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AGE-RAGE Axis in the Aging and Diabetic Heart
Published in Sara C. Zapico, Mechanisms Linking Aging, Diseases and Biological Age Estimation, 2017
Karen M. O’Shea, Ann Marie Schmidt, Ravichandran Ramasamy
sRAGE has been shown to have cardio-protective properties by acting as a decoy for pro-injury RAGE signaling. Endogenous sRAGE is downregulated in the heart following ischemia/reperfusion (Dong et al. 2011). Pretreatment of neonatal cardiomyocytes with exogenous sRAGE decreases hypoxia/reoxygenation induced apoptosis, mPTP opening, caspase activity, and cytochrome c release from the mitochondria (Guo et al. 2012). Paradoxically, however, circulating sRAGE levels are positively correlated with severity of heart failure in patients (Raposeiras-Roubin et al. 2010, Wang et al. 2011). A recent study showed that patients with ST-elevation myocardial infarction, who were treated with remote ischemic conditioning, did not display altered sRAGE concentrations despite an improved myocardial salvage index compared to control patients receiving primary percutaneous intervention (Jensen et al. 2015). These results indicate that sRAGE concentrations do not always reflect functional changes in the heart. A prospective clinical study demonstrated that in patients with acute coronary syndrome, increased sRAGE levels were associated with worsened in-hospital prognosis. In the same study, the investigators reported that fluorescent AGE levels were associated with long-term prognosis (Raposeiras-Roubin et al. 2013). These results show that sRAGE and AGEs may both be important prognostic tools for patients with acute coronary syndrome; however, additional studies are needed to better understand their roles as biomarkers. Furthermore, the exact reason for cardio-protection by sRAGE treatment yet association of endogenous sRAGE levels with worsened function in the heart is not understood.
Remote ischemic conditioning with exercise (RICE) promotes functional rehabilitation following ischemic stroke
Published in Neurological Research, 2021
Qingzhu Wang, Melissa Wills, Fengwu Li, Xiaokun Geng, Yuchuan Ding
Recently, remote ischemic conditioning (RIC) has emerged as a noninvasive and low-cost therapy for victims of cerebrovascular accidents. By way of controlled and transient periods of subcritical ischemia to non-vital arteries [14,15], it works to activate endogenous tissue repair mechanisms to exert neuroprotective effects, cardiovascular protection, and promote neurological recovery [16,17]. We have previously discussed that RIC increases neuroplastic, synaptogenic, and angiogenic processes and thereby confers overlapping benefits as exercise in stroke recovery [18–20]. The neuroprotective effect of RIC has been shown to have an early and a late phase. The early phase occurs immediately and lasts about 2 hours, whereas the late phase reappears 12 to 24 hours later and lasts 48 to 72 hours [21]. Clinical studies have confirmed that RIC is safe and feasible within 24 hours after stroke, including in patients with intravenous thrombolysis or mechanical thrombectomy, which indicates that, unlike exercise, it does not interfere with the standard treatment protocol of stroke [22]. The passive nature of its application also lends RIC to be less dependent on the patients’ motivation, physical activity, endurance, and cardiorespiratory fitness [23]. Therefore, this rehabilitative technique may be more sensible for use in the early stroke patient. However, research on RIC is in its infancy, and whether it can be an effective alternative or augmentative rehabilitation strategy to physical exercise is yet to be thoroughly studied.
Effect of long-term remote ischemic conditioning on inflammation and cardiac remodeling
Published in Scandinavian Cardiovascular Journal, 2019
Kasper Pryds, Michael Rahbek Schmidt, Mette Bjerre, Steffen Thiel, Jens Refsgaard, Hans Erik Bøtker, René Drage Østgård, Roni Ranghøj Nielsen
Remote ischemic conditioning (RIC) by alternating brief episodes of limb ischemia and reperfusion is a promising therapeutic strategy aiming to achieve protection against acute ischemia-reperfusion injury in the heart [6]. RIC has been shown to reduce myocardial injury in patients with ST-segment elevation myocardial infarction [7] and in patients undergoing elective percutaneous coronary intervention [8], which may translate into improved long-term clinical outcome [9,10]. Recent evidence indicates that repeated RIC application may yield beneficial effects in patients with stable cardiovascular conditions [6]. Experimental studies have suggested that repetitive daily RIC administration may confer additional beneficial effects through anti-remodeling [11,12] and anti-inflammatory [13] processes and improvement of endothelial and microcirculatory function [14,15]. We hypothesized that long-term, repetitive RIC application has anti-inflammatory and anti-remodeling effects in patients suffering from stable ischemic heart disease. The aim of the present study was to investigate whether daily RIC application for 4 weeks affects circulating markers of inflammation and cardiac remodeling in patients with stable compensated CIHF and matched control subjects without heart failure or ischemic heart disease.
Preventing acute kidney injury during transplantation: the application of novel oxygen carriers
Published in Expert Opinion on Investigational Drugs, 2019
Raphael Thuillier, Eric Delpy, Xavier Matillon, Jacques Kaminski, Abdelsalam Kasil, David Soussi, Jerome Danion, Yse Sauvageon, Xavier Rod, Gianluca Donatini, Benoit Barrou, Lionel Badet, Franck Zal, Thierry Hauet
Perfusion could also be used to condition the organ itself, such as at the end of a static preservation phase, in order to ‘wake up’ the organ before its transplantation. Several reports reported that abrupt change in temperature from hypothermic preservation to normothermic reperfusion at the time of transplantation produces detrimental effects on renal graft quality [66,67]. Recently, Controlled Oxygenated Rewarming (COR) of grafts immediately before transplantation has been described as a modification of MP and brings new approach for organ conditioning before transplantation and new concept for unit for organ preservation and evaluation. COR following CS demonstrated superior results over MP for liver and kidney [68], avoid ‘heat shock’ and possibly underestimated side effects (including mitochondrial dysfunction) of quick rewarming [69]. Previous studies showed that COR improves renal function after reperfusion (better renal creatinine clearance) and protect mitochondria integrity [70]. An alternative technique is to preserve kidney by hypothermic preservation followed by 2 h of normothermic perfusion using blood. This short period of ex vivo normothermic perfusion (EVNP) immediately before transplantation has a positive conditioning effect on the graft [71]. A first clinical case published in 2015 demonstrates the feasibility and safety of this technique [72]. Finally, recipient conditioning could also be applied: recent reports suggested potential therapeutics to protect organs from reperfusion injury. Limb remote ischemic conditioning was shown to be protective [73].