at baseline and 45 +/- 13% at elevated workload (not significant), confirming oxidation of [2-(13)C]acetate. However, cytosolic glutamate enrichment, a marker of cytosolic NADH transfer to mitochondria, was dramatically reduced at high cardiac workload (11 +/- 1%) vs. baseline (50 +/- 14%, P < 0.05). This reduced exchange of (13)C from alpha-KG to cytosolic glutamate at high work indicates reduced shuttling of cytosolic reducing equivalents into the mitochondria. Myocardial tissue lactate increased 78%, countering this reduced oxidation of cytosolic NADH. The findings elucidate a contributing mechanism to glycolysis outpacing glucose oxidation in the absence of myocardial ischemia. 相似文献
16.
J. Vainer J. H. M. Habets S. Schalla A. H. P. Lousberg C. D. J. M. de Pont S. A. Vöö B. T. Brans J. C. A. Hoorntje J. Waltenberger 《Netherlands heart journal》2016,24(5):343-349
Background
Cardiac shockwave therapy (CSWT) might improve symptoms and decrease ischaemia burden by stimulating collateral growth in chronic ischaemic myocardium. This prospective study was performed to evaluate the feasibility and safety of CSWT.Methods
We included 33 patients (mean age 70?±?7 years, mean left ventricular ejection fraction 55?±?12?%) with end-stage coronary artery disease, chronic angina pectoris and reversible ischaemia on myocardial scintigraphy. CSWT was applied to the ischaemic zones (3–7 spots/session, 100 impulses/spot, 0.09 mJ/mm2) in an echocardiography-guided and ECG-triggered fashion. The protocol included a total of 9 treatment sessions (3 treatment sessions within 1 week at baseline, and after 1 and 2 months). Clinical assessment was performed using exercise testing, angina score (CCS class), nitrate use, myocardial scintigraphy, and cardiac magnetic resonance (CMR) 1 and 4 months after the last treatment session.Results
One and 4 months after CSWT, sublingual nitrate use decreased from 10/week to 2/week (p?<?0.01) and the angina symptoms diminished from CCS class III to CCS class II (p?<?0.01). This clinical improvement was accompanied by an improved myocardial uptake on stress myocardial scintigraphy (54.2?±?7.7?% to 56.4?±?9.4?%, p?=?0.016) and by increased exercise tolerance at 4-month follow-up (from 7.4?±?2.8 to 8.8?±?3.6 min p?=?0.015). No clinically relevant side effects were observed.Conclusion
CSWT improved symptoms and reduced ischaemia burden in patients with end-stage coronary artery disease without relevant side effects. The study provides a solid basis for a randomised multicentre trial to establish CSWT as a new treatment option in end-stage coronary artery disease.17.
Insulin like growth factor-1 selectively regulates the expression of matrix metalloproteinase-2 in malignant H-ras transformed cells 总被引:3,自引:0,他引:3
The present study is designed to investigate the effect of myocardial preconditioning with oxidative stress induced by pyrogallol or H2O2, on ischaemia-reperfusion induced myocardial injuiry. Isolated perfused rat heart was subjected to global ischaemia for 30 min followed by reperfusion for 120 min. Coronary effluent was analysed for LDH and CK release to assess the degree of cardiac injury. Myocardial infarct size was estimated macroscopically using TTC staining. Four episodes of preconditioning induced by pyrogallol or hydrogen peroxide (H2O2) or ischaemia markedly reduced LDH and CK release in coronary effluent and decreased myocardial infarct size. Administration of polymyxin B, a protein kinase C (PKC) inhibitor, during pyrogallol, H2O2 or ischaemic preconditioning markedly attenuated the cardioprotective effect of preconditioning produced with oxidative stress or ischaemia. These results suggest that preconditioning with oxidative stress may provide cardioprotection similar to ischaemic preconditioning, against ischaemia-reperfusion injury and this cardioprotective effect may be mediated through activation of PKC. 相似文献
18.
Marina Prendes MG García JV Testoni G Fernández MA Perazzo JC Savino EA Varela A 《Archives of physiology and biochemistry》2006,112(1):31-36
To assess whether glycolysis, Na+-H+ exchange and oxidation of fatty acid derived from endogenous lipolysis are involved in the beneficial effects of 24-h fasting on the ischaemic - reperfused heart, it was studied the effects of inhibiting Na+ - H+ exchange using 10 muM dimethylamiloride and fatty acid oxidation using 2 mM oxfenicine, on the functional activity, lactate production and cell viability measured with tetrazolium stain. Since fasting accelerates heart fatty acid oxidation, data were compared to those from fed rats; using Langendorff perfused (glucose 10 mM) hearts of 250-350 g Wistar rats exposed to 25 min ischaemia - 30 min reperfusion. Fasting reduced the ischaemic rise of end diastolic pressure (contracture), improved recovery of contraction and lowered lactate production in comparison with the fed whereas cellular viability was similar in both groups. Dimethylamiloride improved the recovery of contraction (fed control 24 +/- 9%, fed treated 68 +/- 11%, P < 0.05 at the end of reperfusion), attenuated the contracture (fed control 40 +/- 9%, fed treated 24 +/- 11%, P < 0.05 at the beginning of reperfusion) and reduced lactate production in the fed group and increased cellular viability in both groups (fed control 21 +/- 6%, fed treated 69 +/- 7%, P < 0.05, and fasted control 18 +/- 7%, fasted treated 53 +/- 8%, P < 0.05). Oxfenicine reduced the recovery of contraction (fasted control 88 +/- 6%, fasted treated 60 +/- 11%, P < 0.05) and increased lactate production of fasted group and attenuated the contracture in the fed. These data suggest that beneficial effects of fasting owe, at least in part, to a lowered glycolysis probably secondary to the increased fatty acid oxidation and to the accumulation of energy supplying acyl esters. Dimethylamiloride slowing of glycolysis might explain functional improvement, whereas it seems unrelated to the protection on cell viability. 相似文献
19.
Roberto Ferrari Claudio Ceconi Salvatore Curello Evasio Pasini Odoardo Visioli 《Molecular and cellular biochemistry》1989,88(1-2):161-168
Summary Reperfusion of isolated rabbit heart after 60 min of ischaemia resulted in poor recovery of mechanical function, release of reduced (GSH) and oxidized glutathione (GSSG), reduction of tissue GSH/GSSG ratio and shift of cellular thiol redox state toward oxidation, suggesting the occurrence of oxidative stress. Pretreatment of the isolated heart with propionyl-L-carnitine (10–7M) improved the functional recovery of the myocardium, reduced GSH and GSSG release and attenuated the accumulation of tissue GSSG. This effect was specific for propionyl-L-carnitine as L-carnitine and propionyl acid did not modify myocardial damage. 相似文献
20.
Sergio Chain Hector Luciardi Gabriela Feldman Sofia Berman Ramón N Herrera Javier Ochoa Juan Muntaner Eduardo M Escudero Ricardo Ronderos 《Cardiovascular ultrasound》2006,4(1):1-7