Humans ; Ischemic Postconditioning ; Myocardial Reperfusion Injury

Humans ; Ischemia ; metabolism ; pathology ; therapy ; Ischemic Postconditioning ; methods ; Myocardial Reperfusion Injury ; metabolism ; pathology ; therapy

OBJECTIVETo investigate the protective effect of ischemic postconditioning (IP) against different degrees of testicular ischemia-reperfusion (IR) injury in rabbits.

METHODSForty-two white male rabbits were equally randomized into 7 groups: a control, 3 IR (R1, R2 and R3), and 3 IP (P1, P2 and P3) groups. Testicular models of different degrees of ischemia were established in the IR and IP groups. Before reperfusion, ultrasonography showed homogeneous echoes with slightly decreased blood flow in R1 and P1, heterogeneous echoes with obviously decreased blood flow in R2 and P2, lamellar or fragmental low echo areas absent of blood flow signals in R3 and P3. Then the IR groups were directly subjected to perfusion, and the IP groups to 3 episodes of 30-second reperfusion followed by 30-second ischemia. All the groups underwent contrast-enhanced ultrasonography (CEUS) before reperfusion and, after 3 days, examined for the contents of malonaldehyde (MDA), superoxide dismutase (SOD) and histology, and observed for the pathological changes of the testicular tissue.

RESULTSBefore reperfusion, no significant differences were found in the CEUS parameters beta, time-to- peak (TTP), peak-base intensity (PBD) and half of declining time (DT/2) between R1 and P1, R2 and P2, and R3 and P3 (P>0.05). There were remarkable differences in MDA and SOD between R1 and P1, and R2 and P2 (P<0.05), but not between R3 and P3 (P >0.05). Johnson's score, apoptosis index and ultrastructure showed marked differences between R1 and P1 (P<0.05) but not between R2 and P2, and R3 and P3 (P >0.05).

CONCLUSIONIP can attenuate IR-induced testis injury, but the effect varies with the degree of ischemia, and its pathological manifestation differs from the biochemical one.

Animals ; Ischemic Postconditioning ; Male ; Malondialdehyde ; analysis ; Rabbits ; Reperfusion Injury ; Superoxide Dismutase ; analysis ; Testis ; pathology

OBJECTIVETo explore the protective effects of two types of ischemic postconditioning (IP) on intestinal mucosa barrier in rabbits with crush injury of the hind limb.

METHODSThis study was conducted between August and December 2008 in the Department of Trauma Surgery, Daping Hospital, Third Military Medical University, Chongqing, China. The model of crush injury to the hind limb of rabbits was firstly developed by a 25 kg object with the right hind limbs fixed by wooden splints, and then two types of IP were established, including occluding/opening the common iliac artery and vein alternatively (traditional IP, IP A) and binding/loosening the proximum of the injured hind limb alternatively (modified IP, IP B). Thirty-six male New Zealand white rabbits were randomly divided into three groups: IP A group, IP B group and control group, with 12 rabbits in each group. The serum levels of diamine oxidase (DAO) and intestinal fatty acid-binding protein (I-FABP) were detected at 2, 6, 12 and 24 hours after injury. Pathological changes of ileum were examined at 24 hours after injury.

RESULTSThe serum levels of I-FABP at 2, 6, 12 and 24 hours after injury in both IP A and IP B groups had a significant decrease, compared with control group. DAO levels also showed the same change trend at 2 and 6 hours after injury, but showed no significant difference between two IP groups. No difference in pathological changes of ileum was found among the three groups.

CONCLUSIONSIP can protect intestinal mucosa barrier function on the model of hind limb crush injury in rabbits. Meanwhile the modified IP B shows the same protection as the traditional IP A, and is worth applying in clinic.

Amine Oxidase (Copper-Containing) ; metabolism ; Animals ; Hindlimb ; injuries ; Intestinal Mucosa ; metabolism ; Ischemic Postconditioning ; Male ; Rabbits

OBJECTIVETo observe whether there are some differences between myocardial postconditioning and remote postconditioning, and whether there is additional cardiac protection when they are used combined during myocardial ischemia/reperfusion injury in rabbits.

METHODSThirty healthy New Zealand rabbits which were randomly divided into 5 groups (n = 5): ischemic control group (CON), sham operation group (Sham), myocardial postconditioning group (MPostC), remote postconditioning group (RPostC), myocardial postconditioning plus remote postconditioning group (MPostC + RPostC). Acute myocardial infarction was induced by 45 minutes occlusion on left circumflex coronary artery (LCX) and 2 hours reperfusion in all anesthetized open-chest rabbits except the Sham, the coronary occlusion and reperfusion were determined by changes of ECG and cardiac color. Skeletal muscle ischemia model was induced by extrinsic iliac arteries occlusion and reperfusion with artery clamps. The condition that the extrinsic iliac arteries were occluded or reperfused could be tested by according to the distal arterial pulse. Plasma creatine kinase (CPK) activity and lactate dehydrogenase (LDH) activity were measured at baseline, the end of ischemia, after 1 hour and 2 hours of reperfusion respectively. The extent of myocardial infarction was assessed by triphenyltetrazolium (TTC) staining and measured by area ratio of AN/AAR.

RESULTSCompared with the Con, myocardial infarct size was significantly reduced in MPostC and RpostC group (P < 0.05). But there was no significant difference between MPostC and RPostC group. Combined MPostC and RPostC markedly enhanced myocardial protection (P < 0.05). The trend of CPK and LDH release was similar to the trend of myocardial infarct size.

CONCLUSIONBoth MPostC and RPostC induced cardiac protection. There was no significant difference between MPostC and RPostC. Combined MPostC and RPostC induced markedly additive effect on myocardial protection.

Animals ; Disease Models, Animal ; Ischemic Postconditioning ; Muscle, Skeletal ; blood supply ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; metabolism ; Rabbits

BACKGROUNDIschemic 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.

METHODSWe 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+IPost, 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.

RESULTSThe 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.

CONCLUSIONSNotch1 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.

Cell Line ; Humans ; Ischemic Postconditioning ; Myocardial Reperfusion Injury ; genetics ; metabolism ; prevention & control ; Receptor, Notch1 ; genetics ; metabolism ; Signal Transduction ; physiology

Animals ; Calcitonin Gene-Related Peptide ; pharmacology ; Ischemic Postconditioning ; Male ; Myocardial Reperfusion Injury ; prevention & control ; Myocardium ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVE: Ischemic postconditioning (IPostC), consisted of transient brain ischemia/reperfusion cycles, is considered to have neuroprotective effect. However, there is no best single protocol of IPostC, because varied factors like species tested and characteristics of the tissue may affect the efficacy of IPostC. Thus, we investgated whether different protocols of IPostC affect neuroprotective effects in experimental animal models. MATERIALS AND METHODS: Through occlusion of middle cerebral artery (MCA) with intraluminal suture, stroke was induced in a transient focal ischemia model in mice. We conducted IPostC via brief and repeated MCA occlusion, 2 minutes after reperfusion, followed by different ischemia and reperfusion protocols. After procedure, functional neurological score and histological examination were evaluated. RESULTS: IPostC with different protocols resulted in diverse effects. Among them, a protocol that consists of 3 cycle of IPostC significantly reduced the infarction size 3 days after stroke. CONCLUSION: IPostC was confirmed to reduce infarction size. The effects of IPostC are definitely affected by differences in the protocol used, including the number of cycles, the duration of individual ischemia/reperfusion episode and the entire duration of the IPostC stimuli.
Animals ; Brain ; Infarction* ; Ischemia ; Ischemic Postconditioning* ; Mice ; Middle Cerebral Artery ; Models, Animal ; Neuroprotective Agents ; Reperfusion ; Stroke* ; Sutures

Ischemic postconditioning (IPost) could decrease ischemia-reperfusion (IR) injury. It has not yet reported whether IPost is useful when ischemic heart disease is accompanied with co-morbidities like hyperthyroidism. The aim of this study was to examine the effect of IPost on myocardial IR injury in hyperthyroid male rats. Hyperthyroidism was induced with administration of thyroxine in drinking water (12 mg/L) over a period of 21 days. After thoracotomy, the hearts of control and hyperthyroid rats were perfused in the Langendorff apparatus and subjected to 30 minutes global ischemia, followed by 120 minutes reperfusion; IPost, intermittent early reperfusion, was induced instantly following ischemia. In control rats, IPost significantly improved the left ventricular developed pressure (LVDP) and +/-dp/dt during reperfusion (p<0.05); however it had no effect in hyperthyroid rats. In addition, hyperthyroidism significantly increased basal NOx (nitrate+nitrite) content in serum (125.5+/-5.4 micromol/L vs. 102.8+/-3.7 micromol/L; p< 0.05) and heart (34.9+/-4.1 micromol/L vs. 19.9+/-1.94 micromol/L; p<0.05). In hyperthyroid groups, heart NOx concentration significantly increased after IR and IPost, whereas in the control groups, heart NOx were significantly higher after IR and lower after IPost (p< 0.05). IPost reduced infarct size (p<0.05) only in control groups. In hyperthyroid group subjected to IPost, aminoguanidine, an inducible nitric oxide (NO) inhibitor, significantly reduced both the infarct size and heart NOx concentrations. In conclusion, unlike normal rats, IPost cycles following reperfusion does not provide cardioprotection against IR injury in hyperthyroid rats; an effect that may be due to NO overproduction because it is restored by iNOS inhibition.
Animals ; Drinking Water ; Heart ; Humans ; Hyperthyroidism ; Ischemia ; Ischemic Postconditioning* ; Male ; Myocardial Ischemia ; Nitric Oxide* ; Rats* ; Reperfusion ; Thoracotomy ; Thyroxine

To investigate whether ischemic postconditioning (IPTC) can promote the recovery of left ventricular impaired regional or global longitudinal systolic function.
 Methods: The trial was divided into a percutaneous coronary intervention (PCI) group, an PCI+IPTC group and a control group. Thirty-two patients with anterior acute anterior wall ST-segment elevation myocardial infarction (STEMI) underwent the first emergency PCI in the PCI group, 28 patients with anterior acute STEMI underwent the combination of PCI and IPTC in the PCI+IPTC group, while 30 patients underwent coronary angiography in the control group. Two-dimensional dynamic echocardiography was collected before operation, 0.5 h, 1 day, 3 days, 1 week, 1 month and 6 months after operation, respectively. The longitudinal strain parameters at different time points were analyzed and compared in the 3 groups.
 Results: The regional longitudinal strain of infracted segments in the PCI+IPTC group after the operation within 1 week was higher than that in the PCI group (P<0.05). The left ventricular global longitudinal strain in the PCI+IPTC group seemed to be higher than that in PCI group after the operation within 1 week, but there was not statistically difference (P>0.05). There was no significant difference in the long-term regional and global longitudinal strains of left ventricle between the PCI+IPTC group and the PCI group (both P>0.05).
 Conclusion: The IPTC can improve the short-term longitudinal systolic function of the reperfused myocardium in patients with acute anterior wall STEMI after PCI.
Anterior Wall Myocardial Infarction ; Humans ; Ischemic Postconditioning ; Myocardium ; Percutaneous Coronary Intervention ; ST Elevation Myocardial Infarction ; Treatment Outcome ; Ventricular Function, Left