Flow chart of selection process of eligible studies. RCT\u200A=\u200Arandomized controlled trial.

Flow chart of selection process of eligible studies. RCT\u200A=\u200Arandomized controlled trial.

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Remote ischemic preconditioning (RIPC) may attenuate acute kidney injury (AKI). However, results of studies evaluating the effect of RIPC on AKI after cardiac surgery have been controversial and contradictory. The aim of this meta-analysis is to examine the association between RIPC and AKI after on-pump cardiac surgery. The authors searched relevan...

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... study selection process is presented in Figure 1. The search strategy identified 1093 studies, of which data from 19 trials [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37] were used comprising 5100 patients (Table 1). ...

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... but no impact on RRT requirement. 201 However, a similar-sized meta-analysis (21 trials, n = 5,262) found no reduced CSA-AKI incidence (a co-primary outcome), and a Cochrane Database Systematic Review (primary outcome, 28 studies, n = 6,851) found similar, reporting a minimal impact for one AKI criteria alone (Acute Kidney Injury Network: risk ratio 0.76 [0.57-1.0]). 202,203 In contrast, another RCT (the RenalRIPC study) reported reductions in CSA-AKI and major adverse kidney events with RIPC compared with a sham intervention (AKI: 38% v 53%, p = 0.02; major adverse kidney events: 14% v 25%, p = 0.03). ...
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Acute kidney injury is one of the most common major complications of cardiac surgery and it is associated with increased morbidity and mortality. Cardiac surgery-associated acute kidney injury has a complex, multifactorial etiology, including numerous factors such as the primary cardiac dysfunction, hemodynamic derangements of cardiac surgery and cardiopulmonary bypass, and the possibility of large volume blood transfusion. There are no truly effective pharmacological therapies for the management of acute kidney injury, and therefore anesthesiologists, intensivists and cardiac surgeons must remain vigilant, and attempt to minimise the risk of developing renal dysfunction. This narrative review describes the current state of the scientific literature concerning the specific aspects of cardiac surgery-associated acute kidney injury and presents it in a chronological fashion to aid the perioperative clinician in their approach to this high-risk patient group. The evidence is considered for risk prediction models, preoperative optimisation, and the intra- and postoperative management of cardiac surgery patients to improve renal outcomes.
... The different patterns observed in the muscle and in remote organs are possibly related to the underlying mechanisms of RIC. Longer cycles are necessary to activate different pathways supposed to be related to this technique and to evoke a protective effect in distant tissues, for instance, a neural pathway, in which sublethal ischemic stimulus provides an afferent signal to the central nervous system 16,20,21 . Consequently, there is an efferent response, through activation of parasympathetic nerves, that plays a role in modulating vascular activity and increasing antiinflammatory substances 16 . ...
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Purpose: To clarify the best protocol for performing remote ischemic conditioning and to minimize the consequences of ischemia and reperfusion syndrome in brain, the present study aimed to evaluate different time protocols and the relation of the organs and the antioxidant effects of this technique. Methods: The rat's left femoral artery was clamped with a microvascular clamp in times that ranged from 1 to 5 minutes, according to the corresponding group. After the cycles of remote ischemic conditioning and a reperfusion of 20 minutes, the brain and the left gastrocnemius were collected. The samples were used to measure glutathione peroxidase, glutathione reductase and catalase levels. Results: In the gastrocnemius, the 4-minute protocol increased the catalase concentration compared to the 1-minute protocol, but the latter increased both glutathione peroxidase and glutathione reductase compared to the former. On the other hand, the brain demonstrated higher catalase and glutathione peroxidase in 5-minute group, and the 3-minute group reached higher values of glutathione reductase. Conclusions: Remote ischemic conditioning increases brain antioxidant capacity in a time-dependent way, while muscle presents higher protection on 1-minute cycles and tends to decrease its defence with longer cycles of intermittent occlusions of the femoral artery.
... Indeed, ischemic preconditioning (by vascular clamping) showed promising protective effects in animal models of I/R and the potential implication of HO-1 in the observed effects was suggested [239,240], since a priori augmentation of the expression of HO-1 induces resistance to apoptosis in human tubular cells [91]. However, HO-1 expression was not increased in such models [241,242] and the results of such procedures on AKI incidence in human cardiac surgery were also contradictory [243,244]. ...
Article
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The incidence of kidney disease is rising, constituting a significant burden on the healthcare system and making identification of new therapeutic targets increasingly urgent. The heme oxygenase (HO) system performs an important function in the regulation of oxidative stress and inflammation and, via these mechanisms, is thought to play a role in the prevention of non-specific injuries following acute renal failure or resulting from chronic kidney disease. The expression of HO-1 is strongly inducible by a wide range of stimuli in the kidney, consequent to the kidney’s filtration role which means HO-1 is exposed to a wide range of endogenous and exogenous molecules, and it has been shown to be protective in a variety of nephropathological animal models. Interestingly, the positive effect of HO-1 occurs in both hemolysis- and rhabdomyolysis-dominated diseases, where the kidney is extensively exposed to heme (a major HO-1 inducer), as well as in non-heme-dependent diseases such as hypertension, diabetic nephropathy or progression to end-stage renal disease. This highlights the complexity of HO-1's functions, which is also illustrated by the fact that, despite the abundance of preclinical data, no drug targeting HO-1 has so far been translated into clinical use. The objective of this review is to assess current knowledge relating HO-1’s role in the kidney and its potential interest as a nephroprotection agent. The potential therapeutic openings will be presented, in particular through the identification of clinical trials targeting this enzyme or its products.
... It reduces the ischemia and reperfusion injury of target organs by stimulating endogenous protection [58,59]. Protective effects of RIPC have been reported on heart as well as kidney, brain, liver, skeletal muscle, small intestine and other organs [60]. Although molecular mechanisms underlying RIPC protective effects remain to be investigated, but as reflected by downregulation of Lcn2, a reduction of subclinical renal damage by RIPC, especially in the early stage of injury, has been reported [59]. ...
Article
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Myocardial infarction (MI) is a leading cause of death worldwide and requires development of efficient therapeutic strategies . Mesenchymal stem cells (MSCs) -based therapy of MI has been promising but inefficient due to undesirable microenvironment of the infarct tissue. Hence, the current study was conducted to fortify MSCs against the unfavorable microenvironment of infarct tissue via overexpression of Lipocalin 2 (Lcn2) as a cytoprotective factor. The engineered cells (Lcn2-MSCs) were transplanted to infarcted heart of a rat model of MI. According to our findings, Lcn2 overexpression resulted in increased MSCs survival in the MI tissue (p < 0.05) compared to non-engineered cells. Furthermore, the infusion of Lcn2-MSCs mitigated Left ventricle (LV) remodeling, decreased fibrosis (p < 0.0001), and reduced apoptotic death of the LVs’ cells (p < 0.0001) compared to the control. Our findings suggest a potential novel therapeutic strategy for MI, however, further investigations such as safety and efficacy assessments in large animals followed by clinical trials are required.
... Importantly, RIPostC provides the possibility that cardioprotection may be initiated at a clinically relevant time, from an organ other than the heart, thereby avoiding damage to the heart. Since this discovery, IPC and RIPostC have been demonstrated to occur in mice, rats, dogs, sheep, pigs, and humans (26,37,38), and the mechanisms have been studied in detail (1,39,51,56), with many attempts to translate via clinical trials (6,8,12,13,25,26,28,29,32,33,36,37,55,60). Although clinical trials have shown some limited benefits, nothing has yet proven reliable and effective in large clinical trials. ...
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Timely reperfusion is still the most effective approach to limit infarct size in humans. Yet, despite advances in care and reduction in door-to-balloon times, nearly 25% of patients develop heart failure postmyocardial infarction, with its attendant morbidity and mortality. We previously showed that cardioprotection results from a skin incision through the umbilicus in a murine model of myocardial infarction. In the present study, we show that an electrical stimulus or topical capsaicin applied to the skin in the same region induces significantly reduced infarct size in a murine model. We define this class of phenomena as nociceptor-induced conditioning (NIC) based on the peripheral nerve mechanism of initiation. We show that NIC is effective both as a preconditioning and postconditioning remote stimulus, reducing infarct size by 86% and 80%, respectively. NIC is induced via activation of skin C-fiber nerves. Interestingly, the skin region that activates NIC is limited to the anterior of the T9T10 vertebral region of the abdomen. Cardioprotection after NIC requires the integrity of the spinal cord from the region of stimulation to the thoracic vertebral region of the origin of the cardiac nerves but does not require that the cord be intact in the cervical region. Thus, we show that NIC is a reflex and not a central nervous system-mediated effect. The mechanism involves bradykinin 2 receptor activity and activation of PKC, specifically, PKC-. The similarity of the neuro-anatomy and conservation of the effectors of cardioprotection supports that NIC may be translatable to humans as a nontraumatic and practical adjunct therapy against ischemic disease.
... Importantly, RIPostC provides the possibility that cardioprotection may be initiated at a clinically relevant time, from an organ other than the heart, thereby avoiding damage to the heart. Since this discovery, IPC and RIPostC have been demonstrated to occur in mice, rats, dogs, sheep, pigs, and humans (26,37,38), and the mechanisms have been studied in detail (1,39,51,56), with many attempts to translate via clinical trials (6,8,12,13,25,26,28,29,32,33,36,37,55,60). Although clinical trials have shown some limited benefits, nothing has yet proven reliable and effective in large clinical trials. ...
Article
Full-text available
Timely reperfusion is still the most effective approach to limit infarct size in humans. Yet, despite advances in care and reduction in door-to-balloon times, nearly 25% of patients develop heart failure postmyocardial infarction, with its attendant morbidity and mortality. We previously showed that cardioprotection results from a skin incision through the umbilicus in a murine model of myocardial infarction. In the present study, we show that an electrical stimulus or topical capsaicin applied to the skin in the same region induces significantly reduced infarct size in a murine model. We define this class of phenomena as nociceptor-induced conditioning (NIC) based on the peripheral nerve mechanism of initiation. We show that NIC is effective both as a preconditioning and postconditioning remote stimulus, reducing infarct size by 86% and 80%, respectively. NIC is induced via activation of skin C-fiber nerves. Interestingly, the skin region that activates NIC is limited to the anterior of the T9T10 vertebral region of the abdomen. Cardioprotection after NIC requires the integrity of the spinal cord from the region of stimulation to the thoracic vertebral region of the origin of the cardiac nerves but does not require that the cord be intact in the cervical region. Thus, we show that NIC is a reflex and not a central nervous system-mediated effect. The mechanism involves bradykinin 2 receptor activity and activation of PKC, specifically, PKC-. The similarity of the neuro-anatomy and conservation of the effectors of cardioprotection supports that NIC may be translatable to humans as a nontraumatic and practical adjunct therapy against ischemic disease.
... Importantly, RIPostC provides the possibility that cardioprotection may be initiated at a clinically relevant time, from an organ other than the heart, thereby avoiding damage to the heart. Since this discovery, IPC and RIPostC have been demonstrated to occur in mice, rats, dogs, sheep, pigs, and humans (26,37,38), and the mechanisms have been studied in detail (1,39,51,56), with many attempts to translate via clinical trials (6,8,12,13,25,26,28,29,32,33,36,37,55,60). Although clinical trials have shown some limited benefits, nothing has yet proven reliable and effective in large clinical trials. ...
Article
Timely reperfusion is still the most effective approach to limit infarct size in humans. Yet, despite advances in care and reduction in door-to-balloon times, nearly 25% of patients develop heart failure postmyocardial infarction, with its attendant morbidity and mortality. We previously showed that cardioprotection results from a skin incision through the umbilicus in a murine model of myocardial infarction. In the present study, we show that an electrical stimulus or topical capsaicin applied to the skin in the same region induces significantly reduced infarct size in a murine model. We define this class of phenomena as nociceptor-induced conditioning (NIC) based on the peripheral nerve mechanism of initiation. We show that NIC is effective both as a preconditioning and postconditioning remote stimulus, reducing infarct size by 86% and 80%, respectively. NIC is induced via activation of skin C-fiber nerves. Interestingly, the skin region that activates NIC is limited to the anterior of the T9−T10 vertebral region of the abdomen. Cardioprotection after NIC requires the integrity of the spinal cord from the region of stimulation to the thoracic vertebral region of the origin of the cardiac nerves but does not require that the cord be intact in the cervical region. Thus, we show that NIC is a reflex and not a central nervous system-mediated effect. The mechanism involves bradykinin 2 receptor activity and activation of PKC, specifically, PKC-α. The similarity of the neuroanatomy and conservation of the effectors of cardioprotection supports that NIC may be translatable to humans as a nontraumatic and practical adjunct therapy against ischemic disease. NEW & NOTEWORTHY This study shows that an electrical stimulus to skin sensory nerves elicits a very powerful cardioprotection against myocardial infarction. This stimulus works by a neurogenic mechanism similar to that previously elucidated for remote cardioprotection of trauma. Nociceptor-induced conditioning is equally potent when applied before ischemia or at reperfusion and has great potential clinically.
... 25,26 Results of recent meta-analyses have failed to demonstrate the efficacy of RIPC in reducing the incidence of AKI or the need for RRT. [197][198][199][200] Importantly, these metaanalyses included studies involving low-risk patients and studies that used propofol. In a subgroup of studies in which propofol was not used, a reduction in AKI was demonstrated, suggesting a possible interaction of propofol with the protective effects of RIPC. ...
... It protects the heart and has a protective effect on the brain, kidney, small intestine, liver, skeletal muscle and other organs, and has the universality of organs. [14,15] In 2000, Ogawa et al [16] found that ischemic preconditioning can alleviate the renal damage in rats after 40-minute ischemia. In the study of 924 patients with cardiac or vascular surgery, it was found that the incidence of acute renal dysfunction in the distal ischemic preconditioning group was significantly lower than that in the control group. ...
Article
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Objective: The aim of this study was to explore the clinical effects of remote ischemic preconditioning (RIPC) on contrast-induced nephropathy after percutaneous coronary intervention (PCI) in patients with acute coronary syndrome (ACS). Patients and methods: The study was a single-center, prospective, randomized, controlled study. A total of 161 patients with ACS and the rate of estimate glomerular filtration (eGFR) 15 to 70 mL/min/1.73 m2 undergoing PCI were randomly assigned to RIPC group (induced by 4 times of 5-minute inflations of a blood pressure cuff to 200 mmHg around the upper arm, followed by 5-min intervals of reperfusion at 1 hour before PCI therapy) or control group (an uninflated cuff around the arm). Successful completion of the PCI eventually included 107 cases of patients, including 50 cases in the RIPC group and 57 cases in the control group. The level of serum creatinine (Scr), CystatinC (CysC), blood neutrophil gelatinase-associated lipocalin (NGAL), eGFR were measured in all patients at 6 AM before the day of PCI, and 4-hour NGAL, 24-hour CysC, 72-hour Scr, and eGFR after PCI in the 2 groups. The incidence of major adverse events in the kidney (including the incidence of CIN, the need for dialysis, or renal replacement therapy after using contrast agent) and the composite endpoint of cardiovascular events were recorded at 6 months after PCI. Results: There were no statistically significant differences in baseline indicators between the 2 groups. Scr, CysC, and blood NGAL levels and the incidence of CIN in patients with RIPC group were significantly lower than those form the control group after PCI (P < .05), but there were no significant differences between the average value of eGFR and occurrence of Major cardiovascular events in the postoperative 6 months (P > .05). Conclusions: RIPC can reduce PCI-related CIN and protect renal function in patients with ACS. The benefits of these patients by RIPC may be related to the reduction of the NGAL and CysC.
... In this meta-analysis, RIPC reduced only marginally and not significantly the incidence of AKI (À13%) and severe AKI (À17%) in the whole group of studies, in line with results of most previous meta-analyses [21, 23, 24-26, 32-36, 38]; as for meta-analyses reporting a significant AKI reduction [29][30][31]37], most of these included studies on vascular or pediatric surgery and PCI (for a weight of up to 48%). ...
Article
Background: The main aim of this systematic review was to assess whether remote ischaemic preconditioning (RIPC) protects kidneys and the heart in cardiac surgery with cardiopulmonary bypass (CPB) and to investigate a possible role of anaesthetic agents. Methods: Randomized clinical trials (RCTs) on the effects of RIPC through limb ischaemia in adult patients undergoing cardiac surgery with CPB were searched (1965-October 2016) in PubMed, Cochrane Library and article reference lists. A random effects model on standardized mean difference (SMD) for continuous outcomes and the Peto odds ratio (OR) for dichotomous outcomes were used to meta-analyse data. Subgroup analyses to evaluate the effects of different anaesthetic regimens were pre-planned. Results: Thirty-three RCTs (5999 participants) were included. In the whole group, RIPC did not significantly reduce the incidence of acute kidney injury (AKI), acute myocardial infarction, atrial fibrillation, mortality or length of intensive care unit (ICU) and hospital stays. On the contrary, RIPC significantly reduced the area under the curve for myocardial injury biomarkers (MIBs) {SMD -0.37 [95% confidence interval (CI) -0.53 to - 0.21]} and the composite endpoint incidence [OR 0.85 (95% CI 0.74-0.97)]. In the volatile anaesthetic group, RIPC significantly reduced AKI incidence [OR 0.57 (95% CI 0.41-0.79)] and marginally reduced ICU stay. Conversely, except for MIBs, RIPC had fewer non-significant effects under propofol with or without volatile anaesthetics. Conclusions: RIPC did not consistently reduce morbidity and mortality in adults undergoing cardiac surgery with CPB. In the subgroup on volatile anaesthetics only, RIPC markedly and significantly reduced the incidence of AKI and composite endpoint as well as myocardial injury.