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*

BACKGROUND AND PURPOSE: Recent single-center series and meta-analyses suggest that mechanical thrombectomy (MT) without prior intravenous thrombolysis (IVT) might be equally effective to bridging therapy. We analyzed, within the Endovascular Treatment in Ischemic Stroke (ETIS) prospective observational registry, the angiographic and clinical outcomes after IVT+MT versus MT alone. METHODS: From December 2012 to December 2016, a total of 1,507 consecutive patients with a proximal arterial occlusion of the anterior circulation were treated by MT. Of these, 975 (64.7%) received prior IVT. Immediate angiographic and clinical outcomes at 90 days (modified Rankin Scale [mRS]) were compared between the two groups while checking for propensity score, matched-propensity score and by inverse probability of treatment weighting (IPTW) propensity score method. RESULTS: Favorable outcome (mRS 0 to 2) was more frequently achieved after IVT+MT (n=523, 53.6%) than after MT alone (n=222, 41.8%) with an unadjusted odds ratio (OR) for bridging therapy of 1.61 (95% confidence interval [CI], 1. 29 to 2.01). This difference remained not significant in matched-propensity score cohort (OR, 1.21; 95% CI, 0.90 to 1.63) although it remained according to adjusted propensity score (OR, 1.31; 95% CI, 1.02 to 1.68) and IPTW (OR, 1.37; 95% CI, 1.09 to 1.73) analyses. A significant difference was found in terms of excellent outcome (mRS 0 to 1) (adjusted OR, 1.63; 95% CI, 1.25 to 2.11) and successful reperfusion (adjusted OR, 1.58; 95% CI, 1.33 to 2.15). No differences in intracerebral hemorrhage or in allcause mortality within 90 days were found between groups. CONCLUSIONS: IVT prior to MT is associated with increased excellent outcome and successful reperfusion rates. These findings support the use of bridging therapy.
Cerebral Hemorrhage ; Cohort Studies ; Humans ; Methods ; Mortality ; Odds Ratio ; Propensity Score ; Prospective Studies ; Reperfusion ; Silver* ; Stroke* ; Thrombectomy* ; Tissue Plasminogen Activator

This study evaluated whether renal perfusion changes can be noninvasively estimated by using contrast-enhanced ultrasonography (CEUS) in renal ischemia-reperfusion injury and investigated the correlation between renal perfusion measured by CEUS and necrosis and apoptosis of renal tubular epithelial cells. In six dogs with experimentally induced renal ischemia-reperfusion injury, changes in time to peak intensity, peak intensity, and area under the curve were measured on CEUS. Peak intensity and area under the curve of the renal cortex began to decrease on day 1 (about 20% lower than baseline) and reached the lowest levels (about 50% of baseline) on day 4. They then gradually increased until day 10, at which time peak intensity was about 87% and area under the curve was about 95% of baseline; neither fully recovered. Both parameters were strongly correlated with the necrosis scores on histopathologic examination on day 4 (r = −0.810 of peak intensity and r = −0.886 of area under the curve). CEUS allowed quantitative evaluation of perfusion changes in acute renal ischemia-reperfusion injury, and CEUS results were correlated with renal tubular damage on histopathologic examination. Thus, CEUS could be a noninvasive, quantitative diagnostic method for determining progress of renal ischemia-reperfusion injury.
Animals ; Apoptosis ; Dogs* ; Epithelial Cells ; Evaluation Studies as Topic* ; Methods ; Necrosis ; Perfusion* ; Reperfusion Injury* ; Ultrasonography*

The prediction of successful recanalization following thrombolytic or endovascular treatment may be helpful to determine the strategy of recanalization treatment in acute stroke. Thrombus can be detected using noncontrast computed tomography (CT) as a hyperdense artery sign or blooming artifact on a T2*-weighted gradient-recalled image. The detection of thrombus using CT depends on slice thickness. Thrombus burden can be determined in terms of the length, volume, and clot burden score. The thrombus size can be quantitatively measured on thin-section CT or CT angiography/magnetic resonance angiography. The determination of thrombus size may be predictive of successful recanalization/non-recanalization after intravenous thrombolysis and endovascular treatment. However, cut-offs of thrombus size for predicting recanalization/non-recanalization are different among studies, due to different methods of measurements. Thus, a standardized method to measure the thrombus is necessary for thrombus imaging to be useful and reliable in clinical practice. Software-based measurements may provide a reliable and accurate assessment. The measurement should be easy and rapid to be more widely used in practice, which could be achieved by improvement of the user interface. In addition to prediction of recanalization, sequential measurements of thrombus volume before and after the treatment may also be useful to determine the efficacy of new thrombolytic drugs. This manuscript reviews the diagnosis of thrombus, prediction of recanalization using thrombus imaging, and practical considerations for the measurement of thrombus burden and density on CT.
Angiography ; Arteries ; Artifacts ; Diagnosis ; Endovascular Procedures ; Fibrinolytic Agents ; Methods ; Reperfusion* ; Stroke* ; Thrombolytic Therapy ; Thrombosis*

BACKGROUNDIt is well documented that sevoflurane postconditioning (SP) has a significant myocardial protection effect. However, the mechanisms underlying SP are still unclear. In the present study, we investigated the hypothesis that the Pim-1 kinase played a key role in SP-induced cardioprotection by regulating dynamics-related protein 1 (Drp1).

METHODSA Langendorff model was used in this study. Seventy-two rats were randomly assigned into six groups as follows: CON group, ischemia reperfusion (I/R) group, SP group , SP+proto-oncogene serine/threonine-protein kinase 1 (Pim-1) inhibitor II group, SP+dimethylsufoxide group, and Pim-1 inhibitor II group (n = 12, each). Hemodynamic parameters and infarct size were measured to reflect the extent of myocardial I/R injury. The expressions of Pim-1, B-cell leukemia/lymphoma 2 (Bcl-2) and cytochrome C (Cyt C) in cytoplasm and mitochondria, the Drp1 in mitochondria, and the total Drp1 and p-Drp1ser637 were measured by Western blotting. In addition, transmission electron microscope was used to observe mitochondrial morphology. The experiment began in October 2014 and continued until July 2016.

RESULTSSP improved myocardial I/R injury-induced hemodynamic parametric changes, cardiac function, and preserved mitochondrial phenotype and decreased myocardial infarct size (24.49 ± 1.72% in Sev group compared with 41.98 ± 4.37% in I/R group; P< 0.05). However, Pim-1 inhibitor II significantly (P < 0.05) abolished the protective effect of SP. Western blotting analysis demonstrated that, compared with I/R group, the expression of Pim-1 and Bcl-2 in cytoplasm and mitochondria as well as the total p-Drp1ser637 in Sev group (P < 0.05) were upregulated. Meanwhile, SP inhibited Drp1 compartmentalization to the mitochondria followed by a reduction in the release of Cyt C. Pretreatment with Pim-1 inhibitor II significantly (P < 0.05) abolished SP-induced Pim-1/p-Drp1ser637 signaling activation.

CONCLUSIONSThese findings suggested that SP could attenuate myocardial ischemia-reperfusion injury by increasing the expression of the Pim-1 kinase. Upregulation of Pim-1 might phosphorylate Drp1 and prevent extensive mitochondrial fission through Drp1 cytosolic sequestration.

Animals ; Dynamins ; metabolism ; Hemodynamics ; drug effects ; Ischemic Postconditioning ; methods ; Male ; Methyl Ethers ; therapeutic use ; Mitochondria ; drug effects ; metabolism ; Myocardial Reperfusion Injury ; metabolism ; prevention & control ; Proto-Oncogene Proteins c-pim-1 ; antagonists & inhibitors ; metabolism ; Quinazolinones ; pharmacology ; Rats ; Rats, Sprague-Dawley

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

Fucoidan has been reported to exhibit various beneficial activities ranging from to antivirus and anticancer properties. However, little information is available about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our study aimed to explore the effects of fucoidan on cerebral IRI, as well as the underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160 mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally injected from 7 days before the rats were induced to cerebral IRI model with middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion, neurological deficits and the total infarct volume were determined. The levels of inflammation-associated cytokines (interleukin (IL)-1β, IL-6, myeloperoxidase (MPO), and tumor necrosis factor (TNF)-α), oxidative stress-related proteins (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen-activated protein kinase (MAPK) pathway (phosphorylation-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were measured. Results showed that administration of fucoidan significantly reduced the neurological deficits and infarct volume compared to the IRI+S group in a dose-dependent manner. Also, fucoidan statistically decreased the levels of inflammation-associated cytokines, and oxidative stress-related proteins, inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a protective role in cerebral IRI might be by inhibition of MAPK pathway.
Animals ; Apoptosis ; Brain ; Cytokines ; Enzyme-Linked Immunosorbent Assay ; Infarction, Middle Cerebral Artery ; Interleukin-6 ; Lymphoma, B-Cell ; Methods ; Peroxidase ; Phosphotransferases ; Protein Kinases ; Rats ; Rats, Sprague-Dawley ; Reperfusion ; Reperfusion Injury* ; Superoxide Dismutase ; Tumor Necrosis Factor-alpha

BACKGROUND: Paraplegia is a devastating complication following operations on the thoracoabdominal aorta. We investigated whether histidine-tryptophan-ketoglutarate (HTK) solution could reduce the extent of ischemia/reperfusion (IR) spinal cord injuries in a rat model using a direct delivery method. METHODS: Twenty-four Sprague-Dawley male rats were randomly divided into four groups. The sham group (n=6) underwent a sham operation, the IR group (n=6) underwent only an aortic occlusion, the saline infusion group (saline group, n=6) underwent an aortic occlusion and direct infusion of cold saline into the occluded aortic segment, and the HTK infusion group (HTK group, n=6) underwent an aortic occlusion and direct infusion of cold HTK solution into the occluded aortic segment. An IR spinal cord injury was induced by transabdominal clamping of the aorta distally to the left renal artery and proximally to the aortic bifurcation for 60 minutes. A neurological evaluation of locomotor function was performed using the modified Tarlov score after 48 hours of reperfusion. The spinal cord was harvested for histopathological and immunohistochemical examinations. RESULTS: The spinal cord IR model using direct drug delivery in rats was highly reproducible. The Tarlov score was 4.0 in the sham group, 1.17±0.75 in the IR group, 1.33±1.03 in the saline group, and 2.67±0.81 in the HTK group (p=0.04). The histopathological analysis of the HTK group showed reduced neuronal cell death. CONCLUSION: Direct infusion of cold HTK solution into the occluded aortic segment may reduce the extent of spinal cord injuries in an IR model in rats.
Animals ; Aorta ; Cell Death ; Constriction ; Humans ; Male ; Methods ; Models, Animal ; Neurons ; Neuroprotective Agents* ; Paraplegia ; Rats ; Rats, Sprague-Dawley ; Renal Artery ; Reperfusion ; Reperfusion Injury ; Spinal Cord Injuries* ; Spinal Cord*