scholarly journals ENDOTHELIAL PROTECTIVE ACTIVITY OF 2,6-DIISOBORNYL-4-METHYLPHENOL IN A MODEL OF MYOCARDIAL ISCHEMIA/REPERFUSION IN RATS

2019 ◽  
pp. 49-52
Author(s):  
PETR P. SHCHETININ ◽  
VERA I. SMOL’YAKOVA ◽  
TATYANA M. PLOTNIKOVA ◽  
ALEKSANDR V. KUCHIN ◽  
AleksandrVLADIMIR V. UDUT
Keyword(s):  
Endothelial Dysfunction ◽  
Myocardial Ischemia ◽  
Vascular Endothelium ◽  
Ischemia Reperfusion ◽  
Vascular Wall ◽  
Control Group ◽  
Protective Effects ◽  
Antiplatelet Activity ◽  
Vasodilating Activity ◽  
Myocardial Ischemia Reperfusion

Objective: Our research focuses on the endothelial protective effects of 2,6-diisobornyl-4-methylphenol. Its effect was revealed while studying rats experiencing myocardial ischemia/reperfusion. The research results demonstrated that there are significant disturbances in the vascular endothelium manifested by a decrease in the vasodilating activity and antiplatelet properties of 2,6-diisobornyl-4-methylphenol. Methods: We designed our own model of myocardial ischemia/reperfusion and applied it to 52 adult outbred Wistar males. We employed some methods of hemostasiological research such as thromboelastography to determine the antiplatelet activity of the vascular wall, G. Born nephelometric method to study platelet aggregation, phase contrast microscopy to count platelet counts in blood plasma, measurement of intra-arterial pressure to study the endothelial vasodilating function, and calculated the endothelial dysfunction coefficient in rats. Results: Preventive intragastric injection of 2,6-diisobornyl-4-methylphenol (100 mg/kg, 3 days before and 5 days after reproducing the myocardial ischemia/reperfusion model) increased the antiplatelet activity of the vascular endothelium in rats by 37% compared to the endothelium of the abdominal aorta segment of untreated animals. Moreover, 2,6-diisobornyl-4-methylphenol decreased the endothelial dysfunction coefficient by 43% in comparison with the value in the control group. Conclusion: 2,6-diisobornyl-4-methylphenol has an endothelial protective effect proved by its ability to increase antiplatelet properties of the endothelium and decrease the endothelial dysfunction coefficient. The revealed endothelial protective properties of 2,6-diisobornyl-4-methylphenol can be regarded as one of the potential mechanisms of cardioprotective activity of the drug.

Renal Damage Induced by Myocardial Ischemia Reperfusion in Mouse: Role of Oxidative Stress

2019 ◽  
Author(s):  
Xue Tong ◽  
Hong Zhao ◽  
Xiaomei Lu
Keyword(s):  
Oxidative Stress ◽  
Renal Function ◽  
Myocardial Ischemia ◽  
Renal Fibrosis ◽  
Renal Damage ◽  
Antioxidant Activities ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion

The aim of this study was to investigate whether oxidative stress has a role in myocardial ischemia reperfusion induced renal damage. The 30 male C57 mice were divided into control group, myocardial ischemia reperfusion (MIR) group and MnTBAP treatment group. In MIR group, the left coronary artery was occluded for 45minutes and reperfusion for 4 weeks. The same procedure was used for the MnTBAP group, with the additional step of MnTBAP (10mg/kg) administered intraperitoneally for 28 days. Before surgery and 4 weeks later, transthoracic echocardiography was performed and urine protein and albumin were measured. At the end of the time, mice were sacrified and kidneys collected for ROS and fibrosis analysis. The plasma was collected for BUN and SCR determination. It was observed that MIR decreased renal function and increased production of ROS, compelled with renal fibrosis. Administration of MnTBAP reduced production of ROS and renal fibrosis and increased renal function. These findings suggest that the MIR plays a causal role in causing renal injury and the MnTBAP exerts renal-protective effects, probably by its antioxidant activities.

Beneficial effects of SPM-5185, a cysteine-containing NO donor in myocardial ischemia-reperfusion

1992 ◽  
Vol 263 (3) ◽  
pp. H771-H777 ◽  
Author(s):  
M. R. Siegfried ◽  
C. Carey ◽  
X. L. Ma ◽  
A. M. Lefer
Keyword(s):  
At Risk ◽  
Endothelial Dysfunction ◽  
Myocardial Ischemia ◽  
Ethyl Ester ◽  
Ischemia Reperfusion ◽  
Myocardial Oxygen Demand ◽  
Area At Risk ◽  
No Donor ◽  
Beneficial Effects ◽  
Myocardial Ischemia Reperfusion

Intravenous administration of SPM-5185 [N-nitratopivaloyl-S-(N–-acetylalanyl)-cysteine ethyl ester], a cysteine-containing nitric oxide (NO) donor, or SPM-5267 [pivaloyl-S-(N–-acetylalanyl)-cysteine ethyl ester], an analogue of SPM-5185 that lacks the NO moiety, was studied in a feline myocardial ischemia-reperfusion model. Administration of SPM-5185 (1 mg/kg), followed by a 2-mg.kg-1.h-1 infusion starting 10 min before reperfusion, resulted in significant protection 4.5 h postreperfusion. In the myocardial ischemia (MI)+SPM-5267 group, 38 +/- 4% of the area at risk was necrotic, whereas the necrotic area/area at risk was only 7 +/- 2% in the MI+SPM-5185 group (P less than 0.01). Moreover, SPM-5185 treatment markedly attenuated the endothelial dysfunction observed in the left anterior descending coronary artery after reperfusion by 50%. These beneficial effects occurred despite the absence of a significant change in myocardial oxygen demand, as measured by the pressure-rate index. In vitro experiments demonstrated that SMP-5185, but not SPM-5267, decreased adherence of neutrophils to the coronary vascular endothelium and decreased production of superoxide radicals. Therefore, a likely mechanism of the observed cardioprotection by SPM-5185 involves attenuation of polymorphonuclear leukocyte-induced endothelial dysfunction.

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

2013 ◽  
Vol 2013 ◽  
pp. 1-8
Author(s):  
Fadhil G. Al-Amran ◽  
Najah R. Hadi ◽  
Haider S. H. Al-Qassam
Keyword(s):  
Myocardial Ischemia ◽  
Heart Transplantation ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Treated Group ◽  
Control Group ◽  
Group I ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

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.

scholarly journals The Cardioprotective Effects of Citric Acid and L-Malic Acid on Myocardial Ischemia/Reperfusion Injury

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Xilan Tang ◽  
Jianxun Liu ◽  
Wei Dong ◽  
Peng Li ◽  
Lei Li ◽  
...  
Keyword(s):  
Citric Acid ◽  
Myocardial Ischemia ◽  
Organic Acids ◽  
Reperfusion Injury ◽  
Malic Acid ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Protective Effects ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Myocardial Ischemia Reperfusion

Organic acids in Chinese herbs, the long-neglected components, have been reported to possess antioxidant, anti-inflammatory, and antiplatelet aggregation activities; thus they may have potentially protective effect on ischemic heart disease. Therefore, this study aims to investigate the protective effects of two organic acids, that is, citric acid and L-malic acid, which are the main components ofFructus Choerospondiatis, on myocardial ischemia/reperfusion injury and the underlying mechanisms. Inin vivorat model of myocardial ischemia/reperfusion injury, we found that treatments with citric acid and L-malic acid significantly reduced myocardial infarct size, serum levels of TNF-α, and platelet aggregation.In vitroexperiments revealed that both citric acid and L-malic acid significantly reduced LDH release, decreased apoptotic rate, downregulated the expression of cleaved caspase-3, and upregulated the expression of phosphorylated Akt in primary neonatal rat cardiomyocytes subjected to hypoxia/reoxygenation injury. These results suggest that both citric acid and L-malic acid have protective effects on myocardial ischemia/reperfusion injury; the underlying mechanism may be related to their anti-inflammatory, antiplatelet aggregation and direct cardiomyocyte protective effects. These results also demonstrate that organic acids, besides flavonoids, may also be the major active ingredient ofFructus Choerospondiatisresponsible for its cardioprotective effects and should be attached great importance in the therapy of ischemic heart disease.

Mechanism of decreased adenosine protection in reperfusion injury of aging rats

2000 ◽  
Vol 279 (1) ◽  
pp. H329-H338 ◽  
Author(s):  
Feng Gao ◽  
Theodore A. Christopher ◽  
Bernard L. Lopez ◽  
Eitan Friedman ◽  
Guoping Cai ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Protective Effects ◽  
No Release ◽  
Myocardial Ischemia Reperfusion Injury ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

The purpose of this study was to determine whether the protective effects of adenosine on myocardial ischemia-reperfusion injury are altered with age, and if so, to clarify the mechanisms that underlie this change related to nitric oxide (NO) derived from the vascular endothelium. Isolated perfused rat hearts were exposed to 30 min of ischemia and 60 min of reperfusion. In the adult hearts, administration of adenosine (5 μmol/l) stimulated NO release (1.06 ± 0.19 nmol · min−1 · g−1, P < 0.01 vs. vehicle), increased coronary flow, improved cardiac functional recovery (left ventricular developed pressure 79 ± 3.8 vs. 57 ± 3.1 mmHg in vehicle, P < 0.001; maximal rate of left ventricular pressure development 2,385 ± 103 vs. 1,780 ± 96 in vehicle, P < 0.001), and reduced myocardial creatine kinase loss (95 ± 3.9 vs. 159 ± 4.6 U/100 mg protein, P < 0.01). In aged hearts, adenosine-stimulated NO release was markedly reduced (+0.42 ± 0.12 nmol · min−1 · g−1 vs. vehicle), and the cardioprotective effects of adenosine were also attenuated. Inhibition of NO production in the adult hearts significantly decreased the cardioprotective effects of adenosine, whereas supplementation of NO in the aged hearts significantly enhanced the cardioprotective effects of adenosine. The results show that the protective effects of adenosine on myocardial ischemia-reperfusion injury are markedly diminished in aged animals, and that the loss in NO release in response to adenosine may be at least partially responsible for this age-related alteration.

scholarly journals ERK1/2-Egr-1 Signaling Pathway-Mediated Protective Effects of Electroacupuncture in a Mouse Model of Myocardial Ischemia-Reperfusion

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Juan Zhang ◽  
Jiangang Song ◽  
Jin Xu ◽  
Xuemei Chen ◽  
Peihao Yin ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Signaling Pathway ◽  
Target Genes ◽  
Troponin I ◽  
Inflammatory Responses ◽  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Protective Effects ◽  
Downstream Target ◽  
Myocardial Ischemia Reperfusion

Early growth response- (Egr-) 1 is an upstream master switch in controlling inflammatory responses following myocardial ischemia-reperfusion (I/R). Activation of extracellular signal-regulated protein kinase-1 and kinase-2 (ERK1/2) signaling is known to upregulate Egr-1. ERK1/2 pathway has been previously shown to mediate the therapeutic action of electroacupucture (EA). Thus, we hypothesized that EA would reduce myocardial I/R injury and inflammatory responses through inhibiting Egr-1 expression via the ERK1/2 pathway. Mice were pretreated with EA, U0126, or combination of EA and U0126 and then underwent 1 h myocardial ischemia and 3 h reperfusion. We investigated that EA significantly attenuated the I/R-induced upregulation of both Egr-1 and phosporylated-ERK1/2 (p-ERK1/2), decreased myocardial inflammatory cytokines including tumor necrosis factor-α(TNF-α) and interleukin-1β(IL-1β), and reduced the infarct size and the release of cardiac troponin I (cTnI). U0126 treatment also exhibited the same effect as EA on Egr-1 level and subsequent cardioprotective effects. There was no additive effect of cotreatment with EA and U0126 on the expression of Egr-1 and its downstream target genes (TNF-α, IL-1β) or serum cTnI level. Collectively, these observations suggested that EA attenuates myocardial I/R injury, possibly through inhibiting the ERK1/2-Egr-1 signaling pathway and reducing the release of proinflammatory cytokines.

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