Review and Meta-Analysis of Randomized Controlled Clinical Trials of Remote Ischemic Preconditioning in Cardiovascular Surgery

Takagi, Hisato; Manabe, Hideaki; Kawai, Norikazu; Goto, Shin-nosuke; Umemoto, Takuya

doi:10.1016/j.amjcard.2008.07.036

Cited by 42 publications

(22 citation statements)

References 5 publications

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“…However, protection of the human heart was reportedly achieved by an inhibitor of mPTP, cyclosporine A, 110 ischemic preconditioning, [113][114][115] and postconditioning. 116 If the roles of GSK-3β in mPTP opening, ischemic preconditioning and postconditioning are similar between human, rat and rabbit hearts, we could expect that GSK-3β inhibitors afford significant protection in human hearts as well.…”

Section: Gsk-3β Inhibitors For Clinical Applicationmentioning

confidence: 99%

GSK-3.BETA., a Therapeutic Target for Cardiomyocyte Protection

Miura

Miki

2009

Circ J

127

111

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lycogen synthase kinase-3β (GSK-3β) is a constitutively active 47-kDa Ser/Thr protein kinase that was purified more than 2 decades ago as a kinase that reduces glycogen synthase activity. However, GSK-3β is now known as a multifunctional kinase having more than 40 substrates, playing roles not only in glycogen metabolism but also cell proliferation, growth and death. [1][2][3] To properly execute its functions, GSK-3β has multiple regulatory mechanisms including phosphorylation at Ser and Tyr residues, complex formation with scaffold proteins, priming of substrates and intracellular translocation. Recently, pathophysiological roles of GSK-3β have also received attention because it is involved in common and serious diseases such as Alzheimer's disease, bipolar mood disorder, cancer and ischemia/reperfusion injury. 1,3 In the cardiovascular system, GSK-3β has major roles in glucose metabolism, 4 cardiomyocyte hypertrophy 5 and cell death. The roles of GSK-3β in hypertrophy have recently been reviewed by Sugden et al 5 , so therefore we have focused on the roles of this protein kinase in myocyte death, particularly that after ischemia/ reperfusion. We first briefly overview mechanisms of ischemia/reperfusion injury and then discuss the contribution of GSK-3β to cardiomyocyte death and manipulation of GSK-3β for myocardial protection. Mechanisms of Cardiomyocyte Necrosis During Ischemia/ReperfusionWhen myocardial blood perfusion is interrupted, for example by occluding the coronary artery, ischemic cardiomyocytes suffer from several critical intracellular events that can lead to cell necrosis and/or prime the cells to reperfusion-induced necrosis. First, intracellular level of highenergy phosphate is reduced due to oxygen deficiency. Although ischemic cardiomyocytes cease contraction within a few minutes after the onset of ischemia, adenosine triphosphate (ATP) consumption continues during ischemia mainly by mitochondrial ATPase for maintenance of mitochondrial membrane potential. 6,7 Anaerobic glycolysis supplies ATP during the early period of ischemia, but it is ultimately halted by inhibition of glyceraldehyde phosphate dehydrogenase due to accumulated H + and NADH. 7,8 Second, intracellular Na + accumulates due to Na + influx via Na + -H + exchangers and Na + channels and due to reduced Na + efflux via the Na + -K + pump. [9][10][11] This Na + overload predisposes ischemic cardiomyocytes to Ca 2+ influx by the Na + -Ca 2+ exchanger. Third, Ca 2+ influx via the Na + -Ca 2+ exchanger, reduced Ca 2+ uptake into the sarcoplasmic reticulum and reduced Ca 2+ efflux via the sarcolemmal Ca 2+ pump induce Ca 2+ overload in ischemic cardiomyocytes. 9-12 However, elevation of intracellular Ca 2+ is modest during ischemia because acidosis inhibits the Na + -Ca 2+ exchanger and cytosolic Ca 2+ is taken up by the mitochondria as long as its membrane potential is maintained by use of ATP. [9][10][11]13 Severely ischemic cardiomyocytes ultimately 'starve to death', although sarcolemmal damage by detergent actions of accumulated...

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Section: Gsk-3β Inhibitors For Clinical Applicationmentioning

confidence: 99%

GSK-3.BETA., a Therapeutic Target for Cardiomyocyte Protection

Miura

Miki

2009

Circ J

127

111

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“…Takagi et al authored the first meta-analysis rendering comparable results, yet he only assessed myocardial necrosis markers and combined outcomes from cardiac and vascular surgery, with a modest number of patients submitted to rIPC [12,13,35]. We believe that the sensitivity analysis and nearly one thousand patients included in our analysis, along with an additional risk of bias assessment, makes this document the primary source of evidence for the usefulness of rIPC in cardiac surgery.…”

Section: Comparison Of Our Study With Other Meta-analysesmentioning

confidence: 92%

“…Finally, fifteen papers were found to present the best available evidence. These studies pertained to: adult coronary bypass grafting surgery with or without AVR [9,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27], adult valvular surgery [28][29][30], and pediatric cardiac surgery [31][32][33]. All the available papers were designed as prospective randomized controlled trials.…”

Section: Literature Search and Study Characteristicsmentioning

confidence: 99%

“…Over the decade, leading cardiovascular researchers have gone from great excitation to dramatic disappointment with the clinical application of rIPC [8,9]. The frustration could not be overcome by the recent metaanalyses and narrative reviews, due to their low quality or lack of objective quantitative measures of the effect, respectively [10][11][12][13]. This review and meta-analysis provides the most up-to-date and in-depth quantitative analysis of rIPC in adult and pediatric cardiac surgery.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Experimental cardiovascular and lung research Remote ischemic preconditioning versus standard myocardial protection in cardiac surgery: ten years of clinical trials. A systematic review and meta-analysis

Marczak¹,

Bańkowski²,

Płonek³

et al. 2013

kitp

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StreszczenieCelem niniejszej metaanalizy jest systematyczny przegląd dowodów obrazujących wpływ odległego hartowania niedokrwiennego (rIPC) na mięsień serca pacjentów poddanych operacjom kardiochirurgicznym. Materiały i metody: Przeglądu literatury dokonano na podstawie pełnotekstowych prac publikowanych w bazach danych Medline, Cochrane itp. Włączono badania kontrolowane z randomizacją, porównujące rIPC oraz standardową ochronę mięśnia serca u pacjentów poddanych zabiegom kardiochirurgicznym, jeżeli raportowały co najmniej jeden z wyników: markery uszkodzenia mięśnia sercowego, pooperacyjne zapotrzebowanie na leki wykazujące dodatni efekt inotropowy, czas hospitalizacji na oddziale intensywnej terapii. 268 EXPERIMENTAL CARDIOVASCULAR AND LUNG RESEARCH SummaryObjectives: To systematically review and assess the existing evidence for the applicability of remote ischemic preconditioning (rIPC) in cardiac surgery. Material and methods: Major biomedical databases: Medline, Cochrane, etc. were searched. All randomized controlled trials (RCTs) comparing rIPC and standard myocardial protection in patients submitted to cardiac surgery were included if they reported at least one of the outcomes of interest: myocardial injury markers, postoperative inotropic support, or length of ICU stay. Results: 991 patients were included in the analysis. rIPC was shown to reduce myocardial injury markers postoperatively by -0.63 SMD [-0.99 to -0.28] and postoperative inotropic requirement by -0.40 SMD [-0.66 to -0.16] in the adult patients submitted to cardiac surgery. There has been significant, yet correctable, heterogeneity of the primary outcome of interest, and the available RCTs were small sample studies. Conclusions: This meta-analysis provides evidence confirming that rIPC has potential benefits with regard to myocardial protection.

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“…Recently, Zhou et al [24] reported that RIPC protects against myocardial and pulmonary IRI (n = 60). A meta-analysis carried by Takagi et al [25] demonstrated that RIPC significantly reduced biomarkers of myocardial injury in cardiovascular surgery patients over control treatment. Whether adenosine pretreatment provides better protection than RIPC against IRI in the clinical setting of congenital heart surgery warrants further investigation.…”

Section: Clinical Study Of Remote Ischemic Preconditioning (Ripc)mentioning

confidence: 98%