Restricted feeding improves postischemic recovery of Langendorff-perfused rat hearts

2010 ◽  
Vol 88 (10) ◽  
pp. 1002-1009 ◽  
Author(s):  
María M. Jaitovich ◽  
Alicia Varela ◽  
Cintia Sbarbati ◽  
Romina Hermann ◽  
María E. Torresín ◽  
...  
Keyword(s):  
Thiobarbituric Acid ◽  
Restricted Feeding ◽  
Thiobarbituric Acid Reactive Substances ◽  
G6pdh Activity ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
The One ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Postischemic Recovery ◽  
Contractile Recovery

The goal of the present study was to assess the effects of a restricted feeding schedule (RFS) on postischemic contractile recovery in relation to triacylglycerol (TAG), glycogen, and ATP content. Glucose-6-phosphate dehydrogenase (G6PDH) activity, reduced/oxidized glutathione ratio (GSH/GSSG), and thiobarbituric acid reactive substances (TBARS) levels were also determined. Isolated rat hearts entrained to daily RFS (2 h food access starting at 1200) or fed ad libitum (FED) for 3 weeks were Langendorff-perfused (25 min ischemia, 30 min reperfusion) with Krebs–Ringer bicarbonate solution (10 mmol/L glucose). RFS improved the recovery of contractility and reduced creatine kinase (CK) release upon reperfusion. Further, at the end of reperfusion, RFS hearts exhibited increased G6PDH activity and repletion of tissue glycogen, TAG, and ATP that was not observed in the FED hearts. GSH/GSSG at the end of reperfusion fell to the same value in both nutritional states, and TBARS levels were higher in the RFS hearts. In conclusion, RFS improved postischemic functional recovery, which was accompanied by a reduction in CK release and a striking energy recovery. Although enhanced G6PDH activity was displayed, RFS was unable to reduce lipid peroxidation, supporting a clear dissociation between protection against mechanical dysfunction and CK release on the one hand and oxidative damage on the other.

Protection effect of endurance training against reoxygenation-induced injuries in rat heart

1990 ◽  
Vol 68 (4) ◽  
pp. 1672-1678 ◽  
Author(s):  
M. Kihlstrom
Keyword(s):  
Right Ventricle ◽  
Endurance Training ◽  
Flow Characteristics ◽  
Thioredoxin Reductase ◽  
Thiobarbituric Acid ◽  
Enzymatic Antioxidants ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
The Right ◽  
Glucose 6 Phosphate Dehydrogenase

Endurance training by swimming (219-229 h) resulted in a significant protection against hypoxia/reoxygenation-induced injuries in Langendorff-perfused rat hearts. The protection was manifested as improved flow characteristics and a smaller release of creatine kinase into the perfusate. The concentration of thiobarbituric acid reactive substances (TBARS) was lower in the trained than in the respective control hearts. The trained hearts also showed a lower reoxygenation-induced increase in TBARS. The myocardium of the right ventricle and that of the left subepimyocardium were the most affected by reoxygenation. The swimming program induced a decrease in the activities of catalase and glutathione reductase in all parts of the myocardium measured. A decrease in vitamin E concentration in the subendomyocardium of the left ventricle and an increase in the activity of thioredoxin reductase also occurred. An increase in the concentration of reduced glutathione due to training was also observed, especially in the left subepimyocardium, whereas the glutathione disulfide concentration and the activity of superoxide dismutase were unaffected. The activity of glucose 6-phosphate dehydrogenase increased in the right ventricle. The results suggest both the importance of cellular redox state and the role of a lower degree of enzymatic antioxidants in training-induced protection against ischemic injuries.

Effect of diazoxide on flavoprotein oxidation and reactive oxygen species generation during ischemia-reperfusion: a study on Langendorff-perfused rat hearts using optic fibers

2008 ◽  
Vol 294 (5) ◽  
pp. H2088-H2097 ◽  
Author(s):  
Philippe Pasdois ◽  
Bertrand Beauvoit ◽  
Liliane Tariosse ◽  
Béatrice Vinassa ◽  
Simone Bonoron-Adèle ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Reactive Oxygen Species Generation ◽  
Left Ventricular ◽  
Rate Pressure Product ◽  
Control Group ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Optic Fibers ◽  
The One ◽  
Isolated Perfused Rat Hearts

This study analyzed the oxidant generation during ischemia-reperfusion protocols of Langendorff-perfused rat hearts, preconditioned with a mitochondrial ATP-sensitive potassium channel (mitoKATP) opener (i.e., diazoxide). The autofluorescence of mitochondrial flavoproteins, and that of the total NAD(P)H pool on the one hand and the fluorescence of dyes sensitive to H2O2 or O2•− [i.e., the dihydrodichlorofluoroscein (H2DCF) and dihydroethidine (DHE), respectively] on the other, were noninvasively measured at the surface of the left ventricular wall by means of optic fibers. Isolated perfused rat hearts were subjected to an ischemia-reperfusion protocol. Opening mitoKATP with diazoxide (100 μM) 1) improved the recovery of the rate-pressure product after reperfusion (72 ± 2 vs. 16.8 ± 2.5% of baseline value in control group, P < 0.01), and 2) attenuated the oxidant generation during both ischemic (−46 ± 5% H2DCF oxidation and −40 ± 3% DHE oxidation vs. control group, P < 0.01) and reperfusion (−26 ± 2% H2DCF oxidation and −23 ± 2% DHE oxidation vs. control group, P < 0.01) periods. All of these effects were abolished by coperfusion of 5-hydroxydecanoic acid (500 μM), a mitoKATP blocker. During the preconditioning phase, diazoxide induced a transient, reversible, and 5-hydroxydecanoic acid-sensitive flavoprotein and H2DCF (but not DHE) oxidation. In conclusion, the diazoxide-mediated cardioprotection is supported by a moderate H2O2 production during the preconditioning phase and a strong decrease in oxidant generation during the subsequent ischemic and reperfusion phases.

scholarly journals Postischemic Na+-K+-ATPase reactivation is delayed in the absence of glycolytic ATP in isolated rat hearts

2001 ◽  
Vol 280 (5) ◽  
pp. H2189-H2195 ◽  
Author(s):  
Jan G. Van Emous ◽  
Carmen L. A. M. Vleggeert-Lankamp ◽  
Marcel G. J. Nederhoff ◽  
Tom J. C. Ruigrok ◽  
Cees J. A. Van Echteld
Keyword(s):  
Pyruvate Dehydrogenase ◽  
Functional Coupling ◽  
Glycogen Depletion ◽  
Postischemic Reperfusion ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Glycolytic Atp ◽  
Contractile Recovery ◽  
Isolated Rat ◽  
Isolated Perfused Rat Hearts

Normalization of intracellular sodium (Na[Formula: see text]) after postischemic reperfusion depends on reactivation of the sarcolemmal Na+-K+-ATPase. To evaluate the requirement of glycolytic ATP for Na+-K+-ATPase function during postischemic reperfusion, 5-s time-resolution23Na NMR was performed in isolated perfused rat hearts. During 20 min of ischemia, Na[Formula: see text] increased approximately twofold. In glucose-reperfused hearts with or without prior preischemic glycogen depletion, Na[Formula: see text]decreased immediately upon postischemic reperfusion. In glycogen-depleted pyruvate-reperfused hearts, however, the decrease of Na[Formula: see text] was delayed by ∼25 s, and application of the pyruvate dehydrogenase (PDH) activator dichloroacetate (DA) did not shorten this delay. After 30 min of reperfusion, Na[Formula: see text]had almost normalized in all groups and contractile recovery was highest in the DA-treated hearts. In conclusion, some degree of functional coupling of glycolytic ATP and Na+-K+-ATPase activity exists, but glycolysis is not essential for recovery of Na[Formula: see text] homeostasis and contractility after prolonged reperfusion. Furthermore, the delayed Na+-K+-ATPase reactivation observed in pyruvate-reperfused hearts is not due to inhibition of PDH.

Role of dual-site phospholamban phosphorylation in the stunned heart: insights from phospholamban site-specific mutants

2003 ◽  
Vol 285 (3) ◽  
pp. H1198-H1205 ◽  
Author(s):  
M. Said ◽  
L. Vittone ◽  
C. Mundiña-Weilenmann ◽  
P. Ferrero ◽  
E. G. Kranias ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Phosphorylation Sites ◽  
Adrenergic Stimulation ◽  
Rat Hearts ◽  
Adrenergic Blocker ◽  
Perfused Rat Hearts ◽  
A Site ◽  
Contractile Recovery ◽  
Mechanical Recovery

Phosphorylation of phospholamban (PLB) at Ser16 (protein kinase A site) and at Thr17 [Ca2+/calmodulin kinase II (CaMKII) site] increases sarcoplasmic reticulum Ca2+ uptake and myocardial contractility and relaxation. In perfused rat hearts submitted to ischemia-reperfusion, we previously showed an ischemia-induced Ser16 phosphorylation that was dependent on β-adrenergic stimulation and an ischemia and reperfusion-induced Thr17 phosphorylation that was dependent on Ca2+ influx. To elucidate the relationship between these two PLB phosphorylation sites and postischemic mechanical recovery, rat hearts were submitted to ischemia-reperfusion in the absence and presence of the CaMKII inhibitor KN-93 (1 μM) or the β-adrenergic blocker dl-propranolol (1 μM). KN-93 diminished the reperfusion-induced Thr17 phosphorylation and depressed the recovery of contraction and relaxation after ischemia. dl-Propranolol decreased the ischemia-induced Ser16 phosphorylation but failed to modify the contractile recovery. To obtain further insights into the functional role of the two PLB phosphorylation sites in postischemic mechanical recovery, transgenic mice expressing wild-type PLB (PLB-WT) or PLB mutants in which either Thr17 or Ser16 were replaced by Ala (PLB-T17A and PLB-S16A, respectively) into the PLB-null background were used. Both PLB mutants showed a lower contractile recovery than PLB-WT. However, this recovery was significantly impaired all along reperfusion in PLB-T17A, whereas it was depressed only at the beginning of reperfusion in PLB-S16A. Moreover, the recovery of relaxation was delayed in PLB-T17A, whereas it did not change in PLB-S16A, compared with PLB-WT. These findings indicate that, although both PLB phosphorylation sites are involved in the mechanical recovery after ischemia, Thr17 appears to play a major role.

Catecholamines and preconditioning: studies of contraction and function in isolated rat hearts

1999 ◽  
Vol 277 (1) ◽  
pp. H136-H143 ◽  
Author(s):  
David J. Hearse ◽  
Fiona J. Sutherland
Keyword(s):  
Ischemic Preconditioning ◽  
Untreated Control ◽  
Vehicle Control ◽  
Left Ventricular ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Developed Pressure ◽  
And Function ◽  
Postischemic Recovery ◽  
Isolated Perfused Rat Hearts

The aims of this study were to determine whether 1) like ischemic preconditioning, transient exposure to norepinephrine before ischemia exacerbates contracture during ischemia and 2) protection afforded by norepinephrine is stereospecific (receptor mediated). Isolated perfused rat hearts were randomized into five groups ( n = 6/group): 1) ischemic preconditioning (3 min of ischemia + 3 min of reperfusion + 5 min of ischemia + 5 min of reperfusion), 2) untreated control, 3) vehicle control (ascorbic acid), 4) substitution of preconditioning ischemia by perfusion with d-norepinephrine, and 5) substitution of preconditioning ischemia by perfusion with l-norepinephrine. This was followed by 40 min of zero-flow ischemia and 50 min of reperfusion. Ischemic preconditioning and l-norepinephrine exacerbated contracture (time to 50% contracture = 9.2 ± 1.1 and 9.0 ± 1.1 vs. 13.3 ± 0.3, 12.4 ± 0.5, and 13.2 ± 0.4 min for untreated control, vehicle control, and d-norepinephrine, respectively, P < 0.05). Postischemic left ventricular developed pressure was poor in untreated control (23.0 ± 2.2%), vehicle control (26.9 ± 2.3%), and d-norepinephrine (19.8 ± 2.8%) groups but good in preconditioned (52.4 ± 5.1%) and l-norepinephrine (52.5 ± 1.1%) groups ( P < 0.05). Thus norepinephrine preconditioning, like ischemic preconditioning, causes a paradoxical exacerbation of contracture coupled with enhanced postischemic recovery; both effects are stereospecific.

Role of antioxidant defenses during estivation and anoxia exposure in the freshwater snail Biomphalaria tenagophila (Orbigny, 1835)

2003 ◽  
Vol 81 (7) ◽  
pp. 1239-1248 ◽  
Author(s):  
Marcus V.R Ferreira ◽  
Antonieta C.R Alencastro ◽  
Marcelo Hermes-Lima
Keyword(s):  
Thiobarbituric Acid ◽  
Freshwater Snail ◽  
Antioxidant Defenses ◽  
Oxygen Species ◽  
Thiobarbituric Acid Reactive Substances ◽  
Glutathione S Transferase ◽  
Sod Activity ◽  
Glucose 6 Phosphate Dehydrogenase ◽  
Gpx Activity

The effects of 24 h of exposure to underwater anoxia and 15 days of estivation (at 26–27°C) on the enzymatic antioxidant system of the hepatopancreas of the freshwater snail Biomphalaria tenagophila (Planorbidae) are described. The effect of 24 h of recovery was also investigated. Catalase activity dropped by 31% during 24 h of anoxia, and superoxide dismutase (SOD) activity was reduced by 43% during the 15 days of estivation. This is consistent with the overall decrease in metabolic rate during estivation or anoxia. Indeed, the heartbeat diminished by 28–36% during estivation (determination was possible for only 4 days) and by 66% after 24 h of anoxia. On the other hand, selenium-dependent glutathione peroxidase (Se-GPX) activity increased during anoxia (from 10 to 14 mU/mg protein) and estivation (by 14%). Glutathione S-transferase (GST) and glutathione reductase activities remained unchanged during estivation and anoxia. Glucose 6-phosphate dehydrogenase activity was unchanged during estivation and recovery. Recovery restored SOD activity. Catalase, Se-GPX, and GST activities during recovery were significantly lower than those of the respective controls. Lipid peroxidation, determined as the level of thiobarbituric acid-reactive substances, was unchanged in the hepatopancreas after 15 days of estivation and 26 h of recovery from estivation. It is possible that the increase in Se-GPX activity during anoxia and estivation, and the maintenance of GST activity, are relevant in minimizing the effects of reactive oxygen species that can be formed upon resumption of aerobic metabolism. Thus, B. tenagophila may have a biochemical strategy of preparation for oxidative stress such as that observed in several other species of anoxia/hypoxia-tolerant animals.

Upregulation of CaMKIIδ during ischaemia–reperfusion is associated with reperfusion-induced arrhythmias and mechanical dysfunction of the rat heart: involvement of sarcolemmal Ca2+-cycling proteins

2012 ◽  
Vol 90 (8) ◽  
pp. 1127-1134 ◽  
Author(s):  
Adriana Adameova ◽  
Slavka Carnicka ◽  
Tomas Rajtik ◽  
Adrian Szobi ◽  
Martina Nemcekova ◽  
...  
Keyword(s):  
Sodium Calcium Exchanger ◽  
Ischaemia Reperfusion Injury ◽  
Global Ischaemia ◽  
Ischaemia Reperfusion ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Dependent Protein ◽  
Chronotropic Effects ◽  
Cardiac Stunning ◽  
Contractile Recovery

Although Ca2+/calmodulin-dependent protein kinase II delta (CaMKIIδ) has been implicated in development of different phenotypes of myocardial ischaemia–reperfusion injury, its involvement in arrhythmogenesis and cardiac stunning is not sufficiently elucidated. Moreover, the mechanisms by which CaMKIIδ mediates disturbances in excitation–contraction coupling, are not exactly known. To investigate this, KN-93 (0.5 µmol/L), a CaMKII inhibitor, was administered before induction of global ischaemia and reperfusion in isolated Langendorff-perfused rat hearts. Expression of CaMKIIδ and the sarcollemal Ca2+-cycling proteins, known to be activated during reperfusion, was analyzed using immunoblotting. KN-93 reduced reperfusion-induced ectopic activity and the incidence of ventricular fibrillation. Likewise, the severity of arrhythmias was lower in KN-treated hearts. During the pre-ischaemia phase, neither inotropic nor chronotropic effects were elicited by KN-93, whereas post-ischaemic contractile recovery was significantly improved. Ischaemia–reperfusion increased the expression of CaMKIIδ and sodium–calcium exchanger (NCX1) proteins without any influence on the protein content of alpha 1c, a pore-forming subunit of L-type calcium channels (LTCCs). On the other hand, inhibition of CaMKII normalized changes in the expression of CaMKIIδ and NCX1. Taken together, CaMKIIδ seems to regulate its own turnover and to be an important component of cascade integrating NCX1, rather than LTCCs that promote ischaemia–reperfusion-induced contractile dysfunction and arrhythmias.

Calcium and cardioplegia in neonates: dose-response and time-response studies in rats

1991 ◽  
Vol 261 (5) ◽  
pp. H1609-H1616 ◽  
Author(s):  
E. Riva ◽  
D. J. Hearse
Keyword(s):  
Recovery Of Function ◽  
Calcium Content ◽  
Neonatal Rat ◽  
Calcium Handling ◽  
Enzyme Leakage ◽  
Rat Hearts ◽  
Perfused Rat Hearts ◽  
Time To Onset ◽  
Postischemic Recovery ◽  
Strong Inverse Relationship

Isolated Langendorff-perfused rat hearts (n = 6/group) were subjected to 60, 90, 120, or 180 min of ischemia with or without a 2-min preischemic infusion with St. Thomas' Hospital cardioplegic solution that had been modified to contain concentrations of calcium of 0, 0.5, 0.8, 1.0, 1.2, 1.8, or 2.4 mM. In general, irrespective of the calcium concentration, hearts in the cardioplegia group recovered better than those in the noncardioplegia group. There was no consistent relationship between calcium content and postischemic recovery of function or enzyme leakage after any of the durations of ischemia studied. However, as expected, there was a strong inverse relationship between recovery and duration of ischemia. The recovery of function correlated with enzyme leakage but not with the time to onset or magnitude of ischemic contracture. In conclusion, although the neonatal rat heart benefits from cardioplegia the protection is less impressive than that reported for adult hearts. Nonetheless, the neonatal heart appears to be very resistant to ischemia. We propose that many of these differences can be explained on the basis of differences in myocardial calcium handling between neonate and adult.

scholarly journals Triglycerides impair postischemic recovery in isolated hearts: roles of endothelin-1 and trimetazidine

2001 ◽  
Vol 281 (3) ◽  
pp. H1122-H1130 ◽  
Author(s):  
Lucilla D. Monti ◽  
Sonia Allibardi ◽  
Pier Marco Piatti ◽  
Gianpietro Valsecchi ◽  
Sabrina Costa ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Low Flow ◽  
Myocardial Recovery ◽  
Ex Vivo Model ◽  
Endothelin 1 ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
Postischemic Recovery ◽  
Contractile Recovery ◽  
Krebs Henseleit Buffer

There is growing evidence that hypertriglyceridemia exacerbates ischemic injury. We tested the hypothesis that triglycerides impair myocardial recovery from low-flow ischemia in an ex vivo model and that such an effect is related to endothelin-1. Hyperglycemic (glucose concentration = 12 mmol/l) and hyperinsulinemic (insulin concentration = 1.2 μmol/l) isolated rat hearts were perfused with Krebs-Henseleit buffer (Po 2 = 670 mmHg, pH 7.4, 37°C) added with increasing triglycerides (0, 1,000, 2,000, and 4,000 mg/dl, n = 6–9 rats/group). Hearts were exposed to 60 min of low-flow ischemia (10% of basal coronary flow), followed by 30 min of reperfusion. We found that increasing triglycerides impaired both the diastolic ( P< 0.005) and systolic ( P < 0.02) recovery. The release of endothelin-1 during reperfusion increased linearly with triglyceride concentration ( P = 0.0009). Elevated triglycerides also increased the release of nitrite and nitrate (NOx), the end products of nitric oxide, up to 6 μmol/min. Trimetazidine (1 μmol) further increased NOxrelease, blunted endothelin-1 release, and protected myocardial function during recovery. We conclude that high triglyceride levels impair myocardial recovery after low-flow ischemia in association with endothelin-1 release. The endothelium-mediated effect of triglycerides on both contractile recovery and endothelin-1 release is prevented by 1 μM trimetazidine.

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