PURPOSE: Remote ischemic preconditioning (RIPC), induced by repeated bouts of ischemia followed by reperfusion of the arm or leg is a noninvasive strategy to protect a target organ against oxidative stress and injury caused by ischemia and reperfusion. Interestingly, recent evidence suggests that RIPC may also improve exercise performance by increasing maximal oxygen consumption, but such finding remain equivocal. As such, the purpose of the study was to examine the effect of RIPC on exercise performance in healthy individuals. METHODS: In a randomized cross-over design, 17 healthy male participants (age, 23±3 years) were exposed to either a sham control (six cycles of 5 minutes bilateral thigh cuff occlusion at 20 mm Hg) or RIPC (six cycles of 5 minutes bilateral thigh cuff occlusion at 180 mm Hg) an hour before a maximal exercise test. We measured maximal oxygen consumption, power output, heat rate, blood pressure, and blood lactate as exercise performance parameters during a maximal exercise test performed on an upright bicycle. RESULTS: Compared with the sham control, RIPC improved maximal oxygen consumption (7.4%, p=0.025) and maximal power output (11.5%, p=0.010), whereas other exercise performance parameters remained unchanged with RIPC (p>0.05). CONCLUSION: Taken together, the improvements in maximal oxygen consumption and maximal power output induced by RIPC may suggest that RIPC should be considered as a method for improving exercise performance.
Arm ; Blood Circulation ; Blood Pressure ; Cross-Over Studies ; Exercise Test ; Exercise Tolerance* ; Hot Temperature ; Humans ; Ischemia ; Ischemic Preconditioning* ; Lactic Acid ; Leg ; Male ; Methods ; Oxidative Stress ; Oxygen Consumption ; Reperfusion ; Thigh ; Young Adult*

BACKGROUNDPlasma transfusion is a common clinical practice. Remote ischemic preconditioning (RIPC) protects organs against ischemia-reperfusion (IR) injury. Whether preconditioned plasma (PP), collected at late phase after RIPC, could protect organs against IR injury in vivo is unknown. This study explored whether transfusion of PP could reduce myocardial infarct size (IS) after IR in rat in vivo.

METHODSEighty Lewis rats were randomized to eight groups (n = 10 for each group). Two groups of plasma donor rats donated plasma at 48 h after transient limb ischemia (PP) or control protocol (nonpreconditioned plasma [NPP]). Six groups of recipient rats received normal saline (NS; NS-IR 1, and NS-IR 24 groups), NPP (NPP-IR 1 and NPP-IR 24 groups), or PP (PP-IR 1 and PP-IR 24 groups) at one or 24 h before myocardial IR. Myocardial IR consisted of 30-min left anterior descending (LAD) coronary artery occlusion and 180-min reperfusion. The area at risk (AAR) and infarct area were determined by double-staining with Evans blue and triphenyltetrazolium chloride. IS was calculated by infarct area divided by AAR. This was a 3 × 2 factorial design study, and factorial analysis was used to evaluate the data. If an interaction between the fluid and transfusion time existed, one-way analysis of variance with Bonferroni correction for multiple comparisons was used to analyze the single effects of fluid type when the transfusion time was fixed.

RESULTSIS in the NPP-IR 1 and PP-IR 1 groups was smaller than in the NS-IR 1 group (F = 6.838, P = 0.005; NPP-IR 1: 57 ± 8% vs. NS-IR1: 68 ± 6%, t = 2.843, P = 0.020; PP-IR 1: 56 ± 8% vs. NS-IR 1: 68 ± 6%, t = 3.102, P = 0.009), but no significant difference was detected between the NPP-IR 1 and PP-IR 1 groups (57 ± 8% vs. 56 ± 8%, t = 0.069, P = 1.000). IS in the NPP-IR 24 and PP-IR 24 groups was smaller than in the NS-IR 24 group (F = 24.796, P< 0.001; NPP-IR 24: 56% ± 7% vs. NS-IR 24: 68 ± 7%, t = 3.102, P = 0.026; PP-IR 24: 40 ± 9% vs. NS-IR 24: 68 ± 7%, t = 7.237, P< 0.001); IS in the PP-IR 24 group was smaller than in the NPP-IR 24 group (40 ± 9% vs. 56 ± 7%, t = 4.135, P = 0.002).

CONCLUSIONTransfusion of PP collected at late phase after remote ischemic preconditioning could reduce IS, suggesting that late-phase cardioprotection was transferable in vivo.

Animals ; Blood Component Transfusion ; methods ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Infarction ; etiology ; prevention & control ; Myocardial Reperfusion Injury ; complications ; Plasma ; Rats

BACKGROUND: The aim of this study was to investigate the effects of remote ischemic conditioning on ischemia-reperfusion injury in rat muscle flaps histopathologically and biochemically. METHODS: Thirty albino rats were divided into 5 groups. No procedure was performed in the rats in group 1, and only blood samples were taken. A gracilis muscle flap was elevated in all the other groups. Microclamps were applied to the vascular pedicle for 4 hours in order to achieve tissue ischemia. In group 2, no additional procedure was performed. In groups 3, 4, and 5, the right hind limb was used and 3 cycles of ischemia-reperfusion for 5 minutes each (total, 30 minutes) was applied with a latex tourniquet (remote ischemic conditioning). In group 3, this procedure was performed before flap elevation (remote ischemic preconditoning). In group 4, the procedure was performed 4 hours after flap ischemia (remote ischemic postconditioning). In group 5, the procedure was performed after the flap was elevated, during the muscle flap ischemia episode (remote ischemic perconditioning). RESULTS: The histopathological damage score in all remote conditioning ischemia groups was lower than in the ischemic-reperfusion group. The lowest histopathological damage score was observed in group 5 (remote ischemic perconditioning). CONCLUSIONS: The nitric oxide levels were higher in the blood samples obtained from the remote ischemic perconditioning group. This study showed the effectiveness of remote ischemic conditioning procedures and compared their usefulness for preventing ischemia-reperfusion injury in muscle flaps.
Animals ; Extremities ; Ischemia ; Ischemic Preconditioning ; Latex ; Methods* ; Nitric Oxide ; Rats* ; Reperfusion Injury* ; Tourniquets

BACKGROUND: The aim of this study was to investigate the effects of remote ischemic conditioning on ischemia-reperfusion injury in rat muscle flaps histopathologically and biochemically. METHODS: Thirty albino rats were divided into 5 groups. No procedure was performed in the rats in group 1, and only blood samples were taken. A gracilis muscle flap was elevated in all the other groups. Microclamps were applied to the vascular pedicle for 4 hours in order to achieve tissue ischemia. In group 2, no additional procedure was performed. In groups 3, 4, and 5, the right hind limb was used and 3 cycles of ischemia-reperfusion for 5 minutes each (total, 30 minutes) was applied with a latex tourniquet (remote ischemic conditioning). In group 3, this procedure was performed before flap elevation (remote ischemic preconditoning). In group 4, the procedure was performed 4 hours after flap ischemia (remote ischemic postconditioning). In group 5, the procedure was performed after the flap was elevated, during the muscle flap ischemia episode (remote ischemic perconditioning). RESULTS: The histopathological damage score in all remote conditioning ischemia groups was lower than in the ischemic-reperfusion group. The lowest histopathological damage score was observed in group 5 (remote ischemic perconditioning). CONCLUSIONS: The nitric oxide levels were higher in the blood samples obtained from the remote ischemic perconditioning group. This study showed the effectiveness of remote ischemic conditioning procedures and compared their usefulness for preventing ischemia-reperfusion injury in muscle flaps.
Animals ; Extremities ; Ischemia ; Ischemic Preconditioning ; Latex ; Methods* ; Nitric Oxide ; Rats* ; Reperfusion Injury* ; Tourniquets

The expression changes of Rars gene in ischemia-injured neurons were investigated by detecting its translational product arginyl-tRNA synthetase (ArgRS), and the inhibitory effects of ischemic preconditioning (IPC) on Rars gene were explored. Both IPC model and prolonged ischemia (PI) model were established by using the classic oxygen glucose deprivation (OGD) method. The primary cultured neurons were assigned into the following groups: the experimental group (IPC+PI group), undergoing PI after a short period of IPC; the conditional control group (PI control group), subjected to PI without IPC; blank control group, the normally cultured neurons. The Rars transcriptional activities and ArgRS expression levels were measured at different time points after re-oxygenation (3 h/6 h/12 h/24 h). Data were collected and statistically analyzed. Compared to the blank control group, the Rars activities and ArgRS levels were significantly increased in PI control group, peaking at the time point of 6 h after re-oxygenation. Rars activities and ArgRS levels were significantly lower in the experimental group than in the PI control group at different time points after re-oxygenation. PI insult can induce an escalating activity of Rars and lead to ArgRS over-expression in primary cultured neurons. IPC can inhibit the increased Rars activity and down-regulate ArgRS expression of ischemia-insulted neurons. This mechanism may confer ischemic tolerance on neurons.
Animals ; Arginine-tRNA Ligase ; biosynthesis ; genetics ; metabolism ; Brain Ischemia ; genetics ; metabolism ; pathology ; Gene Expression Regulation ; genetics ; Glucose ; metabolism ; Humans ; Ischemic Preconditioning ; methods ; Neurons ; metabolism ; pathology ; Oxygen ; metabolism ; Primary Cell Culture ; Rats

PURPOSE: Ischemic preconditioning (IPC), including remote IPC (rIPC) and direct IPC (dIPC), is a promising method to decrease ischemia-reperfusion (IR) injury. This study tested the effect of both rIPC and dIPC on the genes for antioxidant enzymes and endoplasmic reticulum (ER) stress-related proteins. MATERIALS AND METHODS: Twenty rats were randomly divided into the control and study groups. In the control group (n=10), the right hind limb was sham-operated. The left hind limb (IscR) of the control group underwent IR injury without IPC. In the study group (n=10), the right hind limb received IR injury after 3 cycles of rIPC. The IscR received IR injury after 3 cycles of dIPC. Gene expression was analyzed by Quantitative real-time polymerase chain reaction from the anterior tibialis muscle. RESULTS: The expression of the antioxidant enzyme genes including glutathione peroxidase (GPx), superoxide dismutase (SOD) 1 and catalase (CAT) were significantly reduced in IscR compared with sham treatment. In comparison with IscR, rIPC enhanced the expression of GPx, SOD2, and CAT genes. dIPC enhanced the expression of SOD2 and CAT genes. The expression of SOD2 genes was consistently higher in rIPC than in dIPC, but the difference was only significant for SOD2. The expression of genes for ER stress-related proteins tended to be reduced in IscR in comparison with sham treatment. However, the difference was only significant for C/EBP homologous protein (CHOP). In comparison with IscR, rIPC significantly up-regulated activating transcription factor 4 and CHOP, whereas dIPC up-regulated CHOP. CONCLUSION: Both rIPC and dIPC enhanced expression of genes for antioxidant enzymes and ER stress-related proteins.
Activating Transcription Factor 4 ; Animals ; Catalase ; Cats ; Endoplasmic Reticulum* ; Extremities ; Gene Expression ; Glutathione Peroxidase ; Ischemic Preconditioning* ; Methods ; Muscle, Skeletal* ; Placebos ; Rats* ; Real-Time Polymerase Chain Reaction ; Reperfusion Injury ; Superoxide Dismutase

OBJECTIVE: To investigate the effect of limb remote ischemic preconditioning (RIPC) on hepatic ischemia/reperfusion (IR) injury and the underlying mechanisms.
 METHODS: Rats were subjected to partial hepatic IR (60 min ischemia followed by 24 hours reperfusion) with or without RIPC, which was achieved by 3 cycles of 10 min-occlusion and 10 min-
reperfusion at the bilateral femoral arteries interval 30 min before ischemia. Some rats were treated with a new PPAR-γ inhibitor, T0070907, before RIPC.
 RESULTS: At the end of reperfusion, liver injury was significantly increased (increases in Suzike's injury score, AST and ALT release), concomitant with elevated oxidative stress (increases in MDA formation, MPO activity, as well as the decrease in SOD activity) and inflammation (increases in TNF-α and IL-6 levels, decrease in IL-10 content). RIPC improved liver function and reduced histologic damage, accompanied by the increased PPAR-γ activation and autophagosome formation as well as the reduced autophagosome clearance. The beneficial effects of RIPC were markedly attenuated by T0070907, an inhibitor of PPAR-γ.
 CONCLUSION RIPC exerts the protective effects on liver by activation of autophagy via PPAR-γ.
Animals ; Autophagy ; drug effects ; genetics ; physiology ; Extremities ; Interleukin-10 ; metabolism ; Interleukin-6 ; metabolism ; Ischemia ; Ischemic Preconditioning ; methods ; Liver ; injuries ; Liver Diseases ; prevention & control ; Oxidative Stress ; drug effects ; PPAR gamma ; antagonists & inhibitors ; Rats ; Reperfusion Injury ; prevention & control ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo study the protective effect of sufentanil preconditioning against myocardial ischemia-reperfusion (I/R) injury and the role of PI3K/Akt signaling pathway.

METHODSSixty male SD rats weighing 250-350 g were randomly divided into 5 equal groups, namely the sham-operated group, I/R group, sufentanil preconditioning group (Spc group), sufentanil preconditioning +PI3K inhibitor group (Spc+W group), and PI3K inhibitor group (W group). Myocardial I/R model was established by ligation of the anterior descending branch of the left coronary artery for 30 min followed by reperfusion for 120 min. Sufentanil was administered in 3 doses via the femoral vein before the occlusion, each at 1 µg/kg infused within 5 min at a 5-min interval. In Spc+W and W groups, PI3K inhibitor wortmannin (15 µg/kg) was given intravenously 5 min before sufentanil preconditioning and 35 min before ischemia, respectively. Heart rate and mean arterial pressure (MAP) were continuously monitored during I/R. At the end of reperfusion, blood samples were obtained to determine plasma activation of CK-MB and LDH. Acute infarct size was measured by triphenyltetrazolium chloride staining, and the myocardial tissues were obtained to detect the expression of phosphorylated Akt using Western blotting.

RESULTSPhosphorylated Akt expression was significantly up-regulated in I/R and Spc groups as compared with the sham group, and was significantly higher in Spc group than in I/R group. After reperfusion, sufentanil preconditioning significantly decreased myocardial infarct size (P<0.01) and lowered the levels of CK-MB (P<0.01) and LDH (P<0.01) compared with those in the I/R group. The I/R , Spc+W and W groups showed no significant differences in myocardial infarct size or the levels of CK-MB and LDH.

CONCLUSIONThe protective effect of sufentanil preconditioning against myocardium against I/R injury in rats may involve PI3K/Akt signaling pathway activation.

Animals ; Ischemic Preconditioning, Myocardial ; methods ; Male ; Myocardial Reperfusion Injury ; metabolism ; prevention & control ; Proto-Oncogene Proteins c-akt ; metabolism ; Rats ; Signal Transduction ; Sufentanil ; pharmacology

OBJECTIVETo study the effect of adenosine preconditioning on cell apoptosis and expressions of glucose-regulated protein (GRP-78) and cysteinyl aspartate-specific protease 12 (caspase-12) in rats with spinal cord ischemia-reperfusion injury.

METHODSTwenty-seven rats were randomized into 3 equal groups and subjected to sham operation (group A), spinal cord ischemia-reperfusion injury (group B), or ischemia-reperfusion injury with adenosine treatment. Spinal cord ischemia-reperfusion injury was induced by cross-clamping of the abdominal aorta inferior to the left renal artery. The spinal cord function was assessed using the Modified Tarlov Scale at 6, 12, and 24 h after reperfusion. At 24 h after reperfusion, histological analysis was carried out with HE staining; cell apoptosis and viability were determined with TUNEL staining, and the expressions of GRP-78 and caspase-12 proteins were determined with Western blotting.

RESULTSHE staining of the spinal cord showed extensive spinal cord injury such as cell edema in group B as compared with group C. Compared with group A, group B showed a significantly increased number of apoptotic cells; the number of apoptotic cells in group B was greater than that in group C. Compared with group B, group C showed significantly increased GRP-78 expression (P<0.01) and decreased caspase-12 expression (P<0.01).

CONCLUSIONAdenosine can up-regulate GRP-78 expression and down-regulate caspase-12 expression, and protects the spinal cord against ischemia-reperfusion injury by inhibiting cell apoptosis.

Adenosine ; pharmacology ; Animals ; Apoptosis ; drug effects ; Caspase 12 ; metabolism ; Heat-Shock Proteins ; metabolism ; Ischemic Preconditioning ; methods ; Male ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury ; metabolism ; Spinal Cord Ischemia ; metabolism

OBJECTIVETo explore the expression of p-p38 MAPK protein and the number of astrocytes expressing p-p38 MAPK in CA1 hippocampus in rats during the induction of brain ischemic tolerance induced by intermittent hypobaric hypoxia (IH) preconditioning.

METHODSThirty healthy adult male Wistar rats were randomly divided into 6 groups (n = 5 in each group): sham 0 min group, IH + sham 0 min group, sham 7 d group, IH + sham 7 d group, Ischemia (Is) 7 d group, and IH + Is 7 d group. Neuropathological evaluation was performed by thionine staining in CA1 hippocampus in rats. The expression of p-p38 MAPK in CA1 hippocampus was observed by immunohistochemical staining. And the number of astrocytes expressing p-p38 MAPK was observed by immunofluorescent double labeling.

RESULTSThe results showed that IH preconditioning induced brain ischemic tolerance successfully. At the same time, IH preconditioning obviously up-regulated the expression of p-p38 MAPK protein in CA1 hippocampus, and also increased the number of astrocytes expressing p-p38 MAPK.

CONCLUSIONIt might be concluded that IH preconditioning induced brain ischemic tolerance by up-regulating the expression of p-p38 MAPK protein in pyramidal neurones and astrocytes.

Animals ; Astrocytes ; enzymology ; pathology ; Brain Ischemia ; enzymology ; pathology ; Disease Models, Animal ; Hippocampus ; enzymology ; Hypoxia ; Ischemic Preconditioning ; methods ; Male ; Phosphorylation ; Pressure ; Rats ; Rats, Wistar ; p38 Mitogen-Activated Protein Kinases ; metabolism