2006; van Kuijk et al 2009) Patients older than 80 years of age

2006; van Kuijk et al. 2009). Patients older than 80 years of age or patients with diabetes were excluded by study design in many clinical trials (Ali et al. 2007; Hausenloy et al. 2007; Hoole et al. 2009b; Venugopal et al. 2009, 2010; Rahman et al. 2010; Thielmann et al. 2010; Choi et al. 2011). A subgroup analysis in the study by Pedersen et al. (2012) suggests that age stratification might have an important role in the selection of patients who should undergo RIPC procedures (Pedersen et al. 2012; Tweddell 2012), and this potential confounder should be seriously taken into account Inhibitors,research,lifescience,medical when interpreting the available trial data. In all trials, no

severe local adverse events were observed, except in the study by Walsh et al. Inhibitors,research,lifescience,medical (2009) with iliac cross-clamping, in which three patients died (asystole, myocardial infarction, and cardiac arrest) and four patients developed lower limb ischemia requiring intervention. Minor local adverse events

occurred in the study by Cai et al., with slight skin erythema developing in two patients and a temporally constriction feeling in one patient after RIPC (Li et al. 2013). In addition, a phase Ib study of 33 patients by Koch et al. (2011) confirmed that RIPC with limb ischemia is feasible, safe, and well tolerated in alert patients with subarachnoid hemorrhage. Therefore, we may hypothesize that RIPC Inhibitors,research,lifescience,medical protocols with limb ischemia are potentially safe and hence can be tested with safety in larger scale randomized clinical trials. Most of the trials focused on postoperative cardiac and/or renal function after RIPC with conflicting results (Tables ​(Tables4).4). Preconditioned patients undergoing abdominal Inhibitors,research,lifescience,medical aneurysm artery repair were found to have lower rates of renal injury when compared with controls in a metanalysis by Alreja et al. (2012). In the same metanalysis, RIPC was related

to lower levels of postoperative myocardial injury, although the results from the trials that Inhibitors,research,lifescience,medical were analyzed were highly heterogeneous (Alreja et al. 2012). In another metanalysis of randomized clinical trials, Pilcher et al. (2012) found that 12 h after open cardiac surgery, RIPC subgroups had significantly lower troponin levels compared with controls. However, Nature Immunology there is see more uncertainty regarding the correctness of the aforementioned result due to the statistical heterogeneity between the studies, as the effect of RIPC on postoperative troponin concentration was significantly milder in fully blinded studies, compared with partially blinded (Pilcher et al. 2012). Similarly, in a metanalysis by Brevoord et al. (2012), troponin release and the incidence of periprocedural myocardial infarction were both significantly decreased in preconditioned patients undergoing cardiac surgery, PCI, or vascular surgery. However, no difference in mortality rates or major adverse cardiovascular events has been found between RIPC subgroup and controls (Brevoord et al. 2012).

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