Alterations in heart membrane calcium transport during the development of ischemia-reperfusion injury

Dhalla, Naranjan S.; Panagia, Vincenzo; Singal, Pawan K.; Makino, Naoki; Dixon, Ian M.C.; Eyolfson, Douglas A.

doi:10.1016/0022-2828(88)90327-6

Cited by 72 publications

(29 citation statements)

References 36 publications

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“…Evidence has been provided in various studies for a decrease of SR Ca2' uptake in ischemic hearts. [17][18][19][20][21][22][23] Since the net Ca21 uptake in the SR is a result of the activity of Ca2+-ATPase and of the SR Ca2+-release channel, an abnormal Ca21 uptake may be the result of the dysfunction of either or both structures. The effect of ischemia on the SR Ca 2+_ release channel remains unclear.…”

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confidence: 99%

Effect of ischemia and reperfusion on sarcoplasmic reticulum calcium uptake.

Kaplán

Hendrikx

Mattheussen

et al. 1992

Circulation Research

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To investigate the mechanism underlying postischemic cardiac dysfunction (myocardial stunning), contractility and adenine nucleotide metabolism were studied in three groups of isolated perfused rabbit hearts (control, ischemic, and reperfused), whereas Ca2`uptake by the sarcoplasmic reticulum (SR) was measured in homogenates obtained from them. The hearts were Langendorff-perfused as being the major mechanism underlying postischemic myocardial dysfunction. The hypothesis that a decrease of ATP levels underlies stunning has been tested in a number of studies, and the conclusion has been reached that the ATP levels and the available free energy during reperfusion after short ischemia are sufficient to sustain the energetic needs of contraction.12 It is found that ATP levels can recover to near normal values without improvement in contractility. Conversely, contractility can be made to increase during stunning,13 even in the presence of decreased ATP levels. Finally, recent studies of mitochondrial function, including one from this laboratory,14 suggest that mitochondria isolated from stunned hearts retain normal function. Thus, research efforts on the mechanisms of myocardial stunning now focus on a possible abnormality of the excitation-contraction coupling. Among the cellular organelles whose altered functions might account for the contractile deficiency in stunned hearts are the sarcoplasmic reticulum (SR), the contractile myofilaments, and the cell surface membrane. The discovery of a Ca21 overload during ischemia and/or reperfusion suggests that a deficient cellular Ca2' homeostasis may be the major characteristic of an abnormal excitationcontraction coupling in stunned myocardium.15"6 Because of its role in intracellular Ca2+ regulation and in excitation-contraction coupling, the SR has been sug-

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confidence: 99%

Effect of ischemia and reperfusion on sarcoplasmic reticulum calcium uptake.

Kaplán

Hendrikx

Mattheussen

et al. 1992

Circulation Research

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“…ATPase activity would be responsible for a reduced calcium ion exit from the cell. This would lead to an increase in calcium ion accumulation, which has already taken place probably due to impairment of the sarcoplasmic reticulum calcium pump and a probable impairment to the sodium-calcium exchanger (2). The mechanisms responsible for the reduction of Ca 2 § ATPase activity may be decreased level of ATP, alterations in metabolism of lipids (4) or free radical damage (21).…”

Section: Discussionmentioning

confidence: 99%

“…Abnormal handling of calcium at the sarcolemma in myocardial ischemia has been reported by different investigators (2,3). Myocardial ischemia is responsible for disturbances in lipid metabolism.…”

Section: Introductionmentioning

confidence: 99%

Characterisation of the canine cardiac sarcolemma in experimental myocardial ischemia

Netticadan

Ashavaid

Nair

1997

Indian J Clin Biochem

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The cardiac sarcolemma was characterized in 13 normal and 11 ischemic dog hearts by enzyme analysis and compositional assays. Significant decreases in the activities of the sodium-potassium and calcium pumps and structural compositional disturbances were observed in ischemia. High concentrations of oleic acid, a fatty acid and palmitoyl carnitine, a fatty acid intermediate caused inhibition of the enzyme pump activities of the normal sarcolemma. Thus, ischemia results in the functional impairment of the sarcolemma. Accumulation of fatty acid and fatty acid intermediates, occurring in myocardial ischemia, could be an underlying mechanism.

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“…Thus, it is possible that the formation of oxyradicals and accumulation of lipid metabolites due to I/R may result in membrane defects, and these can then cause the occurrence of intracellular Ca 2þ -overload, with subsequent cardiac dysfunction and myocardial cell damage. The role of intracellular Ca 2þ -overload in causing cardiac dysfunction and cell damage is now well accepted [15,[71][72][73][74]. The different mechanisms by which the intracellular Ca 2þ -overload can be seen to cause a wide variety of subcellular defects and cardiac dysfunction due to I/R injury are shown in Fig.…”

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confidence: 98%

Potential role and mechanisms of subcellular remodeling in cardiac dysfunction due to ischemic heart disease

Dhalla

Saini

Tappia

et al. 2007

Journal of Cardiovascular Medicine

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Several studies have revealed varying degrees of changes in sarcoplasmic reticular and myofibrillar activities, protein content, gene expression and intracellular Ca-handling during cardiac dysfunction due to ischemia-reperfusion (I/R); however, relatively little is known about the sarcolemmal and mitochondrial alterations, as well as their mechanisms in the I/R hearts. Because I/R is associated with oxidative stress and intracellular Ca-overload, it has been indicated that changes in subcellular activities, protein content and gene expression due to I/R are related to both oxidative stress and Ca-overload. Intracellular Ca-overload appears to induce changes in subcellular activities, protein contents and gene expression (subcellular remodeling) by activation of proteases and phospholipases, as well as by affecting the genetic apparatus, whereas oxidative stress is considered to cause oxidation of functional groups of different subcellular proteins in addition to modifying the genetic machinery. Ischemic preconditioning, which is known to depress the development of both intracellular Ca-overload and oxidative stress due to I/R, was observed to attenuate the I/R-induced subcellular remodeling and improve cardiac performance. It is suggested that a combination therapy with antioxidants and interventions, which reduce the development of intracellular Ca-overload, may improve cardiac function by preventing or attenuating the occurrence of subcellular remodeling due to ischemic heart disease. It is proposed that defects in the activities of subcellular organelles may serve as underlying mechanisms for I/R-induced cardiac dysfunction under acute conditions, whereas subcellular remodeling due to alterations in gene expression may explain the impaired cardiac performance under chronic conditions of I/R.

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Alterations in heart membrane calcium transport during the development of ischemia-reperfusion injury

Cited by 72 publications

References 36 publications

Effect of ischemia and reperfusion on sarcoplasmic reticulum calcium uptake.

Effect of ischemia and reperfusion on sarcoplasmic reticulum calcium uptake.

Characterisation of the canine cardiac sarcolemma in experimental myocardial ischemia

Potential role and mechanisms of subcellular remodeling in cardiac dysfunction due to ischemic heart disease

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