Effect of Ischemic Preconditioning on Mitochondrial Oxidative Phosphorylation and High Energy Phosphates in Rat Hearts

1996 ◽  
Vol 28 (2) ◽  
pp. 417-428 ◽  
Author(s):  
M Kobara
Keyword(s):  
Oxidative Phosphorylation ◽  
Ischemic Preconditioning ◽  
High Energy ◽  
High Energy Phosphates ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Rat Hearts

Pyruvate increases threshold for preconditioning in globally ischemic rat hearts

1994 ◽  
Vol 267 (4) ◽  
pp. H1403-H1409 ◽  
Author(s):  
C. A. Sargent ◽  
S. Dzwonczyk ◽  
P. Sleph ◽  
M. Wilde ◽  
G. J. Grover
Keyword(s):  
Lactate Dehydrogenase ◽  
Ischemic Preconditioning ◽  
Enhanced Recovery ◽  
Recovery Of Function ◽  
High Energy ◽  
Global Ischemia ◽  
High Energy Phosphates ◽  
Lactate Dehydrogenase Release ◽  
Rat Hearts ◽  
Isolated Rat

Isolated rat hearts can be protected by preconditioning, although this has not been found when they are perfused with pyruvate. We addressed the question of whether pyruvate could increase the threshold for preconditioning in isolated rat hearts and whether this could be overcome with increased durations of ischemia. A protocol of four periods of 5 min of ischemic preconditioning (4 x 5 min) protected hearts (improved recovery of function, reduced lactate dehydrogenase release) not perfused with pyruvate from a subsequent 30-min period of global ischemia, but did not protect pyruvate-perfused hearts. Pilot studies indicated that hearts perfused in the presence of pyruvate must be ischemic for approximately 40% longer to produce equivalent ischemic damage in nonpyruvate-treated hearts. Thus the preconditioning period of 5 min was increased by approximately 40% to 7 min to produce equivalent degrees of preconditioning. Hearts preconditioned with the 4 x 7 min protocol with pyruvate were significantly protected against a subsequent severe global ischemia (enhanced recovery of function, reduced lactate dehydrogenase release). High-energy phosphates were measured at the end of the preconditioning protocol (before final global ischemia) to determine whether there was a correlation between cardioprotection and high-energy phosphate levels. There was no correlation between ATP, ADP, or AMP levels and the efficacy of preconditioning. However, an increase in creatine phosphate was associated with cardioprotection, although the importance of this in mediating preconditioning is doubtful. Thus the ability to precondition rat hearts is somewhat dependent on their energy source, but this appears to be due to changes in the severity of the ischemic preconditioning event.

Mitochondrial oxidative phosphorylation in hearts subjected to Ca2+ depletion and Ca2+ repletionThis article is one of a selection of papers published in a special issue celebrating the 125th anniversary of the Faculty of Medicine at the University of Manitoba.

2009 ◽  
Vol 87 (10) ◽  
pp. 789-797 ◽  
Author(s):  
Zhanna Makazan ◽  
Harjot K. Saini-Chohan ◽  
Naranjan S. Dhalla
Keyword(s):  
Oxidative Phosphorylation ◽  
Mitochondrial Function ◽  
Cell Damage ◽  
Respiratory Control ◽  
Myocardial Cell ◽  
High Energy ◽  
Mitochondrial Oxidative Phosphorylation ◽  
Rat Hearts ◽  
Intracellular Ca ◽  
125Th Anniversary

Repletion of Ca2+ in the Ca2+-depleted heart has been shown to produce cardiac dysfunction, myocardial cell damage, intracellular Ca2+ overload, and defects in sarcolemmal and sarcoplasmic reticulum function (Ca2+ paradox). Although these alterations in the Ca2+-paradox heart are associated with a depression in the high-energy phosphate stores, little information regarding changes in mitochondrial oxidative phosphorylation is available. Perfusion of rat hearts with Ca2+-free medium for 5 min followed by reperfusion with a medium containing 1.25 mmol/L Ca2+ for 10 min depressed mitochondrial state 3 respiration, respiratory control index, ADP/O ratio, and rate of oxidative phosphorylation without any change in state 4 respiration. These alterations were partially prevented when the reperfusion was carried out with a medium containing low Ca2+ (0.10–0.50 mmol/L). Treatment of heart with inhibitors of sarcolemmal Ca2+ channels (verapamil and diltiazem) or inhibitors of Na+/Ca2+ exchange (KB-R7943) and Na+/H+ exchange (amiloride) failed to modify changes in mitochondrial function due to Ca2+ paradox. Likewise, antioxidants N-acetylcysteine and N-(2-mercaptopropionyl)-glycine and an oxyradical-scavenging mixture of superoxide dismutase and catalase were ineffective in preventing the mitochondrial alterations in the Ca2+-paradox heart. Incubation of mitochondria with various concentrations of Ca2+ inhibited oxidative phosphorylation; this Ca2+-induced change in mitochondrial function was not affected by different oxyradical-scavenging systems. These observations suggest that defects in mitochondrial function in the Ca2+-paradox heart may be due to the occurrence of intracellular Ca2+ overload rather than the development of oxidative stress.

Cardioprotective Effects of Propofol and Sevoflurane in Ischemic and Reperfused Rat Hearts 

1999 ◽  
Vol 91 (5) ◽  
pp. 1349-1349 ◽  
Author(s):  
Sanjiv Mathur ◽  
Parviz Farhangkhgoee ◽  
Morris Karmazyn
Keyword(s):  
High Energy ◽  
Left Ventricular ◽  
High Energy Phosphates ◽  
Constant Flow Rate ◽  
Rat Hearts ◽  
Reperfusion Period ◽  
Coronary Syndromes ◽  
Cardioprotective Effects ◽  
Developed Pressure

Background Sodium ion-hydrogen ion (Na(+)-H(+)) exchange inhibitors are effective cardioprotective agents. The N(+)-H(+) exchange inhibitor HOE 642 (cariporide) has undergone clinical trials in acute coronary syndromes, including bypass surgery. Propofol and sevoflurane are also cardioprotective via unknown mechanisms. The authors investigated the interaction between propofol and HOE 642 in the ischemic reperfused rat heart and studied the role of adenosine triphosphate-sensitive potassium (K(ATP)) channels in the myocardial protection associated with propofol and sevoflurane. Methods Isolated rat hearts were perfused by the Langendorff method at a constant flow rate, and left ventricular function and coronary pressures were assessed using standard methods. Energy metabolites were also determined. To assess the role of K(ATP) channels, hearts were pretreated with the K(ATP) blocker glyburide (10 microM). Hearts were then exposed to either control buffer or buffer containing HOE 642 (5 microM), propofol (35 microM), sevoflurane (2.15 vol%), the K(ATP) opener pinacidil (1 microM), or the combination of propofol and HOE 642. Each heart was then subjected to 1 h of global ischemia followed by 1 h of reperfusion. Results Hearts treated with propofol, sevoflurane, pinacidil, or HOE 642 showed significantly higher recovery of left ventricular developed pressure and reduced end-diastolic pressures compared with controls. The combination of propofol and HOE 642 provided superior protection toward the end of the reperfusion period. Propofol, sevoflurane, and HOE 642 also attenuated the onset and magnitude of ischemic contracture and preserved high-energy phosphates (HEPs) compared with controls. Glyburide attenuated the cardioprotective effects of sevoflurane and abolished the protection observed with pinacidil. In contrast, glyburide had no effect on the cardioprotection associated with propofol treatment. Conclusion HOE 642, propofol, and sevoflurane provide cardioprotection via different mechanisms. These distinct mechanisms may allow for the additive and superior protection observed with the combination of these anesthetics and HOE 642.

scholarly journals Impaired Cerebral Mitochondrial Oxidative Phosphorylation Function in a Rat Model of Ventricular Fibrillation and Cardiopulmonary Resuscitation

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Jun Jiang ◽  
Xiangshao Fang ◽  
Yue Fu ◽  
Wen Xu ◽  
Longyuan Jiang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Ventricular Fibrillation ◽  
Cardiopulmonary Resuscitation ◽  
Oxidative Phosphorylation ◽  
Mitochondrial Dysfunction ◽  
Rat Model ◽  
Mitochondrial Function ◽  
High Energy ◽  
Mitochondrial Morphology ◽  
High Energy Phosphates

Postcardiac arrest brain injury significantly contributes to mortality and morbidity in patients suffering from cardiac arrest (CA). Evidence that shows that mitochondrial dysfunction appears to be a key factor in tissue damage after ischemia/reperfusion is accumulating. However, limited data are available regarding the cerebral mitochondrial dysfunction during CA and cardiopulmonary resuscitation (CPR) and its relationship to the alterations of high-energy phosphate. Here, we sought to identify alterations of mitochondrial morphology and oxidative phosphorylation function as well as high-energy phosphates during CA and CPR in a rat model of ventricular fibrillation (VF). We found that impairment of mitochondrial respiration and partial depletion of adenosine triphosphate (ATP) and phosphocreatine (PCr) developed in the cerebral cortex and hippocampus following a prolonged cardiac arrest. Optimal CPR might ameliorate the deranged phosphorus metabolism and preserve mitochondrial function. No obvious ultrastructural abnormalities of mitochondria have been found during CA. We conclude that CA causes cerebral mitochondrial dysfunction along with decay of high-energy phosphates, which would be mitigated with CPR. This study may broaden our understanding of the pathogenic processes underlying global cerebral ischemic injury and provide a potential therapeutic strategy that aimed at preserving cerebral mitochondrial function during CA.

scholarly journals Effects of oxidant exposure on substrate utilization and high-energy phosphates in isolated rat hearts.

1994 ◽  
Vol 75 (1) ◽  
pp. 97-104 ◽  
Author(s):  
K P Burton ◽  
J G Jones ◽  
T H Le ◽  
A D Sherry ◽  
C R Malloy
Keyword(s):  
High Energy ◽  
Substrate Utilization ◽  
High Energy Phosphates ◽  
Rat Hearts ◽  
Isolated Rat

Adrenergic influences on cardiac function during ventricular fibrillation in isolated rat hearts

1991 ◽  
Vol 261 (5) ◽  
pp. H1452-H1456
Author(s):  
I. Derad ◽  
I. Funk ◽  
P. Pauschinger ◽  
J. Born
Keyword(s):  
Blood Flow ◽  
Oxygen Consumption ◽  
Ventricular Fibrillation ◽  
Cardiac Function ◽  
Coronary Blood Flow ◽  
High Energy ◽  
High Energy Phosphates ◽  
Tissue Concentrations ◽  
Rat Hearts ◽  
Isolated Rat

Effects of norepinephrine (NE, 10(-6) M), epinephrine (E, 10(-6) M), and vehicle on coronary blood flow (CF), oxygen consumption, and lactate release were compared in 32 isolated rat hearts during 5 min of ventricular fibrillation (VF). After VF, tissue concentrations of ATP, AMP, creatinine phosphate (CP), and lactate were measured. Perfusion of treatments started 30 s after onset of VF and was maintained throughout VF. CF during VF was greater (P less than 0.005) during perfusion of E (mean +/- SE, 5.73 +/- 0.15 ml/min) than NE (5.06 +/- 0.32 ml/min) or vehicle (5.11 +/- 0.18 ml/min). Oxygen consumption during VF was higher during perfusion of E (29.5 +/- 0.9 microliters.min(-1).g wet heart wt(-1)) than vehicle (27.3 +/- 0.7 microliters.min(-1).g(-1); P less than 0.05); average oxygen consumption during NE (27.6 +/- 1.4 microliters.min(-1).g(-1)) and vehicle were comparable. After NE, but not E, tissue AMP concentrations were significantly increased, and CP concentrations were reduced compared with vehicle (P less than 0.05). Enhanced consumption of high-energy phosphates during NE suggests that there is also an enhanced demand for oxygen. However, unlike during E, during NE this demand is not met by an augmented CF. Thus, compared with E, NE treatment during VF may increase the risk of hypoxic damage.

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