Remote Ischemic Postconditioning Group Research Articles

Effects of remote ischemic postconditioning on hepatic injury in lipopolysaccharide-induced endotoxemic rats.

Remote ischemic postconditioning (RIPoC) is that several cycles of brief, reversible, mechanical blood flow occlusion and reperfusion of distal organ make protection to target organ. We investigate whether RIPoC ameliorates liver injury in lipopolysaccharide (LPS)-induced sepsis model. Protocol 1) Rats were administered LPS solution and samples were collected at 0, 2, 6, 12, and 18 h after that. Protocol 2) After RIPoC at 2, 6, and 12 h (L+2R+18H, L+6R+18H, L+12R+18H), samples were analyzed at 18 h. Protocol 3) RIPoC performed at 2 h, analysis samples at 6, 12, 18 h (L+2R+6H, L+2R+12H, L+2R+18H), and RIPoC at 6 h, analysis at 12 h (L+6R+12H). Protocol 4) Rats were divided control group, which were injected with only ketamine and RIPoC group, which RIPoC was performed at 2, 6, 10, and 14 h, samples were analyzed at 18 h. In protocol 1, liver enzymes, MDA, TNF-α and NF-kB increased, and SOD decreased over time. In protocol 2, liver enzyme and MDA level were lower and SOD level was higher in L+12R+18H and L+6R+18H groups, compared with L+2R+18H group. In protocol 3, liver enzyme and MDA level were lower and SOD level was higher in L+2R+6H and L+6R+12H groups, compared with L+2R+12H and L+2R+18H groups. In protocol 4, liver enzyme, MDA, TNF-α, and NF-kB levels were lower and SOD level was higher in RIPoC group, compared with control group. RIPoC attenuated liver injury in LPS-induced sepsis model by modifying inflammatory responses and oxidative stress response for a limited period.

Participation of Leptin and Corticosterone in the Decrease in Infarct-Limiting Efficiency of Remote Postconditioning and in the Development of Arterial Hypertension in Metabolic Syndrome in Rats

We studied the effect of induced metabolic syndrome (MetS) on the effectiveness of the infarct-limiting effect of remote ischemic postconditioning (RP) in Wistar rats. The involvement of leptin and corticosterone in the formation of arterial hypertension (AH) and in reduction of the effectiveness of RP in MetS was also studied. MetS was induced by high-carbohydrate high-fat diet with replacement of drinking water with 20% fructose solution for 90 days. MetS simulation led to obesity, AH, impaired lipid and carbohydrate metabolism, hyperleptinemia, and moderate stress. All animals were subjected to 45-min coronary occlusion and 120-min reperfusion. In the RP groups, tourniquets were applied on the hind limbs in the area of the hip joint immediately after the end of ischemia (3 cycles consisting of 5-min ischemia and 5-min reperfusion). A direct correlation was found between the severity of AH in rats with MetS and the levels of corticosterone and leptin. In rats with MetS, the effectiveness of RP decreased: a direct correlation between the infarct size and serum content of leptin was revealed in rats with MetS+RP. Corticosterone seems to be one of the factors of AH development in rats with MetS.

Safety and efficacy of remote ischemic postconditioning after thrombolysis in patients with stroke.

To determine the effect of remote ischemic postconditioning (RIPC) on patients with acute ischemic stroke (AIS) undergoing IV thrombolysis (IVT). A single-center randomized controlled trial was performed with patients with AIS receiving IVT. Patients in the RIPC group were administered RIPC treatment (after IVT) during hospitalization. The primary endpoint was a score of 0 or 1 on the modified Rankin scale (mRS) at day 90. The safety, tolerability, and neuroprotection biomarkers associated with RIPC were also evaluated. We collected data from both the RIPC group (n = 34) and the control group (n = 34). The average duration of hospitalization was 11.2 days. There was no significant difference between 2 groups at admission for the NIH Stroke Scale score (p = 0.364) or occur-to-treatment time (p = 0.889). Favorable recovery (mRS score 0-1) at 3 months was obtained in 71.9% of patients in the RIPC group vs 50.0% in the control group (adjusted odds ratio 9.85, 95% confidence interval 1.54-63.16; p = 0.016). We further found significantly lower plasma S100-β (p = 0.007) and higher vascular endothelial growth factor (p = 0.003) levels in the RIPC group than in the control group. Repeated RIPC combined with IVT can significantly facilitate recovery of nerve function and improve clinical prognosis of patients with AIS. NCT03218293. This study provides Class IV evidence that RIPC after tissue plasminogen activator treatment of AIS significantly increases the proportion of patients with an MRS score of 0 or 1 at 90 days.

Rt-PA with remote ischemic postconditioning for acute ischemic stroke.

ObjectiveTo investigate the feasibility and safety of remote ischemic postconditioning (RIPC) in acute ischemic stroke patients after intravenous recombinant tissue plasminogen activator (rt‐PA) thrombolysis (IVT).MethodsWe performed a pilot randomized trial involving acute ischemic stroke patients with IVT. The patients were randomized 1:1 to receive RIPC or standard medical therapy. In the RIPC group, the participants underwent instant RIPC within 2 h of IVT, followed by repeated RIPC therapy for 7 days. The feasibility end point was the completion of RIPC and time from the first RIPC to finishing IVT in the RIPC group. The safety end point included tissue and neurovascular injury resulting from RIPC, changes in vital signs, level of plasma myoglobin, any hemorrhagic transformation, and other adverse events.ResultsThirty patients (15 RIPC and 15 Control) were recruited after IVT. The mean age was 65.7 ± 10.2 years, with a National Institutes of Health Stroke Scale (NIHSS) score of 6.5 (4.0–10.0). The completion rate for RIPC was 97.0%. The mean time from first RIPC to completing IVT was 66.0 (25.0–75.0) min in the RIPC group. One case of hemorrhagic transformation was observed in the RIPC group. No significant difference was found in the level of myoglobin between the two groups (P > 0.05).Interpretation RIPC is effective and safe for AIS patients after intravenous rt‐PA thrombolysis.

Remote Ischemic Postconditioning Protects against Myocardial Ischemia-Reperfusion Injury by Inhibition of the RAGE-HMGB1 Pathway.

Background The aim of the present study was to observe the effect of RAGE-HMGB1 signal pathway on remote ischemic postconditioning in mice with myocardial ischemia reperfusion injury. Methods Mice model of MIRI was established and randomly divided into three groups: control group, ischemia reperfusion group, and remote ischemic postconditioning group. Infarction size was detected by Evans blue and TTC staining. Cardiac function was detected by echocardiography measurement. The protein levels of RAGE, HMGB1, P-AKT, and ERK1/2 were detected by Western blot 120 min following reperfusion. Results RIPostC could decrease the infarct size and increase LVEF and FS compared with I/R group. Two hours after myocardial ischemia reperfusion, the levels of RAGE and HMGB1 were significantly decreased in RIPostC group compared with those in I/R group. The level of p-AKT was significantly higher in the RIPostC group than in the I/R group. LY294002 significantly attenuated RIPostC-increased levels of Akt phosphorylation. Conclusion RIPostC may inhibit the expression of RAGE and HMGB1 and activate PI3K/Akt signaling pathway to extenuate ischemic reperfusion injury in mice. It could further suppress the oxidative stress, have antiapoptosis effect, and reduce inflammatory reaction, but this effect has certain timeliness.

Cardioprotective and anti-inflammatory effects of combined α7 nicotinic acetylcholine receptor agonist and limb remote ischemic postconditioning in rats with myocardial ischemia/reperfusion injury

Objective To assess the cardioprotective and anti-inflammatory effects of combined α7 nicotinic acetylcholine receptor(α7nAChR) agonist and limb remote ischemic postconditioning in rats with myocardial ischemia/reperfusion injury(I/RI). Methods Sixty male SD rats were randomly divided equally into six groups(n=10): sham group(S group), control group(C group), ischemia preconditioning group(IPC group), special α7nAChR agonist PNU282987 postconditioning group(P group), lime remote ischemic postconditioning group(L group), combined PNU282987 and lime remote ischemic postconditioning group(P+L group). Throughout the experiment, HR, MAP, and a lead Ⅱ electrocardiogram were continuously monitored. Blood samples were taken at 120 min of reperfusion for measuring serum concentrations of troponin I(TnI), myocardial-bound creatine kinase(CK-MB), TNF-α, high mobility group box 1 protein(HMGB-1), IL-6 and IL-10 by the kits specifically for rats. At the end of experiment, the infarct size(IS) was assessed using excised hearts by Evans blue and triphenyltetrazolium chloride staining. Results Compared with C group, the IS,serum cTnI and CK-MB concentrations were significantly decreased in IPC, P, L and P+L groups. Compared to IPC group, the IS and serum cTnI concentration were significantly higher in P, L and P+L groups. Compared to P and L groups, the IS, serum cTnI and CK-MB concentrations were significantly decreased in P+L group. At 120 min of reperfusion, serum TNF-α concentration was significantly increased in C, IPC and L groups. Also, serum IL-6 and HMGB1 concentrations were significantly increased in C, IPC, P and L groups compared with S group. Compared to C group, serum TNF-α, IL-6 and HMGB1 concentrations were significantly decreased in IPC, P, L and P+L group. Compared to IPC and L groups, serum TNF-α, IL-6 and HMGB1 concentrations were significantly decreased in P and P+L groups. Conclusions Combined α7nAChR agonist and limb remote ischemic postconditioning can provide an improved cardioprotection, but not an enhanced anti-inflammatory effect. Key words: Myocardial; Ischemia/reperfusion injury; Inflammation; Cholinergic anti-inflammatory pathway; Limb remote ischemic postconditioning

Effect of remote ischemic postconditioning during thrombolysis in STEMI.

Remote ischemic postconditioning (RIPC) is suggested to protect the myocardium against ischemia in various settings. However, the effect of RIPC in patients with acute ST-elevation myocardial infarction (STEMI) who undergo thrombolysis has yet to be examined. In this single-center, randomized controlled trial, we examined the effect of RIPC on the resolution of ST-segment elevation (STR) in response to thrombolysis. Patients in the RIPC group had threecycles of 5‑min cuff inflation followed by 5‑min deflation to the upper arm. The study comprised 78 patients (15women), of whom 41 were randomized to the RIPC group and 37to the control group. STR occurred in 61% of the patients in the RIPC group, while it was detected only in 35% of controls (p= 0.026). Although STR was more common in the RIPC group, there was no difference in the extent of ΣCK-48 h between the two groups. Furthermore, the length of hospital stay and the frequency of adverse events were similar between the RIPC and control groups. RIPC during thrombolytic therapy in STEMI was associated with ahigher frequency of STR. However, it did not affect enzymatic infarct size or the frequency of adverse events. (Clinical trial registration number: IRCT2014011916229N2.).

Combined morphine and limb remote ischemic postconditioning provides an enhanced protection against myocardial ischemia/reperfusion injury

Objective To determine whether combined morphine and limb remote ischemic postconditioning could provide an enhanced protection against myocardial ischemia/reperfusion injury. Methods Using rat in vivo myocardio ischemia/reperfusion injury(I/RI) model, sixty male SD rats were allocated into six groups(n=10) by random number method: control group (group sham), ischema/reperfusion(I/R) group(group I/R), ischemic preconditioning group(group IPC), remote ischemic postconditioning group(group RIP), morphine postconditioning group(group M), and combined morphine and remote ischemic postconditioning groups (group M+ RIP). Arrhythmias were monitored continuously during the experiment and scored in early I/R period. Serum creatine kinase MB(CK-MB) and cardiac troponin I(cTnI) levels were assayed. The infarction area was determined by Evans blue and triphenyltetrazolium chloride(TTC) staining method. Results The infarction area was (56.0±9.1)%, (23.9±5.5)%, (40.4±11.1)%, (47.7±9.3)% and (27.2±6.7)% in the I/R, IPC, RIP, M and M+RIP groups, respectively. The infarction area, serum CK-MB, cTnI level, incidence and score of arrhythmias during early reperfusion period were significantly reduced in group M+RIP compared to group I/R(P 0.05). Conclusions This experiment demonstrates that combined morphine and limb remote ischemic postconditioning provides an enhanced protection against myocardial I/RI which is comparable to ischemic preconditioning. Key words: Ischemia/reperfusion injury; Ischemic postconditioning; Limb remote ischemic; Morphine; Myocardial protection

Remote Ischemic Postconditioning Ameliorates the Mesenchymal Stem Cells Engraftment in Reperfused Myocardium.

ObjectivesRemote Ischemic postconditioning (RIPoC) is a cardioprotective strategy for alleviating the reperfusion injury. We hypothesized that RIPoC or ischemic postconditioning (IPoC) could protect the engrafted mesenchymal stem cells (MSCs) in reperfusion myocardium.MethodsFemale Sprague-Dawley rats were subject to 30 minutes of occlusion of left anterior descending (LAD). Ischemia reperfusion (IR) received reperfusion without interruption after ischemia. RIPoC received 3 cycles of 30 seconds reperfusion and re-occlusion on the limb at the onset of reperfusion. IPoC received 3 cycles of 30 seconds reperfusion and re-occlusion on the LAD at the same time. Male MSCs were intramyocardially administered after ischemia.ResultsCompared with that in IR group, ischemic myocardium in RIPoC+IPoC group, RIPoC group and IPoC group were found to have higher anti-oxidative stress and mitochondrial function level, lower lipid peroxidation and inflammational injury level, higher level of stromal cell derived factor-1 alpha and vascular endothelium growth factor gene expression at 3 days later. By immunohistochemical examination and quantitative polymerase chain reaction, more engrafted MSCs, better cardiac function and less cardiac fibrosis in RIPoC+IPoC group, RIPoC group and IPoC group were detected at 3 weeks after delivery. There were no significant differences between RIPoC and RIPoC+IPoC group.ConclusionsCombination therapy using intramyocardial MSCs transplantation with RIPoC enhanced transplantation efficiency and cardiac function, and reduced cardiac fibrosis. These beneficial effects were mainly attributed to hospitable milieu for engrafted cells. IPoC could not render additional effect on MSCs engraftment elicited by RIPoC.

Effect of remote ischemic post-conditioning on oxidative stress in blood of STEMI patients treated with primary angioplasty.

Introduction: This study designed to use remote ischemic post conditioning (RIPC) as a protective strategy during percutaneous coronary intervention (PCI) in patients with ST segment elevation myocardial infarction (STEMI) to reduce myocardial cells damage due to reperfusion injury. Methods: Sixty-one patients were divided into test group (32 patients) receiving RIPC and control group (29 patients). Patients were included with first MI who had 20-80 years old. The RIPC protocol was applied on patients arm in three successive episodes during the opening of infarct-related artery (IRA). Whole blood sample were taken from patients after the first episode before IRA opening and after the third episode after IRA opening. The serums were extracted and stored in the freezer -70˚C to determine the levels of glutathione peroxidase (GPX), superoxide dismutase (SOD), total antioxidant capacity (TAC) and malondialdehyde (MDA). Results: The levels of GPX and SOD after the first episode of RIPC were significantly higher in test group than control group (P < 0.001). Similar alterations of these enzymes were obtained after IRA opening (after third episode). In addition, the levels of TAC remained unchanged in control patients but it was significantly increased after the third episode of RIPC in test patients (P < 0.001). Finally, the MDA level was increased in control group in comparison with test group, and administration of RIPC in test group prevented the enhancement of MDA levels significantly (P < 0.001). Conclusion: The results indicated that RIPC protocol has protective properties in patients with STEMI through enhancing the antioxidant potentials and decreasing lipid peroxidation.

The effect of remote ischemic postconditioning on graft function in patients undergoing living donor kidney transplantation.

We evaluated whether remote ischemic postconditioning (RiPoC) could improve initial graft function in living donor kidney transplantation (KT). Patients undergoing living donor KT were randomly assigned to either RiPoC (n=30) or control group (n=30). Immediately after reperfusion in the RiPoC group, three cycles of ischemia and reperfusion, lasting 5 min each, were performed on one upper limb. Renal function was assessed before surgery, 2 hr after surgery, and at 12-hr intervals for 96 hr postsurgery by measuring serum creatinine (sCr) and the estimated glomerular filtration rate (eGFR). Urine output and urine creatinine were assessed until postoperative day 7, and hospital stay and complication rates were compared. The time for sCr to reach 50% of its preoperative level was significantly shorter in the RiPoC group than in the control group [12 (12-24) hr for RiPoC vs. 24 (21-36) hr for the control, P=0.005]. The number of patients whose sCr was reduced by 50% within 24 hr was significantly greater in the RiPoC group than in the control group [n=26 (87%) in RiPoC vs. n=18 (60%) in control, P=0.020]. However, there were no differences in sCr and eGFR thereafter, the incidence of graft dysfunction or complication rates between groups. In this study, RiPoC appeared to hasten the recovery of graft function within 24 hr but did not affect the graft function thereafter. However, considering most recipients had immediate graft function, further studies with deceased donors or studies powered to detect a smaller difference are needed.

Remote Ischemic Post-Conditioning of the Lower Limb During Primary Percutaneous Coronary Intervention Safely Reduces Enzymatic Infarct Size in Anterior Myocardial Infarction: A Randomized Controlled Trial

This study sought to evaluate whether remote ischemic post-conditioning (RIPC) could reduce enzymatic infarct size in patients with anterior ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention (pPCI). Myocardial reperfusion injury may attenuate the benefit of pPCI. In animal models, RIPC mitigates myocardial reperfusion injury. One hundred patients with anterior ST-segment elevation myocardial infarction and occluded left anterior descending artery were randomized to pPCI + RIPC (n = 50) or conventional pPCI (n = 50). RIPC consisted of 3 cycles of 5 min/5 min ischemia/reperfusion by cuff inflation/deflation of the lower limb. The primary endpoint was infarct size assessed by the area under the curve of creatinine kinase-myocardial band release (CK-MB). Secondary endpoints included the following: infarct size assessed by cardiac magnetic resonance delayed enhancement volume; T2-weighted edema volume; ST-segment resolution >50%; TIMI (Thrombolysis In Myocardial Infarction) frame count; and myocardial blush grading. Four patients (2 RIPC, 2 controls) were excluded due to missing samples of CK-MB. A total of 96 patients were analyzed; median area under the curve CK-MB was 8,814 (interquartile range [IQR]: 5,567 to 11,325) arbitrary units in the RIPC group and 10,065 (IQR: 7,465 to 14,004) arbitrary units in control subjects (relative reduction: 20%, 95% confidence interval: 0.2% to 28.7%; p = 0.043). Seventy-seven patients underwent a cardiac magnetic resonance scan 3 to 5 days after randomization, and 66 patients repeated a second scan after 4 months. T2-weighted edema volume was 37 ± 16 cc in RIPC patients and 47 ± 22 cc in control subjects (p = 0.049). ST-segment resolution >50% was 66% in RIPC and 37% in control subjects (p = 0.015). We observed no significant differences in TIMI frame count, myocardial blush grading, and delayed enhancement volume. In patients with anterior ST-segment elevation myocardial infarction, RIPC at the time of pPCI reduced enzymatic infarct size and was also associated with an improvement of T2-weighted edema volume and ST-segment resolution >50%. (Remote Postconditioning in Patients With Acute Myocardial Infarction Treated by Primary Percutaneous Coronary Intervention [PCI] [RemPostCon]; NCT00865722).

Comparison of the effects of ischemic preconditioning and limb remote ischemic postconditioning on inflammatory response during myocardial ischemia/reperfusion injury in rats in vivo

Objective To compare the effects of ischemic preconditioning with limb remote ischemic postconditioning on inflammatory response during myocardial ischemia/reperfusion injury (I/RI) in rat in vivo.Methods Eighty male Sprague-Dawley rats weighing 250 g-350 g were randomly allocated into four groups (n=20 in each group):sham group (S group); ischemia reperfusion group (I/R group); ischemic preconditioning group (IPC group) and limb remote ischemic postconditioning group (LRIPOC group).In the groups other than the sham group,the myocardial ischemia reperfusion model was preparated by ligation of left anterior descending coronary artery for 30 min followed by 120 min reperfusion.During the process of ischemia and reperfusion,HR and MAP were recorded and the rate pressure product (RPP) at every measuring point was calculated as the index of myocardial oxygen consumption.In ten rats randomly selected from each group,the blood samples were collected from jugular vein at 30,60 min and 120 min after reperfusion.Then,serum concentrations of cardiac troponin I (cTnI),creatine kinase-MB (CK-MB),tumor necrosis factor αt (TNF-α),high mobility group box-1 protein (HMGB-1),intercellular adhesion molecule 1 (ICAM-1),interleukin1 (IL-1),IL-6 and IL-10 were all assessed.At the end of experiment,the infarct volumes were assessed by evans blue and triphenyltetrazolium chloride (TTC) staining.In another ten rats randomly selected from each group,the myocardial contents of TNF-α,HMGB-1,ICAM-1,IL-1,IL-6 and IL-10 in ischemic and non-ischemic regions were all measured after the rats were euthanized.Results The infarct volume was (72±9)％ in I/R group,(36±13)％ in IPC group,and (57±9)％ in LRIPOC group,respectively.And the serum concentration of cTnI was (0.99 ± 0.14) μg/L in I/R group,(0.37 ±0.08) μg/L in IPC group,and (0.54±0.07) μg/L in LRIPOC group,separately.In addition,the serum concentration of CK-MB was (110±13) μg/L in I/R group,(38±8) μ g/L in IPC group,and (45±6) μg/L in LRIPOC group,respectively.Compared to the I/R group,the infarct volume,serum concentrations of cTnI and CK-MB in both IPC and LRIPOC groups,the serum concentrations of TNF-α at 30,60 min and 120 min after reperfusion,serum concentrations of HMGB-1 at 60 min and 120 min,serum concentrations of ICAM-1,IL-1 and IL-6,myocardial concentrations of TNF-α,HMGB-1,ICAM-1,IL-1 and IL-6 in ischemic region,myocardial concentrations of TNF-α,ICAM-1,IL-1 and IL-6 in non-ischemic region in the IPC group,the serum concentrations of TNF-α at 30,60 min and 120 min after reperfusion,serum concentrations of HMGB-1,ICAM-1,IL-1 and IL-6 at 120 min after reperfusion,myocardial concentrations of TNF-α,HMGB-1,ICAM-1,IL-1 and IL-6 in both ischemic and non-ischemic regions in the LRIPOC group all significantly decreased(P＜0.05).As compared to the IPC group,the infarct volume,serum concentrations of cTnI and CK-MB,serum concentration of TNF-α at 60 min after reperfusion,serum concentrations of HMGB-1 and ICAM-1 at 120 min after reperfusion,myocardial concentrations of TNF-α,ICAM-1,IL-1 and IL-6 in ischemic region,myocardial concentrations of ICAM-1,IL-1 and IL-6 in non-ischemic region significantly increased in the LRIPOC group (P＜0.05).Conclusions The inflammation inhibiting effect of IPC is stronger than that of LRIPOC during myocardial I/RI,which may be one of reasons why the IPC can provide a more powerful protection against myocardial I/RI than the LRIPOC. Key words: Myocardial ischemia/reperfusion injury; Inflammatory response; Ischemic preconditioning; Limb remote ischemic postconditioning

Renoprotective Effect of Remote Ischemic Post-Conditioning by Intermittent Balloon Inflations in Patients Undergoing Percutaneous Coronary Intervention

The aim of the present study was to assess the efficacy of remote ischemic post-conditioning (RIPC) by repeated intermittent balloon inflations in preventing acute kidney injury (AKI) in patients with a non-ST-segment elevation myocardial infarction undergoing percutaneous coronary intervention (PCI). AKI complicating PCI is associated with increased morbidity and mortality. Remote ischemic preconditioning, using cycles of upper limb ischemia-reperfusion as a conditioning stimulus, has been recently shown to prevent AKI in patients undergoing elective coronary angiography. Eligible patients were randomized to receive RIPC by cycles of inflation and deflation of the stent balloon during PCI or a sham procedure (control patients). The primary endpoint was AKI, defined as an increase of ≥ 0.5 mg/dl or ≥ 25% in serum creatinine within 96 h from PCI. The 30-day rate of death or re-hospitalization for any cause was one of the secondary endpoints. A total of 225 patients were included (median age, 68 years; 36% female). The AKI rate in the RIPC group was 12.4% versus 29.5% in the control group (p = 0.002; odds ratio: 0.34; 95% confidence interval: 0.16 to 0.71). The number needed to treat to avoid 1 case of AKI was 6 (95% confidence interval: 3.6 to 15.2). The 30-day rate of death or re-hospitalization for any cause was 22.3% in the control group versus 12.4% in RIPC patients (p = 0.05). RIPC by serial balloon inflations and deflations during PCI was found to confer protection against AKI in patients with a non-ST-segment elevation myocardial infarction undergoing PCI. The reduction in the rate of AKI translated into a clear trend (of borderline significance) toward better 30-day clinical outcome.

Effects of edaravone postconditioning and remote ischemic postconditioning on myocardial ischemia/reperfusion injury in rats

Objective To evaluate the effects of edaravone postconditioning and remote ischemic postconditioning on myocardial ischemia/reperfusion (I/R) injury in rats.Methods Forty male Sprague-Dawley rats,aged 8 weeks,weighing 250-300 g,were randomly divided into 5 groups (n =8 each):sham operation group (group S); group I/R; edaravone postconditioning group (group E); remote ischemic postconditioning group (group P); edaravone postconditioning and remote ischemic postconditioning group (group EP).Myocardial I/R was induced by occlusion of anterior desending branch of left coronary artery for 30 min followed by 180 min reperfusion.Edaravone 3 mg/kg was injected intravenously at 1 min before reperfusion in groups E and EP.The animals underwent 10 min ischemia of bilateral hind limbs starting from 20 min of myocardial ischemia in groups P and EP.Left ventricular systolic pressure (LVSP),left ventricular end-diastolic pressure (LVEDP) and ± dp/dtmax were measured and recorded during reperfusion.Results Compared with group S,LVSP and ± dp/dtmax were significantly decreased and LVEDP was increased in the other groups (P ＜ 0.05).LVSP and ± dp/dtmax were significantly higher and LVEDP was lower during reperfusion in groups E,P and EP than in group I/R,and in group EP than in groups E and P (P ＜ 0.05).Conclusion Edaravone postconditioning and remote ischemic postconditioning can alleviate myocardial I/R injury and offers better efficacy than either alone. Key words: Free radical scavengers; Myocardial reperfusion injury; Ischemic postconditioning

Effect of remote ischemic postconditioning on an intracerebral hemorrhage stroke model in rats

Background and purpose: While recent studies suggest that remote ischemic postconditioning (RIP) therapy may be of benefit to patients with acute ischemic stroke, RIP’s effects on intracerebral hemorrhage (ICH) still remains unclear. In the present study, the use of RIP in a rat model ICH was investigated to elucidate any potential beneficial or detrimental effects as determined by motor testing, blood brain barrier integrity, and brain water content, as well as aquaporin-4 (AQP-4) and matrix metalloproteinase-9 (MMP-9) expression.Methods: ICH was induced in Sprague–Dawley rats and they were randomized into either a control (n = 24) or RIP treatment (n = 24) group. RIP was performed by repetitive, brief occlusion and release of the bilateral femoral arteries. Functional outcome in each group was assessed by neurologic deficits on vibrissae-elicited forelimb placing test and a 12-point outcome scale. At 72 hours, brain blood volume, water content, blood–brain barrier (BBB) permeability, and protein expression of AQP-4 and MMP-9 were determined.Results: This collagenase model yielded well-defined striatal hematomas. Vibrissae-elicited forelimb placement was significantly (P<0·01) affected by ICH. However, there was no significant difference between the RIP and control groups at either 24 or 72 hours. A 12-point neurological deficit score also failed to differentiate between the RIP and control. There were no significant differences between the two groups in cerebral blood volumes, brain water content, Evans blue extravasations, and expressions of AQP-4 and MMP-9.Conclusions: Although RIP did not show a beneficial effect in our ICH model, treatment with RIP did not exacerbate ICH.

Effects of combined vagus nerve electric stimulation postconditioning and limb remote ischemic postconditioning on myocardial ischemia-reperfusion injury in rats

Objective To evaluate the effects of combined vagus nerve electric stimulation postconditioning and limb remote ischemic postconditioning on myocardial ischemia-reperfusion (I/R) injury in rats.Methods One hundred male SD rats aged 8 weeks weighing 250-350 g were randomly allocated into 5 groups ( n =20 each):sham operation group (group S); I/R group; vagus nerve electric stimulation postconditioning group (group POES) ; limb remote ischemic postconditioning group (group RP) and vagus nerve electric stimulation postconditioning + limb remote ischemic postconditioning group (group POES-RP).Myocardial I/R was induced by occlusion of left anterior descending branch (LAD) of coronary artery for 30 min followed by 120 min reperfusion in groups I/R,POES,RP and POES-RP.In groups POES and POES-RP,right cervical vagus nerve trank was stimulated for 30 min with continuous electric rectangular pulses (2 ms,10 Hz) starting from 15 min of myocardial ischemia.The voltage of the pulses was adjusted to decrease HR by 10％ of the baseline HR before stimulation.In groups RP and POES-RP the animals underwent 10 min ischemia of bilateral hind limbs starting from 20 min of myocardial ischemia.Arterial blood samples were collected from 10 rats in each group at 120 min of reperfusion for determination of serum concentrations of cTnI,CK-MB,TNF-α,high mobility group box 1 protein (HMGB1),intercellular adhesion molecule-1(ICAM-1),IL-1,IL-6 and IL-10 (by ELISA).The animals were then sacrificed and myocardial infarct size was measured by Evans blue and TTC staining.Another 10 rats were sacrificed at 120 min of reperfusion for determination of myocardial contents of TNF-α,HMGB-1,ICAM-1,IL-1,ID6 and IL-10 (by ELISA).Results I/R induced myocardial infarct and significantly increased serum concentrations of cTnI,CK-MB,TNF-α,HMGBi,ICAM-1,IL-1 and IL-6 and increased myocardial contents ofTNF-α,HMGB1,ICAM-1,IL-1,IL-6 and IL-10 in both ischemic and non-ischemic regions in group I/R as compared with group S.Vagus nerve electric stimulation postconditioning,limb remote ischemic postconditioning and vagus nerve electric stimulation postconditioning + limb remote ischemic postconditioning significantly decreased myocardial infarct size and serum concentrations of cTnI,CK-MB,TNF-α,HMGB1,ICAM-1,IL-1 and IL-6 and decreased myocardial contents of TNF-α,HMGB1,ICAM-1,IL-1,IL-6 in groups POES,RP and POES-RP as compared with group I/R.Compared with group I/R,myocardial IL-10 content in both ischemic and non-ischemic regions was significantly increased in groups POES and POES-RP.Compmared with group POES,myocardial infarct size,serum concentrations of cTnI,CK-MB,TNF-α,ICAM-1 and myocardial contents of ICAM-1 and IL-6 in ischemic region were significantly decreased,while myocardial content of IL-10 in non-ischemic region was increased in group POES-RP.Compared with group RP,myocardial infarct size,serum concenuations of cTnI,CK-MB,TNF-α,HMGB1,ICAM-1,IL-1,IL-6 and myocardial contents of TNF-α,ICAM-1,IL-1 and IL-6 in ischemic region were significantly decreased,myocardial content of IL-10 in ischemic region was increased and HMGB1,ICAM-1,IL-1 and IL-6 contents were decreased,IL-10 content was increased in myocardial of ischemic region in group POES-RP.Conclusion Myocardial I/R injury is attenuated and myocardial protection is enhanced by combination of vagus nerve electric stimulation postconditioning and limb remote ischemic postconditioning in rats by inhibiting inflammatory response in rats. Key words: Electric stimulation; Vagus nerve; Hindlimb; Myocardial reperfusion injury; Ischemic postconditioning

Effects of combination of ischemic postconditioning and remote ischemic postconditioning on focal cerebral ischemia-reperfusion injury in rats

Objective To investigate the effects of combination of ischemic postconditioning (IPC) and remote IPC on the focal cerebral ischemia-reperfusion (I/R) injury in rats. Methods Eighty-six adult male SD rats were randomly divided into 5 groups: sham operation group (group Ⅰ, n = 19) , I/R group (group Ⅱ, n=19) , IPC group (group Ⅳ, n = 16) , remote>IPC group (group Ⅳ, n = 16), and IPC + remote IPC group (group V , n = 16) . Focal cerebral I/R was produced by occlusion of the right middle cerebral artery (MCA) for 1.5 h followed by 24 h of reperfusion. In group Ⅰ, operation was performed but focal cerebral I/R was not produced. In group Ⅲ , the rats were subjected to 3 episodes of 30 s ischemia at 30 s intervals before 24 h of reperfusion. In group Ⅳ, after 1.5 h of the right MCA occlusion, remote IPC was performed by occluding the right femoral artery for 5 min before 24 h of reperfusion. In group Ⅴ, IPC and remote IPC were performed as described in group Ⅲ and Ⅳ respectively before 24 h of reperfusion. The neurologic deficit scores (NDSs) were measured at 2 and 24 h of reperfusion. Ten rats in each group were decapitated at 24 h of reperfusion and brains rapidly . removed for measuring the cerebral infarct size (IS). The expression of microtubule-associated protein 2 (MAP2) were detected. The animals received iv injection of fluorescein isothiocyanate (FICT)-dextran via the femoral vein 1 min before decapitation, for laser confocal scanning. The contralateral side was served as control. Results As compared with group Ⅰ, the NDSs and cerebral IS on the ischemic side were significantly increased, and the cerebral expression of MAP2, plasma volume of the cerebral tissues, and diameter and length of the cerebral microvessel on the ischemic side significantly decreased in group Ⅱ, Ⅲ , Ⅳ and Ⅴ ( P < 0.05 ) . As compared with group Ⅱ, the NDSs and cerebral IS on the ischemic side were significantly decreased, and the cerebral expression of MAP2, plasma volume of the cerebral tissues, and diameter and length of the cerebral microvessel on the ischemic side significantly increased in group ID , Ⅳ and Ⅴ( P < 0.05). Conclusion Although the combination of IPC and remote IPC can attenuate the focal cerebral I/R injury in rats, the efficacy is similar to that of either of them alone. Key words: Reperfusion injury; Brain; Ischemia postconditioning