Normothermic ischaemic cardiac arrest of the isolated perfused rat heart: effects of trifluoperazine and lysolecithin on mechanical and metabolic recovery

Lochner, Amanda; Niekerk, I. van; Kotzé, J.C.N.

doi:10.1007/bf01908180

Cited by 10 publications

(8 citation statements)

References 20 publications

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“…However, the effects of fatty acids on liver metabolism are multiple and difficult to disentangle at present (see Schonfeld et al, 1988;Nobes et al, 1990b). Lochner et al (1981) found that increased content of acyl-CoA in isolated rat hearts during ischaemia actually increased ANC activity.…”

Section: Control Over the Adenine Nucleotide Carriermentioning

confidence: 93%

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Brown

1992

Biochemical Journal

564

308

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We have seen that there is no simple answer to the question ‘what controls respiration?’ The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS)

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Section: Control Over the Adenine Nucleotide Carriermentioning

confidence: 93%

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Brown

1992

Biochemical Journal

564

308

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“…The Ca2+-calmodulin complex antagonists, such as TFP, have been shown to have no effect on mitochondrial oxidative function or tissue high-energy phosphate contents [23]. In spite of that, TFP has been found to protect myocardial cells against damage resulting from the Ca 2+ paradox [24].…”

Section: Discussionmentioning

confidence: 99%

Moderation of myocardial ischemia reperfusion injury by calcium channel and calmodulin receptor inhibition

et al. 1992

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Intracellular Ca2+ accumulation is implicated in the pathogenesis of myocardial reperfusion injury. To study approaches designed to modify Ca2+ uptake during coronary revascularization after acute infarction, a pig heart surgical infarct model (left anterior descending artery occlusion for 60 min) was subjected to 60 min hypothermic potassium cardioplegic arrest, followed by 60 min of global reperfusion. Four groups of six hearts each were studied in a randomized manner, i.e., cardioplegia alone (control), cardioplegia + 10 microM diltiazem (Ca2+ slow channel blocker), cardioplegia + 10 microM trifluoperazine (TFP), (a Ca(2+)-calmodulin antagonist), and cardioplegia+diltiazem (10 microM) + TFP (10 microM). Left ventricular contractility (global and segmental), metabolism (coronary blood flow and O2 consumption), and creatine kinase generation were measured during reperfusion. Both the Ca2+ channel blocker, diltiazem, and the calmodulin antagonist, TFP, improved myocardial global and regional function as well as myocardial metabolism. While diltiazem better restored global and regional contractility, trifluoperazine had a greater effect on coronary blood flow and myocardial oxygen consumption. Enzyme release and lipid peroxidation were equally moderated by both drugs. From this study it can be concluded that Ca2+ influx does play a role in ischemic and reperfusion injury. The mechanisms of its effect are complex, but can be successfully antagonized by Ca2+ blockers as well as by calmodulin antagonists, with improved myocardial preservation.

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“…Normothermic ischaemic cardiac arrest (NICA) was used as model of myocar dial ischaemia [18]. After the heart was removed from the rat and arrested in ice-cold saline, the aorta was mounted onto the aortic cannula followed by retro grade perfusion using the Langendorff technique in a non-recirculating manner at 90 cm H2O pressure for 10 min at a perfusate temperature of 37 °C.…”

Section: Methodsmentioning

confidence: 99%

“…The combined ox * Statistical significance (p < 0.05): NICA or NICA followed by reperfusion versus unperfused, and NICA versus NICA followed by reperfusion. [18]. It has recently been discovered that oxygen radicals contribute at least in part to the damage which occurs during myocardial ischaemia [1][2][3][4][5], As the mitochondria are organelles which utilise oxygen, it is possible that this mechanism plays an important role in the mitochondria.…”

Section: Effect Of Nica and Of Nica Followed By Reperfusion On The Acmentioning

confidence: 99%

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Effect of Normothermic Ischemic Cardiac Arrest and of Reperfusion on the Free Oxygen Radical Scavenger Enzymes and Xanthine Oxidase (a Generator of Superoxide Anions)

Aj²,

Gm³

et al. 1988

Enzyme

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Recent evidence suggests that free oxygen radicals are produced by ischaemic tissues, accounting for at least part of the damage that results. These free oxygen radicals are produced by xanthine oxidase, amongst others, and removed by scavenger enzymes (catalase, superoxide dismutase and glutathione peroxidase) and anti-oxidants. As mitochondria are oxygen-utilising organelles, they are capable of producing free oxygen radicals. Our results indicate that the removal of free oxygen radicals are not diminished during ischaemia, but the activity of the free oxygen radical generator, xanthine oxidase, is increased. This could lead to an increased superoxide anion concentration.

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Normothermic ischaemic cardiac arrest of the isolated perfused rat heart: effects of trifluoperazine and lysolecithin on mechanical and metabolic recovery

Cited by 10 publications

References 20 publications

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Control of respiration and ATP synthesis in mammalian mitochondria and cells

Moderation of myocardial ischemia reperfusion injury by calcium channel and calmodulin receptor inhibition

Effect of Normothermic Ischemic Cardiac Arrest and of Reperfusion on the Free Oxygen Radical Scavenger Enzymes and Xanthine Oxidase (a Generator of Superoxide Anions)

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