Developmental differences in cytosolic calcium accumulation associated with surgically induced global ischemia: Optimization of cardioplegic protection and mechanism of action

Tsukube, Takuro; McCully, James D.; Federman, Micheline; Krukenkamp, Irvin B.; Levitsky, Sidney

doi:10.1016/s0022-5223(96)70194-0

Cited by 41 publications

(28 citation statements)

References 18 publications

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“…13,19,20 Tsukube and colleagues reported that magnesium cardioplegia and magnesium-supplemented potassium cardioplegia, which were used in the present study, both inhibit cytosolic Ca 2+ accumulation in a manner similar to that seen with the combined use of ryanodine or nifedipine and potassium Fig 3. Representative Western blot analysis of the microsomal fraction rich in sarcoplasmic reticulum vesicles from each group. Semiquantitative analysis using densitometry of the Western blots indicates that there were no significant differences in the expression levels of ryanodine receptor protein among the 3 groups.…”

Section: Discussionsupporting

confidence: 67%

“…cardioplegia during global ischemia. 13 They concluded that the modulating action of magnesium-supplemented potassium cardioplegia on cytosolic Ca 2+ accumulation was exerted through an inhibition of both the myocardial L-type Ca 2+ channel and the SR RyR. The effects of magnesium on RyR have been examined by several investigators.…”

Section: Discussionmentioning

confidence: 99%

“…Its effectiveness in myocyte protection has been well established. 11,12 The observation that intracellular Ca 2+ accumulation in the myocardium is attenuated during an arrest produced by the potassium/magnesium cardioplegia suggests that cardioplegia might act on the SR. 13 However, the effects of cardioplegia on RyR remain unknown.The present study was designed to investigate the effects of cold crystalloid cardioplegia (potassium/magnesium cardioplegia) on RyR in isolated rabbit hearts during ischemia …”

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confidence: 99%

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Effects of Cardioplegic Arrest and Reperfusion on Rabbit Cardiac Ryanodine Receptors

Ikeda¹,

Gohra²,

Hamano³

et al. 2001

Jpn Circ J

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yocardial contraction and relaxation are regulated by intracellular Ca 2+ concentration, and cardiac sarcoplasmic reticulum (SR) plays an important role in Ca 2+ uptake, storage, and release. Under normal conditions, the entry of extracellular Ca 2+ via L-type Ca 2+ channels in the sarcolemma of the myocardium triggers the release of Ca 2+ from the SR, leading to myocardial contraction. 1 Conversely, Ca 2+ uptake by the SR results in myocardial relaxation. The SR contains 2 important constituents, Ca 2+ -ATPase and the ryanodine receptor (RyR). 2 Ryanodine receptor is the Ca 2+ release channel on which ryanodine has one of 2 effects, depending on its concentration. Low concentrations of ryanodine bind to the high-affinity site and open the Ca 2+ channel; high concentrations of ryanodine close the Ca 2+ channel. 3,4 During global ischemia, intracellular Ca 2+ is increased (the so-called 'Ca 2+ overload'), which leads to myocardial dysfunction. 5 In this situation, the Na + -Ca 2+ exchanger, RyR, and/or SR Ca 2+ -ATPase play important roles in maintaining intracellular Ca 2+ homeostasis. Such Ca 2+ overload is considered to be a primary contributor to ischemia-reperfusion injury.During ischemia, the SR is one of the targets for ischemic myocardial injury. A number of reports indicate that ischemia depresses SR function; however, both the nature and cause of this effect remain controversial. 6-10 Darling and coworkers reported that the maximum number of binding sites (Bmax) for ryanodine binding to isolated dog SR vesicles was reduced after 60 min of ischemia. 6 In addition, Zucchi and colleagues noted that in rat hearts the Bmax for high-affinity ryanodine binding to an enriched fraction of SR vesicles was reduced after 20 min of ischemia, and that the reduction persisted after reperfusion. 7 These investigators concluded that the number of RyR was reduced after ischemia, and that this effect might contribute to an alteration in SR function. Using a mature rabbit heart homogenate, Matsuda and colleagues observed that while the Bmax for high-affinity ryanodine binding was reduced after 30 min of ischemia, there was no difference between ischemia and non-ischemia in the expression levels of RyR mRNA or protein. 10 Cold crystalloid cardioplegia is a widely used technique for myocardial protection during heart operations. Its effectiveness in myocyte protection has been well established. 11,12 The observation that intracellular Ca 2+ accumulation in the myocardium is attenuated during an arrest produced by the potassium/magnesium cardioplegia suggests that cardioplegia might act on the SR. 13 However, the effects of cardioplegia on RyR remain unknown.The present study was designed to investigate the effects of cold crystalloid cardioplegia (potassium/magnesium cardioplegia) on RyR in isolated rabbit hearts during ischemia

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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Effects of Cardioplegic Arrest and Reperfusion on Rabbit Cardiac Ryanodine Receptors

Ikeda¹,

Gohra²,

Hamano³

et al. 2001

Jpn Circ J

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“…The augmented vulnerability to calcium of senescent cardiomyocytes (Tsukube et al 1996;Hansford et al 1999;Lakatta et al 2001;Jahangir et al 2001) might be responsible for the amplified oxidative stress during ischemia/reperfusion. Indeed, rising levels of matrix calcium favors mitochondrial ROS release (Martin et al 2007) through a mechanism that can imply succinate accumulation (Sentex et al 1999).…”

Section: Introductionmentioning

confidence: 99%

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Mourmoura

Leguen

Dubouchaud

et al. 2010

AGE

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Aging compromises restoration of the cardiac mechanical function during reperfusion. We hypothesized that this was due to an ampler release of mitochondrial reactive oxygen species (ROS). This study aimed at characterising ex vivo the mitochondrial ROS release during reperfusion in isolated perfused hearts of middle-aged rats. Causes and consequences on myocardial function of the observed changes were then evaluated. The hearts of rats aged 10-or 52-week old were subjected to global ischemia followed by reperfusion. Mechanical function was monitored throughout the entire procedure. Activities of the respiratory chain complexes and the ratio of aconitase to fumarase activities were determined before ischemia and at the end of reperfusion. H 2 O 2 release was also evaluated in isolated mitochondria. During ischemia, middle-aged hearts displayed a delayed contracture, suggesting a maintained ATP production but also an increased metabolic proton production. Restoration of the mechanical function during reperfusion was however reduced in the middle-aged hearts, due to lower recovery of the coronary flow associated with higher mitochondrial oxidative stress indicated by the aconitase to fumarase ratio in the cardiac tissues. Surprisingly, activity of the respiratory chain complex II was better maintained in the hearts of middle-aged animals, probably because of an enhanced preservation of its membrane lipid environment. This can explain the higher mitochondrial oxidative stress observed in these conditions, since cardiac mitochondria produce much more H 2 O 2 when they oxidize FADH 2 -linked substrates than when they use NADH-linked substrates. In conclusion, the lower restoration of the cardiac mechanical activity during reperfusion in the middle-aged hearts was due to an impaired recovery of the coronary flow and an insufficient oxygen supply. The deterioration AGE (2011) of the coronary perfusion was explained by an increased mitochondrial ROS release related to the preservation of complex II activity during reperfusion.

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“…The mechanisms by which DSA cardioplegia affords enhanced cardioprotection involve the amelioration of cytosolic, mitochondrial, and nuclear calcium overload, enhanced preservation and resynthesis of high-energy phosphates, and the modulation of nuclear and mitochondrial function [1][2][3]. The end effector of these mechanisms remains to be elucidated; however, recent investigations have suggested that the mitochondrial ATP-sensitive potassium (mitoK ATP ) channels play a predominant role in the infarct-limiting effects afforded by DSA cardioplegia [4,5].…”

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confidence: 99%

Diazoxide amelioration of myocardial injury and mitochondrial damage during cardiac surgery

McCully

Wakiyama

Cowan

et al. 2002

The Annals of Thoracic Surgery

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Developmental differences in cytosolic calcium accumulation associated with surgically induced global ischemia: Optimization of cardioplegic protection and mechanism of action

Cited by 41 publications

References 18 publications

Effects of Cardioplegic Arrest and Reperfusion on Rabbit Cardiac Ryanodine Receptors

Effects of Cardioplegic Arrest and Reperfusion on Rabbit Cardiac Ryanodine Receptors

Middle age aggravates myocardial ischemia through surprising upholding of complex II activity, oxidative stress, and reduced coronary perfusion

Diazoxide amelioration of myocardial injury and mitochondrial damage during cardiac surgery

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