Effect Of Remote Ischemic Preconditioning Research Articles

Renal protective effect of remote ischemic preconditioning: a meta-analysis of randomized controlled trials

Background The incidence of acute kidney injury (AKI) is ∼21.6% in hospitalized patients with an increased incidence of mortality. Although many trials have been done to prevent or treat AKI, most of these efforts have yielded limited success.Objectives This study aimed to detect the effects of remote ischemic preconditioning (RIPC) on the incidence and outcomes of AKI.Study design A meta-analysis was used to address this concern.Settings A meta-analysis-based study following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines was conducted.Methods The databases such as MEDLINE, EMBASE, PubMed, and Cochrane were systemically searched to identify all published prospective, randomized, and controlled clinical trials in the last 5 years comparing RIPC with control in different procedures.Results A total of 26 studies were identified for inclusion in this study, involving 3978 patients. The risk of bias was low. Meta-analysis showed that the rate of AKI was significantly lower in the RIPC group, there was no statistically significant difference in the overall mortality, and there was no significant change in serum creatinine value. Regarding serum neutrophil gelatinase-associated lipocalin and estimated glomerular filtration rate, the study favors the RIPC group than the control group. There was no significant difference in the period of hospital stays, whereas the length of ICU stay was remarkably reduced in the RIPC group.Limitations The definitions of AKI adopted in respective trials were different. Comorbidities among the studies that may raise protective threshold were different. In our analysis, preoperative kidney function of the studies was different, and the use of different anesthetic protocols might confound the effect of RIPC.Conclusion RIPC offers a novel, noninvasive, and inexpensive treatment strategy for decreasing AKI incidence and improving the outcome in high-risk patients.

Organoprotective Effect of Remote Ischemic Preconditioning during Living Donor Liver Transplantation, A Prospective Randomized Double-Blinded Study

Background: Ischemia reperfusion injury (IRI) during liver transplantation carries a substantial risk for graft damage, and other major organ injury. Strategies to minimize IRI in the grafted liver are of paramount importance. Remote ischemic preconditioning (RIP) is a recently described technique that can offer a liver protective effect against IRI. Patients and Methods: In this prospective randomized study, consent was obtained from 80 couples (donor– recipient) prepared for liver transplantation (LT). Patients were divided randomly (using closed envelope technique) into two groups: RIP group (n=35) as RIP procedure was run in the donor non-dominant hand just at the start of parenchymal transection and control group (n= 35). In all the study cases, the pressure cuff was wrapped around the recipient arm. In RIP group, four sets of 5 minutes manual pressure cuff elevation to 200 mmHg, separated by 5 minutes of release (Using the non-dominant hand). Results: No statistically significant difference was found between the biochemical profile (SGPT, CRP, and bilirubin) of the recipients in both of the study groups. Similarly, post-operative kidney function (Serum creatinine) was comparable findings in the two studied groups. Conclusion: RIP in living donor liver transplantation failed to show a protective effect neither on the graft response to reperfusion injury, nor the on the postoperative kidney functions. Future studies are recommended taking into consideration histopathological, tissue damage scores.

Remote Ischemic Preconditioning in Prevention of Contrast Induced Nephropathy in Patients Undergoing Lower Limb Angioplasty Revascularization for Peripheral Arterial Disease: A Randomized Control Trial

Background: Contrast induced nephropathy (CIN) following angiography is one of the leading causes of in-hospital acute kidney injury (AKI). The aim of this study was to investigate the renoprotective effect of remote ischemic preconditioning (RIPC) to prevent CIN in patients with peripheral arterial disease (PAD) undergoing lower limb angioplasty with standard preventative measures. Methods: 40 adult patients (eGFR >45 ml/min) undergoing peripheral arterial angioplasty received either: (1) Control: standard preventative measures comprising intravenous (IV) hydration with 0.9% normal saline (1ml/kg/hour) or (2) RIPC: four-5 min inflations and deflations of a pneumatic cuff placed on the upper arm in addition to IV hydration prior to the angiographic procedure. Serial measurements of serum creatinine, serum cystatin and urinary NGAL were taken at baseline and 2, 24, 48- and 72-hours post-procedure. The primary outcome was CIN as defined by a rise of creatinine by > 26.5umol/L above baseline within 48 hours of contrast exposure. Other outcome measures included the rise in urine NGAL and serum cystatin from base line at 2 hours, as an early marker of acute kidney injury (AKI). Results: Both groups had similar baseline characteristics. All recruited patients had eGFR >45 ml/min, and RIPC had no renoprotective effect. AKI occurred in five (13%) patients. Changes in serum creatinine at 2 hours post-procedure did not correlate with changes in urine NGAL or serum Cystatin C. Conclusion: In stable PAD patients (eGFR >45ml/min) undergoing lower limb angioplasty with standard preventative measures, RIPC did not offer any protection against development of CIN.

Organoprotective Effect of Remote Ischemic Preconditioning during Living Donor Liver Transplantation, A Prospective Randomized Double-Blinded Study

Background: Ischemia reperfusion injury (IRI) during liver transplantation carries a substantial risk for graft damage, and other major organ injury. Strategies to minimize IRI in the grafted liver are of paramount importance. Remote ischemic preconditioning (RIP) is a recently described technique that can offer a liver protective effect against IRI. Patients and Methods: In this prospective randomized study, consent was obtained from 80 couples (donor– recipient) prepared for liver transplantation (LT). Patients were divided randomly (using closed envelope technique) into two groups: RIP group (n=35) as RIP procedure was run in the donor non-dominant hand just at the start of parenchymal transection and control group (n= 35). In all the study cases, the pressure cuff was wrapped around the recipient arm. In RIP group, four sets of 5 minutes manual pressure cuff elevation to 200 mmHg, separated by 5 minutes of release (Using the non-dominant hand). Results: No statistically significant difference was found between the biochemical profile (SGPT, CRP, and bilirubin) of the recipients in both of the study groups. Similarly, post-operative kidney function (Serum creatinine) was comparable findings in the two studied groups. Conclusion: RIP in living donor liver transplantation failed to show a protective effect neither on the graft response to reperfusion injury, nor the on the postoperative kidney functions. Future studies are recommended taking into consideration histopathological, tissue damage scores.

Effect of remote ischemic preconditioning on cerebral vasospasm, biomarkers of cerebral ischemia, and functional outcomes in aneurysmal subarachnoid hemorrhage (ERVAS): A randomized controlled pilot trial.

BACKGROUND:Cerebral vasospasm can complicate aneurysmal subarachnoid hemorrhage (aSAH), contributing to cerebral ischemia. We explored the role of remote ischemic preconditioning (RIPC) in reducing cerebral vasospasm and ischemia and improving outcomes after aSAH.MATERIALS AND METHODS:Patients with ruptured cerebral aneurysm undergoing surgical clipping and meeting the trial criteria were randomized to true RIPC (n = 13) (inflating upper extremity blood pressure cuff thrice to 30 mmHg above systolic pressure for 5 min) or sham RIPC (n = 12) (inflating blood pressure cuff thrice to 30 mmHg for 5 min) after ethical approval. A blinded observer assessed outcome measures-cerebral vasospasm and biomarkers of cerebral ischemia. We also evaluated the feasibility and safety of RIPC in aSAH and Glasgow Outcome Scale-Extended (GOSE).RESULTS:Angiographic vasospasm was seen in 9/13 (69%) patients; 1/4 patients (25%) in true RIPC group, and 8/9 patients (89%) in sham RIPC group (P = 0.05). Vasospasm on transcranial Doppler study was diagnosed in 5/25 (20%) patients and 1/13 patients (7.7%) in true RIPC and 4/12 patients (33.3%) in sham RIPC group, (P = 0.16). There was no difference in S100B and neuron-specific enolase (NSE) levels over various time-points within groups (P = 0.32 and 0.49 for S100B, P = 0.66 and 0.17 for NSE in true and sham groups, respectively) and between groups (P = 0.56 for S100B and P = 0.31 for NSE). Higher GOSE scores were observed with true RIPC (P = 0.009) unlike sham RIPC (P = 0.847) over 6-month follow-up with significant between group difference (P = 0.003). No side effects were seen with RIPC.CONCLUSIONS:RIPC is feasible and safe in patients with aSAH and results in a lower incidence of vasospasm and better functional outcome.

Effects of remote ischemic preconditioning on platelet activation and reactivity in patients undergoing cardiac surgery using cardiopulmonary bypass: a randomized controlled trial

During cardiopulmonary bypass (CPB), platelet activation and dysfunction are associated with adverse outcomes. Remote ischemic preconditioning (RIPC) has been shown to attenuate platelet activation. We evaluated the effects of RIPC on platelet activation during CPB in patients undergoing cardiac surgery. Among 58 randomized patients, 26 in the RIPC group and 28 in the sham-RIPC group were analyzed. RIPC consisted of 4 cycles of 5-min ischemia induced by inflation of pneumatic cuff pressure to 200 mmHg, followed by 5-min reperfusion comprising deflation of the cuff on the upper arm. Platelet activation was assessed using flow cytometry analysis of platelet activation markers. The primary endpoint was the AUC of CD62P expression during the first 3 h after initiation of CPB. Secondary outcomes were the AUC of PAC-1 expression and monocyte-platelet aggregates (MPA) during 3 h of CPB. The AUCs of CD62P expression during 3 h after initiation of CPB were 219.4 ± 43.9 and 211.0 ± 41.2 MFI in the RIPC and sham-RIPC groups, respectively (mean difference, 8.42; 95% CI, −14.8 and 31.7 MFI; p =.471). The AUCs of PAC-1 expression and MPA did not differ between groups. RIPC did not alter platelet activation and reactivity during CPB in patients undergoing cardiac surgery.

Remote ischemic preconditioning effects on inflammatory markers and myocardial protection in coronary artery bypass graft surgery.

Induction of short episodes of ischemia to remote organs, namely upper or lower limbs, literally known as remote ischemic preconditioning (RIPC) has been suggested as a preconditioning approach to ameliorate ischemia/reperfusion injury (IRI). RIPC has been demonstrated to effectively protect various vital organs, including heart, against the next ischemic events in preclinical studies. However, human studies are required to approve its clinical applicability. Present study was performed to evaluate the effect of RIPC on the myocardial protection and inflammatory response markers in patients undergoing coronary artery bypass graft surgery. In this randomized clinical trial, 43 coronary artery bypass graft (CABG) patients from Imam Hossein educational hospital were allocated in two groups, RIPC (21 patients) and control (22 patients). Serum level of interleukin (IL)-4, IL-8, and IL-10, interferon (IFN)-γ and Cardiac Troponin-I (cTnI) were measured in (1) after induction of anesthesia (before incision of skin), (2) after separation from CPB and (3) 24 hours after ICU arrival.Results:increase pack cell transfusions were observed in control group in ICU. Serum level of IL-10 at 24 hours after ICU admission was significantly higher in the RIPC group. Significantly lower amounts of IL-8 at post-CPB time were observed in the RIPC group in comparison with control.Conclusion:RIPC regulates the circulatory inflammatory cytokines, IL-8 decrement and IL-10 elevation, which could be translated into protection against IRI. However, further studies with larger sample sizes with careful consideration of parameters such as use of propofol as an anesthetic in the patients should be conducted to consolidate the findings from the current study.

The effect of remote ischaemic preconditioning on endothelial function after hip fracture surgery

Endothelial dysfunction seems to play a role in the pathophysiology of myocardial injury after surgery. The aim of this randomised clinical trial was to examine whether remote ischaemic preconditioning in relation to hip fracture surgery ameliorates post-operative systemic endothelial dysfunction. This was a planned single-centre pilot sub-study of a multicentre, randomised clinical trial. Patients ≥45years with a cardiovascular risk factor were randomised to remote ischaemic preconditioning (RIPC) or control (standard treatment) performed in relation with their hip fracture operation. RIPC consisted of four cycles of 5minutes forearm ischaemia and reperfusion. The procedure was performed non-invasively with a tourniquet. The endothelial function was assessed with non-invasive digital pulse amplitude tonometry on post-operative day 1 and expressed as the reactive hyperaemia index (RHI). Endothelial dysfunction was defined as RHI<1.22. Between February 2015 and December 2016, 18 patients were allocated to the RIPC group and 20 patients to the control group. The endothelial function was impaired in both groups on post-operative day 1. RHI did not differ between the groups, 1.47 (95% CI 1.20-1.75) in the RIPC group vs. 1.54 (95% CI 1.17-1.91) in the control group, P=.76. Endothelial dysfunction was present in 3/18 patients (16.7%) in the RIPC group and 8/20 patients (40%) in the control group, P=.11. No beneficial effect of remote ischaemic preconditioning on the systemic endothelial dysfunction, assessed at a single time point on post-operative day one, was detected after hip fracture surgery.

Remote ischemic preconditioning in isolated valve intervention. A pooled meta-analysis

ObjectiveRecent studies have shown no benefits from remote ischemic preconditioning (RIPC) in patients undergoing coronary artery bypass surgery. One possible explanation is that given previous exposure to angina and ischemia/reperfusion injury these patients, may be already ‘naturally preconditioned’. The role of RIPC in a context of isolated valve intervention, both surgical and particularly transcatheter is less clear and remains under investigated, with few high-quality studies. MethodsA systematic literature review identified 8 candidate studies that met the meta-analysis criteria. We analyzed outcomes of 610 subjects (312 RIPC and 298 SHAM) with random effects modeling. Each study was assessed for heterogeneity. The primary outcome was the extent of periprocedural myocardial injury, as reflected by the area under the curve for serum troponin concentration. Secondary endpoints included relevant intra- and post-operative outcomes; sensitivity and high-quality subgroup analysis was also carried out. ResultsSix and two studies reported the effect of RIPC in surgical and transcatheter valve intervention. There was a significant difference between-group in terms of periprocedural Troponin release (standardized mean difference (SMD: 0.74 [95% CI: 0.52; 0.95], p = 0.02) with no heterogeneity (χ2 2.40, I2 0%, p = 0.88). RIPC was not associated with any improvement in post-operative outcomes. No serious adverse RIPC related events were reported. ConclusionsRIPC seems to elicit overall periprocedural cardioprotection in patients undergoing valvular intervention, yet with no benefit on early clinical outcomes.

Remote ischaemic preconditioning influences the levels of acylcarnitines in vascular surgery: a randomised clinical trial

BackgroundVascular surgery patients have reduced tissues` blood supply, which may lead to mitochondrial dysfunction and accumulation of acylcarnitines (ACs).It has been suggested that remote ischaemic preconditioning (RIPC) has its organ protective effect via promoting mitochondrial function.The aim of this study was to evaluate the effect of RIPC on the profile of ACs in the vascular surgery patients.MethodsThis is a randomised, sham-controlled, double-blinded, single-centre study. Patients undergoing open surgical repair of abdominal aortic aneurysm, surgical lower limb revascularisation surgery or carotid endarterectomy were recruited non-consecutively. The RIPC protocol consisting of 4 cycles of 5 min of ischaemia, followed by 5 min of reperfusion, was applied. A blood pressure cuff was used for RIPC or a sham procedure. Blood was collected preoperatively and approximately 24 h postoperatively. The profile of ACs was analysed using the AbsoluteIDQp180 kit (Biocrates Life Sciences AG, Innsbruck, Austria).ResultsNinety-eight patients were recruited and randomised into the study groups and 45 patients from the RIPC group and 47 patients from the sham group were included in final analysis. There was a statistically significant difference between the groups regarding the changes in C3-OH (p = 0.023)—there was a decrease (− 0.007 µmol/L, ± 0.020 µmol/L, p = 0.0233) in the RIPC group and increase (0.002 µmol/L, ± 0.015 µmol/L, p = 0.481) in the sham group. Additionally, a decrease from baseline to 24 h after surgery (p < 0.05) was detected both in the sham and the RIPC group in the levels of following ACs: C2, C8, C10, C10:1, C12, C12:1, C14:1, C14:2, C16, C16:1, C18, C18:1, C18:2. In the sham group, there was an increase (p < 0.05) in the levels of C0 (carnitine) and a decrease in the level of C18:1-OH. In the RIPC group, a decrease (p < 0.05) was noted in the levels of C3-OH, C3-DC (C4-OH), C6:1, C9, C10:2.ConclusionsIt can be concluded that RIPC may have an effect on the levels of ACs and might therefore have protective effects on mitochondria in the vascular surgery patients. Further larger studies conducted on homogenous populations are needed to make more definite conclusions about the effect of RIPC on the metabolism of ACs.Trial registrationClinicalTrials.gov database, NCT02689414. Registered 24 February 2016—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02689414.

Remote ischemic preconditioning in a setting of electrical cardioversion of early onset persistent atrial fibrillation (RIP CAF trial): Rationale and study design

BackgroundThe beneficial effect of remote ischemic preconditioning (RIP) on electrophysiological parameters resulting in lower inducibility and sustainability of atrial fibrillation (AF) in patients with paroxysmal AF has been recently demonstrated in a randomized trial. However, the potential clinical impact of RIP on persistent AF (CAF) has not been investigated. Therefore, we designed a randomized trial set in a setting of electrical cardioversion (CV) of early onset CAF. AimThe aim of the study is to answer the following questions: I) Does RIP have impact on rate of spontaneous conversion into sinus rhythm (SR) within 24 h after first RIP intervention? II) Does RIP have the potential to improve the acute outcome of CV following a standardized protocol? MethodsThe presented study is a two-armed randomized, placebo-controlled, double-blinded, multi-center trial in a cohort of 588 patients with early onset CAF referred for electrical CV. The patients will undergo 3 sessions (immediately after randomization, the following morning, and directly before scheduled CV 24 h after randomization) of either RIP intervention or a sham procedure. The primary outcome of the study, i.e. documentation of SR 24 h after randomization as well secondary outcome i.e. stable SR first CV without usage of anti-arrhythmic drugs will be documented by 12-lead surface electrocardiography. ConclusionPreviously observed positive effect of RIP on atrial electrophysiology might be also implemented in a clinical setting of CV and therefore simplified and improve patient treatment.

Exploring the Role of Remote Ischemic Preconditioning In Long Term Cognitive Impairment after Global Ischemia-Reperfusion-Induced Vascular Dementia in Mice

Aim: The aim of the present study is to explore the neuroprotective effects of remote ischemic preconditioning in long term cognitive impairment after global cerebral ischemia induced-vascular dementia in mice. Material and methods: The mice were subjected to global cerebral ischemia by occluding the bilateral common carotid arteries for 12 minutes followed by the 24 hours of the reperfusion. The remote ischemic preconditioning stimulus was delivered in the form of 4 cycles of ischemia/reperfusion for 5 minutes each. The cerebral ischemic injury induced-long term cognitive impairment-related learning and memory alterations was assessed using morris water maze, the motor performances of the animals were evaluated using rota-rod test and neurological severity score. The cerebral infract size of the brain were quantified using triphenyltetrazolium chloride staining. Results: Global cerebral ischemia causes long term memory impairment, decreases motor performances and increases the brain infract size in animals. The delivery of remote ischemic preconditioning stimulus significantly abolished the long-term cognitive impairment and ameliorates the motor performances as well as cerebral infract size in brain. Conclusion: The remote ischemic preconditioning mediates neuro protection against global cerebral ischemic injury induced long-term cognitive impairment.

Two weeks of remote ischaemic preconditioning alters sympathovagal balance in healthy humans.

What is the central question of this study? Delayed cardiovascular responses occur following a single bout of remote ischaemic preconditioning (RIPC). Is heart rate variability (HRV), a surrogate marker of cardiac vagal control, able to detect a delayed effect after a single bout of RIPC? Do repeated bouts of RIPC further alter HRV? What is the main finding and its importance? Indices of HRV indicated a shift in sympathovagal balance toward greater parasympathetic activity following 2weeks of RIPC but not after a single bout of RIPC. Thus, repeated bouts of RIPC were necessary to elicit changes in autonomic function. Remote ischaemic preconditioning (RIPC), induced by brief periods of ischaemia followed by reperfusion, protects against ischaemia-reperfusion injury and improves microvascular function. However, the effect of RIPC on autonomic function remains unclear. We hypothesized that RIPC, administered as a single bout or repeated over a 2-week period, will increase markers of cardiac vagal control measured by heart rate variability (HRV). Thirty-two young adults performed a single bout (n=13), repeated bouts (n=11), or served as a time control (n=8). RIPC sessions consisted of four repetitions of 5min unilateral brachial artery occlusion interspersed by 5min of reperfusion. For the single bout protocol, resting lead II electrocardiogram (ECG) was collected before and 24, 48, 72 and 168h post-RIPC. The repeated bout protocol consisted of three 4-day periods of RIPC training, each interspersed by a 1-day break. Similar to time controls, ECG was collected before and 24h after the last RIPC bout. HRV was analysed by power spectral density and symbolic dynamics using 350-beat ECG segments. After a single bout of RIPC, no changes in HRV were observed at any time point (P>0.05). After 2weeks of repeated RIPC, the percentage of zero-variation fragments (baseline=13.1±1.9%, post-RIPC=6.9±1.5%, P<0.05) and the LF/HF ratio decreased (baseline=1.1±0.2, post-RIPC=0.7±0.1, P<0.01), whereas the percentage of two-variation fragments increased (baseline=42.9±3.6%, post-RIPC=52.5±3.0%, P<0.01). These data indicate that repeated RIPC is necessary to elicit changes in sympathovagal balance, specifically resulting in increased vagal and decreased sympathetic activity.

90 days impacts of remote ischemic preconditioning on patients undergoing open total aortic arch replacement: a post-hoc analysis of previous trial

BackgroundIn the previous randomized controlled trial by our research group, we evaluated the effect of remote ischemic preconditioning (RIPC) in 130 patients (65 per arm) on acute kidney injury (AKI) within 7 days of open total aortic arch replacement. Significantly fewer RIPC-treated patients than sham-treated patients developed postoperative AKI, and, epically, RIPC significantly reduced serious AKI (stage II–III). However, the long-term effect of RIPC in patients undergoing open total aortic arch replacement is unclear.MethodsThis study was a post-hoc analysis. We aimed to assess the roles of RIPC in major adverse kidney events (MAKE), defined as consisting persistent renal dysfunction, renal replacement therapy and mortality, within 90 days after surgery in patients receiving open total aortic arch replacement.ResultsIn this 90-day follow-up study, data were available for all study participants. We found that RIPC failed to improve the presence of MAKE within 90 days after surgery (RIPC: 7 of 65[10.8%]) vs sham: 15 of 65[23.1%]; P = 0.061). In those patients who developed AKI after surgery, we found that the rate of MAKE within 90 days after surgery differed between the RIPC group and the sham group (RIPC: 4 of 36[11.2%]; sham: 14 of 48[29.2%]; P = 0.046).ConclusionsAt 90 days after open total aortic arch replacement, we failed to find a difference between the renoprotective effects of RIPC and sham treatment. The effectiveness or ineffectiveness of RIPC should be further investigated in a large randomized sham-controlled trial.Trial registrationThis study was approved by the Ethics Committee of Fuwai Hospital (No. 2016–835) and our previous study was registered at clinicaltrials.gov before patient enrollment (NCT03141385; principal investigator: G.W.; date of registration: March 5, 2017).

Role of Remote Ischemic Preconditioning in Hepatic Ischemic Reperfusion Injury.

The effect of remote ischemic preconditioning (RIPC) has been proposed that mediates the protective response in ischemia reperfusion injury (IRI) of various organs. In this study, we investigated the effect of RIPC in hepatic IRI, by assessing biomarker of oxidative stress and inflammatory cytokines. Moreover, we intended to demonstrate any such protective effect through nitric oxide (NO). Twenty-five rats were divided into the 5 groups: (1) Sham; (2) RIPC; (3) hepatic IRI; (4) RIPC + hepatic IRI; (5) C-PTIO, 2-(4-carboxyphenyl)-4,5dihydro-4,4,5,5-tetramethyl-1H-imidazolyl-1-oxy-3oxide, + RIPC + hepatic IRI. RIPC downregulated the level of aspartate aminotransferase (AST), alanine aminotransferase (ALT), histologic damage, and activity of Malondialdehyde (MDA). However, there was no significant reduction in the level of tumor necrosis factor-alpha (TNF-α) and nuclear factor kappa B (NF-κB). AST and ALT levels, and hepatic tissue morphology in the C-PTIO group showed a significant improvement compared to those of the RIPC + hepatic IRI group. The application of RIPC before hepatic ischemia downregulated the oxidative stress, not the inflammatory cytokines. Moreover, these protective effect of RIPC would be mediated through the activation of NO as well as anti-oxidant effect.

Remote ischemic preconditioning reduces myocardial ischemia-reperfusion injury through unacylated ghrelin-induced activation of the JAK/STAT pathway.

Remote ischemic preconditioning (RIPC) offers cardioprotection against myocardial ischemia-reperfusion injury. The humoral factors involved in RIPC that are released from parasympathetically innervated organs have not been identified. Previous studies showed that ghrelin, a hormone released from the stomach, is associated with cardioprotection. However, it is unknown whether or not ghrelin is involved in the mechanism of RIPC. This study aimed to determine whether ghrelin serves as one of the humoral factors in RIPC. RIPC group rats were subjected to three cycles of ischemia and reperfusion for 5min in two limbs before left anterior descending (LAD) coronary artery ligation. Unacylated ghrelin (UAG) group rats were given 0.5 mcg/kg UAG intravenously 30min before LAD ligation. Plasma levels of UAG in all groups were measured before and after RIPC procedures and UAG administration. Additionally, JAK2/STAT3 pathway inhibitor (AG490) was injected in RIPC and UAG groups to investigate abolishment of the cardioprotection of RIPC and UAG. Plasma levels of UAG, infarct size and phosphorylation of STAT3 were compared in all groups. Infarct size was significantly reduced in RIPC and UAG groups, compared to the other groups. Plasma levels of UAG in RIPC and UAG groups were significantly increased after RIPC and UAG administration, respectively. The cardioprotective effects of RIPC and UAG were accompanied by an increase in phosphorylation of STAT3 and abolished by AG490. This study indicated that RIPC reduces myocardial ischemia and reperfusion injury through UAG-induced activation of JAK/STAT pathway. UAG may be one of the humoral factors involved in the cardioprotective effects of RIPC.

A RANDOMIZED COMPARATIVE STUDY BETWEEN REMOTE ISCHEMIC PRECONDITIONING AND PHARMACOLOGICAL PRECONDITIONING IN MAJOR AORTIC SURGERIES

Background: Cardiopulmonary bypass (CPB) remains an essential element of the surgical correction of most majorcardiovascular lesions. CPB is complicated by multisystem injury, the mechanisms of which include ischemia–reperfusion injury (IRI) and a detrimental systemic inflammatory response. Cardiac, pulmonary and neuronal injury and dysfunction remain important clinical problems after CPB. Aim of the study: The aim of this study was to compare and evaluate the effectiveness of remote ischemic preconditioning and pharmacological preconditioning in reducing cardiac injury inducedby cardiopulmonary bypass in adult patients undergoing major aortic surgeries. Patients and Methods: This study included (42) patients, divided into two groups 21 patients each, Group R: Remote Ischemic Preconditioning (cycles of ischemia and reperfusion of lower limb using blood pressure cuff) and Group P: pharmacological preconditioning (administration of sevoflurane and dexmedetomidine). Results: The current studyshowed postoperative lower elevation in CK total enzyme, CK MB enzyme and troponin I enzyme and decreased inotropic support(adrenaline infusion) requirements post-operatively along with shorter duration of postoperative intubation and postoperative ICU stay in group Pcompared to group R. Conclusion: Pharmacological preconditioning using sevoflurane and dexmedetomidine hasmyocardial protective effect after CPB in adult patients undergoing major aortic surgeries more than remote ischemic preconditioning as reflected by lower elevation in CK total enzyme, CK MB enzyme and troponin I enzyme and decreased inotropic support (adrenaline infusion) requirements postoperatively along with shorter duration of both postoperative intubation and postoperative ICU stay.

Remote ischemic preconditioning for prevention of contrast-induced nephropathy – A randomized control trial

BackgroundThere is a lack of sufficient data regarding the protective effects of remote ischemic preconditioning (RIPC) in patients at risk of developing contrast-induced nephropathy (CIN). Thus, this study was conducted to determine whether RIPC as an adjunct to standard therapy prevents CIN in high-risk patients undergoing coronary intervention. MethodsIn a single-center, double-blinded, randomized controlled trial, 162 patients who were at risk of CIN received standard hydration combined with RIPC or hydration with sham preconditioning. RIPC was accomplished by four cycles of 5 min ischemia and 5 min reperfusion of the forearm. The primary endpoint was a rise in serum creatinine (>0.5 mg/dL or >25%) from baseline to serum creatinine 48–72 h after contrast administration. ResultsOf the 162 patients, 81 were randomly allocated to receive sham preconditioning and 81 to receive RIPC. Significantly reduced serum creatinine levels were observed in patients with a Mehran moderate risk allocated to sham group compared to the RIPC group (0.070 ± 0.16 mg/dL vs. 0.107 ± 0.13 mg/dL, p = 0.001). With regards to the primary endpoint, a significantly higher change in serum creatinine from baseline to 48–72 h was observed in the sham group compared to the RIPC group (0.023 ± 0.2 μmol/L vs −0.064 ± 0.1 μmol/L, p < 0.001). ConclusionRIPC as an alternative to standard therapy, improved serum creatinine levels after contrast administration in patients at risk of CIN. However, present data indicate that RIPC might have beneficial effects in patients with a moderate or high risk of CIN.

Remote ischemic preconditioning inhibits platelet αIIbβ3 activation in coronary artery disease patients receiving dual antiplatelet therapy: A randomized trial

ObjectivesWe investigated whether remote ischemic preconditioning (RIPC) inhibits agonist‐induced conformational activation of platelet αIIbβ3 in patients with coronary artery disease already receiving conventional antiplatelet therapy. Patients/MethodsConsecutive patients with angiographically confirmed coronary artery disease were randomized to RIPC or sham treatment. Venous blood was collected before and immediately after RIPC/sham. Platelet aggregometry (ADP, arachidonic acid) and whole blood platelet flow cytometry was performed for CD62P, CD63, active αIIbβ3 (PAC‐1 binding) before and after stimulation with ADP, thrombin ± collagen, or PAR‐1 thrombin receptor agonist. ResultsPatients (25 RIPC, 23 sham) were well matched, 83% male, age (mean ± standard deviation) 63.3 ± 13.2 years, 95% aspirin, 81% P2Y12 inhibitor. RIPC did not affect platelet aggregation, nor agonist‐induced expression of CD62P, but selectively and significantly decreased αIIbβ3 activation after stimulation with either PAR‐1 agonist peptide or the combination of thrombin + collagen, but not after ADP nor thrombin alone. The effect of RIPC on platelet αIIbβ3 activation was evident in patients receiving both aspirin and P2Y12 inhibitor, and was not associated with an increase in vasodilator‐stimulated phosphoprotein phosphorylation. ConclusionsRemote ischemic preconditioning inhibits conformational activation of platelet αIIbβ3 in response to exposure to thrombin and collagen in patients with coronary artery disease receiving dual antiplatelet therapy. These findings indicate agonist‐specific inhibition of platelet activation by RIPC in coronary artery disease that is not obviated by the prior use of P2Y12 inhibitors.

Cardioprotective effects of remote ischemic preconditioning and its challenges in clinical application

Remote ischemic preconditioning (RIPC) is a novel preventative treatment approach that is proposed in recent years. It is a non-invasive and clinically relevant preventative strategy of cardiac muscles, that is, to carry out acute transient ischemia in the distant limb before surgery, so as to possibly relieve ischemia/perfusion injury (I/RI) in distant organs (including the heart and brain, etc.). A large number of animal studies and human clinical trials have demonstrated that remote ischemic preconditioning can reduce myocardial infarction size to prevent reperfusion injury. Unfortunately, it is difficult to transform from experiments to clinical application and finally benefit patients. Therefore, the efficient and effective method has yet to be developed. In this review, now analyzed the studies concerning cardioprotective effects by RIPC and summarized the difficulties of clinical practice. Key words: Remote ischemic preconditioning; Myocardial protection; Ischemia/reperfusion injury; Clinical application