Effects of Thyroid Hormone Analogue and a Leukotrienes Pathway-Blocker on Reperfusion Injury Attenuation after Heart Transplantation

Background. Global myocardial ischemia reperfusion injury after heart transplantation is believed to impair graft function and aggravate both acute and chronic rejection episodes. Objectives. To assess the possible protective potential of MK-886 and 3,5-diiodothyropropionic acid DITPA against global myocardial ischemia reperfusion injury after heart transplantation. Materials and Methods. Adult albino rats were randomized into 6 groups as follows: group I sham group; group II, control group; groups III and IV, control vehicles (1,2); group V, MK-886 treated group. Donor rats received MK-886 30 min before transplantation, and the same dose was repeated for recipients upon reperfusion; in group VI, DITPA treated group, donors and recipients rats were pretreated with DITPA for 7 days before transplantation. Results. Both MK-886 and DITPA significantly counteract the increase in the levels of cardiac TNF-α, IL-1β, and ICAM-1 and plasma level of cTnI (). Morphologic analysis showed that both MK-886 and DITPA markedly improved () the severity of cardiac injury in the heterotopically transplanted rats. Conclusions. The results of our study reveal that both MK-886 and DITPA may ameliorate global myocardial ischemia reperfusion injury after heart transplantation via interfering with inflammatory pathway.

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

Physiological Research ◽

10.33549/physiolres.931944 ◽

2011 ◽

pp. 271-279 ◽

Cited By ~ 16

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.

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Study on the Protective Effect of Edaravone on Myocardial Ischemia Reperfusion Injury

Advanced Emergency Medicine ◽

10.18686/aem.v2i1.4 ◽

2013 ◽

Vol 2 ◽

pp. 10

Author(s):

Hui Hou

Keyword(s):

Treatment Group ◽

Myocardial Ischemia ◽

Protective Effect ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Acute Myocardial Ischemia ◽

Control Group ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

<div>Objective: Discussion the role of edaravone as a free radical scavenger in protective effect of thrombolysis in acute myocardial ischemia reperfusion injury. Besides compared with the control group and analyze the possible mechanism which is widely used in clinical setting. Method: 80 patients hospitalized within year 2012−2013 with acute myocardial infarction (AMI) were treated with intravenous thrombolytic therapy, and were divided into treatment group (n = 41) and control group (n = 39). Edaravone injection 30 mg + 0.9% normal saline solution 100 mL with intravenous drip, BID for 14 days was given to the treatment group before and after thrombolytic treatment. Whereas, control group was treated with intravenous drip of placebo. Both groups were monitored by echocardiography and hemodynamic monitoring, and the myocardium was measured by echocardiography. Coronary artery CT was used to determine the degree of obstruction. Results: Compared with the control group, pain and reperfusion arrhythmia in treatment group was reduced. The area of myocardial wall movement disorder was significantly decreased (p < 0.05), the difference was statistically significant. CT result comparing treatment group and control group and show that rate of coronary recanalization increases 1.7 times (p < 0.01), the differences were statistically significant. Conclusion: For acute myocardial ischemia injection of edaravone before reperfusion and combine with pharmacological treatment can alleviate myocardial ischemia reperfusion injury, effectively scavenge oxygen free radicals and improve the ability of antioxidant. Both improve the thrombolytic treatment and protective effect for acute myocardial ischemia were significant. Hence, edaravone can is a kind of new milestone in the clinical cardiovascular drugs.</div>

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The intermediary metabolite pyruvate attenuates stunning and reduces infarct size in in vivo porcine myocardium

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00777.2003 ◽

2004 ◽

Vol 286 (2) ◽

pp. H517-H524 ◽

Cited By ~ 23

Author(s):

Gentian Kristo ◽

Yukihiro Yoshimura ◽

Jianli Niu ◽

Byron J. Keith ◽

Robert M. Mentzer ◽

...

Keyword(s):

Myocardial Ischemia ◽

Infarct Size ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Group I ◽

Intermediary Metabolite ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

The intermediary metabolite pyruvate has been shown to exert significant beneficial effects in in vitro models of myocardial oxidative stress and ischemia-reperfusion injury. However, there have been few reports of the ability of pyruvate to attenuate myocardial stunning or reduce infarct size in vivo. This study tested whether supraphysiological levels of pyruvate protect against reversible and irreversible in vivo myocardial ischemia-reperfusion injury. Anesthetized, open-chest pigs ( n = 7/group) underwent 15 min of left anterior descending coronary artery (LAD) occlusion and 3 h of reperfusion to induce stunning. Load-insensitive contractility measurements of regional preload recruitable stroke work (PRSW) and PRSW area (PRSWA) were generated. Vehicle or pyruvate (100 mg/kg iv bolus + 10 mg·kg–1·min–1 intra-atrial infusion) was administered during ischemia and for the first hour of reperfusion. In infarct studies, pigs ( n = 6/group) underwent 1 h of LAD ischemia and 3 h of reperfusion. Group I pigs received vehicle or pyruvate for 30 min before and throughout ischemia. In group II, the infusion was extended through 1 h of reperfusion. In the stunning protocol, pyruvate significantly improved the recovery of PRSWA at 1 h (50 ± 4% vs. 23 ± 3% in controls) and 3 h (69 ± 5% vs. 39 ± 3% in controls) reperfusion. Control pigs exhibited infarct sizes of 66 ± 1% of the area at risk. The pyruvate I protocol was associated with an infarct size of 49 ± 3% ( P < 0.05), whereas the pyruvate II protocol was associated with an infarct size of 30 ± 2% ( P < 0.05 vs. control and pyruvate I). These findings suggest that pyruvate attenuates stunning and decreases myocardial infarction in vivo in part by reduction of reperfusion injury. Metabolic interventions such as pyruvate should be considered when designing the optimal therapeutic strategies for limiting myocardial ischemia-reperfusion injury.

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Effects of Morphine Postconditioning on Myocardial Ischemia-Reperfusion Injury in Rats In Vivo

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.680.617 ◽

2013 ◽

Vol 680 ◽

pp. 617-619 ◽

Cited By ~ 1

Author(s):

Da Peng Gao ◽

Guo Qing Zhao ◽

Jia Wang ◽

Ming Gao

Keyword(s):

Superoxide Dismutase ◽

Myocardial Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Group I ◽

Cardiac Apoptosis ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Objective.To investigate the effects of morphine postconditioning on Myocardial ischemia reperfusion injury in rats in vivo. Methods. To randomly divide 40 male SD rats equally into 4 groups, including Sham group in which the chest was opened without ligating the left coronary artery, ischemia-reperfusion group(Group I/R ), ischemic preconditioning group(Group IPC ) and morphine postconditioning group(GroupMOR) in which 0. 3 mg/kg morphine was given intravenously 5 min before reperfusion. The left anterior descending coronary arterys(LAD) of rats in five groups are ligated for 30 minutes and are re-perfused for 90 minutes. Cardiac Apoptosis was determined quantitatively by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling （TUNEL） methods． To calculate the concentration of the serum malondialdehyde(MDA) with Thiobarbituric acid (TBA) reaction method and the activity of the superoxide dismutase (SOD) with xanthine oxidase reaction method. Result. Comparing with Group S, the quantity of the cardiac apoptosis in Group I/R, IPC and MOR rised in different levels. Comparing with Group 1/R, the quantity of the cardiac apoptosis in Group IPC and MOR reduced obviously. Comparing with Group 1/R, the concentration of the serum malondialdehyde (MDA) in the other four groups all reduced and the activity of the superoxide dismutase increased. Conclusion. Morphine postconditioning can significantly reduce myocardial apoptosis induced by ischemia-reperfusion injury，reduce myocardial infarct size, decrease the concentration of MDA, and increase the activity of SOD. Therefore, morphine postconditioning has protective effects on myocardial ischemia-reperfusion injury in rats in vivo. Morphine is a potent kind of opioid analgesics, which is widely used in clinical anesthesia. However, further studies are needed on effects of morphine postconditioning on myocardial ischemia reperfusion injury. In order to provide the foundations for clinical application, the authors investigate the effects of morphine postconditioning on myocardial ischemia reperfusion injury through comparison and analysis of the cardiac apoptosis, the concentration of the serum malondialdehyde (MDA) and the activity of the superoxide dismutase (SOD) in Group S, I/R, IPC and MOR.

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15-F2t-isoprostane exacerbates myocardial ischemia-reperfusion injury of isolated rat hearts

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00042.2005 ◽

2005 ◽

Vol 289 (4) ◽

pp. H1366-H1372 ◽

Cited By ~ 23

Author(s):

Zhengyuan Xia ◽

Kuo-Hsing Kuo ◽

David V. Godin ◽

Michael J. Walker ◽

Michelle C. Y. Tao ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Saline Control ◽

Control Group ◽

Endothelin 1 ◽

Rat Hearts ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Reactive oxygen species induce formation of 15-F2t-isoprostane (15-F2t-IsoP), a specific marker of in vivo lipid peroxidation, which is increased after myocardial ischemia and during the subsequent reperfusion. 15-F2t-IsoP possesses potent bioactivity under pathophysiological conditions. However, it remains unknown whether 15-F2t-IsoP, by itself, can influence myocardial ischemia-reperfusion injury (IRI). Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit (KH) solution at a constant flow rate of 10 ml/min. 15-F2t-IsoP (100 nM), SQ-29548 (1 μM, SQ), a thromboxane receptor antagonist that can abolish the vasoconstrictor effect of 15-F2t-IsoP, 15-F2t-IsoP + SQ in KH, or KH alone (vehicle control) was applied for 10 min before induction of 40 min of global ischemia followed by 60 min of reperfusion. During ischemia, saline (control), 15-F2t-IsoP, 15-F2t-IsoP + SQ, or SQ in saline was perfused through the aorta at 60 μl/min. 15-F2t-IsoP, 15-F2t-IsoP + SQ, or SQ in KH was infused during the first 15 min of reperfusion. Coronary effluent endothelin-1 concentrations were significantly higher in the group treated with 15-F2t-IsoP than in the control group during ischemia and also in the later phase of reperfusion ( P < 0.05). Infusion of 15-F2t-IsoP increased release of cardiac-specific creatine kinase, reduced cardiac contractility during reperfusion, and increased myocardial infarct size relative to the control group. SQ abolished the deleterious effects of 15-F2t-IsoP. 15-F2t-IsoP exacerbates myocardial IRI and may, therefore, act as a mediator of IRI. 15-F2t-IsoP-induced endothelin-1 production during cardiac reperfusion may represent a mechanism underlying the deleterious actions of 15-F2t-IsoP.

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Remote Ischemic Postconditioning Protects against Myocardial Ischemia-Reperfusion Injury by Inhibition of the RAGE-HMGB1 Pathway

BioMed Research International ◽

10.1155/2018/4565630 ◽

2018 ◽

Vol 2018 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Xiangming Wang ◽

Junhong Wang ◽

Tiantian Tu ◽

Zakaria Iyan ◽

Deeraj Mungun ◽

...

Keyword(s):

Myocardial Ischemia ◽

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Ischemic Postconditioning ◽

Control Group ◽

Mice Model ◽

Remote Ischemic Postconditioning ◽

Myocardial Ischemia Reperfusion Injury ◽

Myocardial Ischemia Reperfusion

Background. The aim of the present study was to observe the effect of RAGE-HMGB1 signal pathway on remote ischemic postconditioning in mice with myocardial ischemia reperfusion injury. Methods. Mice model of MIRI was established and randomly divided into three groups: control group, ischemia reperfusion group, and remote ischemic postconditioning group. Infarction size was detected by Evans blue and TTC staining. Cardiac function was detected by echocardiography measurement. The protein levels of RAGE, HMGB1, P-AKT, and ERK1/2 were detected by Western blot 120 min following reperfusion. Results. RIPostC could decrease the infarct size and increase LVEF and FS compared with I/R group. Two hours after myocardial ischemia reperfusion, the levels of RAGE and HMGB1 were significantly decreased in RIPostC group compared with those in I/R group. The level of p-AKT was significantly higher in the RIPostC group than in the I/R group. LY294002 significantly attenuated RIPostC-increased levels of Akt phosphorylation. Conclusion. RIPostC may inhibit the expression of RAGE and HMGB1 and activate PI3K/Akt signaling pathway to extenuate ischemic reperfusion injury in mice. It could further suppress the oxidative stress, have antiapoptosis effect, and reduce inflammatory reaction, but this effect has certain timeliness.

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