Evidence for increased lipid peroxidation in the non-ischaemic portion of the heart with coronary occlusion

Herbaczyńska-Cedro, K; Gordon-Majszak, W

doi:10.1093/cvr/23.2.98

Cited by 11 publications

(3 citation statements)

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“…Even in nonpreconditioned hearts, regional ischemia leads to a global increase in lipid peroxidation products. 33,34 Our data indicate that the accumulation of these products per se does not lead to tissue injury, and that high levels of these oxidants can be tolerated by nonischemic myocardium, whereas ischemic/reperfused myocardium is more sensitive to their toxic actions.…”

Section: Shinmura Et Al Role Of Aldose Reductase In Late Preconditionmentioning

confidence: 72%

Aldose Reductase Is an Obligatory Mediator of the Late Phase of Ischemic Preconditioning

Shinmura

Bolli

Liu

et al. 2002

Circulation Research

123

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Abstract-Aldose reductase (AR), a member of the aldo-keto reductase superfamily, has been shown to metabolize toxic aldehydes generated by lipid peroxidation, suggesting that it may serve as an antioxidant defense. To investigate its role in the late phase of ischemic preconditioning (PC), conscious rabbits underwent 6 cycles of 4-minute coronary occlusion/4-minute reperfusion. Twenty-four hours later, there was a marked increase in AR protein and activity and in the myocardial content of sorbitol, a unique product of AR catalysis. Pretreatment with N -nitro-L-arginine, a nitric oxide synthase inhibitor, or chelerythrine, a protein kinase C inhibitor (both given at doses that block late PC in this model), prevented the increase in AR protein 24 hours later, demonstrating that ischemic PC upregulates AR via nitric oxide-and protein kinase C-dependent signaling pathways. The AR-selective inhibitors tolrestat and sorbinil prevented AR-mediated accumulation of sorbitol and abrogated the infarct-sparing effect of late PC, demonstrating that enhanced AR activity is necessary for this cardioprotective phenomenon to occur. Inhibition of AR did not affect infarct size or the myocardial accumulation of the lipid peroxidation product 4-hydroxy trans-2-nonenal (HNE) in nonpreconditioned rabbits. The accumulation of HNE was inhibited by late PC, and this effect was abrogated by sorbinil. Taken together, these results establish AR as an essential mediator of late PC. Furthermore, the data suggest that myocardial ischemia/reperfusion injury is due in part to the generation of lipid peroxidation products and that late PC diminishes this source of injury by upregulating AR. Key Words: myocardial ischemia/reperfusion injury Ⅲ aldose reductase Ⅲ myocardial infarction Ⅲ 4-hydroxy-trans-2-nonenal Ⅲ ischemic preconditioning A ldose reductase (AR) is a member of the aldo-keto reductase superfamily. 1 Although this enzyme is expressed in most eukaryotic cells and is known to catalyze the reduction of a several aldehydes including aldo-sugars, its physiological role remains unclear. 2 Recent investigations have shown that AR exhibits high affinity for hydrophobic aldehydes, such as those generated during lipid peroxidation. 3 The most abundant among the lipid-derived aldehydes, 4-hydroxy trans-2-nonenal (HNE) and its glutathione conjugate, are excellent substrates of AR. 3 Because lipid-derived aldehydes are cytotoxic, 4 the ability of AR to metabolize them suggests that this enzyme may be involved in protection against oxidative injury. This function of AR could be important in myocardial ischemia/reperfusion, which is associated with increased generation of reactive oxygen species. 5 Indeed, mounting evidence indicates that HNE is a major product of lipid peroxidation during myocardial ischemia/ reperfusion 6 and that the formation of HNE and the accumulation of HNE-modified proteins are related to the extent of tissue damage. 7,8 The late phase of ischemic preconditioning (PC) is a long-lasting adaptive response of the myocardium...

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Section: Shinmura Et Al Role Of Aldose Reductase In Late Preconditionmentioning

confidence: 72%

Aldose Reductase Is an Obligatory Mediator of the Late Phase of Ischemic Preconditioning

Shinmura

Bolli

Liu

et al. 2002

Circulation Research

123

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“…The same lack of augmentation has been noted in the right ventricle [28]. This may be explained partly by "free radicals" released by ischaemia contributing to myocardial damage in the seemingly normal region [29], but another explanation is in the selection of, and amount of, the coronary artery bed made ischaemic.…”

Section: Discussionmentioning

confidence: 65%

Regional myocardial function during contiguous ischaemia in an anaesthetized canine model: comparison of six methods of measurement

Reitan

Kien

Moore

et al. 1994

British Journal of Anaesthesia

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During acute myocardial ischaemia, the function of the unaffected muscle is the primary determinant of residual cardiac performance. We compared six methods of measuring regional function in the remaining non-ischaemic segment after acute ligation of the left anterior descending (LAD) coronary artery in 16 dogs. Preparation included left ventricular micromanometers, regional sonomicrometer transducers to measure segment length and wall thickness, caval occluders and left atrial catheters for injection of radioactive microspheres to measure regional blood flow. Pulmonary artery, central venous and systemic arterial pressures were measured and regional coronary venous blood was collected for direct myocardial oxygen consumption (VO2) calculations. Under basal high-dose fentanyl-neuromuscular blocker anaesthesia, the LAD was occluded after addition of halothane or isoflurane at 0.5 or 1.5 MAC concentrations. Regional myocardial function of the non-ischaemic segment was assessed by the following computer-derived indices: percent systolic wall thickening (% WT), velocity of shortening (vs), percent systolic shortening (%SS), regional stroke work (RSW), regional preload recruitable stroke work (RPRSW) and regional end-systolic elastance (Ees). No index demonstrated enhanced function in the non-ischaemic segment after LAD ligation and all monitors, except Ees, were sensitive to depression of function represented by a decrease in values after administration of halothane and isoflurane (P < 0.05). Ees values increased with the addition of isoflurane and remained constant with halothane. Circulating concentrations of catecholamines were unchanged after ischaemia, while inhalation agents caused a decrease in the concentrations of adrenaline and dopamine (P < 0.05), but not noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Even though the portion of the Cu(II) present in the uncharged complex is small, significant amounts of this lipophilic species could traverse the cell walls over the time of the trials, so that intracellular as well as extracellular mechanisms can function. There is strong evidence for the role of oxygen-derived free radicals in the development of lipid peroxidation and subsequent cell damage in reperfusion and heart preservation injury [14,22,23]. Biological mechanisms for the generation during ischemia of low-molecular-weight chelates of iron (LMWC), and for the production of superoxide radicals leading to elevated levels of hydrogen peroxide, have been found.…”

Section: Discussionmentioning

confidence: 99%

Twenty-Four-Hour Heart Preservation Using Continuous Cold Perfusion and Copper (II) Complexes

Sellke

Richter

Dunphy

et al. 1998

Journal of Surgical Research

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Evidence for increased lipid peroxidation in the non-ischaemic portion of the heart with coronary occlusion

Cited by 11 publications

References 0 publications

Aldose Reductase Is an Obligatory Mediator of the Late Phase of Ischemic Preconditioning

Aldose Reductase Is an Obligatory Mediator of the Late Phase of Ischemic Preconditioning

Regional myocardial function during contiguous ischaemia in an anaesthetized canine model: comparison of six methods of measurement

Twenty-Four-Hour Heart Preservation Using Continuous Cold Perfusion and Copper (II) Complexes

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