Abstract： Ischemia postconditioning is a new concept based on ischemic preconditioning. It has become a hot topic in protection of ischemic-reperfusion injury because of its effective protection, relative ease of application, and postconditioning. However, its precise mechanisms and most effective application methods are still unclear. This review covers recent progress in the understanding, developments (in remote postconditioning and pharmacological postconditioning), applications to the protection of heart, lung, liver, kidney, and brain, mechanisms and appropriate protocol of ischemic post-conditioning.
Objective To investigate the effect of ischemic preconditioning(IPC) on myocardial ischemic reperfusion injury(I/R) of elderly rats. Methods Fiftysix Wistar rats, of which there were 28 aged from 21-23months(elderly rat) and 28 aged from 4-5months(young rat), were used to build isolated heart perfusion Langendorff model. The rats were divided into 7 groups with random number table（8 in each group）: adult control group, adult I/R group, adult IPC group, elderly control group, elderly I/R group, elderly IPC group and elderly enhanced IPC group. The control group underwent a 90-min perfusion without any intervention; the I/R group underwent a 30-min equilibration period, then a 30-min ischemia and a 30-min reperfusion; the IPC group underwent a 10-min equilibration period, then a 5-min ischemia for twice and a 5-min reperfusion, after that a 30-min ischemia and [CM(158-3mm]a 30-min reperfusion; the enhanced IPC group underwent a 10-min equilibration period, then a 5-min ischemia for 4-times and a 5-min reperfusion, after that a 30-min ischemia and a 30-min reperfusion. The recovery rates of cardiac output(CO), left ventricular developed pressure (LVDP), the maximum rising and descending rate of left ventricular pressure (±dp/dtmax) after a 30-min reperfusion were compared among groups. The activity of creatine kinase (CK) in coronary outflow, the level of malonyldialdehyde (MDA) and superoxide dismutase (SOD) before ischemia and after a 30min reperfusion were detected. The myocardial infarction areas were compared among groups. Results After a 30min reperfusion, compared with adult I/R group, in adult IPC group CK reduced significantly(89.48±18.72 U/L vs. 115.76±16.72 U/L，q=6.061，Plt;0.01)，the level of MDA decreased significantly（9.53±3.44 nmol/ml vs. 16.84±2.29 nmol/ml，q=7.732，Plt;0.01)，the level of SOD increased significantly（584.7±122.62 U/ml vs. 429.46±85.24 U/ml，q=4.754，Plt;0.01)，the recovery rates of CO,LVDP,+dp/dtmax and -dp/dtmax increased ignificantly(78.69%±9.68% vs. 65.10%±8.63%，83.61%±8.46% vs. 67.23±8.68%，81.68±8.68% vs. 67.89%±6.89%，89.79%±7.78% vs. 66.79%±8.46%，Plt;0.01), the myocardial infarction areas reduced significantly (5.25%±4.33% vs. 14.75%±8.02%,q=7.458，Plt;0.01)。There was no statistical significance between elderly IPC group and elderly I/R group in the above indexes（Pgt;0.05）.However, There was statistical significances between elderly enhanced IPC group and I/R group. CK reduced significantly (88.60±28.32 U/L vs. 105.76±9.64 U/L，q=5.620，Plt;0.01)，the level of MDA decreased significantly（8.38±3.36 nmol/ml vs. 16.80±3.06 nmol/ml，q=7.500，Plt;0.01)，the level of SOD increased significantly（558.87±78.66 U/ml vs. 433.75±86.65 U/ml，q=7.335，Plt;0.01)，the recovery rates of CO,LVDP,+dp/dtmax and -dp/dtmax increased significantly (77.99%±10.02% vs. 66.26%±9.78%，85.59%±6.67% vs. 73.90%±6.66%，83.87%±9.98% vs. 68.90%±8.68%，86.01%±766% vs. 70.39%±7.98%，Plt;0.01)， the myocardial infarction areas reduced significantly (795%±6.32% vs. 1568%±10.36%,q=8.680， Plt;0.01). 〖WTHZ〗Conclusion The protective effect of IPC on I/R elderly rat hearts has weakened. The enhanced IPC is able to regain the protective effect of IPC on elderly rat hearts.
【Abstract】 Objective To analyze the influencing factors of no-reflow phenomenon after reperfusion in patients with chronic limb ischemia associated with acute thrombosis. Methods Between January 2009 and December 2010, 59 patients (67 limbs) with chronic limb ischemia associated with acute thrombosis were treated. According to whether the no-reflow phenomenon occurred or not, the patients were divided into no-reflow group (19 patients, 21 limbs) and reflow group (40 patients, 46 limbs). Logistic regression was used to analyze the roles of ischemia time, ischemia extent, smoking, hypertension, cardiovascular and cerebrovascular disease, diabetes, surgical procedure, platelet count, fibrinogen (FBG), prostaglandin I2 (PGI2), and thromboxane A2 (TXA2) on no-reflow phenomenon after reperfusion. Results The results of the logistic regression analysis indicated that ischemia time (OR=7.196; 95%CI: 1.679-27.960), ischemia extent (OR=5.116; 95%CI: 1.399-109.338), smoking (OR=6.893; 95%CI: 3.704-2 291.003), diabetes (OR=3.864; 95%CI: 1.009-421.702), PGI2 (OR=7.985; 95%CI: 1.001-1.043), and TXA2 (OR=7.643; 95%CI: 1.011-1.065) were the high risk factors of no-reflow phenomenon. The levels of TXA2 and FBG in no-reflow group were significantly increased and the level of PGI2 was decreased, showing significant differences when compared with the reflow group (P lt; 0.05). However, no significant difference was found in the platelet count between 2 groups (P gt; 0.05). Conclusion Ischemia extent and ischemia time are the main influencing factors of no-reflow phenomenon after reperfusion in patients with chronic limb ischemia associated with acute thrombosis, and the patients combined with smoking or diabetes are high risk population of the no-reflow phenomenon. Postoperative patients with no-reflow phenomenon are at a hypercoagulable state in vivo, in which prostacyclin plays an important role.
Perfusion of free flaps from groin of rabbits, after 12 hours of complete ischemia, with superoxide dismutase (SOD), an oxygen free radical scavenger, would significantly increase the survival rate of these flaps from 18.75% to 75% in the control group. Tissue levels of SOD and malonydialdehyde (MDA, an end product of lipoperoxidation) were measured before ischemia, after ischemia but before reperfusion, and 60 minites after reperfusion. In untreated flap, after 12 hours- ischemia, the SOD content of skin decreased significantly as compared with the SOD content before ischemia, and reperfusion further decreased SOD activity, while the concentration of MDA increased after ischemia and further increased after reperfusion. In the treated flaps, the concentration of SOD was not decrease and MADnot increased after reperfusion. There was a negative correlation between the values of SOD and MDA. These findings suggested that free oxygen radicals playedan important role in the free flap ischemia reperfusion injury. SOD could increase the survival of ischemic free-flaps by reducing lipoperoxidation. The results had significant clinical implications with regard to organ preservation and transplantation.
Objective To collect and analyze published experimental and clinical studies about the protective function of ischemic preconditioning (IPC) to organs, in order to learn the history of IPC, the progress of experimental as well as clinical studies, and explore the mechanism of IPC in organ transplantation. Methods The electronic search of MEDLINE (1966 to Aug. 2009), EMbase (1974 to Aug. 2009) and The Cochrane Library (Issue 2, 2009) were performed to include and exclude the retrieved articles by two reviewers independently. The included studies were further treated for analysis and discriptive review. Results A total of 1 398 papers were included, of which about 75 percent were experimental studies, and only about 25 percent were clinical studies. About 73 percent studies focused on the heart and liver. Althrough the studies about the effects induced by IPC on the heart, brain, spinal cord and liver increased obviously in recent years, the clinical studies concerned the heart and liver operation and transplantation still far lagged behind experimental studies, especially very few clinical studies on the effect induced by IPC on kidney, lung, gastrointestinal tract and pancreas. Conclusion IPC intervention can effectively protect the heart and lung from the I/RI during the surgical and transplatational operations, and the hepat-surgical and living liver transplantational operations. IPC can effectively protect the brain and spinal cord from I/RI, but no protective function to cadaveric liver transplantation. However, the IPC effects on the kidney and gastrointestinal tract are not confirmed and neither is the mechanism of the effect induced by IPC.
Objective To review the research progress of Toll-like receptors （TLRs） signaling and its effects in organ transplantation. Methods The structural and functional features of TLRs and their ligands were summarized，the literatures in recent years about the research progress of TLRs signaling in animal experiment and clinical organ transplantation were reviewed. Results TRLs played an important role in the organ transplantation，the activation of TLRs could activate the specific immune system，and contribute to ischemic reperfusion injury，acute and chronic allograft rejections，and induce the immune tolerance. Early treatment intervention could reduce the activation of TRLs through ischemic reperfusion injury in the organ transplantation，and improve the allograft survival. The efficient immunosuppressive drugs which aimed at the related immunosuppressive target in immune and its signal transduction pathway could reduce ischemic reperfusion injury in the organ transplantation and immune rejection. Conclusions TRLs signaling plays an important role in ischemic reperfusion injury，immune rejection，and immune regulation.
ObjectivesTo explore the mechanisms by which ischmic preconditioning (IPC), ischemic postconditioning (IPO) and IPCIPO exert influence on ischemic reperfusion injury (IRI) of the graft of SD rat after pancreas transplantation. MethodsAfter the establishment of diabetic SD rats model by using streptozotocin, 24 rats suffered from pancreas transplantation and were randomly averagely divided into four groups: I/R group, IPC group, IPO group, and IPC-IPO group. Six diabetic SD rats suffered with sham operation were served as SO group. The blood glucose level of rats in each group was detected before and after reperfusion, the contents of malonaldehyde (MDA) and super oxide dismutase (SOD) of pancreas allograft were tested at 2 h after reperfusion, and the apoptosis index (AI) of pancreas allograft was monitored by using TUNEL method. ResultsThe blood glucose level of rats in each group was not significantly different (Pgt;0.05). In SO group, the blood glucose level of rats was significantly higher than other groups (Plt;0.01). The blood glucose levels of rats after reperfusion decreased from the levels before reperfusion in I/R group, IPC group, IPO group, and IPC-IPO group (Plt;0.05 or Plt;0.01), furthermore the blood glucose level of rats in I/R group was significantly higher than that in abovementioned three groups (Plt;0.01), although among which the difference was not markedly (Pgt;0.05). When compared with I/R group, the MDA contents of rats after reperfusion in IPC group, IPO group， and IPC-IPO group decreased (Plt;0.01), while the SOD contents of rats after reperfusion increased (Plt;0.01). In rats of SO group, the MDA and SOD contents were significantly higher and lower than other groups, respectively (Plt;0.01). The MDA and SOD contents in IPC group, IPO group, and IPC-IPO group were not different (Pgt;0.05). The AI of pancreas allograft at 2 h after reperfusion in I/R group 〔(47.31±4.52)%〕, IPC group 〔(26.25±3.17)%〕, IPO group 〔(24.73±3.62)%〕, and IPC-IPO group 〔(25.5±4.15)%〕 were higher than that in SO group 〔(3.16±0.53)%〕, Plt;0.01. The AI of pancreas allograft in IPC group, IPO group, and IPC-IPO group were not different (Pgt;0.05), but they were lower than that in I/R group (Plt;0.01). Pathological results showed that injury of pancreas allograft in I/R group was most severe. ConclusionsIPO and IPC are associated with comparable effectiveness to protect graft from IRI during pancreas transplantation. The combined protective effects of IPC and IPO do not appear to be additive, which is equal to IPC or IPO alone.
【Abstract】 Objective To investigate the protective role of recombinant human growth hormone (rhGH )in ischemic reperfusion injury of rat liver and its mechanism. Methods One hundred Male rats were randomly divided into two groups: the rhGH group and the control group. In the rhGH group, rhGH were injected （0.2U/100g weight） to rats seven days before the ischemic reperfusion injury, and in the control group, normal saline was injected instead. Serum levels of ALT， TNF-α and IL-1α were tested. Hepatic tissue was sectioned for to detect the level of EC and MDA, the expression of NF-κB and ICAM-1 mRNA on SEC. Ultrastructural characteristics histopathological characteristics were determined also. Results Serum levels of ALT, TNF-α, IL-1α and the contents of MDA in the control group were significantly higher than those in the rhGH group （P＜0.05）. Comparied with control group, rhGH also decreased NF-κB activation, and reduced the expression of ICAM-1 mRNA of SEC in the liver cells （P＜0.05）. Electronic microscopic revealed that the hepatic sinusoidal endothelial cells and the hepatocellular mitochondria were injured in the control group. Pretreatment with the rhGH was able to significantly improved the pathological changes. Conclusion rhGH might confer the protection to ischemic reperfusion injury of rat liver through reducing the expression of NF-κB to down-regulate cytokine (IL-1α,TNF-α), MDA and inhibition the expression of ICAM-1 mRNA.
Objective To study the effects of heat shock proteins (HSPs) in the course of hepatic ischemia reperfusion injury (HIRI), and analyze its mechanism. Methods The relationship between HSPs and HIRI was studied by reviewing literatures. Results HSPs was a kind of stress protein induced after cell was sitmulated by the stress. It could improve body′s tolerance to tough situation. Though hepatic ischemia reperfusion usually results in serious hepatic injury, at the same time it could induce can increase the production of HSPs that can protect liver from and lessen ischemia reperfusion injury. Conclusion HSPs can improve the tolerance to HIRI and lessen injury. In addition, HSPs is thought to be markers of HIRI, and can be used as a efficient indicator to test the level of hepatic injury and assess prognosis.