scholarly journals CIBER-CLAP (CIBERCV Cardioprotection Large Animal Platform): A multicenter preclinical network for testing reproducibility in cardiovascular interventions

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Xavier Rossello ◽  
Antonio Rodriguez-Sinovas ◽  
Gemma Vilahur ◽  
Verónica Crisóstomo ◽  
Inmaculada Jorge ◽  
...  
Keyword(s):  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Control Group ◽  
Large Animal ◽  
Open Label ◽  
C Protein ◽  
Need To Evaluate ◽  
Set Up ◽  
Cardiovascular Interventions

AbstractDespite many cardioprotective interventions have shown to protect the heart against ischemia/reperfusion injury in the experimental setting, only few of them have succeeded in translating their findings into positive proof-of-concept clinical trials. Controversial and inconsistent experimental and clinical evidence supports the urgency of a disruptive paradigm shift for testing cardioprotective therapies. There is a need to evaluate experimental reproducibility before stepping into the clinical arena. The CIBERCV (acronym for Spanish network-center for cardiovascular biomedical research) has set up the “Cardioprotection Large Animal Platform” (CIBER-CLAP) to perform experimental studies testing the efficacy and reproducibility of promising cardioprotective interventions based on a pre-specified design and protocols, randomization, blinding assessment and other robust methodological features. Our first randomized, control-group, open-label blinded endpoint experimental trial assessing local ischemic preconditioning (IPC) in a pig model of acute myocardial infarction (n = 87) will be carried out in three separate sets of experiments performed in parallel by three laboratories. Each set aims to assess: (A) CMR-based outcomes; (B) histopathological-based outcomes; and (C) protein-based outcomes. Three core labs will assess outcomes in a blinded fashion (CMR imaging, histopathology and proteomics) and 2 methodological core labs will conduct the randomization and statistical analysis.

Remote ischemic conditioning for acute moderate ischemic stroke (RICAMIS): Rationale and design

2019 ◽  
Vol 15 (4) ◽  
pp. 454-460
Author(s):  
Xiao-Qiu Li ◽  
Lin Tao ◽  
Zhong-He Zhou ◽  
Yu Cui ◽  
Hui-Sheng Chen ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Clinical Studies ◽  
Ischemia Reperfusion Injury ◽  
Neuroprotective Effect ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Open Label ◽  
Remote Ischemic Conditioning ◽  
Ischemic Conditioning ◽  
Experimental Group

Rationale A large number of basic and clinical studies have proved that remote ischemic conditioning has neuroprotective effect. For example, remote ischemic conditioning showed a neuroprotective role in cerebral ischemia-reperfusion injury model. Recent clinical studies suggested that remote ischemic conditioning may improve neurological function and reduce the risk of recurrence in ischemic stroke patients. However, there is a lack of convincing evidence for the neuroprotective effect of remote ischemic conditioning on ischemic stroke, which deserves further study. Aim To explore the efficacy and safety of remote ischemic conditioning for acute moderate ischemic stroke. Sample size estimates A maximum of 1800 subjects are required to test the superiority hypothesis with 80% power according to a one-sided 0.025 level of significance, stratified by gender, age, time from onset to treatment, National Institutes of Health Stroke Scale (6–10 vs. 11–16), degree of responsible vessel stenosis, location of stenosis, and stroke etiology. Methods and design Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke is a prospective, random, open label, blinded endpoint and multi-center study. The subjects are divided into experimental group and control group randomly. The experimental group was treated with remote ischemic conditioning twice daily with 200 mmHg pressure for 10–14 days besides guideline-based therapy. The control group was treated according to the guidelines. Study outcome The primary efficacy endpoint is favorable functional outcome, defined as modified Rankin Scale 0–1 at 90 days post-randomization.

scholarly journals Losartan Protects the Heart Against Ischemia Reperfusion Injury: Sirtuin3 Involvement

2015 ◽  
Vol 18 (1) ◽  
pp. 112 ◽  
Author(s):  
Mohsen Sharifi Klishadi ◽  
Farideh Zarei ◽  
Seyyed Hassan Hejazian ◽  
Ali Moradi ◽  
Mahdieh Hemati ◽  
...  
Keyword(s):  
Protein Level ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mrna Level ◽  
Experimental Studies ◽  
Control Group ◽  
Signaling Mechanism ◽  
Survival Factors ◽  
Protein Levels ◽  
Ischemic Tissue

PURPOSE: Sirtuin-3 (SIRT3) deacetylase protects the heart against oxidative stress via survival factors upregulation. Clinical and experimental studies have demonstrated that activation of systemic and local renin-angiotensin system (RAS) is implicated in ischemia-induced cardiac injury. However, the relation between RAS and SIRT3 in pathophysiology of myocardial ischemia reperfusion is unknown. In this study, the cardiac transcription and expression of SIRT3 levels was examined in response to ischemia reperfusion in untreated and losartan treated rats. METHODS: Rats were divided into control group, losartan group (L), and ischemia reperfusion (IR) groups with (L+IR) or without losatran pretreatment. Some rats were included as sham-operated and saline groups. IR was induced by left anterior descending artery occlusion. SIRT3 protein levels were determined by Western blot technique. The genes expression was specified by real-time RT-PCR. Arrhythmias were assessed according to the Lambeth conventions. RESULTS: In L+IR group a significant reduction was noted in the number of ventricular ectopic beats (VEBs) and episodes of ventricular tachycardia (VT) (VEBs: P<0.001; VT: P<0.01 vs. IR). In IR group, SIRT3 protein level was decreased in the ischemic tissue by 26.7±5.9% (P<0.01 vs. Control). However, in the non-ischemic tissue the changes of SIRT3 protein content were not significant. In L+IR group SIRT3 protein levels in the ischemic part of Left ventricle were significantly different from IR group (P<0.001). SIRT3 mRNA level did not change significantly among the experimental groups. Thioredoxin-1 and catalase transcription level was increased in L+IR group compared to IR group (P<0.01). CONCLUSION: A decreased SIRT3 protein levels subsequent to IR might be a novel signaling mechanism involved in IR injury. Losartan at non–hypotensive dose exerts anti-ischemic effects in part by normalizing the SIRT3 protein level and upregulating the survival factors encoding genes transcription in ischemic tissue of the heart. This article is open to POST-PUBLICATION REVIEW. Registered readers (see “For Readers”) may comment by clicking on ABSTRACT on the issue’s contents page.

Favorable Effects of Astaxanthin on Brain Damage due to Ischemia- Reperfusion Injury

2020 ◽  
Vol 23 (3) ◽  
pp. 214-224 ◽  
Author(s):  
Esra Cakir ◽  
Ufuk Cakir ◽  
Cuneyt Tayman ◽  
Tugba Taskin Turkmenoglu ◽  
Ataman Gonel ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Reperfusion Injury ◽  
Brain Damage ◽  
Neurological Deficit ◽  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Degradation Products ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Cortex Cell

Background: Activated inflammation and oxidant stress during cerebral ischemia reperfusion injury (IRI) lead to brain damage. Astaxanthin (ASX) is a type of carotenoid with a strong antioxidant effect. Objective: The aim of this study was to investigate the role of ASX on brain IRI. Methods: A total of 42 adult male Sprague-Dawley rats were divided into 3 groups as control (n=14) group, IRI (n=14) group and IRI + ASX (n=14) group. Cerebral ischemia was instituted by occluding middle cerebral artery for 120 minutes and subsequently, reperfusion was performed for 48 hours. Oxidant parameter levels and protein degradation products were evaluated. Hippocampal and cortex cell apoptosis, neuronal cell count, neurological deficit score were evaluated. Results: In the IRI group, oxidant parameter levels and protein degradation products in the tissue were increased compared to control group. However, these values were significantly decreased in the IRI + ASX group (p<0.05). There was a significant decrease in hippocampal and cortex cell apoptosis and a significant increase in the number of neuronal cells in the IRI + ASX group compared to the IRI group alone (p<0.05). The neurological deficit score which was significantly lower in the IRI group compared to the control group was found to be significantly improved in the IRI + ASX group (p<0.05). Conclusion: Astaxanthin protects the brain from oxidative damage and reduces neuronal deficits due to IRI injury.

scholarly journals Rationale and design of the expanded combination of evolocumab plus empagliflozin in diabetes: EXCEED-BHS3 trial

2020 ◽  
Vol 11 ◽  
pp. 204062232095924
Author(s):  
Ikaro Breder ◽  
Jessica Cunha Breder ◽  
Isabella Bonilha ◽  
Daniel B. Munhoz ◽  
Sheila T. Kimura Medorima ◽  
...  
Keyword(s):  
Endothelial Dysfunction ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Open Label ◽  
Lipoprotein Subfractions ◽  
Regular Treatment ◽  
Hdl Function ◽  
Cell Adhesion Molecule 1

Background: Patients with type 2 diabetes mellitus (T2DM) remain at increased cardiovascular residual risk and endothelial dysfunction, even after optimizing metabolic control and treatment by sodium-glucose-2 transporter inhibitors (SGLT2-is). The present study was based on the hypothesis that proprotein convertase subtilisin/kexin 9 inhibitor (PCSK9i) therapy may mitigate endothelial dysfunction in T2DM patients who are on regular treatment by SGLT2-i. Methods: The EXCEED-BHS3 is a prospective, single-center, investigator-blinded, open-label, randomized clinical trial. Participants ( n = 110) will be randomized (1:1) to either empagliflozin 25 mg/day alone or empagliflozin 25 mg/day plus evolocumab 140 mg every 2 weeks in addition to optimal medical care. The primary endpoint was defined as the change in the 1-min flow-mediated dilation (FMD) after 16 weeks of treatment. The secondary endpoint is the FMD change after ischemia/reperfusion injury protocol (reserve FMD) after 16 weeks of treatment. Exploratory outcomes comprise the change in FMD and reserve FMD after 8 weeks of treatment and the change after 16 weeks of treatment in the following parameters: plasma levels of nitric oxide, vascular cell adhesion molecule-1 and isoprostane, high-density lipoprotein (HDL) and low-density lipoprotein subfractions profile, HDL function, blood pressure, body mass index, waist circumference and adipokines. Conclusion: This will be the first study to evaluate the add-on effect of PCSK9i on endothelial function of T2DM patients under regular use of empagliflozin. Trial registration: ClinicalTrials.gov identifier: NCT03932721

Role of Platelet-Activating Factor in Cardiovascular Pathophysiology

2000 ◽  
Vol 80 (4) ◽  
pp. 1669-1699 ◽  
Author(s):  
Giuseppe Montrucchio ◽  
Giuseppe Alloatti ◽  
Giovanni Camussi
Keyword(s):  
Cardiovascular System ◽  
Cell Biology ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Critical Role ◽  
Experimental Studies ◽  
Platelet Activating Factor ◽  
Biologically Active ◽  
Endothelial Cell Migration

Platelet-activating factor (PAF) is a phospholipid mediator that belongs to a family of biologically active, structurally related alkyl phosphoglycerides. PAF acts via a specific receptor that is coupled with a G protein, which activates a phosphatidylinositol-specific phospholipase C. In this review we focus on the aspects that are more relevant for the cell biology of the cardiovascular system. The in vitro studies provided evidence for a role of PAF both as intercellular and intracellular messenger involved in cell-to-cell communication. In the cardiovascular system, PAF may have a role in embryogenesis because it stimulates endothelial cell migration and angiogenesis and may affect cardiac function because it exhibits mechanical and electrophysiological actions on cardiomyocytes. Moreover, PAF may contribute to modulation of blood pressure mainly by affecting the renal vascular circulation. In pathological conditions, PAF has been involved in the hypotension and cardiac dysfunctions occurring in various cardiovascular stress situations such as cardiac anaphylaxis and hemorrhagic, traumatic, and septic shock syndromes. In addition, experimental studies indicate that PAF has a critical role in the development of myocardial ischemia-reperfusion injury. Indeed, PAF cooperates in the recruitment of leukocytes in inflamed tissue by promoting adhesion to the endothelium and extravascular transmigration of leukocytes. The finding that human heart can produce PAF, expresses PAF receptor, and is sensitive to the negative inotropic action of PAF suggests that this mediator may have a role also in human cardiovascular pathophysiology.

Abstract 138: Remote Ischemic Postconditioning Alleviates Postresuscitation Inflammatory Response and Pulmonary Edema in a Porcine Model of Cardiac Arrest

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Jiefeng Xu ◽  
Sen Ye ◽  
Zilong Li ◽  
Moli Wang ◽  
Zhengquan Wang ◽  
...  
Keyword(s):  
Cardiac Arrest ◽  
Inflammatory Response ◽  
Pulmonary Edema ◽  
Porcine Model ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Limb Ischemia ◽  
Multiple Organ ◽  
Control Group ◽  
Lung Water

Introduction: Systemic ischemia-reperfusion injury produced by CA and resuscitation can result in severe post-cardiac arrest syndrome; which includes systemic inflammatory response and multiple organ dysfunction syndrome such as acute pulmonary edema. We previously demonstrated that remote ischemic post-conditioning (RIpostC) improved post-resuscitation myocardial and cerebral function in a rat model of CA. In this study, we investigated the effects of RIpostC on inflammatory response and pulmonary edema after CPR in a porcine model. Hypothesis: RIpostC would alleviate post-resuscitation inflammatory response and pulmonary edema in a porcine model of CA. Methods: Fourteen male domestic pigs weighing 37 ± 2 kg were utilized. Ventricular fibrillation was electrically induced and untreated for 10 mins. The animals were then randomized to receive RIpostC or control. Coincident with the start of CPR, RIpostC was induced by four cycles of 5 mins of limb ischemia and then 5 mins of reperfusion. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were monitored for 4 hrs and observed for an additional 68 hrs. Results: Six of the seven animals in each group were successfully resuscitated. After resuscitation, significantly lower levels of tumor necrosis factor-α and interleukin-6 were measured in the animals that received RIpostC when compared with the control group. Post-resuscitation extra-vascular lung water index was lower in the RIpostC group than in the control group; in which the differences were significant at 2,3 and 4 hrs (Table). Conclusion: In a porcine model of CA, RIpostC significantly alleviates post-resuscitation inflammatory response and pulmonary edema.

scholarly journals Preconditioning with L-alanyl-L-glutamine in a Mongolian Gerbil model of acute cerebral ischemia/reperfusion injury

2011 ◽  
Vol 26 (suppl 1) ◽  
pp. 14-20 ◽  
Author(s):  
Vilma Leite de Sousa Pires ◽  
José Reniclebson Feitosa de Souza ◽  
Sergio Botelho Guimarães ◽  
Antonio Ribeiro da Silva Filho ◽  
José Huygens Parente Garcia ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Femoral Vein ◽  
Control Group ◽  
Mongolian Gerbils ◽  
Cerebral Tissue ◽  
Arterial Blood ◽  
Cerebral Ischemia Reperfusion ◽  
Acute Cerebral Ischemia

PURPOSE: To investigate the effect of L-alanyl-L-glutamine (L-Ala-Gln) preconditioning in an acute cerebral ischemia/reperfusion (I/R) model in gerbils. METHODS: Thirty-six Mongolian gerbils (Meriones unguiculatus), (60-100g), were randomized in 2 groups (n=18) and preconditioned with saline 2.0 ml (Group-S) or 0.75g/Kg of L-Ala-Gln, (Group-G) administered into the femoral vein 30 minutes prior to I/R. Each group was divided into three subgroups (n=6). Anesthetized animals (urethane, 1.5g/Kg, i.p.) were submitted to bilateral occlusion of common carotid arteries during 15 minutes. Samples (brain tissue and arterial blood) were collected at the end of ischemia (T0) and after 30 (T30) and 60 minutes (T60) for glucose, lactate, myeloperoxidase (MPO), thiobarbituric acid reactive substances (TBARS), glutathione (GSH) assays and histopathological evaluation. RESULTS: Glucose and lactate levels were not different in studied groups. However glycemia increased significantly in saline groups at the end of the reperfusion period. TBARS levels were significantly different, comparing treated (Group-G) and control group after 30 minutes of reperfusion (p<0.05) in cerebral tissue. Pretreatment with L-Ala-Gln promoted a significant increase in cerebral GSH contents in Group-G at T30 (p<0.001) time-point compared with Group-S. At T30 and T60, increased levels of GSH occurred in both time-points. There were no group differences regarding MPO levels. Pyknosis, presence of red neurons and intracellular edema were significantly smaller in Group-G. CONCLUSION: Preconditioning with L-Ala-Gln in gerbils submitted to cerebral ischemia/reperfusion reduces oxidative stress and degeneration of the nucleus (pyknosis) and cell death (red neurons) in the cerebral tissue.

scholarly journals The protective effect of L-arginine, tadalafil, and their combination in rat testes after ischemia and reperfusion injury

2017 ◽  
Vol 11 (1-2) ◽  
pp. 19 ◽  
Author(s):  
Gokhun Ozmerdiven ◽  
Burhan Coskun ◽  
Onur Kaygisiz ◽  
Berna Aytac Vuruskan ◽  
Burak Asiltas ◽  
...  
Keyword(s):  
Protective Effect ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Combination Group ◽  
Control Group ◽  
Ischemia And Reperfusion ◽  
Contralateral Testis ◽  
Treatment Groups ◽  
Testis Torsion

Introduction: Nitric oxide (NO) plays an important role in the ischemia and reperfusion process. In this study, we aimed to examine the effect of L-arginine, tadalafil, and their combination for preventionof the ischemia reperfusion injury after testis torsion in rats.Methods: A total of 40 adult, male Sprague-Dawley rats were allocated into five groups. Three hours of left testicular torsion was performed in each group, excluding the control group. While the ischemia reperfusion (I/R) group had no treatment, I/R + Arg group received L-arginine, I/R + Td group received tadalafil and I/R + Arg + Td group received tadalafil and L-arginine 30 minutes before the detorsion. Then the left testis was untwisted for four hours of reperfusion. After bilateral orchiectomy, lipid peroxidation (LPx) and glutathione (GSH) activities were examined in testicular tissue.Spermatogenesis was evaluated with Johnsen’s score.Results: LPx levels of the I/R group were found to be significantly higher than for groups that received drugs for both testes (p<0.001). GSH levels of the combination group were higher than I/R group inipsilateral testis (p<0.01) and it was significantly higher than other groups for contralateral testis (p<0.001 for I/R group, p<0.01 for I/R + Arg, p<0.05 for I/R + Td). Mean Johnsen’s score of the I/Rgroup was found to be significantly lower than treatment groups in ipsilateral testis (p<0.001 for I/R + Arg + Td group, p<0.01 for other treatment goups) and contralateral testis (p<0.001). The meanJohnsen score of the combination group was significantly higher than that of other treatment groups in ipsilateral testis (p<0.05) and it was significantly higher than in the I/R + Td group in the contralateral testis (p<0.05).Conclusions: L-arginine, tadalafil, and combination of these two molecules showed protective effect against ischemia/reperfusion injury for both testes after unilateral testis torsion.

Exercise training improves myocardial tolerance to in vivo ischemia-reperfusion in the rat

1998 ◽  
Vol 275 (5) ◽  
pp. R1468-R1477 ◽  
Author(s):  
Scott K. Powers ◽  
Haydar A. Demirel ◽  
Heather K. Vincent ◽  
Jeff S. Coombes ◽  
Hisashi Naito ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Exercise Training ◽  
Endurance Exercise ◽  
Ischemia Reperfusion ◽  
Experimental Studies ◽  
Control Group ◽  
Sprague Dawley ◽  
Endurance Exercise Training ◽  
Nonprotein Thiols

Experimental studies examining the effects of regular exercise on cardiac responses to ischemia and reperfusion (I/R) are limited. Therefore, these experiments examined the effects of endurance exercise training on myocardial biochemical and physiological responses during in vivo I/R. Female Sprague-Dawley rats (4 mo old) were randomly assigned to either a sedentary control group or to an exercise training group. After a 10-wk endurance exercise training program, animals were anesthetized and mechanically ventilated, and the chest was opened by thoracotomy. Coronary occlusion was achieved by a ligature around the left coronary artery; occlusion was maintained for 20 min, followed by a 10-min period of reperfusion. Compared with untrained, exercise-trained animals maintained higher ( P < 0.05) peak systolic blood pressure throughout I/R. Training resulted in a significant ( P < 0.05) increase in ventricular nonprotein thiols, heat shock protein (HSP) 72, and the activities of superoxide dismutase (SOD), phosphofructokinase (PFK), and lactate dehydrogenase. Furthermore, compared with untrained controls, left ventricles from trained animals exhibited lower levels ( P < 0.05) of lipid peroxidation after I/R. These data demonstrate that endurance exercise training improves myocardial contractile performance and reduces lipid peroxidation during I/R in the rat in vivo. It appears likely that the improvement in the myocardial responses to I/R was related to training-induced increases in nonprotein thiols, HSP72, and the activities of SOD and PFK in the myocardium.

scholarly journals Effect of Tourniquet Use in Ankle Arthroscopic Surgery on Postoperative Recovery: A Prospective Non- Randomized Controlled Study

2020 ◽  
Author(s):  
Tingting Huang ◽  
Haixiao Liu ◽  
Yuezheng Hu ◽  
Xinxian Xu
Keyword(s):  
Functional Outcome ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Arthroscopic Surgery ◽  
Randomized Controlled Study ◽  
Controlled Study ◽  
Control Group ◽  
Complication Rates ◽  
Randomized Controlled ◽  
The Mean

Abstract The aim of this prospective non- randomized controlled study was to explore the effect of tourniquet use on joint swelling, pain, functional outcome, and tourniquet- related ischemia- reperfusion injury (IRI) during ankle arthroscopic surgery.52 patients who received ankle arthroscopy were allocated to had the procedure done with the tourniquet inflated (the Control group, n= 27) or without the tourniquet inflated (the NT group, n= 25). The main outcome measures were: (1) The amount of swelling of the ankle; (2) Pain as measured by a visual analog scale (VAS); (3) The levels of MDA, IMA,TOS, TAS and OSI at 10 min before incision (T1)，after the completion of surgery (T2), and 30 min after tourniquet deflation (T3); (4) The functional outcome as measured by American Orthopaedic Foot and Ankle Society (AOFAS) ankle hindfoot score; (5) The rate of complication. All patients were reviewed at a mean follow- up of 14.2 months (range, 12- 19 months). The mean circumferences of the ankle in the NT group were significantly lower than those in the Control group on postoperative day 2 and 5 (p<0.05). The mean level of VAS in the Control group was significantly higher on postoperative day 2 (p<0.05). The outcomes of AOFAS ankle hindfoot score were comparable between groups postoperatively (p>0.05). The levels of MDA, IMA, TOS and OSI were all significantly lower in the NT group compared at T2 and T3 (p<0.05), and the level of TAS was significantly lower in the NT group at T3 (p<0.05). The complication rates of two groups were comparable (p>0.05).With the use of tourniquet during ankle arthroscopic surgery, there was increased joint swelling and pain postoperatively, and a trend toward increased levels of MDA, IMA, TOS, TAS and OSI intraoperatively. Thus, we do not recommend using a tourniquet in this type of procedure.

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