Postconditioning Group Research Articles

Effect of morphine-induced postconditioning in corrections of tetralogy of fallot

BackgroundResults of previous reports on ischemic postconditioning in animals and humans were very encouraging. Although ischemic postconditioning possessed a wide prospect of clinical application, debates on the precise ischemic postconditioning algorithm to use in clinical settings were ongoing. In this regard, pharmacological strategies were possible alternative methods. Accumulating data demonstrated that pharmacological postconditioning with morphine conferred cardioprotection in animals. This trial aimed to evaluate the effect of morphine-induced postconditioning on protection against myocardial ischemia/reperfusion injury in patients undergoing corrections of Tetralogy of Fallot (TOF).MethodsEight-nine consecutive children scheduled for corrections of TOF were enrolled and randomly assigned to either a postconditioning group (patients received a dose of morphine (0.1 mg/kg) injected via a cardioplegia needle into the aortic root for direct and focused delivery to the heart within 1 minute starting at 3 min before aorta cross-clamp removal, n=44) or a control group (the same protocol was performed as in the postconditioning group except that patients received the same volume of saline instead, n=45). The peri-operative relevant data were investigated and analyzed, and the cardiac troponin I (cTnI) was assayed preoperatively, and then 4 h, 8 h, 12 h, 24 h and 48 h after reperfusion.ResultsMorphine-induced postconditioning reduced postoperative peak cTnI release as compared to the control group (0.57 ± 0.15 versus 0.75 ± 0.20 ng/mL, p<0.0001). Morphine-induced postconditioned patients had lower peak inotropic score (5.7 ± 2.4 versus 8.4 ± 3.6, p<0.0001) and shorter duration of mechanical ventilation as well as ICU stay (20.6 ± 6.8 versus 28.5 ± 8.3 hours, p<0.0001 and 40.4 ± 10.3 versus 57.8 ± 15.2 hours, p<0.0001, respectively), while higher left ventricular ejection fraction as well as cardiac output (0.57±0.15 versus 0.51±0.13, p=0.0467 and 1.39 ± 0.25 versus 1.24 ± 0.21 L/min, p=0.0029, respectively) as compared to the control group during the first postoperative 24 hours.ConclusionsMorphine-induced postconditioning may provide enhanced cardioprotection against ischemia/reperfusion injury in children undergoing corrections of TOF.

Role of mitochondrial function in the protective effects of ischaemic postconditioning on ischaemia/reperfusion cerebral damage

To investigate the effects of ischaemic postconditioning on brain injury and mitochondria in focal ischaemia and reperfusion, in rats. Adult male Wistar rats (n = 15 per group) underwent sham surgery, ischaemia (2-h middle cerebral artery occlusion), or ischaemia followed by ischaemic postconditioning (three cycles of 30 s reperfusion/30 s reocclusion). Brain infarction size, neurological function, mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential and mitochondrial swelling were evaluated 24 h postsurgery. Infarct size was significantly smaller, and neurological function was significantly better, in the ischaemic postconditioning group than in the ischaemia group. Ischaemia resulted in significant increases in mitochondrial ROS production and swelling, and a reduction in mitochondrial membrane potential, all of which were significantly reversed by postconditioning. The protective role of ischaemic postconditioning in focal ischaemia/reperfusion may be due to decreased mitochondrial ROS production, reduced mitochondrial membrane potential and suppressed mitochondria swelling. Mitochondria are potential targets for new therapies to prevent brain damage caused by ischaemia and reperfusion.

Effects of sevoflurane postconditioning on intestinal ischemia-reperfusion injury in rats

Objective To investigate the effects of sevoflurane postconditioning on intestinal ischemiareperfusion (I/R) injury in rats.Methods Thirty-six adult male Sprague-Dawley rats,weighing 200-220 g,were randomly divided into 4 groups (n =9 each):sham operation group (group Sham),group I/R,ischemic postconditioning group (group Ipo) and sevoflurane postconditioning group (group Sevo).Intestinal I/R was induced by clamping the superior mesenteric artery (SMA) for 60 min followed by 120 min of reperfusion in groups I/R,Ipo and Sevo.In group Ipo the animals were subjected to 3 cycles of 30 min reperfusion-30 min ischemia starting from the beginning of reperfusion.The animals inhaled 1.15％ sevoflurane for 30 min starting from the beginning of reperfusion in group Sevo.The animals were sacrificed at 120 min of reperfusion and then the small intestines were removed for determination of malondialdehyde (MDA) content and superoxide dismutase (SOD) activity (by colorimetric method) and caspase-3 protein expression in intestinal tissues (by Western blot).The density of apoptotic cells was calculated by TUNEL.Results Compared with group Sham,the intestinal injury score,density of apoptotic cells and MDA content were significantly increased,SOD activity was decreased,and caspase-3 protein expression was up-regulated in groups I/R,Ipo and Sevo (P ＜ 0.05).Compared with group l/R,the intestinal injury score,density of apoptotic cells and MDA content were significantly decreased,SOD activity was increased,and caspase-3 protein expression was down-regulated in groups Ipo and Sevo (P ＜ 0.05).There was no significant difference in the intestinal injury score,density of apoptotic cells,SOD activity,MDA content and caspase-3 protein expression between Sevo and Ipo groups (P ＞ 0.05).Conclusion Sevoflurane postconditioning can attenuate intestinal I/R injury through reducing lipid peroxidation and cell apoptosis in rats,and the protective effect is similar to that of ischemic post-conditioning. Key words: Anesthetics, inhalationg; Reperfusion injury ; Intestine, small

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

Effective Neuroprotection by Ischemic Postconditioning is Associated with a Decreased Expression of RGMa and Inflammation Mediators in Ischemic Rats

Whether ischemic postconditioning (IPC) can significantly alleviate ischemic injury hinges on the appropriate measure. In this study, the expression RGMa and IL-1β, IL-6 are investigated to estimate the therapeutic benefits of various postconditioning strategies after cerebral ischemia/reperfusion. The study consists of the sham-operated group and five treatment groups: ischemia/reperfusion (I/R), two proximate ischemic postconditioning (IPC-S and IPC-M), remote postconditioning (RIPC) and delayed postconditioning (DIPC) groups. We find that rats in IPC and RIPC groups exhibit significantly less neural deficit and lower infarct volume than that in I/R and DIPC groups after ischemia/reperfusion. Moreover, in ischemic cortex and hippocampus, the mRNA level of RGMa is much lower in IPC and RIPC groups. Immunohistochemical analysis indicates that the expression of RGMa, IL-1β and IL-6 are reduced in IPC and RIPC groups (especially in IPC-S group). Furthermore, neurofilament staining reveals that the rats in IPC and RIPC groups have less axonal injury than that in I/R and DIPC groups. Our studies suggest that the optimal strategy to attenuate cerebral ischemia/reperfusion is achieved by early, short-term, and multiple cycles of proximal IPC. The cerebral protective effect of IPC may be associated with the decreased expression of RGMa and inflammation mediators.

Abstract WP110: TLR5 Is Related To Neuroprotective Mechanism Of Postconditioning Through NF-κB-Akt Survival Pathway In Cerebral Ischemia

Background and Purpose: Although postconditioning following stroke has indicated neuroprotective mechanisms, little is known about the mechanisms that lead to neuroprotection. Using flagellin, NF-kB activators and agonists of TLR5, we tested whether TLR5 plays an integral role in NF-kB activation and postconditioning-induced neuroprotection. Method: For the postconditioning group, 30 min of MCAO was induced, then 5 min of reperfusion was performed, after which the MCA was again occluded for 5 min. Using an anaerobic chamber, bEnd.3 and BV-2 cells in the postconditioning group were subjected to 180 min OGD (oxygen and glucose deprivation) and were allowed to recover for 10 min before being subjected to 10 more min of OGD. The control group was subjected to 180 min of OGD. Flagellin, an agonist of TLR5, was used to clarify the association between TLR5 and postconditioning in vivo (ICV; 50, 100 ng/mouse) and in vitro (0.1, 0.25, 0.5, 1 ng/ ml) experiments. Immunoprecipitation and immunoblotting were used to determine the interactions of TLR5, MyD88, p-Akt, and NF-κB. Results: Animals treated with postconditioning showed significant differences in infarct volumes compared with the MCAO group up to 60.51%. Postconditioning elevated NF-κB translocation to the nuclei (p&lt;0.001) as early as 1 hour after postconditioning following tFCI and OGD. The protein interactions and expressions of TLR5, MyD88 and p-Akt (p&lt;0.05) were increased in in vivo and in vitro postconditioning. Additionally, inhibition of Akt phosphorylation by Akt inhibitor IV decreased NF-κB translocation after postconditioning. To clarify the role of NF-κB in postconditioning, flagellin was used as a postconditioning mimicking agent. The treatment of flagellin reduced hypoxic-ischemic injury and increased nuclear accumulation of NF-κB and activation of Akt up to 4 hr. Conclusions: Postconditioning has neuroprotective effects by activating NF-κB and Akt survival pathway under TLR5 after stroke. Agonist of TLR5, flagellin simulated NF-κB and Akt survival pathways in cerebral ischemia. Our results suggested new mechanisms of postconditioning through TLR-5 and NF-κB, which leads to the possibility of development of a postconditioning mimicking agent using NF-κB activators such as flagellin.

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

Different postconditioning cycles affect prognosis of aged patients undergoing primary percutaneous coronary intervention.

Postconditioning can affect the infarct size in acute myocardial infarction (AMI). How-ever, few studies show an effect of different postconditioning cycles on AMI aged patients. This study sought to assess the effect of different postconditioning cycles on prognosis in aged patients with AMI who underwent primary percutaneous coronary intervention (PCI). Seventy four aged patients were randomly assigned to three groups. Control group; PC-1 group accepted postconditioning 4 cycles of 30 s inflation and 30 s deflation; PC-2 group accepted postconditioning 4 cycles of 60 s. Creatine kinase MB (CK-MB), troponin I (cTnI), high-sensitive C-reactive protein (hs-CRP) and corrected Thrombolysis in Myocardial Infarction (TIMI) frame counts (CTFC) were analyzed before and after treatment. All patients received an echocardiographic examina-tion for whole heart function, wall motion score index (WMSI) and single-photon emission computed tomography (SPECT) examination at 7 days and 6 months after treatment. The peak of CK-MB, postoperative 72 h cTnI and CTFC were significantly attenuated by postconditioning when compared with the control group. The hs-CRP of the postconditioning group was lower than the control group 24 h postoperative. No difference was observed between PC-1 and PC-2 group about the effect described above. At 7 days, heart function in the postconditioning group was im-proved when compared with the control group. At 6 months, the WMSI and SPECT score significantly reduced in the PC-2 group compared with the control and PC-1 groups, but there was no difference among the three groups about echo data except the left ventricular end-systolic diameter. Postconditioning is significantly beneficial to prognosis in aged patients with AMI. The cardiac protective effect of 4 cycles of 60 s procedure was observed in WMSI and SPECT. It is favorable to implement this procedure in aged patients with AMI in clinic.

Ischemic Postconditioning may Increase Serum Fetuin-A Level in Patients with Acute ST-Segment Elevation Myocardial Infarction Undergoing Percutaneous Intervention

Fetuin-A inhibits inflammation and has a protective effect against myocardial ischemia. We investigated the influence of ischemic postconditioning on serum fetuin-A levels and high-sensitive C-reactive protein (hs-CRP) in patients with acute ST-segment elevation myocardial infarction undergoing percutaneous intervention. Forty-five patients undergoing percutaneous coronary intervention (PCI) were randomly assigned to a control (n = 21) or postconditioning (PC, n = 24) group within 90 minutes after admission. After predilatation, in the control group, no intervention was applied in the first 3 minutes of reperfusion, while in the postconditioning group, three cycles of 30-second angioplasty balloon deflation and 30-second inflation were repetitively applied. Blood samples were obtained and assayed for creatine kinase MB (CK-MB), fetuin-A and hs-CRP. The control group presented with higher peak CK-MB as compared with the PC group (123.67 +/- 44.19 vs. 93.08 +/- 35.29 U/L, p < 0.05). After PCI, PC was associated with a lower level of hs-CRP in comparison with the control group (6.07 +/- 1.35 vs. 7.03 +/- 1.27 mg/L, p < 0.05). Serum fetuin-A levels in the PC group was higher than in the control (161.06 +/- 23.98 mg/L vs. 144.59 +/- 22.76 mg/L, p < 0.05). Postconditioning may increase serum fetuin-A levels and decrease high-sensitive C-reactive protein in myocardial infarction patients.

Reduction of Infarct Size in Patients with Acute ST Elevation Myocardial Infarction by Postconditioning during Percutaneous Coronary Intervention : A Meta Analysis

BACKGROUND: Following an acute coronary artery occlusion, timely myocardial reperfusion by primary percutaneous coronary intervention (PCI) is the recommended therapy, but restoring blood flow can induce reperfusion injury. Myocardial postconditioning (POC), defined as a sequence of intermittent interruptions of coronary blood flow applied at the onset of reperfusion after a period of sustained ischemia, has been shown to attenuate infarct size and reperfusion injury in patients with acute myocardial infarction undergoing PCI. METHODS: This is a meta-analysis of the available data from randomized trials on the effects of postconditioning on infarct size, as measured by single-photon emission computed tomography (SPECT) in ST elevation myocardial infarction (STEMI) patients who underwent PCI . RESULTS: Four randomized control trial studies were identified, comprising 244 patients with STEMI undergoing PCI with or without postconditioning. No adverse events occurred in the postconditioning group. Pooled analysis of all studies demonstrated a significant reduction in infarct size with postconditioning relative to standard care (standard mean difference -0.82, 95% CI -1.10 to -0.55; p=0.00005) as measured by SPECT. CONCLUSION: Postconditioning is a safe and feasible strategy that may reduce the infarct size in patients with STEMI and confer cardioprotection in the clinical setting.

English

To investigate heme oxygenase-1(HO-1) expression induced by sevoflurane in lipopolysaccharide (LPS)-induced acute lung injury (ALI). Forty-eight rats were randomly designated into six groups to receive normal saline (NS), ZnPPIX(a specific HO-1 inhibitor), or sevoflurane: A (control, NS&nbsp;only),&nbsp;B (ZnPPIX&nbsp;only), C (sevoflurane only), D (LPS + 1.0 minimum alveolar concentration (MAC) sevoflurane), E (ZnPPIX + LPS +1.0 MAC sevoflurane) and F (LPS only).&nbsp;We evaluated the histopathologic changes, W/D ratio, and the activity of SOD, MDA, MPO, and HO-1 using the traditional methods. The mRNA and protein expression of ICAM-1, CINC, and HO-1 was detected by&nbsp;RT-PCR and western blotting. No significant difference was observed between group A, B, and C. LPS treatment (group D, E and F) could&nbsp;elicit serious&nbsp;lung injury in histopathology. The wet/dry ratio, MDA, MPO, and HO-1 activity, the mRNA and protein expression of ICAM-1 and CINC were significantly increased after LPS treatment (p &lt; 0.05). Sevoflurane post-conditioning (Group F) could further promote HO-1 up-regulated expression and effectively protect ALI with decreasing pathomorphological scores, MPO activity, W/D, and the mRNA and protein expression of ICAM-1, and CINC. Sevoflurane post-conditioning may be an effective inducer to up-regulate HO-1 expression to alleviate ALI. &nbsp; Key words:&nbsp;Sevoflurane,&nbsp;acute lung injury, HO-1.

Roles of reactive oxygen species in the reduction of myocardial ischemia-reperfusion injury by fentanyl postconditioning and remote limb ischemic postconditioning in rats

Objective To investigate the role of reactive oxygen species (ROS) in the reduction of myocardial ischemia-reperfusion (I/R) injury by fentanyl postconditioning and remote limb ischemic postconditioning in rats.Methods Sixty-three male Sprague-Dawley rats,aged 8 weeks,weighing 250-350 g,were equally and randomly allocated into 7 groups:sham operation group (group S),group I/R,fentanyl postconditioning group (group F),remote limb ischemic postconditioning group (group R),ROS scavenger N-(2-Mercaptopropionyl) glycine (MPG) group (group M),MPG + fentanyl postconditioning group (group MF),and MPG + remote limb ischemic postconditioning group (group MR).Myocardial I/R was induced by occlusion of anterior descending branch of left coronary artery for 30 min followed by 180 min of reperfusion.In group S the anterior descending branch was only exposed but not ligated.MPG 5 mg/kg was infused intravenously from 5 min before ischemia to 15 min of reperfusion in groups M,MF and MR,while the equal volume of normal saline was given in the other four groups.In groups F and MF,fentanyl 30 μg/kg was injected intravenously at 15 min of myocardial ischemia.In groups R and MR,the animals underwent 10 min ischemia of bilateral hind limbs starting from 15 min of myocardial ischemia.Arterial blood samples were taken at 180 min of reperfusion to determine the serum cardiac troponin I (cTnI) concentration.The rats were then sacrificed.The infarct size was measured by TTC.Results Compared with group S,the serum cTnI concentration and infarct size were significantly increased in the other six groups (P ＜0.05).Compared with group I/R,no significant change was found in the serum cTnI concentration and infarct size in M group,and the serum cTnI concentration and infarct size were significantly decreased in F and R groups (P ＜ 0.05).There was no significant difference in the serum cTnI concentration and infarct size between MF group and F group (P ＞ 0.05).The serum cTnI concentration was significantly higher and the infarct size was larger in group MR than in group R (P ＜ 0.05).Conclusion ROS is involved in the reduction of myocardial I/R injury by remote limb ischemic postconditioning in rats,but not in the myocardial protection provided by fentanyl postconditioning. Key words: Reactive oxygen species; Fentanyl ; Lower extremity ; Myocardial reperfusion injury; Ischemic postconditioning

Ischemic Postconditioning Alleviates Neuronal Injury Caused by Relief of Carotid Stenosis in a Rat Model of Cerebral Hypoperfusion

The effects of early relief of heavy bilateral carotid stenosis and ischemic postconditioning on hippocampus CA1 neurons are still unclear. In this study, we used a rat model to imitate severe bilateral carotid stenosis in humans. The rats were divided into sham group, carotid stenosis group, stenosis relief group and ischemic postconditioning group. Ischemic postconditioning consisted of three cycles of 30 s ischemia and 30 s reperfusion. The cerebral blood flow was measured with a laser Doppler flowmeter. Neuronal death in the CA1 region was observed by hematoxylin-eosin staining, and the number of live neurons was assessed by cell counting under a light microscope. The levels of oxidative products MDA and 8-iso-PGF2α, inflammatory factors IL-1β and TNF-α, and the activities of anti-oxidative enzymes SOD and CAT were assayed by specific enzyme-linked immunosorbent assay (ELISA) kits, respectively. We found that relief of carotid stenosis and ischemic postconditioning could increase cerebral blood flow. When stenosis was relieved, the percentage of live neurons was 66.6% ± 6.2% on day 3 and 62.3% ± 9.8% on day 27, which was significantly higher than 55.5% ± 4.8% in stenosis group. Ischemic postconditioning markedly improved the live neurons to 92.5% ± 6.7% on day 3 and 88.6% ± 9.1% on day 27. Further study showed that, neuronal death caused by relief of stenosis is associated with increased oxidative stress and enhanced inflammatory response, and the protection of ischemic postconditioning is related to inhibition of oxidative stress and suppression of inflammatory response.

EFFECT OF POSTCONDITIONING AND DELAYED POSTCONDITIONING ON ENDOTHELIAL FUNCTION IN ELDERLY PATIENTS WITH CORONARY DISEASE DURING ISCHAEMIA-REPERFUSION

ObjectivesAlthough successful restoration of blood flow is mandatory of salvage of ischaemic tissue, reperfusion can paradoxically place tissue of further injury. The aim of this study was to observe the...

P32 H2S post-conditioning protect rat myocardium from ischemia reperfusion injury involved in endoplasmic reticulum stress

Background In the process of myocardial ischemia and reperfusion (I/R), hypoxia, deficient glucose, ATP depletion, calcium overload and a large number of free radicals can induce endoplasmic reticulum stress (ERS), and excessive endoplasmic reticulum stress will induce apoptosis and increase the myocardial I/R injury. Recent studies have found that the new endogenous gaseous signal molecule hydrogen sulfide (H 2 S) was involved in myocardial ischemia postconditioning and alleviated ischemia/reperfusion injury, and that exogenous H 2 S postconditioning has a protective effect on the isolated heart ischemia–reperfusion injury. However, the precise mechanism that hydrogen sulfide protect heart from myocardial I/R injury remain unclear. Our study aimed to investigate whether hydrogen sulfide protect myocardium from I/R injury by inhibiting the I/R-induced excessive endoplasmic reticulum stress in rat heart. Methods Sprague–Dawley rats were randomly divided into 5 groups ( n = 12 in each): Sham group, I/R group, I/R + NaHS (sodium hydrosulfide, an H 2 S donor) groups (H 2 S post-conditioning group), I/R + TUDCA (Tauro Ursodesoxy Cholic Acid, an endoplasmic reticulum stress blocker) group and I/R + TUDCA + NaHS group. NaHS 14 μmol/kg and TUDCA 25 mg/kg were injected i.p. after 30 min of myocardial ischemia and within reperfusion 10 min. The myocardial I/R rats were subjected to ischemia by 30 min of coronary artery branch of left anterior descending occlusion followed by 2 h of reperfusion. During myocardial I/R, electrocardiogram (ECG, lead II) was monitored continuously, arrhythmias rating was assessed according to the standard of Lambeth meeting. At the end of the reperfusion, myocardial infarct size was examined by triphenyltetrazolium chloride (TTC) staining, serum concentration of H 2 S was determined with a spectrophotometer, myocardial apoptosis was detected by TUNEL and the protein levels of GRP78, CHOP were assayed by Western blotting. Results Compared with the Sham group, the H 2 S concentration in the serum of the I/R group was significantly decrease ( p p p 2 S concentrations of I/R + NaHS group were significantly increased ( p 2 S into rat/H 2 S post-conditioning could decrease the arrhythmia score and reduce myocardial infarct size significantly. The apoptotic rate was also decreased by exogenous H 2 S post-conditioning. The decrease of GRP78 and CHOP protein level in I/R could be partly reversed by H 2 S post-conditioning ( p Conclusions NaHS postconditioning could protect rat myocardiocytes from myocardial ischemia–reperfusion injury partly by inhibition of H 2 S on excessive endoplasmic reticulum stress induced by myocardiac ischemia/reperfusion.

Posztkondicionálás – A távoli szervi dysfunctiók ellenszere?

The ischemia-reperfusion injury of the small intestine is a condition of high mortality, which occurs following superior mesenteric artery (SMA) embolization or circulatory redistribution. The aim of the study was to evaluate the local and systemic effects of postconditioning in a rat model of small intestine ischemia-reperfusion. Male Wistar rats underwent 60 min ischemia by the clamping of the SMA, followed by 6 hrs of reperfusion. The animals (n = 30) were randomized into three groups: sham-operated, control-, and postconditioned. Postconditioning was performed at the very onset of reperfusion by 6 alternating cycles of 10-10 seconds reperfusion/reocclusion, for a total of 2 min. At the end of the reperfusion blood and tissue (small intestine, lungs, kidney, liver) samples were taken for histological examination. The antioxidant status of small intestine was measured from intestinal homogenates. Histologic results revealed increased damage in control-group lungs, kidney, liver and small intestine in comparison with the postconditioned group. The injury was supported by significantly higher wet/dry weight ratio (p = 0.026), and serum levels of creatinine (p = 0.013), ASAT (p = 0.038), LDH (p = 0.028) and CK (p = 0.038) in the control group. The postconditioned group showed lower serum IL-6 levels (420 pg/ml vs. 188 pg/ml), as well as significantly higher mucosal antioxidant concentration. Postconditioning was able to decrease not only local, but the systemic damage intensity also, after a small intestinal ischemic-reperfusion episode.

Roles of PI3K/Akt and JAK/STAT signal transduction pathways in reduction of myocardial ischemia/reperfusion injury by postconditioning with α7nAChR agonist in rats

Objective To evaluate the roles of PI3K/Akt and JAK/STAT signal transduction pathways in reduction of myocardial ischemia/reperfusion (I/R) injury by postconditioning with α subunit-containing nicotinic acetylcholine receptor (α7nAChR) agonist in rats.Methods Sixty Sprague-Dawley rats,weighing 290-320 g,were randomly divided into 4 groups (n =15 each):I/R group,ischemic preconditioning group (IPC group),ischemic postconditioning group (IPOC group) and postconditioning with specific α7nAChR agonist PNU282987 group ( PNU group ).Myocardial I/R was produced by 30 min occlusion of left anterior descending coronary artery followed by 180 min reperfusion in the 4 groups.The animals were subjected to 3 cycles of 5 min myocardial ischemia and 5 min reperfusion before 30 min myocardial ischemia in IPC group.The animals underwent 3 cycles of 10 s myocardial ischemia at 5 s intervals before 180 min reperfusion in group IPOC.PNU282987 2.4 mg/kg was injected intraperitoneally immediately before the reperfusion.At 60 min of reperfusion,5 rats in each group were sacrificed and the hearts were removed to determine the expression of Akt and STAT3 mRNA,phosphorylated Akt (p-Akt) and phosphorylated STAT3 (p-STAT3) in myocardial tissues.The left 10 rats in each group were sacrificed at 180 min of reperfusion and the hearts were removed to measure the infarct size.Results Compared with I/R group,the expression of STAT3 mRNA and p-Akt was significantly up-regulated in IPC group,and the expression of p-Akt and p-STAT3 was significantly up-regulated in IPOC group ( P ＜ 0.05).The infarct size was significantly reduced in IPC,IPOC and PNU groups compared with I/R group ( P ＜ 0.05 ).Conclusion The mechanism by which α7nAChR agonist postconditioning reduces myocardial I/R injury is not related to PI3K/Akt and JAK/STAT signal transduction pathways in rats. Key words: 1-Phosphatidylinositol 3-kinase; Protein-serine-threonine kinases; Receptors, nicotinic; Myocardial reperfusion injury

Effect of Ischaemic Postconditioning on Recovery of Left Ventricular Contractile Function after Acute Myocardial Infarction

This study investigated whether ischaemic postconditioning can improve recovery of myocardial contractile function in acute myocardial infarction patients 1 week and 6 months after angioplasty. A total of 62 patients undergoing direct percutaneous coronary intervention after acute myocardial infarction were randomly assigned to receive four episodes of inflation and deflation of the angioplasty balloon in the early reperfusion period (postconditioned group, n = 32), or no additional intervention (control group, n = 30). Two-dimensional size and left ventricular (LV) global and regional contractile functions were then evaluated by echocardiography at 1 week and 6 months after angioplasty. At 1 week, there were no significant differences in left atrial diameter, LV enddiastolic diameter, LV end-diastolic volume, cardiac output, LV ejection fraction or wall motion score index between the two groups. At 6 months, LV ejection fraction was significantly increased and the wall motion score index significantly reduced in the postconditioned group compared with the control group. Ischaemic postconditioning can improve long-term LV contractile function 6 months after reperfusion following acute myocardial infarction.

Ischaemic Postconditioning Rescues Brain Injury Caused by Focal Ischaemia/Reperfusion via Attenuation of Protein Oxidization

To investigate the effects of ischaemic postconditioning on brain injury and protein oxidization in focal ischaemia/reperfusion. Adult male Wistar rats (n = 30) were randomly divided into sham-operated, ischaemia, and ischaemic postconditioning groups. Ischaemia was produced by middle cerebral artery occlusion and ischaemic postconditioning was performed using three cycles of 30-s/30-s reperfusion/reocclusion after 2 h of ischaemia. Brain infarction size, hydrogen peroxide concentration, superoxide dismutase (SOD), catalase (CAT) and proteasome activities, protein carbonyl derivatives and advanced oxidized protein products (AOPPs) were evaluated. The size of brain infarction after ischaemic postconditioning was significantly smaller compared with the ischaemia group, and was concomitant with significant reduction in protein carbonyl derivatives and AOPPs. The activities of SOD, CAT and proteasomes were elevated by ischaemic postconditioning compared with the ischaemia group. Ischaemic postconditioning is an effective way of reducing the size and effects of brain infarction caused by focal ischaemia/reperfusion, possibly due to a decrease in oxidized protein levels. Decreasing protein oxidization may, therefore, be a useful target for preventing cerebral injury.

Ischemic Postconditioning Inhibits the Renal Fibrosis Induced by Ischemia-reperfusion Injury in Rats

To investigate whether ischemic postconditioning effects on the development of tubulointerstitial fibrosis follow acute renal ischemia-reperfusion. Rat models of warm renal I/R were established by clamping left pedicles for 45 minutes after right nephrectomy, both with and without treatment with ischemic postconditioning, and then reperfused for up to 12 weeks. Hematoxylin-eosin (H&E) and Masson's trichrome staining were used to assess renal fibrosis. The expression spot and protein levels of α-smooth muscle actin (α-SMA), transforming growth factor-β1 (TGF-β1), and phospho-Smad2 were also analyzed. Our data showed that patchy inflammation and tubulointerstitial fibrosis were found 12 weeks later in rats subjected to I/R alone or with postconditioning. Tubulointerstitial fibrosis worsened further in rats subjected to 45-minute ischemia-reperfusion, accompanied by the increased expressions of α-SMA, TGF-β1, and phospho-Smad2 at the end of 12 weeks. In contrast, the above histologic changes and molecular expressions were significantly attenuated in rats of ischemic postconditioning group. The results indicated that 45-minute I/R injury may cause tubulointerstitial fibrosis in the long term, and ischemic postconditioning has beneficial effects on renal fibrosis. Its mechanisms may involve inhibition of the TGF-β1/phospho-Smad2 pathway to exert protective effects.