Beneficial postoperative micro-rheological effects of intraoperative administration of diclophenac or ischemic preconditioning in patients with lower extremity operations –Preliminary data

2021 ◽  
pp. 1-9
Author(s):  
Bela Turchanyi ◽  
Csaba Korei ◽  
Viktoria Somogyi ◽  
Ferenc Kiss ◽  
Katalin Peto ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Blood Rheology ◽  
Erythrocyte Aggregation ◽  
Rheological Parameters ◽  
Control Group ◽  
Tourniquet Time ◽  
Total Knee ◽  
Anti Inflammatory ◽  
Group 5

BACKGROUND: Ischemia-reperfusion (I/R) may worsen blood rheology that has been demonstrated by clinical and experimental data. It is also known that anti-inflammatory agents and preconditioning methods may reduce I/R injury. OBJECTIVE: We aimed to analyze hemorheological alterations in elective knee operations and the effects of intraoperative nonsteroidal anti-inflammatory drug (NSAID) administration and application of ischemic preconditioning. METHODS: Hemorheological variables of 17 patients with total knee replacement or anterior crucial ligament replacement were analyzed. The ischemic (tourniquet) time was 92±15 minutes. Seven patients did not receive NSAID (Control group), 5 patients got i.v. sodium-diclophenac 10 minutes before and 6 hours after reperfusion. Five patients had ischemic preconditioning (3×15 minutes). Blood samples were collected before the ischemia, 10 minutes after reperfusion, on the 1st and 2nd p.o. day. RESULTS: Whole blood viscosity didn’t show notable inter-group differences, except for a slight decrease in the preconditioning group. RBC deformability decreased, erythrocyte aggregation enhanced by the 1st and 2nd p.o. days in Control group. In NSAID and preconditioning groups the changes were moderate, aggregation values significantly lowered compared to the Control group. CONCLUSION: Intraoperatively administered diclophenac or ischemic preconditioning could moderate the deterioration in micro-rheological parameters caused by I/R in patients.

scholarly journals Kidney ischemia and reperfunsion syndrome: effect of lidocaine and local postconditioning

2016 ◽  
Vol 43 (5) ◽  
pp. 348-353 ◽  
Author(s):  
IGOR NAGAI YAMAKI ◽  
RUY VICTOR SIMÕES PONTES ◽  
FELIPE LOBATO DA SILVA COSTA ◽  
VITOR NAGAI YAMAKI ◽  
RENAN KLEBER COSTA TEIXEIRA ◽  
...  
Keyword(s):  
Ischemia Reperfusion ◽  
Serum Levels ◽  
Saline Group ◽  
Renal Ischemia ◽  
Ischemic Postconditioning ◽  
Control Group ◽  
Ischemia And Reperfusion ◽  
Lidocaine Group ◽  
Group 5 ◽  
Group 2

ABSTRACT Objective: to evaluate the effects of blocking the regulation of vascular tone on the ischemia and reperfusion syndrome in rats through the use of lidocaine in the postconditioning technique. Methods: we randomized 35 rats into seven groups of five animals: Group 1- Control; Group 2- Ischemia and Reperfusion; Group 3- Ischemia, Reperfusion and Saline; Group 4- Ischemic Postconditioning; Group 5- Ischemic Postconditioning and Saline; Group 6- Lidocaine; Group 7- Ischemic Postconditioning and Lidocaine. Except for the control group, all the others were submitted to renal ischemia for 30 minutes. In postconditioning groups, we performed ischemia and reperfusion cycles of five minutes each, applied right after the main ischemia. In saline and lidocaine groups, we instilled the substances at a rate of two drops per minute. To compare the groups, we measured serum levels of urea and creatinine and also held renal histopathology. Results: The postconditioning and postconditioning + lidocaine groups showed a decrease in urea and creatinine values. The lidocaine group showed only a reduction in creatinine values. In histopathology, only the groups submitted to ischemic postconditioning had decreased degree of tubular necrosis. Conclusion: Lidocaine did not block the effects of postconditioning on renal ischemia reperfusion syndrome, and conferred better glomerular protection when applied in conjunction with ischemic postconditioning.

Remote Ischemic Preconditioning Protects Against Endothelial Dysfunction in a Human Model of Systemic Inflammation: A Randomized Clinical Trial

2021 ◽  
Author(s):  
Marco Orlandi ◽  
Stefano Masi ◽  
Devina Bhowruth ◽  
Yago Leira ◽  
Georgios Georgiopoulos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Endothelial Dysfunction ◽  
Systemic Inflammation ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Remote Ischemic Preconditioning ◽  
Human Model ◽  
Control Group ◽  
Flow Mediated Dilatation ◽  
And Oxidative Stress

Objective: Inflammation, oxidative stress, and endothelial dysfunction are known to contribute to ischemia-reperfusion injury. Remote ischemic preconditioning (RIPC) protects from endothelial dysfunction and the damage induced by ischemia-reperfusion. Using intensive periodontal treatment (IPT), an established human model of acute systemic inflammation, we investigated whether RIPC prevents endothelial dysfunction and modulates systemic levels of inflammation and oxidative stress. Approach and Results: Forty-nine participants with periodontitis were randomly allocated to receive either 3 cycles of ischemia-reperfusion on the upper limb (N=25, RIPC) or a sham procedure (N=24, control) before IPT. Endothelial function assessed by flow-mediated dilatation of the brachial artery, inflammatory cytokines, markers of vascular injury, and oxidative stress were evaluated at baseline, day 1, and day 7 after IPT. Twenty-four hours post-IPT, the RIPC group had lower levels of IL (interleukin)-10 and IL-12 compared with the control group ( P <0.05). RIPC attenuated the IPT-induced increase in IL-1β, E-selectin, sICAM-3 (soluble intercellular adhesion molecule 3), and s-thrombomodulin levels between the baseline and day 1 ( P for interaction <0.1). Conversely, oxidative stress was differentially increased at day1 in the RIPC group compared with the control group ( P for interaction <0.1). This was accompanied by a better flow-mediated dilatation (mean difference 1.75% [95% CI, 0.428–3.07], P =0.011). After 7 days from IPT, most of the inflammatory markers endothelial-dependent and -independent vasodilation were similar between groups. Conclusions: RIPC prevented acute endothelial dysfunction by modulation of inflammation and oxidation processes in patients with periodontitis following exposure to an acute inflammatory stimulus. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03072342.

scholarly journals The Effects of Coenzyme Q10 on Inflammation Markers in Streptozotocin-Induced Diabetic Rats

2017 ◽  
Vol 45 (1) ◽  
pp. 5
Author(s):  
Deniz Uluisik ◽  
Ercan Keskin
Keyword(s):  
Coenzyme Q10 ◽  
Inflammatory Cytokine ◽  
Diabetic Group ◽  
Control Group ◽  
Inflammation Markers ◽  
Citrate Buffer ◽  
Group 4 ◽  
Cytokine Levels ◽  
Anti Inflammatory ◽  
Group 5

Background: Coenzyme Q10 is a well-known cofactor in the mitochondrial electron transport chain required for ATP production. Coenzyme Q10 is recognized as an intracellular antioxidant that protects cell membrane phospholipids, mitochondrial membrane protein, and plasma low-density lipoprotein against oxidative damage caused by free radicals. Diabetes and its complications have been related to increased levels of free radicals and systemic proinflammatory cytokines and to an abnormal lipid profile. The aim of this study was to investigate the effects of coenzyme Q10 supplementation on some cytokine levels in streptozotocin-induced diabetic rats.Materials, Methods & Results: In this study, 38 healthy, adult male rats were used. The rats were divided into 5 groups. All animals were housed in separated cages during the four weeks. The animals in group 1 was fed standard rat pellets for 4 weeks. It was administered at 0.3 mL corn oil intraperitoneally daily for four weeks in group 2 animals. The animals in group 3 was injected intraperitoneally with 10 mg/kg CoQ10 daily for 4 weeks. Group 4 was made diabetic by subcutaneous injections of streptozotocin at dose of 40 mg/kg in 0.1 M citrate buffer (pH 4.5) single daily dose for two days and group 5 was made diabetic by subcutaneous injections of streptozotocin at dose of 40 mg/kg in 0.1 M citrate buffer (pH 4.5) single daily dose for two days and then was injected intraperitoneally with 10 mg/kg CoQ10 daily for 4 weeks. During the experiment, three animals from group 4 and one animals from group 5 were died due to streptozotocin-induced hypoglycemia. At the end of the study, blood samples were taken from all animals. In these blood samples, IL-4, IL-6, IL-10 and TNF-α plasma levels were determined with ELISA using sandwich enzyme-linked immunosorbent method via commercial kits. In this study, IL-4 level as an anti-inflammatory cytokine significantly decreased (P < 0.05) with diabetes induction compared to control group level. IL-10 level in diabetic group was statistically different (P < 0.05) from control group level. CoQ10 application to diabetic animals improved the falling in IL-10 level of diabetic group (P < 0.05). IL-6 and TNF-α levels in diabetic group significantly increased (P < 0.05) in parallel with each other compared to control group levels. The same parameters were reduced (P < 0.05) by CoQ10 application in diabetic animals.Discussion: In this study, the occurred changes in pro- and anti-inflammatory cytokines with experimentally induced diabetes are expected results and these results are consistent with some studies related diabetes. These results may be considered to hazardous effects and inflammation caused by diabetes on liver, pancreas and other tissues. CoQ10 suppressed the increments in plasma pro-inflammatory cytokine levels, whereas it restored the reducing in anti-inflammatory cytokine levels arising due to diabetes. The obtained results from this study after CoQ10 application supported similar studies used CoQ10 application against deleterious effects of diabetes in animals and humans. Therefore, it is possible to say that CoQ10 may play important role in regulation of imbalance between inflammation markers in diabetes conditions and further studies are needed to clear the beneficial effects of CoQ10 treatment on the other inflammation markers in diabetes status.

Ischemic preconditioning and morphine attenuate myocardial apoptosis and infarction after ischemia-reperfusion in rabbits: role of δ-opioid receptor

2004 ◽  
Vol 287 (4) ◽  
pp. H1786-H1791 ◽  
Author(s):  
Shinji Okubo ◽  
Yujirou Tanabe ◽  
Kenji Takeda ◽  
Michihiko Kitayama ◽  
Seiyu Kanemitsu ◽  
...  
Keyword(s):  
Infarct Size ◽  
Opioid Receptor ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Control Group ◽  
Apoptotic Cells ◽  
Protective Effects ◽  
Δ Opioid Receptor

We examined whether ischemic preconditioning (IPC) attenuates ischemia-reperfusion injury, in part, by decreasing apoptosis and whether the δ-opioid receptor (DOR) plays a pivotal role in the regulation of apoptosis. Rabbits were subjected to 30-min coronary artery occlusion (CAO) and 180 min of reperfusion. IPC was elicited with four cycles of 5-min ischemia and 10-min reperfusion before CAO. Morphine (0.3 mg/kg iv) was given 15 min before CAO. Naloxone (Nal; 10 mg/kg iv) and naltrindole (Nti; 10 mg/kg iv), the respective nonselective and selective DOR antagonists were given 10 min before either morphine or IPC. Infarct size (%risk area) was reduced from 46 ± 3.8 in control to 11.6 ± 1.0 in IPC and 19.5 ± 3.8 in the morphine group (means ± SE; P < 0.001 vs. control). Nal blocked the protective effects of IPC and morphine, as shown by the increase in infarct size to 38.6 ± 7.2 and 44.5 ± 1.8, respectively. Similarly, Nti blocked IPC and morphine-induced protection. The percentage of apoptotic cells (revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay) decreased in IPC (3.6 ± 1.9) and morphine groups (5.2 ± 1.2) compared with control group (12.4 ± 1.6; P < 0.001). Nti pretreatment increased apoptotic cells 11.2 ± 2.2% in IPC and 12.1 ± 0.8% in morphine groups. Nal failed to block inhibition of apoptosis in the IPC group (% of cells: 5.7 ± 1.3 vs. 3.6 ± 1.9 in IPC alone; P > 0.05). These results were also confirmed by nucleosomal DNA laddering pattern. We conclude that IPC reduces lethal injury, in part, by decreasing apoptosis after ischemia-reperfusion and activation of the DOR may play a crucial role in IPC or morphine-induced myocardial protection.

Beneficial effects of remote organ ischemic preconditioning on micro-rheological parameters during liver ischemia-reperfusion in the rat

2018 ◽  
Vol 70 (2) ◽  
pp. 181-190 ◽  
Author(s):  
Zsuzsanna Magyar ◽  
Anita Mester ◽  
Gabor Nadubinszky ◽  
Gabor Varga ◽  
Souleiman Ghanem ◽  
...  
Keyword(s):  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Rheological Parameters ◽  
Liver Ischemia ◽  
Beneficial Effects ◽  
Remote Organ

scholarly journals Noninvasive Delayed Limb Ischemic Preconditioning Attenuates Myocardial Ischemia-Reperfusion Injury in Rats by a Mitochondrial KATP Channel-Dependent Mechanism

2011 ◽  
pp. 271-279 ◽  
Author(s):  
Y.-N. WU ◽  
H. YU ◽  
X.-H. ZHU ◽  
H.-J. YUAN ◽  
Y. KANG ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemic Preconditioning ◽  
Katp Channel ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion ◽  
Dependent Mechanism

We previously demonstrated in rats that noninvasive delayed limb ischemic preconditioning (LIPC) induced by three cycles of 5-min occlusion and 5-min reperfusion of the left hind limb per day for three days confers the same cardioprotective effect as local ischemic preconditioning of the heart, but the mechanism has not been studied in depth. The aim of this project was to test the hypothesis that delayed LIPC enhances myocardial antioxidative ability during ischemia-reperfusion by a mitochondrial KATP channel (mito KATP)-dependent mechanism. Rats were randomized to five groups: ischemia-reperfusion (IR)-control group, myocardial ischemic preconditioning (MIPC) group, LIPC group, IR-5HD group and LIPC-5HD group. The MIPC group underwent local ischemic preconditioning induced by three cycles of 5-min occlusion and 5-min reperfusion of the left anterior descending coronary arteries. The LIPC and LIPC-5HD groups underwent LIPC induced by three cycles of 5-min occlusion and 5-min reperfusion of the left hind limb using a modified blood pressure aerocyst per day for three days. All rats were subjected to myocardial ischemia-reperfusion injury. The IR-5HD and LIPC-5HD groups received the mito KATP channel blocker 5-hydroxydecanoate Na (5-HD) before and during the myocardial ischemia-reperfusion injury. Compared with the IR-control group, both the LIPC and MIPC groups showed an amelioration of ventricular arrhythmia, reduced myocardial infarct size, increased activities of total superoxide dismutase, manganese-superoxide dismutase (Mn-SOD) and glutathione peroxidase, increased expression of Mn-SOD mRNA and decreased xanthine oxidase activity and malondialdehyde concentration. These beneficial effects of LIPC were prevented by 5-HD. In conclusion, delayed LIPC offers similar cardioprotection as local IPC. These results support the hypothesis that the activation of mito KATP channels enhances myocardial antioxidative ability during ischemia-reperfusion, thereby contributing, at least in part, to the anti-arrhythmic and anti-infarct effects of delayed LIPC.

Protective Effects of Astaxanthin on Nephrotoxicity in Rats with Induced Renovascular Occlusion

2020 ◽  
Vol 23 ◽  
Author(s):  
Erkan Arslan ◽  
Hakan Turk ◽  
Murat Caglayan ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Olive Oil ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Control Group ◽  
Tubular Damage ◽  
Total Thiol ◽  
Tnf Α ◽  
Anti Inflammatory

Background: Various effects of Astaxanthin was shown in the studies including its antioxidant, anti-inflammatory, anti-tumor and immunregulator effects. Objective: The aim of this study was to evaluate the beneficial effects of Astaxanthin on renovascular occlusion induced renal injury and to investigate the possible mechanisms. Methods: The rats were randomly assigned into three groups as follows: Group 1: control group (n=12), Group 2: renal ischemiareperfusion injury group (n=12), Group 3: renal ischemia-reperfusion + asthaxantine treated group (n=12). The control group and the renal ischemia-reperfusion group were given 2cc/kg/g olive oil for 7 days before establishing ischemia to renal tissue. Astaxanthin dissolved in olive oil was given orally to the renal ischemia+astaxanthin group for 7 days before inducing renal ischemia. Caspase-(3, 8, 9), GSH, SOD, Total Thiol, TNF-α, IL-6, 8-OHdG were performed for each group. Results: Renal IRI was verified by analysing the pathological changes of renal tissues and the renal functions after renal reperfusion. Much less renal tubular damage was determined the IRI+ASX group in comparison to the IRI group. Caspase-8, -9 and -3 immunoreactivity was observed to be minimal in the control group. Apoptosis was observed to be significantly reduced in the IRI + ASX group with respect to IRI group and close to the level of the control group (p <0.05). Caspase-3 levels of tissue samples were significantly increased in IRI group compared to other groups, but significantly lower in IRI+ASX group with respect to the IRI group (p<0.05). The TOS and OSI levels, indicating increased oxidative stress, were significantly lower in the IRI+ASX group with respect to the IRI group (p <0.001), but still higher than the control group (p <0.001). In addition to GSH, SOD and Total Thiol levels, TAS levels were also significantly higher in IRI + ASX group in comparison to the IRI group (p <0.05). TNF-α, IL-6, lipid hydroperoxide, AOPP and 8-OHdG levels were lower in the IRI+ASX group than the IRI group (p <0.001). MPO, IL-6, TNF-α levels, representing the parameters indicating neutrophil infiltration and inflammation of the renal tissues, significantly increased in IRI group with respect to the other groups (p <0.005). Conclusion: When all the data obtained in our study were evaluated, ASX was determined to prevent renal damage due to renovascular occlusion to a great extent, through complex mechanisms involving antioxidant, anti-inflammatory and antiapopitotic effects. Biochemical, histological and oxidative stress parameters were improved due to ASX.

Abstract 13914: Ischemic Preconditioning Induces MG53 Secretion From the Heart Through H 2 O 2 /PKC-delta Signaling

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Dan Shan ◽  
Yan Zhang ◽  
Rui-ping Xiao
Keyword(s):  
Ischemic Preconditioning ◽  
Cell Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Embryonic Stem ◽  
Underlying Mechanism ◽  
Neonatal Rat ◽  
Control Group ◽  
Systemic Delivery

Introduction: Ischemic heart disease is the leading cause of morbidity and mortality worldwide. Ischemic preconditioning (IPC) is the most powerful intrinsic protection against cardiac ischemia/reperfusion (I/R) injury. Previous studies have shown that a multifunctional TRIM family protein, MG53 (or TRIM72), not only plays an essential role in IPC-mediated cardioprotection, but also as a myokine/cardiokine, can be secreted from the heart and skeletal muscle in response to metabolic stress in addition to its intracellular actions. Hypothesis: We hypothesized that IPC-mediated cardioprotection is causally related to MG53 secretion and figured out the underlying mechanism. Methods and Results: Using proteomic analysis in conjunction with genetic and pharmacological approaches, we examined MG53 secretion in response to IPC and explored the underlying mechanism using rodents in in vivo , isolated perfused hearts, and cultured neonatal rat ventricular cardiomyocytes. IPC profoundly increased perfusate MG53 levels in mouse hearts by 5.50 ± 0.32 and 4.26 ± 0.40 folds from baseline over 0-60 and 60-120 min of reperfusion, respectively. Mechanistically, IPC-induced MG53 secretion is dependent on H 2 O 2 -evoked, Src-mediated phosphorylation of PKC-δ-Y311. Functionally, systemic delivery of recombinant human MG53 proteins (rhMG53) to mimic elevated circulating MG53 not only restored IPC function in MG53-deficient mice, but also protected rodent hearts from I/R injury even in the absence of IPC. Treatment of rhMG53 overtly decreased the infarct size (IF/AAR) induced by I/R compared to the BSA-treated control group (11.9 ± 1.8% vs 27.3 ± 2.0%, P <0.01), and reduced the mortality from 44.7% to 5.3% in rats. Moreover, H 2 O 2 augmented MG53 secretion, and MG53 knockdown exacerbated H 2 O 2 -induced cell injury in human embryonic stem cell-derived cardiomyocytes. Conclusions: In conclusion, IPC and oxidative stress can trigger MG53 secretion from the heart via an H 2 O 2 -PKC-δ-dependent mechanism, and secreted MG53 acts as an essential factor conveying IPC-induced cardioprotection against ischemia/reperfusion injury. Recombinant MG53 proteins can be developed into a novel treatment for various diseases of human heart in which the endogenous MG53 is low.

A Recombinant Thrombomodulin Improves Haemostatic Disturbance and Inflammation in Setpic Patients with DIC

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 2293-2293
Author(s):  
Noritaka Yada ◽  
Kenji Nishio ◽  
Hidetada Fukushima ◽  
Tadahiko Seki ◽  
Yasuyuki Urizono ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Clinical Course ◽  
Conflicts Of Interest ◽  
Control Group ◽  
Fibrinogen Degradation Product ◽  
Soluble Thrombomodulin ◽  
Anti Inflammatory ◽  
Group 5 ◽  
Group Control Group ◽  
Inflammatory Effect

Abstract Abstract 2293 Background: Recently, a recombinant human soluble thrombomodulin (rTM) has become commercially available for patients with disseminated intravascular coagulation (DIC) in Japan, which is composed of the active, extracellular domain of thrombomodulin. However, its anti-thromobotic and anti-inflammatory effect during the clinical course in patients with DIC has not been reported. Aim: To investigate the effect of rTM on mortality, haemostatic disturbance, and inflammation in septic patients with DIC. Methods: The patients with sepsis who met the Japanese diagnostic criteria for acute DIC and showed a level of antithrombin (AT) lower than 70% were recruited and divided into two groups, one group (Control group) treated with AT products and Gabexate mesilate (GM), and the other group (TM group) treated with rTM (0.06 mg kg(-1) for 30 min, once daily) in addition to AT and GM. The effect of rTM during the clinical course were investigated from the differences between TM and Control groups in mortality, DIC scoring, haemostatic and inflammatory markers on days 0, 3, 5, 7 (day 0 is just before initiation of therapy). Results & Discussion: Eighteen patients were included in the TM group, and 16 patients in the Control group. There were no differences in APACHEII score at day 0, DIC score at day 0, or mortality at day 28 between the groups. The effects of the rTM were as follows; 1) Patients in the TM group showed earlier DIC resolution at day 5 than Control at day 7. 2) Hypercoagulable state expressed by the increased levels of soluble fibrin monomer (SF) or thrombin-antithrombin complex (TAT) was improved more quickly in TM group compared with Control group, suggesting that rTM decreased thrombin generation. 3) AT was increased much more at day 3 after AT product administration in TM group than in Control group, which also can be explained by suppression of thrombin generation by rTM. 4) Increased levels of the complex of α2PI/plasmin, D-dimer, and fibrin/fibrinogen degradation product were also improved earlier in TM group than Control group. 5) Plasmin-alfa2 plasmin inhibitor complex (PIC) was significantly lower at day 7 in TM group than Control group, suggesting anti-fibrinolytic effect of rTM. 6) Decreased level of ADAMTS13 increased more quickly in TM group. 5) TNF-α, IL-6, HMGB1 were decreased significantly at day 3 compared with day 1 only in TM group. These anti-inflammatory effect can be evoked through direct sequestration of HMGB1 by rTM or decreased thrombin generation by rTM, because thrombin is a strong pro-inflammatory molecule through PAR1. Conclusion: rTM may be beneficial in improving septic DIC via its anti-thrombotic and anti-inflammatory properties. Disclosures: No relevant conflicts of interest to declare.

Ceramide in the antiapoptotic effect of ischemic preconditioning

2004 ◽  
Vol 286 (1) ◽  
pp. H246-H251 ◽  
Author(s):  
Laurent Argaud ◽  
Annie-France Prigent ◽  
Lara Chalabreysse ◽  
Joseph Loufouat ◽  
Michel Lagarde ◽  
...  
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Ischemia Reperfusion ◽  
Kinase Assay ◽  
Control Group ◽  
Blue Dye ◽  
Triphenyltetrazolium Chloride ◽  
Antiapoptotic Effect ◽  
Ceramide Production

Although the mechanism by which ischemic preconditioning (PC) inhibits myocardial apoptosis during ischemia-reperfusion is unclear, evidence indicates a role for the secondary messenger ceramide. We investigated in vivo whether PC may affect ceramide and sn-1,2-diacylglycerol (DAG) production, and attenuate apoptosis during ischemia. Rabbits underwent 30 min of ischemia, followed by 4 h of reperfusion. Before this, they received either no intervention (control group) or one episode of 5 min of ischemia, followed by 5 min of reperfusion (PC group), or an intravenous administration of the sphingomyelinase inhibitor D609. Myocardial content of ceramide and DAG was measured using the DAG kinase assay at different time points of the experiment. Apoptosis was detected and quantified by a sandwich enzyme immunoassay. Both AR and infarct size were measured using blue dye injection and triphenyltetrazolium chloride staining. Control hearts exhibited a peak of ceramide production at 5 min of the prolonged ischemia, with a mean value averaging 64 ± 5 ng/mg tissue ( P < 0.05 vs. 48 ± 4 ng/mg at baseline). In contrast, ischemic PC and D609 prevented ceramide increase during the prolonged ischemia. Myocardial DAG content was increased only in PC hearts at 30 min of ischemia. Preconditioned and D609 groups developed less apoptosis, as well as a limited infarct size, compared with the control group. These results suggest that the antiapoptotic effect of PC may be due to a reduced ceramide production during sustained ischemia in the rabbit heart.

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