Remote ischemic preconditioning in cardiac surgery: caught between clinical relevance and statistical significance?

Thielmann, Matthias

doi:10.1007/s00395-012-0259-3

Cited by 11 publications

(8 citation statements)

References 28 publications

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“…For example, some studies enrolled only stable patients undergoing CABG, whereas others included valve surgeries, patients with unstable coronary disease, and high-risk patients (ie, double and triple valve surgeries, mitral valve surgery, and combined CABG and valve surgery). 16,98,[123][124][125] Attempting to draw conclusions from mixed populations is problematic, as it assumes that the effects of remote conditioning will be comparable among all cohorts-an assumption that has not been tested and may be flawed. Additional sources of variation among studies include the choice of anesthetic and cardioplegic agents, the inclusion versus exclusion of patients with diabetes mellitus, and the temporal aspects of the remote conditioning algorithm.…”

Section: Future Of Remote Conditioning: Establishing the Determinantsmentioning

confidence: 99%

“…Among these, the 2 most important confounders might potentially be the anesthetic regimen (in particular, the use of propofol), 123,126 together with variability in the time at which the remote stimulus was applied (after induction of anesthesia but before the first surgical incision versus after the first incision but before cardiopulmonary bypass). 120,121,[123][124][125] However, this raises the second issue: we have limited insight into the consequences of this variability. In contrast to pre-and postconditioning, which underwent exhaustive and systematic preclinical investigation, 127 our understanding of the biology of remote conditioning is derived from a relatively small number of basic science studies together with 1 recent report based on analysis of human cardiac biopsy samples.…”

Section: Future Of Remote Conditioning: Establishing the Determinantsmentioning

confidence: 99%

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Myocardial Conditioning

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Thibault

Przyklenk

2013

Circulation Research

100

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Myocardial conditioning is an endogenous cardioprotective phenomenon that profoundly limits infarct size in experimental models. The current challenge is to translate this paradigm from the laboratory to the clinic. Accordingly, our goal in this review is to provide a critical summary of the progress toward, opportunities for, and caveats to, the successful clinical translation of postconditioning and remote conditioning, the 2 conditioning strategies considered to have the broadest applicability for real-world patient care. In the majority of phase II studies published to date, postconditioning evoked a ≈35% reduction of infarct size in ST-segment–elevation myocardial infarction patients. Essential criteria for the successful implementation of postconditioning include the appropriate choice of patients (ie, those with large risk regions and negligible collateral flow), timely application of the postconditioning stimulus (immediately on reperfusion), together with proper choice of end points (infarct size, with concomitant assessment of risk region). Remote conditioning has been applied in planned ischemic events (including cardiac surgery and elective percutaneous coronary intervention) and in ST-segment–elevation myocardial infarction patients during hospital transport. Controversies with regard to efficacy have emerged, particularly among surgical trials. These disparate outcomes in all likelihood reflect the remarkable heterogeneity within and among studies, together with a deficit in our understanding of the impact of these variations on the infarct-sparing effect of remote conditioning. Ongoing phase III trials will provide critical insight into the future role of postconditioning and remote conditioning as clinically relevant cardioprotective strategies.

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Section: Future Of Remote Conditioning: Establishing the Determinantsmentioning

confidence: 99%

Section: Future Of Remote Conditioning: Establishing the Determinantsmentioning

confidence: 99%

Myocardial Conditioning

Ovize

Thibault

Przyklenk

2013

Circulation Research

100

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“…Ischemia-reperfusion (IR) injury has been observed in the heart, brain, liver, and kidney [23, 42]. Remote ischemic preconditioning (RIPC), induced by several episodes of brief ischemia and reper-fusion at a distance, confers systemic multi-organ protection against IR injury [3, 9, 10, 13, 15, 17, 32, 34, 43, 44, 50]. RIPC was developed from the concept of local IPC, in which cardioprotection was generated by briefly occluding and reopening a coronary artery [2, 20, 28, 33].…”

Section: Introductionmentioning

confidence: 99%

Remote ischemic preconditioning confers late protection against myocardial ischemia–reperfusion injury in mice by upregulating interleukin-10

et al. 2012

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Remote ischemic preconditioning (RIPC) induces a prolonged late phase of multi-organ protection against ischemia-reperfusion (IR) injury. In the present study, we tested the hypothesis that RIPC confers late protection against myocardial IR injury by upregulating expression of interleukin (IL)-10. Mice were exposed to lower limb RIPC or sham ischemia. After 24 h, mice with RIPC demonstrated decreased myocardial infarct size and improved cardiac contractility following 30-min ischemia and 120-min reperfusion (I-30/R-120). These effects of RIPC were completely blocked by anti-IL-10 receptor antibodies. In IL-10 knockout mice, RIPC cardioprotection was lost, but it was mimicked by exogenous IL-10. Administration of IL-10 to isolated perfused hearts increased phosphory-lation of the protein kinase Akt and limited infarct size after I-30/R-120. In wild-type mice, RIPC increased plasma and cardiac IL-10 protein levels and caused activation of Akt and endothelial nitric oxide synthase in the heart at 24 h, which was also blocked by anti-IL-10 receptor antibodies. In the gastrocnemius muscle, RIPC resulted in immediate inactivation of the phosphatase PTEN and activation of Stat3, with increased IL-10 expression 24 h later. Myocyte-specific PTEN inactivation led to increased Stat3 phosphorylation and IL-10 protein expression in the gastrocnemius muscle. Taken together, these results suggest that RIPC induces late protection against myocardial IR injury by increasing expression of IL-10 in the remote muscle, followed by release of IL-10 into the circulation, and activation of protective signaling pathways in the heart. This study provides a scientific basis for the use of RIPC to confer systemic protection against IR injury.

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“…Remote ischemic preconditioning (RIPC) is a phenomenon in which a brief ischemia and reperfusion in distant tissues protects a critical target organ or tissue from a subsequent episode of lethal ischemia and reperfusion through either neuronal or humoral pathway [11-13]. Although the kidneys are not directly exposed to ischemia-reperfusion injury, RIPC might preserve kidney function in patients undergoing cardiac and vascular interventions through blocking free radical production and attenuating the inflammatory response involved in pathogenesis of AKI [6,7,14].…”

Section: Introductionmentioning

confidence: 99%

The role of remote ischemic preconditioning on postoperative kidney injury in patients undergoing cardiac and vascular interventions: a meta-analysis

2013

J Cardiothorac Surg

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The objective of this study was to perform a meta-analysis of randomized controlled trials (RCTs) investigating whether a remote ischemic preconditioning (RIPC) protocol provides renal protection to patients undergoing cardiac and vascular interventions. Searches were conducted in the databases PUBMED, EMBASE and Cochrane Library. RCTs that fulfilled the inclusion criteria and addressed the clinical questions of this analysis were further assessed. We identified ten studies with a total of 924 patients undergoing cardiac and vascular interventions with or without RIPC. There was a significantly lower incidence of acute kidney injury in the RIPC group compared with control group using the fixed effect model (RR 0.69, 95% CI 0.53 to 0.90, P = 0.007), but not with the random effects model (RR 0.73, 95% CI 0.50 to 1.06, P = 0.10). There was no difference in the levels of renal biomarkers, incidence of renal replacement therapy, mortality, hospital stay, and intensive care unit stay between two groups. In conclusion, there is no enough evidence that RIPC provided renal protection in patients undergoing cardiac and vascular interventions. Large-scale RCTs are necessary to confirm the potential role of RIPC on renal impairment.

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Remote ischemic preconditioning in cardiac surgery: caught between clinical relevance and statistical significance?

Cited by 11 publications

References 28 publications

Myocardial Conditioning

Myocardial Conditioning

Remote ischemic preconditioning confers late protection against myocardial ischemia–reperfusion injury in mice by upregulating interleukin-10

The role of remote ischemic preconditioning on postoperative kidney injury in patients undergoing cardiac and vascular interventions: a meta-analysis

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