The Relationship of Regional Coronary Blood Flow to Mitoehondrial Function during Reperfusion of the Ischemic Myocardium

Weishaar, Ronald E.; Tschurtschenthaler, Gertraud V.; Ashikawa, Kouichi; Bing, Richard J.

doi:10.1159/000170633

Cited by 23 publications

(4 citation statements)

References 38 publications

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“…Different models of myocardial ischemia (coronary artery ligation and auto lysis) suggest that of the five complexes in the mitochondrial inner membrane, the first complex (complex I or NADH-ubiquinone reductase) is the most sensitive to ischemic conditions [29][30][31]39], This observation was confirmed by polarographic studies where the mitochondrial oxygen uptake was deter mined using glutamate, succinate [30,31,39], and ascorbate [39] as substrates and by Coronary artery disease with its complica tions of myocardial ischemia, infarction, and, finally, irreversible tissue damage is one of the most important diseases of Western civilization. It is well known that myocardial ischemia results in significant impairment of mitochondrial function [15,38,42], The mi tochondrial electron transport chain is af fected relatively early as indicated by the depression in mitochondrial oxygen uptake, measurement of the enzyme activities of the five individual complexes of the electron transport chain [30,31]. Rouslin et al [32,33] suggested a loss of FMN to account for these observations.…”

Section: Introductionmentioning

confidence: 99%

Changes in NADH-Ubiquinone Reductase (Complex I) with Autolysis in the Rat Heart as Experimental Model

Jaarsveld¹,

Potgieter²,

Lochner³

1986

Enzyme

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Complex I (NADH-ubiquinone reductase) is a complex system located in the inner mitochondrial membrane and has the ability to catalyse several different enzymatic reactions concerned in electron transport. It is known to be one of the first components of the respiratory chain to be damaged by ischemia. Our results, using autolysis in the rat heart as experimental model, indicate that the NADH dehydrogenase system was impaired relatively early during ischemia while transhydrogenation and NADPH dehydrogenation appeared to be relatively resistant.

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Section: Introductionmentioning

confidence: 99%

Changes in NADH-Ubiquinone Reductase (Complex I) with Autolysis in the Rat Heart as Experimental Model

Jaarsveld¹,

Potgieter²,

Lochner³

1986

Enzyme

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“…On the other hand, only scattered and conflicting information regarding the status of mitochondrial function with respect to their respiratory and oxidative phosphorylation activities in the I/R hearts is available in the literature (3,19). It is pointed out that, whereas prolonged ischemia has been reported to depress mitochondrial state 3 respiration and slightly reduce their ability to generate ATP (8,23), reperfusion of the ischemic heart has been shown to produce no change (1,45), further depression (17,22), or increase in the oxidative phopshorylation rate (OPR) (24,35). In addition, some investigators (13,16) have shown depressions in both mitochondrial state 3 and state 4 respiration without any change in respiratory control index (RCI), whereas others (9) have reported no change in state 3 respiration but an increase in state 4 respiration in I/R hearts.…”

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confidence: 99%

Role of oxidative stress in alterations of mitochondrial function in ischemic-reperfused hearts

Makazan¹,

Saini²,

Dhalla³

2007

American Journal of Physiology-Heart and Circulatory Physiology

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Makazan Z, Saini HK, Dhalla NS. Role of oxidative stress in alterations of mitochondrial function in ischemic-reperfused hearts. Am J Physiol Heart Circ Physiol 292: H1986 -H1994, 2007. First published December 15, 2006; doi:10.1152/ajpheart.01214.2006.-To study the mechanisms of mitochondrial dysfunction due to ischemiareperfusion (I/R) injury, rat hearts were subjected to 20 or 30 min of global ischemia followed by 30 min of reperfusion. After recording both left ventricular developed pressure (LVDP) and end-diastolic pressure (LVEDP) to monitor the status of cardiac performance, mitochondria from these hearts were isolated to determine respiratory and oxidative phosphorylation activities. Although hearts subjected to 20 min of ischemia failed to generate LVDP and showed a marked increase in LVEDP, no changes in mitochondrial respiration and phosphorylation were observed. Reperfusion of 20-min ischemic hearts depressed mitochondrial function significantly but recovered LVDP completely and lowered the elevated LVEDP. On the other hand, depressed LVDP and elevated LVEDP in 30-min ischemic hearts were associated with depressions in both mitochondrial respiration and oxidative phosphorylation. Reperfusion of 30-min ischemic hearts elevated LVEDP, attenuated LVDP, and decreased mitochondrial state 3 and uncoupled respiration, respiratory control index, ADP-to-O ratio, as well as oxidative phosphorylation rate. Alterations of cardiac performance and mitochondrial function in I/R hearts were attenuated or prevented by pretreatment with oxyradical scavenging mixture (superoxide dismutase and catalase) or antioxidants [N-acetyl-L-cysteine or N-(2-mercaptopropionyl)-glycine]. Furthermore, alterations in cardiac performance and mitochondrial function due to I/R were simulated by an oxyradical-generating system (xanthine plus xanthine oxidase) and an oxidant (H 2O2) either upon perfusing the heart or upon incubation with mitochondria. These results support the view that oxidative stress plays an important role in inducing changes in cardiac performance and mitochondrial function due to I/R. cardiac performance; oxidative phosphorylation; mitochondrial respiration; oxyradicals; antioxidants BY VIRTUE OF THEIR ABILITY to carry on the processes of oxidative phosphorylation and electron transport, mitochondria are the major source of energy production in the form of ATP, which is required for cardiac contraction and relaxation (19,26,46). Mitochondria are also known to accumulate a substantial amount of Ca 2ϩ and are considered to serve as a sink to maintain the intracellular concentration of free Ca 2ϩ within certain limits (18,19,26). However, an excessive amount of intracellular Ca 2ϩ results in the overloading of mitochondria with Ca 2ϩ

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“…Reperfusion has been reported to cause an extension of mitochondrial damage [5,6], no change [7,8], or an increase in the oxidative phosphorylation rate [9,10]. The discrepancies in findings are attributable to differences in the age of the animals and in the protocols, in particular the duration of ischemia.…”

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Effects of myocardial ischemia and reperfusion on mitochondrial function and susceptibility to oxidative stress

Venditti¹,

Masullo²,

Meo³

2001

CMLS, Cell. Mol. Life Sci.

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We investigated the effects of ischemia duration on the functional response of mitochondria to reperfusion and its relationship with changes in mitochondrial susceptibility to oxidative stress. Mitochondria were isolated from hearts perfused by the Langendorff technique immediately after different periods of global ischemia or reperfusion following such ischemia periods. Rates of O2 consumption and H2O2 release with complex I- and complex II-linked substrates, lipid peroxidation, overall antioxidant capacity, capacity to remove H2O2, and susceptibility to oxidative stress were determined. The effects of ischemia on some parameters were time dependent so that the changes were greater after 45 than after 20 min of ischemia, or were significantly different to the nonischemic control only after 45 min of ischemia. Thus, succinate-supported state 3 respiration exhibited a significant decrease after 20 min of ischemia and a greater decrease after 45 min, while pyruvate malate-supported respiration showed a significant decrease only after 45 min of ischemia, indicating an ischemia-induced early inhibition of complex II and a late inhibition of complex I. Furthermore, both succinate and pyruvate malate-supported H2O2 release showed significant increases only after 45 min of ischemia. Similarly, whole antioxidant capacity significantly increased and susceptibility to oxidants significantly decreased after 45 min of ischemia. Such changes were likely due to the accumulation of reducing equivalents, which are able to remove peroxides and maintain thiols in a reduced state. This condition, which protects mitochondria against oxidants, increases mitochondrial production of oxyradicals and oxidative damage during reperfusion. This could explain the smaller functional recovery of the tissue and the further decline of the mitochondrial function after reperfusion following the longer period of oxygen deprivation.

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The Relationship of Regional Coronary Blood Flow to Mitoehondrial Function during Reperfusion of the Ischemic Myocardium

Cited by 23 publications

References 38 publications

Changes in NADH-Ubiquinone Reductase (Complex I) with Autolysis in the Rat Heart as Experimental Model

Changes in NADH-Ubiquinone Reductase (Complex I) with Autolysis in the Rat Heart as Experimental Model

Role of oxidative stress in alterations of mitochondrial function in ischemic-reperfused hearts

Effects of myocardial ischemia and reperfusion on mitochondrial function and susceptibility to oxidative stress

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