A feasible strategy for focal cerebral ischemiareperfusion injury: remote ischemic postconditioning

It is difficult to control the degree of ischemic postconditioning in the brain and other isch- emia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on terminal organs. In this study, a focal cerebral ischemia-reperftlsion injury model was established using three cycles of remote ischernic postconditioning, each cycle consisted of 10-minute occlusion of the femoral artery and 10-minute opening. The results showed that, remote ischemic postconditioning significantly decreased the percentage of the in- farct area and attenuated brain edema. In addition, inflammatory nuclear factor-KB expression was significantly lower, while anti-apoptotic Bcl-2 expression was significantly elevated in the ce- rebral cortex on the ischemic side. Our findings indicate that remote ischemic postconditioning attenuates focal cerebral ischemia/reperfusion injury, and that the neuroprotective mechanism is mediated by an anti-apoptotic effect and reduction of the inflammatory response.

Limb remote ischemic postconditioning protects integrity of the blood-brain barrier after stroke

Integrity of the blood-brain barrier structure is essential for maintaining the internal environment of the brain.Development of cerebral infarction and brain edema is strongly associated with blood-brain barrier leakage.Therefore,studies have suggested that protecting the blood-brain barrier may be an effective method for treating acute stroke.To examine this possibility,stroke model rats were established by middle cerebral artery occlusion and reperfusion.Remote ischemic postconditioning was immediately induced by three cycles of 10-minute ischemia/10-minute reperfusion of bilateral hind limbs at the beginning of middle cerebral artery occlusion reperfusion.Neurological function of rat models was evaluated using Zea Longa’s method.Permeability of the blood-brain barrier was assessed by Evans blue leakage.Infarct volume and brain edema were evaluated using 2,3,5-triphenyltetrazolium chloride staining.Expression of matrix metalloproteinase-9 and claudin-5 m RNA was determined by real-time quantitative reverse transcription-polymerase chain reaction.Expression of matrix metalloproteinase-9 and claudin-5 protein was measured by western blot assay.The number of matrix metalloproteinase-9-and claudin-5-positive cells was analyzed using immunohistochemistry.Our results showed that remote ischemic postconditioning alleviated disruption of the blood-brain barrier,reduced infarct volume and edema,decreased expression of matrix metalloproteinase-9 m RNA and protein and the number of positive cells,increased expression of claudin-5 m RNA and protein and the number of positive cells,and remarkably improved neurological function.These findings confirm that by suppressing expression of matrix metalloproteinase-9 and claudin-5 induced by acute ischemia/reperfusion,remote ischemic postconditioning reduces blood-brain barrier injury,mitigates ischemic injury,and exerts protective effects on the brain.

Neuroprotective effects of long noncoding RNAs involved in ischemic postconditioning after ischemic stroke

During acute reperfusion,the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes.However,whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear.In this study,RNA isolation and library preparation was performed for long noncoding RNA sequencing,followed by determining the coding potential of identified long noncoding RNAs and target gene prediction.Differential expression analysis,long noncoding RNA functional enrichment analysis,and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats.Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery.Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke.The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke.The predicted target genes of some of the identified long noncoding RNAs(cis targets)were related to the cellular response to ischemia and stress,cytokine signal transduction,inflammation,and apoptosis signal transduction pathways.In addition,15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning.Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis.Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction.These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke.The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University(approval No.KMMU2018018)in January 2018.

Ischemic postconditioning enhances glycogen synthase kinase-3β expression and alleviates cerebral ischemia/reperfusion injury

The present study established global brain ischemia using the four-vessel occlusion method. Following three rounds of reperfusion for 30 seconds, and occlusion for 10 seconds, followed by reperfusion for 48 hours, infarct area, the number of TUNEL-positive cells and Bcl-2 expression were significantly reduced. However, glycogen synthase kinase-3β activity, cortical Bax and caspase-3 expression significantly increased, similar to results following ischemic postconditioning. Our results indicated that ischemic postconditioning may enhance glycogen synthase kinase-3β activity, a downstream molecule of the phosphatase and tensin homolog deleted on chromosome 10/phosphatidylinositol 3-kinase/protein kinase B signaling pathway, which reduces caspase-3 expression to protect the brain against ischemic injury.

Neuroprotective effect of ischemic postconditioning on sciatic nerve transection

Ischemic preconditioning or postconditioning has been shown to have neuroprotective effect on cerebral ischemia, but it has not been studied in peripheral nerve injury. In this study, a rat model of sciatic nerve transection was established, and subjected to three cycles of ischemia for 10 minutes ＋ reperfusion for 10 minutes, once a day. After ischemic postconditioning, serum insulin-like growth factor 1 expression increased; sciatic nerve Schwann cell myelination increased; sensory function and motor function were restored. These findings indicate that ischemic postconditioning can effectively protect injured sciatic nerve. The protective effect is possibly associated with upregulation of insulin-like growth factor 1.

Ischemic postconditioning protects against ischemic brain injury by up-regulation of acid-sensing ion channel 2a

Ischemic postconditioning renders brain tissue tolerant to brain ischemia,thereby alleviating ischemic brain injury.However,the exact mechanism of action is still unclear.In this study,a rat model of global brain ischemia was subjected to ischemic postconditioning treatment using the vessel occlusion method.After 2 hours of ischemia,the bilateral common carotid arteries were blocked immediately for 10 seconds and then perfused for 10 seconds.This procedure was repeated six times.Ischemic postconditioning was found to mitigate hippocampal CA1 neuronal damage in rats with brain ischemia,and up-regulate acid-sensing ion channel 2a expression at the m RNA and protein level.These findings suggest that ischemic postconditioning up-regulates acid-sensing ion channel 2a expression in the rat hippocampus after global brain ischemia,which promotes neuronal tolerance to ischemic brain injury.

Effect of Minocycline Postconditioning and Ischemic Postconditioning on Myocardial Ischemia-reperfusion Injury in Atherosclerosis Rabbits

This study examined the protective effect of ischemic postconditioning(IPoC) and minocycline postconditioning(MT) on myocardial ischemia-reperfusion(I/R) injury in atherosclerosis(AS) animals and the possible mechanism.Forty male healthy rabbits were injected with bovine serum albumin following feeding on a high fat diet for 6 weeks to establish AS model.AS rabbits were randomly divided into 3 groups:(1) I/R group,the rabbits were subjected to myocardial ischemia for 35 min and then reperfusion for 12 h;(2) IPoC group,the myocardial ischemia lasted for 35 min,and then reperfusion for 20 s and ischemia for 20 s [a total of 3 cycles(R20s/I20s×3)],and then reperfusion was sustained for 12 h;(3) MT group,minocycline was intravenously injected 10 min before reperfusion.The blood lipids,malondialdehyde(MDA),superoxide dismutase(SOD),soluble cell adhesion molecule(sICAM),myeloperoxidase(MPO),and cardiac troponin T(cTnT) were biochemically determined.The myocardial infarction size(IS) and apoptosis index(AI) were measured by pathological examination.The expression of bcl-2 and caspase-3 was detected in the myocardial tissue by using reverse transcription-polymerase chain reaction(RT-PCR).The results showed that the AS models were successfully established.The myocardial IS,the plasma levels of MDA,sICAM,MPO and cTnT,and the enzymatic activity of MPO were significantly decreased,and the plasma SOD activity was significantly increased in IPoC group and MT group as compared with I/R group(P<0.05 for all).The myocardial AI and the caspase-3 mRNA expression were lower and the bcl-2 mRNA expression was higher in IPoC and MT groups than those in I/R group(all P<0.05).It is concluded that the IPoC and MT can effectively reduce the I/R injury in the AS rabbits,and the mechanisms involved anti-oxidation,anti-inflammation,up-regulation of bcl-2 expression and down-regulation of caspase-3 expression.Minocycline can be used as an effective pharmacologic postconditioning drug to protect myocardia from I/R injury.

Spontaneous running wheel improves neuroprotection efficacy of ischemic postconditioning in mice following ischemia/reperfusion injury

Ischemic postconditioning(IP)has been shown to provide protection for ischemia/reperfusion(IR)injury,but its efficacy is limited.In this study we hypothesized that spontaneous running wheel(RW)could improve neuroprotection efficacy of IP for IR.We established mouse models of IR and showed that compared to Sham group,IR group had obvious brain infract and neurological dysfunction.In IR+IP group,brain infract and neurological dysfunction improved compared to IR group.However,in IR+IP+RW group brain infract and neurological dysfunction improved much better.TUNEL assay showed that IP but not RW significantly reduced the number of apoptotic cells after IR.However,the number of apoptotic cells was significantly reduced in RW+IP group.In addition,the levels of pro-apoptotic factors increased in IR group but significantly reduced in IR+IP+RW group,while the levels of antiapoptotic factors decreased in IR group but significantly increased in IR+IP+RW group.Moreover,in IR+IP+RW group,MDA level was further decreased and SOD level was further increased compared to IR+IP group.Finally,both PI3K inhibitor and STAT3 inhibitor significantly worsened brain infract and neurological dysfunction and promoted apoptosis in IR mice.In conclusion,RW combined with IP reduces brain infract and neurological dysfunction in mice after IR,and this is associated with enhanced anti-apoptotic and anti-oxidant benefits via the activation of PI3K and STAT3 pathways.

Influences of ischemic postconditioning at different positions on oxidative stress of myocardial ischemia-reperfusion injury in rats

Objective:To analyze the influences of locial ischemic postconditioning and remote limb ischemic postconditioning on oxidative stress response with myocardial ischemia reperfusion in rats.Methods:Thirty-two SD rats were randomly divided into Sham group,ischemia/reperfusion(I/R)group,local ischemic postconditioning(LIPC)group,and remote limb ischemic postconditioning(RIPC)group,after 3 hourse reperfusion,the contents of serum creatinine kinase,MB isoenzyme(CK-MB),xanthine oxidase(XOD),superoxide dismutase(SOD),myeloperoxidase(MPO),tumor necrosis factor-α(TNF-α)were measured.The 2,3,5-triphenyltetrazolium chloride(TTC)staining was carried out to evaluate the area of myocardial infarction,cardiac function was evaluated by echocardiography,and HE staining was performed to observe the morphology of myocardial cells.Results:Compared with the Sham group,the SOD contents of the I/R group,LIPC group,RIPC group reduced significantly(P<0.05),the XOD,MPO,TNF-αcontents increased significantly(P<0.05);Compared with the I/R group,the TNF-αcontents of the LIPC group reduced significantly(P<0.05),other oxidative stress indicators of the LIPC group had no significant differences;Compared with the I/R group,the MPO and TNF-αcontents reduced(P<0.05),the SOD and XOD contents of the RIPC group had no significant differences;Compared with the LIPC group,the MPO contents reduced(P<0.05)in the RIPC group,other oxidative stress indicators had no significant differences.Compared with the Sham group,myocardial infarction area,CK-MB contents,LVIDs increased with the reduction of EF in I/R group,LIPC group,RIPC group(P<0.05),HE staining had differences;Compared with the I/R group,myocardial infarction area,CK-MB contents,LVIDd,LVIDs,EF and HE staining results had no significant differences in the LIPC group and the RIPC group;Compared with the RIPC group,the LIPC group had no significant differences.Conclusion:Remote limb ischemic postconditioning and local ischemic postconditioning can partially reduce the oxidative stress response,but does not significantly reduce myocardial infarction area,improve cardiac function.

Calcineurin is involved in cardioprotection induced by ischemic postconditioning through attenuating endoplasmic reticulum stress

Background Ischemic postconditioning （I-postC） is a newly discovered and more amenable cardioprotective strategy capable of protecting the myocardium from ischemia/reperfusion （I/R） injury. Endoplasmic reticulum （ER） is a principal site for secretary protein synthesis and calcium storage. Myocardial I/R causes ER stress and emerging studies suggest that the cardioprotection has been linked to the modulation of ER stress. The aim of the present study was to determine whether cardioprotection of I-postC involves reduction in ER stress through calcineurin pathway. Methods In the in vivo model of rat myocardial I/R, myocardial infarct size was measured by triphenyltetrazolium chloride （TTC） staining and apoptosis was detected using terminal eoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling （TUNEL） assay. Expression of calreticulin, C/EBP homologous protein （CHOP）, caspase-12, and activation of caspase-12 in myocardium were detected by Western blotting. The activity and expression of calcineurin in myocardium were also detected. Results I-postC protected the I/R heart against apoptosis, myocardial infarction, and leakage of lactate dehydrogenase （LDH） and creatine kinase-MB （CK-MB）. I-postC suppressed I/R-induced ER stress, as shown by a decrease in the expression of calreticulin and CHOP, and caspase-12 activation. I-postC downregulated calcineurin activation in myocardium subjected to I/R. Conclusion I-postC protects myocardium from I/R injury by suppressing ER stress and calcineurin pathways are not associated with the I-postC-induced suppression of ER stress-related apoptosis.

Ischemic postconditioning alleviates lung injury and maintains a better expression of aquaporin-1 during cardiopulmonary bypass

Background It has found that ischemic postconditioning （IPO） might decrease pulmonary ischemia/reperfusion （I/ R） injury,which is one of the main reasons of lung injury caused by cardiopulmonary bypass （CPB）.It was found that aquaporins （AQPs） play a role in the maintenance of fluid homeostasis.But it is still unclear whether IPO influences the expression of aquaporin-1 （AQP1）.This study was designed to investigate whether IPO can reduce CPB-related lung injury and affect the expression of AQP1 of lungs.Methods Twelve healthy dogs were divided into control group （C group） and ischemia postconditioning group （IPO group）.CPB procedures were implemented.Ten minutes later,the left pulmonary artery was separated and blocked.Postconditioning consisted of two cycles of 5-minute pulmonary artery reperfusion/5-minute reocclusion starting at the beginning of reperfusion.The 2×4 cm tissues of both sides of pulmonary apex,superior,middle and inferior lobe were taken before CPB （T1）,before occlusion and reopening of left pulmonary artery （T2,T3）,and 2 hours after CPB （T4）.Samples were used to evaluate lung injury degrees and to detect the expression of AQP1.At T1 and T4,blood was collected from femoral artery to calculate pulmonary function.Results At T4,each pulmonary function showed significant deterioration compared with T1.Lung injury could be found at the onset of CPB.However,the expression of AQP1 decreased and wet to dry weight ratio （W/D） increased after T2.In the left lung of C group,the worst pulmonary function and structures were detected.The slightest changes were discovered in the right lung of C group.A close relationship between W/D and lung injury score was found.The lung injury score was negatively related with the expression of AQP1.It was found that the expression of AQP1 was negatively connected with W/D.Conclusions In dog CPB models,lung injury induced by CPB was related with down regulated expression of AQP1.AQP1 is believed to be involved in the mechanisms of lung ischemia/reperfusion （I/R） injury caused by CPB.IPO increases the expression of AQP1,provides a protective effect on lung suffering from CPB,and alleviates CPB-related lung injury.

Protective role of mitochondrial K-ATP channel and mitochondrial membrane transport pore in rat kidney ischemic postconditioning

Background Previous studies suggested that mechanical intervention during early reperfusion, or ischemia postconditioning （Ipo）, could protect kidneys against renal ischemia reperfusion injury （RIRI）. However, the mechanisms responsible for this protection remain unclear. This study therefore investigated the protection afforded by Ipo in rat kidneys in vivo, and the roles of mitochondrial KATP channels （mitOKATP） and mitochondrial permeability transition pores （MPTPs）, by inhibiting mitOKATP with 5-hydroxydecanoate （5-HD）, and by directly detecting open MPTPs using calcein-AM and CoCl2.Methods Thirty-five male Sprague-Dawley rats were randomly assigned to sham-operation （S）, ischemia-reperfusion （I/R）,Ipo, ischemia reperfusion with 5-HD （I/R＋5-HD）, or Ipo with 5-HD （Ipo ＋5-HD） groups. Rats in each group were sacrificed after 6 hours of reperfusion by heart exsanguination or cervical dislocation under anesthesia. RIRI was assessed by determination of creatinine and blood urea nitrogen （BUN）, and by examination of histologic sections. The roles of mitoKATP and MPTP were investigated by analyzing fluorescence intensities of mitochondria, mitochondrial membrane potential,intracellular reactive oxygen species （ROS） and intracellular calcium, using appropriate fluorescent markers. The relationship between apoptosis and RIRI was assessed by determining the apoptotic index （Al） of kidney tubular epithelial cells.Results The RIRI model was shown to be successful. Significantly higher levels of creatinine and BUN, and abnormal pathology of histologic sections, were observed in group I/R, compared with group S. 5-HD eliminated the renoprotective effects of Ipo. Mitochondrial and mitochondrial membrane potential fluorescence intensities increased, and intracellular calcium, ROS fluorescence intensities and AI decreased in group Ipo, compared with group I/R. However, mitochondrial and mitochondrial membrane potential fluorescence intensities decreased, and intracellular calcium and ROS fluorescence intensities and AI increased in group Ipo＋5-HD, compared with group Ipo.Conclusions mitoKATP and MPTPs participated in Ipo-induced renoprotective mechanisms in rat kidneys subjected to RIRI, possibly through decreased renal tubular epithelial cell apoptosis.

Remote Ischemic Postconditioning for Ischemic Stroke： A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background：Remote ischemic postconditioning （RIPostC） appears to protect distant organs from ischemia-reperfusion injury （IRI）. However, cerebral protection results have remained inconclusive. In the present study, a meta-analysis was performed to compare stroke patients with and without RIPostC.Methods：CNKI, WanFang, VIP, CBM, PubMed, and Cochrane Library databases were searched up to July 2016. Data were analyzed using both fixed-effects and random-effects models by Review Manager. For each outcome, risk ratio （RR） and mean difference （MD） with 95% confidence interval （CI） were calculated.Results：A total of 13 randomized controlled trials that enrolled a total of 794 study participants who suffered from or are at risk for brain IRI were selected. Compared with controls, RIPostC significantly reduced the recurrence of stroke or transient ischemic attacks （RR = 0.37; 95% CI： 0.26–0.55; P 〈 0.00001）. Moreover, it can reduce the levels of the National Institutes of Health Stroke Scale score （MD： 1.96; 95% CI： 2.18–1.75; P 〈 0.00001）, modified Rankin Scale score （MD： 0.73; 95% CI： 1.20–0.25; P = 0.00300）, and high-sensitivity C-reactive protein （MD： 4.17; 95% CI： 4.71–3.62; P 〈 0.00001） between the two groups. There was no side effect of RIPostC using tourniquet cuff around the limb on ischemic stroke treating based on different intervention duration.Conclusion：The present meta-analysis suggests that RIPostC might offer cerebral protection for stroke patients suffering from or are at risk of brain IRI.

Activated Notch1 reduces myocardial ischemia reperfusion injury in vitro during ischemic postconditioning by crosstalk with the RISK signaling pathway

Background Ischemic postconditioning （IPost）,able to significantly attenuate myocardial ischemia reperfusion injury,is dependent on RISK signaling.Studies have shown that Notch signaling repairs damaged myocardium,and this study aimed to investigate the effect of Notch signaling in myocardial IPost.Methods We used H9c2 cells to establish the myocardial IPost and Hypoxia/Reoxygenation （H/R） model in vitro,which were randomly divided into control,H/R,IPost,Hepatocyte growth factor （HGF）＋IPost and DAPT＋IPost,N1ICD＋IPost,miRNA＋lPost,and Mock treatment groups.The myocardial cell viability was assessed by MTT,the cell apoptosis was detected using Annexin V/PI double staining and flow cytometry analyses.The expression of N1ICD,Hes1,PTEN Phospho-Akt/Akt,Phospho-GSK-3β/GSK-3β were detected by Western blotting.Finally,we assessed the changes in Ψm using the potential-sensitive dye JC-1 and measured using flow cytometry analyses.Results The Notch1 signaling is activated by HGF and ectopic expression of N1ICD during myocardial IPost,which increased myocardial cell viability,prevented cardiomyocyte apoptosis,and reduced loss of the mitochondrial membrane potential.However,myocardial ischemia reperfusion injury was increased in IPost when Notch1 signaling was inhibited using DAPT or with knockdown by Notch1-miRNA.Western blotting found that PTEN was down-regulated by Hes1 when Notch1 was activated,which consequently promoted Akt and GSK-3β phosphorylation.Conclusions Notch1 crosstalk with RISK signaling may be dependent on PTEN,which plays a cardioprotective role during IPost.This mechanism could provide a promising therapeutic target for the treatment of ischemic heart disease.

Effect of ischemic postconditioning on cerebral edema and the AQP4 expression following hypoxic-eschemic brain damage in neonatal rats

Background:A rat model for neonatal hypoxic-ischemic brain damage(HIBD)was established to observe the effect of ischemic postconditioning(IPostC)on cerebral edema and the AQP4 expression following HIBD and to verily the neuroprotection of IPostC and the relationship between changes of AQP4 expression and cerebral edema.Methods:Water content was measured with dry-wet method,and AQP4 transcription and the protein expression of the lesions were detected with real-time PCR and immunohistochemistry staining,respectively.Results:Within 6-48 hours,the degree of ipsilateral cerebral edema was significantly lower in IPostC-15 s/15 s group than in HIBD group.Similar to the HIBD group,the AQP4 transcription and expression in the IPostC group showed a downward and then upward trend.But the expression was still more evident in the HIBD group than in the IPostC-15 s/15 s group.From 24 to 48 hours,IPostC-15 s/15 s decreased the slowing down expression of AQP4.Conclusion:IPostC has neuroprotective effect on neonatal rats with HIBD and it may relieve cerebral edema by regulating the expression of AQP4.

Synergistic Protection of Danhong Injection (丹红注射液) and Ischemic Postconditioning on Myocardial Reperfusion Injury in Minipigs

Objective： To explore the synergistic protection of Danhong Injection （丹红注射液,DHI） and ischemic postconditioning on myocardial reperfusion injury in minipigs.Methods： Acute myocardial infarction model was made by balloon occlusion in left anterior descending coronary artery （LAD） of minipigs,and then postconditioning was simulated through inflation/deflation of the angioplasty balloon.Minipigs were divided into four groups： the sham operation group （SH group）,the ischemia/reperfusion group （I/R group）,the ischemic postconditioning group （POC group） and DHI combined with ischemic postconditioning group （PAD group,DHI 20 mL through ear vein）,six in each group.After 24-h continuous observation,myocardial infarction size was assessed by triphenyltetrazolium staining （TTC）.Morphological changes of ischemic myocardium were observed by light microscopy,and cardiomyocyte ultrastructure was studied with electron microscopy.The superoxide dismutase （SOD） and malondialdehyde （MDA） activity in heart homogenates were measured by a biochemical method.Results： The myocardial infarction size was smaller in the POC group than in the I/R group （0.26±0.02 vs.0.37±0.09,P〈0.05）,and the PAD group （0.14±0.08） displayed a significantly reduced infarction size relative to the I/R group （P〈0.01） and POC group （P〈0.05）.The damage of myocardial tissue was severe in the I/R group shown by light and electron microscopy： myocardial fibers disorder,sarcoplasmic dissolution,myofilament fracture,mitochondria swelling and even vacuolization formation and a large number of inflammatory cell infiltrations.Compared with the I/R group,reduction of reperfusion injury in the PAD group included more orderly arranged myocardial fibers,less infiltration of inflammatory cells and maintenance of mitochondrial integrity.Compared with the I/R group,the damage of myocardial tissue in the POC group was improved,but not as significant as that in the PAD group.SOD levels in the POC group and the PAD group were significantly higher than those in the I/R group （96.96±13.43,112.25±22.75 vs.76.32±10.63,P〈0.05）,and MDA was significantly lower in the POC group and the PAD group compared to the I/R group （1.27±0.19,1.09±0.21 vs.1.47±0.16,P〈0.05）.Conclusion： DHI and ischemic postconditioning show a synergistic cardioprotection on myocardial reperfusion injury in minipigs.

The effects of gradual ischemic postconditioning treatment on patients with STEMI

Background When patients suffering with ST-segment elevation myocardial infarction(STEMI) undergo an percutaneous coronary intervention(PCI) and open the infarct-related coronary artery(IRCA), a myocardial ischemia reperfusion injury(MIRI) will occur. This leads to severe complications, such as an enlarged myocardial infarction area, reperfusion arrhythmia, and heart failure. Finding ways to mitigate the effects of MIRIs is therefore important. Our study aims to observe the effect and significance of the gradual ischemic postconditioning(IPOC)treatment on MIRI and autonomic nerves system(ANS) in patients with STEMI during PCIs. Methods We took the 121 patients diagnosed with STEMI that had been hospitalized in the cardiology department of our hospital from March 2019 to September 2020, and divided them into a control group(60 cases) and treatment group(61 cases). The control group received conventional PCI treatment, and the treatment group received gradual IPOC treatment. Results The gradual IPOC group was shown to achieve significantly better results than the control group(P<0.01) in the following: reduction of the incidence rate of arrhythmia cases during PCI, increase in proportion of ST-segment resolution at 24 hours after PCI, suppression of the postoperative overexcitement of the sympathetic and vagus nerve systems, recovery of the cardiac autonomic nerve function, reduction of c Tn T, NT-pro BNP and hs-CRP concentrations, and improvement of LVEF value. Conclusion During emergency PCIs for patients with STEMI, the operation of an gradual IPOC can lessen the myocardial infarction area, reduce inflammation, improve heart function, reduce reperfusion arrhythmia, and promote the recovery of cardiac autonomic nerve function, thereby reduce MIRI and benefitting patients.

Preconditioning and postconditioning reduce hepatic ischemia-reperfusion injury in rats

BACKGROUND: Ischemia-reperfusion injury occurs when ischemic tissues or organs suffer from further functional and structural damage when their blood supply recovers. This study aimed to contrast the protective effects of ischemic preconditioning and ischemic postconditioning in hepatic ischemia-reperfusion injury in rats. METHODS: Thirty-two healthy male Wistar rats were randomly divided into four groups: sham-operated (SO), ischemia-reperfusion (IR), ischemic preconditioning (I-pre), and ischemic postconditioning (I-post). Blood samples and hepatic tissue were taken from all groups after the experiments. RESULTS: There were significant differences between the IR, I-pre and I-post groups in alanine aminotransferase and aspartate aminotransferase levels, NF-kappa B p65 expression, apoptosis index and superoxide dismutase activity in hepatic tissue. There were no significant differences between the I-pre and I-post groups. CONCLUSIONS: Ischemic postconditioning and ischemic preconditioning reduce hepatic ischemia-reperfusion injury, but in clinical practice the former is a more appropriate choice.

Cardiac Connexin 43 and Ischemic Cardioprotection

The connexin 43 （ Cx43 ） proteins, which is the predominant protein that can form gap junctions and non- junctional hemichannels in ventricular myocardium, are central to the cardioprotection afforded by ischemic preconditioning （IP） and maybe ischemic postconditioning （ PC ） too. Recent studies showed that recruitment of Cx43 to the mitochondria in IP might play a role in the production of reactive oxygen species （ROS） that mediates IP. The localization of Cx43 at mitochondria appears to be important for the achieved cardioprotection and opens a new door for us to reveal the exact mechanisms of ischemia/reperfusion （I/R） injury and cardioprotection, and it might be new targets of pharmacological modulator to achieved cardioprotection.