Remote Ischemic Preconditioning Reduces Perioperative Cardiac and Renal Events in Patients Undergoing Elective Coronary Intervention: A Meta-Analysis of 11 Randomized Trials

<div><p>Background</p><p>Results from randomized controlled trials (RCT) concerning cardiac and renal effect of remote ischemic preconditioning(RIPC) in patients with stable coronary artery disease(CAD) are inconsistent. The aim of this study was to explore whether RIPC reduce cardiac and renal events after elective percutaneous coronary intervention (PCI).</p><p>Methods and Results</p><p>RCTs with data on cardiac or renal effect of RIPC in PCI were searched from <i>Pubmed</i>, <i>EMBase</i>, and <i>Cochrane library</i> (up to July 2014). Meta-regression and subgroup analysis were performed to identify the potential sources of significant heterogeneity(<i>I</i>²≥40%). Eleven RCTs enrolling a total of 1713 study subjects with stable CAD were selected. Compared with controls, RIPC significantly reduced perioperative incidence of myocardial infarction (MI) [odds ratio(OR)  = 0.68; 95% CI, 0.51 to 0.91; <i>P</i> = 0.01; <i>I²</i> = 41.0%] and contrast-induced acute kidney injury(AKI) (OR = 0.61; 95% CI, 0.38 to 0.98; <i>P</i> = 0.04; <i>I²</i> = 39.0%). Meta-regression and subgroup analyses confirmed that the major source of heterogeneity for the incidence of MI was male proportion (coefficient  = −0.049; <i>P</i> = 0.047; adjusted <i>R²</i> = 0.988; <i>P</i> = 0.02 for subgroup difference).</p><p>Conclusions</p><p>The present meta-analysis of RCTs suggests that RIPC may offer cardiorenal protection by reducing the incidence of MI and AKI in patients undergoing elective PCI. Moreover, this effect on MI is more pronounced in male subjects. Future high-quality, large-scale clinical trials should focus on the long-term clinical effect of RIPC.</p></div

Forest plot for the incidence of myocardial infarction (MI).

<p>RIPC significantly decreased the risk of MI [odds ratio (OR)  = 0.68, <i>P</i> = 0.01].RIPC, remote ischemic preconditioning.</p

Forest plot for incidence of acute kidney injury (AKI).

<p>RIPC significantly prevented post-PCI AKI (OR = 0.61, <i>P</i> = 0.04). RIPC, remote ischemic preconditioning.</p

Potential source of heterogeneity for the incidence of MI in PCI.

<p>Note: MI, myocardial infarction; Coeff., coefficient; OR, odds ratio; CI, Confidence Interval.</p><p>Potential source of heterogeneity for the incidence of MI in PCI.</p

Preoperative Medication Use in Patients Undergoing Cardiac Surgery.

<p>ACE: angiotensin-converting enzyme; AKI: acute kidney injury.</p

Summarized study design of included randomized trials.

<p>Note: I/R, ischemia/reperfusion; SBP, systolic blood pressure; DBP, diastolic blood pressure; N.R, not report; RIC, remote ischemic conditioning; Ctrl, control.</p><p>Summarized study design of included randomized trials.</p

Searching process for the eligible studies.

<p>RCT, randomized controlled trial.</p

Meta-regression plots on the incidence of MI in PCI[Male proportion (%); coefficient = −0.049; <i>P</i> = 0.047)].

<p>Meta-regression plots on the incidence of MI in PCI[Male proportion (%); coefficient  = −0.049; <i>P</i> = 0.047)].</p

Tongxinluo attenuates reperfusion injury in diabetic hearts by angiopoietin-like 4-mediated protection of endothelial barrier integrity via PPAR-α pathway

<div><p>Objective</p><p>Endothelial barrier function in the onset and Tongxinluo (TXL) protection of myocardial ischemia/reperfusion (I/R) injury, and TXL can induce the secretion of Angiopoietin-like 4 (Angptl4) in human cardiac microvascular endothelial cells during hypoxia/reoxygenation. We intend to demonstrate whether TXL can attenuate myocardial I/R injury in diabetes, characterized with microvascular endothelial barrier disruption, by induction of Angptl4-mediated protection of endothelial barrier integrity.</p><p>Methods and results</p><p>I/R injury was created by coronary ligation in ZDF diabetic and non-diabetic control rats. The animals were anesthetized and randomized to sham operation or I/R injury with or without the exposure to insulin, rhAngptl4, TXL, Angptl4 siRNA, and the PPAR-α inhibitor MK886. Tongxinluo, insulin and rhAngptl4 have the similar protective effect on diabetic hearts against I/R injury. In I/R-injured diabetic hearts, TXL treatment remarkably reduced the infarct size, and protected endothelial barrier integrity demonstrated by decreased endothelial cells apoptosis, microvascular permeability, and myocardial hemorrhage, fortified tight junction, and upregulated expression of JAM-A, integrin-α5, and VE-cadherin, and these effects of TXL were as effective as insulin and rhAngptl4. However, Angptl4 knock-down with siRNA interference and inhibition of PPAR-α with MK886 partially diminished these beneficial effects of TXL and rhAngptl4. TXL induced the expression of Angptl4 in I/R-injured diabetic hearts, and was canceled by Angptl4 siRNA and MK886. TXL treatment increased myocardial PPAR-α activity, and was abolished by MK886 but not by Angptl4 siRNA.</p><p>Conclusions</p><p>TXL protects diabetic hearts against I/R injury by activating Angptl4-mediated restoration of endothelial barrier integrity via the PPAR-α pathway.</p></div