Limb Remote Ischemic Preconditioning Research Articles

Abstract 186: Remote Limb Ischemic Preconditioning Improves Short and Long Term Survival and Maintains Intravascular Blood Volume During Resuscitation of Hemorrhagic Shock

Background: We further examined the protective effects of experimental bilateral lower limb remote ischemic preconditioning (RIPC) in rats undergoing experimental hemorrhagic shock. Methods: Sprague Dawley rats (both genders) were randomized into RIPC (n= 26) or control group (n= 27), and anesthetized with intraperitoneal ketamine/xylazine. RIPC was induced by 4 cycles of inflating small bilateral pressure cuffs to 200 mmHg around the femoral arteries for 5 minutes, followed by 5 minute deflation of the cuffs. Hemorrhagic shock was induced by withdrawing blood from the carotid artery. Target mean blood pressure of 30 mmHg was maintained for 30 minutes followed by reinfusion of shed blood within the next 30 min. Rats remained anesthetized for another 30 min before recovery; endpoints were survival at 72 hours and 6 weeks. Results: The % of estimated total blood volume withdrawn to maintain a level of 30 mmHg was similar in the RIPC group (41.7 ± 1.0 %) and control group (41.9 ± 1.0 %). Recovery of blood pressure during the early resuscitation phase was significantly improved in the RIPC group. The diastolic internal dimension of the left ventricle (echocardiogram), which indicates circulating intravascular blood volume, was significantly larger in the RIPC group at 1 hour after initiation of shed blood reinfusion (5.8 ± 0.1 mm) compared to 5.4 ± 0.1mm in the control group (p=0.04). Left ventricular fractional shortening was comparable between RIPC (50.9 ± 1.9 %) and control group (49.6 ± 1.8 %; p=0.64) at 1 hour after initiation of resuscitation. At 48 hours after shock, BUN was within normal range in the RIPC group (17.3 ± 1.2 mg/dl); but elevated in the control group (22.0 ± 1.7 mg/dl). At 72 hours after hemorrhagic shock injury, 6 of 27 (22.2 %) rats in the control group and 13 of 26 (50 %, p = 0.047) rats in the RIPC group survived. At 6 weeks, 5 of 27 (18.5 %) rats in the control group and 13 of 26 (50 %; p = 0.021) rats in the RIPC group survived. RIPC significantly increased survival rate at both 72 hours and 6 weeks. Conclusions: RIPC improved recovery of blood pressure and maintained more circulating intravascular blood volume in the early phase of resuscitation, improved BUN, and markedly and significantly improved short and long term survival in rats subjected to hemorrhagic shock.

Impact of Remote Ischemic Preconditioning Post-application Delay on Muscle Oxygenation during Subsequent Cycling Intervals

INTRODUCTION: Remote ischemic preconditioning (RIPC) involves brief, repeated bouts of manually-imposed blood flow restriction of the arms or legs. The alternating periods of occlusion and reperfusion lead to endothelial adaptations, capable of enhancing blood flow and oxygen delivery. PURPOSE: The aim of this study was to investigate the effect of a lower limb RIPC protocol, with either a 5-min or 45-min post-application delay, on muscle oxygen saturation within that same limb at rest and during short- duration intense cycling. METHODS: Subjects included recreationally aerobically trained college-aged students (23± 3 years, 173.5± 5.4 cm, 69.2± 4.0 kg, 15.2± 4.0 % BF, 2peak VO : 46.6± 1.1 mL•kg-1•min-1 at 215± 19 W). All subjects randomly completed four experimental trials: RIPC with 5-min delay, RIPC with 45-min delay, SHAM with 5-min delay, and SHAM with 45-min delay. For the RIPC conditions, each subject received 5-min of alternating-leg blood flow occlusion using a blood pressure cuff (220 mmHg) placed on the upper thighs for a total of 40 min. After a 5 or 45-min delay, the subjects completed 5, 1-min cycle sprints separated by 2 min of recovery. The SHAM conditions were identical to the RIPC, however, subjects laid supine for the same 40-min duration with alternating-leg cuff inflation to 20 mmHg. Muscle oxygen saturation was measured continuously using a portable NIRS-based sensor placed over the vastus lateralis (VL). RESULTS: RIPC decreased muscle oxygen saturation in the VL in a replicable manner (MD: 29.5± 13.4%, mean occlusion slope: -5.0± 2.4 %•min-1, mean reperfusion slope: 38.5± 22.4%•min-1) while SHAM conditions left muscle oxygen saturation largely unchanged (MD: 2.9± 1%). Mean VL oxygen saturation (RIPC45:71.9± 0.7%; RIPC5: 67.3± 1.7%; SHAM45: 72.0± 4.4%; SHAM5: 69.9± 3.0%) and preservation of muscle oxygen saturation (MD: RIPC45: -12.4± 6.2%; RIPC5: -14.4± 9.9%; SHAM45: -11.6± 6.4%; SHAM5: -13.0± 7.1%) during high intensity cycling intervals varied minutely between experimental conditions. CONCLUSIONS: The muscle oxygenation response during a standard occlusion/reperfusion protocol may lack assumed constancy. Furthermore, the use of RIPC and the length of the delay following RIPC did not greatly alter the muscle oxygenation response to repetitive high-intensity cycling intervals.

Remote limb ischemic preconditioning improves post‐resuscitation long term survival in a rat fixed pressure hemorrhagic shock model

BackgroundWe investigated whether bilateral lower limb remote ischemic preconditioning (RIP) could improve long‐term survival in a rat model of hemorrhagic shock/resuscitation.MethodsSprague Dawley rats (both genders) were anesthetized with intraperitoneal ketamine and xylazine, and were intubated and ventilated with room air. Rats were randomly assigned to RIP (n= 26; induced by inflating small bilateral pressure cuffs to 200 mmHg around the femoral arteries for 5 minutes, followed by 5 minute release of the cuffs, repeated 4 times) or control group (n= 27; the blood pressure cuffs are inflated only to 30 mmHg). After heparinization, hemorrhagic shock was induced by withdrawing blood from the left carotid artery to a fixed mean blood pressure of 30 mmHg for 30 minutes, followed by 30 min of resuscitation with shed blood. Rats remained anesthetized for one hour during which hemodynamics were monitored (femoral artery catheter); and then allowed to survive for 6 weeks.ResultsThe survival rate at 6 weeks was 5 out of 27 rats in the control group (18.5%), and 13 out of 26 rats in the RIP group (50%; p<0.05 by Fisher's exact test). Recovery of blood pressure during the early resuscitation phase was significantly improved and the heart rate was significantly lower in the RIP group compared to the control group (Figure below). At 6 weeks, all of the surviving rats were neurologically intact. Histochemistry/histologic staining was performed in the tissues from 9 survived rats, and showed brain infarction in 1 out of 3 rats in control and 1 out of 6 rats in RIP group; no evidence of myocardial or kidney infarction were detected.ConclusionsRIP markedly and significantly improved long term survival after experimental hemorrhagic shock/resuscitation and improved recovery of blood pressure in the early phase of resuscitation.Support or Funding InformationThis work was supported by the Office of the Assistant Secretary of Defense for Health Affairs, through the Peer Reviewed Medical Research Program under Award No.W81XWH‐16‐1‐0606. Opinions, interpretations, conclusion and recommendations are those of the authors and are not necessarily endorsed by the Department of Defense.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Remote Limb Ischemic Preconditioning Attenuates Cerebrovascular Depression During Sinusoidal Galvanic Vestibular Stimulation via α1-Adrenoceptor-Protein Kinase Cε-Endothelial NO Synthase Pathway in Rats.

BackgroundVasovagal syncope (VVS) is characterized by hypotension and bradycardia followed by lowering of cerebral blood flow. Remote limb ischemic preconditioning (RIPC) is well documented to provide cardio‐ and neuroprotection as well as to improve cerebral blood flow. We hypothesized that RIPC will provide protection against VVS‐induced hypotension, bradycardia, and cerebral hypoperfusion. Second, because endothelial nitric oxide synthase has been reported as a mediator of cerebral blood flow control, we hypothesized that the mechanism by which RIPC primes the vasculature against VVS is via the α1‐adrenoceptor–protein kinase Cε–endothelial nitric oxide synthase pathway.Methods and ResultsWe utilized sinusoidal galvanic vestibular stimulation in rats as a model of VVS. RIPC attenuated the lowerings of mean arterial pressure, heart rate, and cerebral blood flow caused by sinusoidal galvanic vestibular stimulation, as well as improving behavior during, and recovery after, stimulation. RIPC induced elevated serum norepinephrine, increased expression of brain α1‐adrenoceptors, and reduced brain expression of norepinephrine transporter 1. Antagonizing adrenoceptors and norepinephrine transporter 1 prevented RIPC protection of cerebral perfusion during sinusoidal galvanic vestibular stimulation.ConclusionsTaken together, this study indicates that RIPC may be a potential therapy that can prevent VVS pathophysiology, decrease syncopal episodes, and reduce the injuries associated with syncopal falls. Furthermore, the α1‐adrenoceptor–protein kinase Cε–endothelial nitric oxide synthase pathway may be a therapeutic target for regulating changes in cerebral blood flow.

Stat5-dependent cardioprotection in late remote ischaemia preconditioning.

To study the protective effects of late remote ischaemic preconditioning (RIPC) against myocardial ischaemia/reperfusion (I/R) injury and determine whether Stat5 is involved in this protection by using cardiomyocyte-specific Stat5 knockout mice (Stat5-cKO). Mice were exposed to lower limb RIPC or sham ischaemia. After 24 h, the left anterior descending artery (LAD) was ligated for 30 min, then reperfused for 180 min. The myocardial infarct size (IS), apoptotic rate of cardiomyocytes, and serum myocardial enzymes were measured to evaluate for cardioprotective effects. Heart tissues were harvested to determine the cardiomyocytes' anti-apoptotic and survival signaling. When compared with the Stat5fl/fl mice without RIPC, Stat5fl/fl mice with RIPC (Stat5fl/fl+RIPC + I/R) displayed a decreased myocardial IS/LV (16 ± 1.5 vs. 30.1 ± 3.1%, P < 0.01; IS/ area at risk (AAR), 42.2 ± 3.5 vs. 69.2 ± 4.9%, P < 0.01), a reduced cardiomyocyte apoptotic rate (2.1 ± 0.37 vs. 5.5 ± 0.53%, P < 0.01), and lower creatine kinase (CK), lactate dehydrogenase (LDH), and creatine kinase-MB (CK-MB) levels. To the contrary, the Stat5-cKO mice (Stat5fl/fl; Tnnt2Cremice with Doxycycline treatment for 7 days) did not exhibit any effect of RIPC-induced cardioprotection. Activation of STAT5 protein was significantly higher in the Stat5fl/fl+RIPC + I/R group than in the Stat5fl/fl+I/R group, while there was no significant difference between the Stat5-cKO + RIPC + I/R and the Stat5-cKO + I/R group. Further analyses with heart tissues detected decreased protein expressions of cytochrome c (Cyt c) and cleaved Caspase-3 in the Stat5fl/fl+RIPC + I/R mice, along with increased anti-apoptotic molecules, including B-cell lymphoma-extra large (Bcl-xL) and B-cell lymphoma-2 (Bcl-2); such changes were not noted in the Stat5-cKO + RIPC + I/R mice. Additionally, RIPC increased cardiac hypoxia inducible factor-1 (HIF-1α) and interleukin-10 (IL10) protein levels and caused activation of AKT, phosphatidylinositol 3 kinase (PI3K), and vascular endothelial growth factor in the heart of the Stat5fl/fl mice. However, these changes were completely inhibited by the absence of Stat5. These results suggest that RIPC-induced late cardioprotection against myocardial I/R injury is Stat5-dependent and is correlated with the activation of anti-apoptotic signaling and cardiomyocyte-survival signaling.

Remote ischemic preconditioning attenuates cardiopulmonary bypass-induced lung injury.

The use of cardiopulmonary bypass (CPB) in cardiac surgeries is known to induce pathological changes in vital organs such as lungs. Remote ischemic preconditioning (RIPC) is a protective strategy that has shown to be able to reduce tissue damage related to ischemia-reperfusion injury (IRI). The current study seeks to evaluate the beneficial effects of limb RIPC on lung tissues and function in a rat CPB model. RIPC, which consisted of three cycles of 5-min ischemia and subsequently 5-min reperfusion, was induced in the hind limbs of the animals via a tourniquet. Bronchoalveolar lavage (BAL) fluid analysis and hematoxylin and eosin staining revealed that limb RIPC could significantly attenuate CPB-induced pulmonary injury, as evidenced by a combination of lower total BAL protein content, less severe alveolar wall thickening and reduced intra-alveolar neutrophil infiltration. Consistently, RIPC was also found to improve the proliferation capacity of the bronchioalveolar stem cells isolated from the lung tissues in rats subjected to surgical procedure with CPB. These beneficial effects translated into significantly improved lung function. Further investigation suggested that RIPC could up-regulate the serum levels of several anti-inflammatory cytokines such as interleukin (IL)-4 and 10, which might play a role in its pulmonoprotective effects. Taken together, the current study provided convincing evidence that limb RIPC could be a useful strategy for minimizing CPB-induced organ injuries in patients undergoing CPB surgery.

Remote Ischemic Preconditioning Decreases Oxidative Lung Damage After Pulmonary Lobectomy: A Single-Center Randomized, Double-Blind, Controlled Trial.

During lobectomy in patients with lung cancer, the operated lung is often collapsed and hypoperfused. Ischemia/reperfusion injury may then occur when the lung is re-expanded. We hypothesized that remote ischemic preconditioning (RIPC) would decrease oxidative lung damage and improve gas exchange in the postoperative period. We conducted a single-center, randomized, double-blind trial in patients with nonsmall cell lung cancer undergoing elective lung lobectomy. Fifty-three patients were randomized to receive limb RIPC immediately after anesthesia induction (3 cycles: 5 minutes ischemia/5 minutes reperfusion induced by an ischemia cuff applied on the thigh) and/or control therapy without RIPC. Oxidative stress markers were measured in exhaled breath condensate (EBC) and arterial blood immediately after anesthesia induction and before RIPC and surgery (T0, baseline); during operated lung collapse, immediately before resuming two-lung ventilation (TLV) (T1); immediately after resuming TLV (T2); and 120 minutes after resuming TLV (T3). The primary outcome was 8-isoprostane levels in EBC at T1, T2, and T3. Secondary outcomes included the following: NO2+NO3, H2O2 levels, and pH in EBC and in blood (8-isoprostane, NO2+NO3) and pulmonary gas exchange variables (PaO2/FiO2, A-aDO2, a/A ratio, and respiratory index). Patients subjected to RIPC had lower EBC 8-isoprostane levels when compared with controls at T1, T2, and T3 (differences between means and 95% confidence intervals): -15.3 (5.8-24.8), P = .002; -20.0 (5.5-34.5), P = .008; and -10.4 (2.5-18.3), P = .011, respectively. In the RIPC group, EBC NO2+NO3 and H2O2 levels were also lower than in controls at T2 and T1-T3, respectively (all P < .05). Blood levels of 8-isoprostane and NO2+NO3 were lower in the RIPC group at T2 (P < .05). The RIPC group had better PaO2/FiO2 compared with controls at 2 hours, 8 hours, and 24 hours after lobectomy in 95% confidence intervals for differences between means: 78 (10-146), 66 (14-118), and 58 (12-104), respectively. Limb RIPC decreased EBC 8-isoprostane levels and other oxidative lung injury markers during lung lobectomy. RIPC also improved postoperative gas exchange as measured by PaO2/FiO2 ratio.

Effects of differential-phase remote ischemic preconditioning intervention in laparoscopic partial nephrectomy: A single blinded, randomized controlled trial in a parallel group design

Study ObjectiveThere are two windows of protection for remote ischemic preconditioning (RIPC), an early (ERIPC) and a late-phase (LRIPC). While ERIPC has been well studied, works on LRIPC are relatively scarce, especially for the kidneys. We aimed to compare the effects of early-phase versus late-phase RIPC in patients with laparoscopic partial nephrectomy (LPN). DesignA randomized controlled study SettingThe Second Affiliated Hospital of Anhui Medical University, 1 May 2012 to 30 October 2013 PatientsSixty-five ASA 1 to 2 patients scheduled for LPN were located randomly to ERIPC group, LRIPC group and CON group (control). InterventionsThree five-minute cycles of right upper limb ischaemia and reperfusion were performed after induction of anesthesia in ERIPC group. Patients in LRIPC group received similar treatment 24h before surgery, while control patients were not subjected to preconditioning. MeasurementsSerum neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C (CysC) were evaluated before the induction of anesthesia (0h), 2h (2h) and 6h (6h) after surgery. Unilateral glomerular filtration rates (GFR) were assessed before and after surgery to evaluate overall renal function. Main ResultsSerum NGAL and CysC were significantly lower in ERIPC and LRIPC groups at 2h post-operation (P<0.001), 6h post-operation (P<0.001). Additionally, The GFR were significantly lower in ERIPC and LRIPC groups than in CON group at the 3rd month after surgery (P=0.019; P<0.001). Moreover, compared to the ERIPC group, concentration of NGAL and CysC in LRIPC group decreased to a greater extent, while GFR and the percentage of decrement was significantly less in the LRIPC group (P=0.016; P<0.001). ConclusionsRegardless of early-phase or late-phase intervention, limb remote ischemic preconditioning confers protection on renal ischemia-reperfusion injury in patients with laparoscopic partial nephrectomy, and the late-phase protection is more prominent.

Remote Limb Ischemic Preconditioning Protects Rats Against Cerebral Ischemia via HIF-1α/AMPK/HSP70 Pathway.

Remote limb ischemic preconditioning (RIPC) is a clinically feasible strategy to protect against ischemia/reperfusion injury, but the knowledge concerning the mechanism underlying RIPC is scarce. This study was performed to examine the effect of RIPC on brain tissue suffering from ischemia challenge and explore its underlying mechanism in a rat model. The animals were divided into four groups: Sham, middle cerebral artery occlusion (MCAO), RIPC, and MCAO+RIPC. We found that previous exposure to RIPC significantly attenuated neurological dysfunction and lessened brain edema in MCAO+RIPC group. Moreover, other important events were observed in MCAO+RIPC group, including substantial decrements in the concentrations of oxidative response indicators [malondialdehyde (MDA), 8-hydroxy-2-deoxyguanosine (8-OHdG), and protein carbonyl], significant reductions in levels of inflammation mediators [myeloperoxidase (MPO), tumor necrosis factor-a (TNF-a), interleukin-1β (IL-1β), and IL-6], and significant decline in neuronal apoptosis revealed by a smaller number of TUNEL-positive cells. Interestingly, both MCAO and RIPC groups exhibited meaningful elevations in the levels of HIF-1a, HSP70, and AMP-activated protein kinase (AMPK) compared to Sham group, and previous exposure to RIPC further elevated the levels of HIF-1a, HSP70, and AMPK in MCAO+RIPC group. Furthermore, the administration of YC-1 (HIF-1 inhibitor), 8-bAMP (AMPK inhibitor), and Quercetin (HSP70 inhibitor) to MCAO+RIPC rats demonstrated that HIF-1α/AMPK/HSP70 was involved in RIPC-mediated protection against cerebral ischemia.

Delayed Effects of Remote Limb Ischemic Preconditioning on Maximum Oxygen Consumption, Lactate Release and Pulmonary Function Tests in Athletes and non-Athletes

Delayed Effects of Remote Limb Ischemic Preconditioning on Maximum Oxygen Consumption, Lactate Release and Pulmonary Function Tests in Athletes and non-Athletes

Limb remote ischemic preconditioning attenuates liver ischemia reperfusion injury by activating autophagy via modulating PPAR-γ pathway

To investigate the effect of limb remote ischemic preconditioning (RIPC) on hepatic ischemia/reperfusion (IR) injury and the underlying mechanisms. Rats were subjected to partial hepatic IR (60 min ischemia followed by 24 hours reperfusion) with or without RIPC, which was achieved by 3 cycles of 10 min-occlusion and 10 min- reperfusion at the bilateral femoral arteries interval 30 min before ischemia. Some rats were treated with a new PPAR-γ inhibitor, T0070907, before RIPC. At the end of reperfusion, liver injury was significantly increased (increases in Suzike's injury score, AST and ALT release), concomitant with elevated oxidative stress (increases in MDA formation, MPO activity, as well as the decrease in SOD activity) and inflammation (increases in TNF-α and IL-6 levels, decrease in IL-10 content). RIPC improved liver function and reduced histologic damage, accompanied by the increased PPAR-γ activation and autophagosome formation as well as the reduced autophagosome clearance. The beneficial effects of RIPC were markedly attenuated by T0070907, an inhibitor of PPAR-γ. RIPC exerts the protective effects on liver by activation of autophagy via PPAR-γ.

Possible Underlying Mechanisms of the Renoprotective Effect of Remote Limb Ischemic Preconditioning Against Renal Ischemia/Reperfusion Injury: A Role of Osteopontin, Transforming Growth Factor-Beta and Survivin

Background: It has been documented that remote limb ischemic preconditioning (rIPC) protect kidneys against renal ischemia/reperfusion (I/R). We hypothesized that osteopontin (OPN), transforming growth factor beta (TGF-β), apoptotic proteins (survivin and caspase-3) and oxidative stress play role in the renoprotective effects of rIPC. Materials and Methods: Fifty-four male Sprague-Dawley rats were randomized into 3 equal groups: sham group, I/R group (left renal 45 min ischemia) and rIPC group (as I/R group with 3 cycles of left hind limb ischemia just before renal ischemia). Each group was subdivided into 24, 48 and 72 h groups according to the time of sacrifice. We measured serum creatinine and blood urea nitrogen (BUN) at the baseline and end points. Also, left kidney was harvested at study end points for assessment of the expression of OPN, TGF-β, apoptotic proteins (survivin and caspase-3) and oxidative stress markers (malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD)) in kidney tissues and histopathological examination. Results: Serum creatinine and BUN levels and histopathological damage score were significantly lower in rIPC group than I/R group (p < 0.005). Also, compared to I/R group, the levels of MDA and the expression of OPN, TGF-β and caspase-3 in kidney tissues were significantly lower in rIPC group, while the levels of SOD and GSH and the expression of survivin in kidney tissues were significantly higher in rIPC group at all time points (p ≤ 0.05). Conclusions: rIPC exhibited protective effects against renal I/R injury which might be due to inhibition of OPN expression, inflammatory cytokine TGF-β and caspase-3 and activation of anti-apoptotic protein survivin as well as improvement of oxidative stress in kidney tissues.

The Interventional Effect of Remote Ischemic Preconditioning on Cerebral Small Vessel Disease: A Pilot Randomized Clinical Trial

Background: Remote ischemic preconditioning (RIPC) of the limb has been shown to induce ischemic tolerance in basic and clinical studies that focused on sustained large artery occlusion rather than small vessel disease (SVD). This study aimed to evaluate the protective effects of brief repetitive limb RIPC on patients with cerebral SVD. Methods: Seventeen patients with cerebral SVD were enrolled. Patients underwent 5 ischemia-reperfusion cycles of preconditioning/sham preconditioning on both upper limbs twice a day for 1 year. Cerebral hemodynamic indexes, brain lesions, cognitive functions and assessment outcomes of dizziness handicap inventory (DHI) were analyzed. Results: In the RIPC group, the mean flow velocity (MFV) of the left middle cerebral artery (MCA) was accelerated (57.33 (52.33-61.34) vs. 51.33 (48.83-58.33), respectively; p = 0.038), and the post-treatment DHI score was reduced (18 (13-19) vs. 34 (21-45), respectively; p = 0.043). The post-treatment volume of the white matter lesions (WMLs) was also reduced (4.19 (2.96-7.25) vs. 6.06 (4.67-10.95), respectively; p = 0.050). There was no remarkable difference between the 2 groups either before or after treatment. Conclusion: The present study indicates that RIPC has potential beneficial effects on cerebral SVD by increasing the MFV of MCA, decreasing the DHI score as well as the volume of WMLs in patients with SVD.

Lung protection of remote limb ischemic preconditioning during one-lung ventilation in patients undergoing esophageal cancer resection

Objective To evaluate the lung protection of remote limb ischemic preconditioning during one-lung ventilation (OLV) in the patients undergoing esophageal cancer resection. Methods Seventy-one patients of both sexes, aged 30-64 yr, with body mass index of 15-28 kg/m2, of American Society of Anesthesiologists physical statusⅠor Ⅱ, scheduled for elective esophageal cancer resection, were randomly divided into control group (group C, n=34) and remote limb ischemic preconditioning group (group RLIP, n=37) using a random number table.Patients in group RLIP received three cycles of 5-min ischemia/5-min reperfusion induced by a blood pressure cuff placed on one upper arm before OLV.Before OLV (T0), at 1 and 2 h of OLV (T1, 2), at 20 min after re-expansion of the collapsed lung (T3), and at 2 h after operation (T4), blood samples were drawn from the radial artery for blood gas analysis, oxygenation index (PaO2/FiO2)and alveolar-arterial oxygen gradient (A-aDO2) were calculated.At T0, T2, T3 and T4, blood samples were collected from the radial artery for determination of plasma tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and IL-10 concentrations. Results Compared with group C, PaO2/FiO2 was significantly increased, and A-aDO2 was decreased at T1, 2, the plasma TNF-α concentrations were decreased at T2-4 (P 0.05). Conclusion Although remote limb ischemic preconditioning can produce lung protection during OLV in the patients undergoing esophageal cancer resection, it provides no clinical significance. Key words: Ischemic preconditioning; Extremities; Respiration, artificial; Respiratory distress syndrome, adult

Effects of Different Limb Remote Ischaemic Preconditioning on Ischaemia Reperfusion Injury in an Acute Left Anterior Descending Artery Occlusion Rat Model

The aim is to compare effects of three different protocols of limb remote ischaemic preconditioning (LRIP) on ischaemia reperfusion injury in an acute left anterior descending artery (LAD) occlusion model rat. Forty adult male Wistar rats were randomly assigned into four groups: group A, control; group B, LRIP in bilateral upper-limb (BUL) IP; group C, LRIP in bilateral lower-limb (BLL) IP; group D, LRIP in bilateral upper and lower limbs (ULL) IP. The 60min ligation and 180min reperfusion in LAD were applied to all rats. Limb remote ischaemic preconditioning was performed using 5min occlusion and 15min reperfusion (six cycles). Heart rate, blood pressure and electrogastrography (EGG) were recorded. Creatine kinase isoenzyme (CK-MB) level and infarct size were measured. Limb remote ischaemic preconditioning did not significantly affect heart rate, systolic blood pressure and arrhythmia score. However, LRIP significantly increased DBP value and decreased CK-MB levels and infarct size in group B, C, and D. Moreover, LRIP in ULL had a significantly better effect on reducing infarct size than LRIP in BUL and BLL. Limb remote ischaemic preconditioning at limbs could significantly reduce reperfusion injury in the heart. Moreover, LRIP in ULL indicated a better effect in reducing infarct size than LRIP in BUL and BLL.

Abstract TP270: Ischemic Preconditioning-afforded Neuroprotection Against Ischemic Stroke is Associated With Altered Peripheral Immune Responses

The limb remote ischemic preconditioning (RIPC) is considered a clinical feasible protective strategy against ischemia-reperfusion injury after stroke. However, its mechanisms of protection remain elusive. Here, we used a rat model of non-invasive RIPC by tourniquet to study the impact of RIPC on the immune cell and cytokine profiles after transient middle cerebral artery occlusion. Our data indicates that RIPC protects against focal ischemia and preserves neurological functions 3 days after stroke. Meanwhile, RIPC results in dramatic changes in several immune cell populations after stroke. Specifically, the RIPC ameliorated the post-MCAO reduction of blood CD3+CD8+ T cells and abolished the reduction of CD3+/CD161a+ NKT cells. Another striking change is that RIPC significantly elevated the B cell percentage in peripheral blood, which reversed the otherwise reduced B cell population after stroke. RIPC also markedly elevated the percentage of CD43+/CD172a+ non-inflammatory residential monocytes, while showing no effect on the percentage CD43-/CD172a+ inflammatory monocytes. In addition, we found that RIPC induced IL-6 expression and enhanced the elevation of TNFα after stroke. Collectively, our results reveal potential immune mechanisms of RIPC-afforded neuroprotection against cerebral ischemia. Further exploration about these immune elements in RIPC-afforded ischemic tolerance may lead to the development of systemically administered immune therapies for stroke patients.

Remote limb ischemic preconditioning (rIPC) activates antioxidant and antiapoptotic genes and inhibits proinflammatory cytokine genes in renal ischemia/reperfusion injury.

The mechanisms underlying the renoprotective effect for remote limb ischemic preconditioning (rIPC) against renal ischemia/reperfusion injury need further elucidation. In our work, one hundred and twenty male Sprague Dawley rats were randomized into 3 groups; sham, I/R group (left renal 45 min ischemia) and rIPC (as I/R group with 3 cycles of left femoral ischemic PC just before renal ischemia). Rats were sacrificed at 2 h, 24 h, 48 h and 7 days. Serum creatinine and urea were measured at the baseline and endpoints. Also, histopathological examination and assessment of the expression of inflammatory cytokines e.g. TNF-α, IL-1β and ICAM-1 and antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 in left kidney were done by the end of experiment. The results of this study demonstrated that, rIPC caused significant improvement in serum creatinine and BUN levels and in the expression of antioxidant genes and Bcl-2 antiapoptotic gene with significant attenuation of pro-inflammatory cytokines and histopathological damage score at all-time points compared to I/R group (p ≤ 0.05). In conclusion, inhibition of inflammatory cytokine (TNF-α, IL-1β and ICAM-1) formation and activation of antioxidant genes: Nrf2, HO-1 and NQO-1 and anti-apoptotic gene Bcl-2 could be possible underlying mechanisms for the renoprotective effect of rIPC.

Safety and Feasibility of Remote Limb Ischemic Preconditioning in Patients With Unilateral Middle Cerebral Artery Stenosis and Healthy Volunteers.

Previous studies have indicated a neuroprotective effect of remote limb ischemic preconditioning. The aim of the present study was to assess whether upper arm ischemic preconditioning is feasible and safe in patients with unilateral middle cerebral artery (MCA) stenosis compared to healthy volunteers. Ten patients with unilateral MCA stenosis and 24 healthy volunteers underwent limb ischemic preconditioning, consisting of five cycles of 5-min inflations of a blood pressure cuff to 200 mmHg around an upper limb followed by 5 min of reperfusion. Limb ischemic preconditioning has no significant effect on the heart rate, oxygenation index, or mean flow velocity in patients with unilateral MCA stenosis or healthy volunteers. However, healthy volunteers showed a reduction in blood pressure 30 min following reperfusion of the last cycle. Limb ischemic preconditioning was found to be safe and well tolerated in both patients and healthy volunteers. We highlight the potential of limb ischemic preconditioning as an adjunct to neuroprotective treatment.

Using the Electroretinogram to Assess Function in the Rodent Retina and the Protective Effects of Remote Limb Ischemic Preconditioning.

The ERG is the sum of all retinal activity. The ERG is usually recorded from the cornea, which acts as an antenna that collects and sums signals from the retina. The ERG is a sensitive measure of changes in retinal function that are pan-retinal, but is less effective for detecting damage confined to a small area of retina. In the present work we describe how to record the 'flash' ERG, which is the potential generated when the retina is exposed to a brief light flash. We describe methods of anaesthesia, mydriasis and corneal management during recording; how to keep the retina dark adapted; electrode materials and placement; the range and calibration of stimulus energy; recording parameters and the extraction of data. We also describe a method of inducing ischemia in one limb, and how to use the ERG to assess the effects of this remote-from-the-retina ischemia on retinal function after light damage. A two-flash protocol is described which allows isolation of the cone-driven component of the dark-adapted ERG, and thereby the separation of the rod and cone components. Because it can be recorded with techniques that are minimally invasive, the ERG has been widely used in studies of the physiology, pharmacology and toxicology of the retina. We describe one example of this usefulness, in which the ERG is used to assess the function of the light-damaged retina, with and without a neuroprotective intervention; preconditioning by remote ischemia.

Using the Electroretinogram to Assess Function in the Rodent Retina and the Protective Effects of Remote Limb Ischemic Preconditioning

Using the Electroretinogram to Assess Function in the Rodent Retina and the Protective Effects of Remote Limb Ischemic Preconditioning