scholarly journals Protective Effects of Kaempferol against Myocardial Ischemia/Reperfusion Injury in Isolated Rat Heart via Antioxidant Activity and Inhibition of Glycogen Synthase Kinase-3β

2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Mingjie Zhou ◽  
Huanhuan Ren ◽  
Jichun Han ◽  
Wenjuan Wang ◽  
Qiusheng Zheng ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Cytochrome C ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Caspase 3 ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Glycogen Synthase Kinase ◽  
Myocardial Ischemia Reperfusion

Objective. This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats.Method. Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dtmax) were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3β(GSK-3β), phospho-GSK-3β(P-GSK-3β), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis.Results. Pretreatment with kaempferol significantly improved the recovery of LVDP and±dp/dtmax, as well as increased the levels of SOD and P-GSK-3βand GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-α.Conclusion. These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3βactivity in rats with I/R.

scholarly journals Acute Intravenous Infusion of Immunoglobulins Protects Against Myocardial Ischemia-Reperfusion Injury Through Inhibition of Caspase-3

2017 ◽  
Vol 42 (6) ◽  
pp. 2295-2306 ◽  
Author(s):  
Waleed Al-Herz ◽  
Fawzi Babiker
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
High Dose ◽  
Protective Effects ◽  
High Doses ◽  
Myocardial Ischemia Reperfusion

Background/Aims: To investigate the cardioprotective effects of intravenous immunoglobulins (IVIG) in rats subjected to regional myocardial ischemia reperfusion (I/R). Methods: Langendorff-perfused rat hearts were used in this study. Hearts subjected to regional ischemia served as a negative untreated control. The effects of IVIG pre- and post-ischemic treatment on left ventricular function, coronary vascular dynamics and contractility were assessed. IVIG were administered in either a low or high dose. The infarct size was determined using triphenyltetrazolium chloride and through biochemical assays using the measured creatine kinase and lactate dehydrogenase levels. Apoptosis was evaluated by the TUNEL assay, and the caspase-3 expression level was assessed by immunoblotting. The cytokine levels were measured by ELISA. Results: Low and high doses of immunoglobulins administered 2 hours before sacrifice, before the ischemic insult or at reperfusion resulted in a significant improvement in cardiac hemodynamics, coronary vascular dynamics and heart contractility. A significant decrease in the infarct size and cardiac enzymes was also evident compared to those in the control. IVIG administered as an infusion at reperfusion or pre-treatment resulted in a marked decrease in myocyte apoptosis, which was associated with decreased levels of caspase-3 expression in the supernatants of homogenized left ventricles. Infusion of IVIG both pre-ischemia and at reperfusion did not show the same protective effects. Conclusions: This study demonstrates a novel protection to the heart by low and high doses of IVIG given either pre- or post-ischemia.

scholarly journals The expression and role of β3AR protein in myocardial ischemia/reperfusion in rats

2021 ◽  
Author(s):  
Zi-Long Wang ◽  
Xiao-Chen Sun ◽  
Rong Luo ◽  
Dong-Ye Li ◽  
Hao-Chen Xuan
Keyword(s):  
Myocardial Ischemia ◽  
Protein Expression ◽  
Caspase 3 ◽  
Sham Group ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Sd Rats ◽  
Group I ◽  
Myocardial Ischemia Reperfusion

IntroductionTo explore serum norepinephrine (NE) concentration and β3-adrenoceptor (β3AR) protein expression at different times during myocardial ischemia/reperfusion (I/R) and examine the role of β3AR in I/R.Material and methods28 Sprague-Dawley (SD) rats were randomly divided into one sham group and six I/R groups. The rats in the I/R groups were subjected to ischemia for 45 minutes. After reperfusion, the serum NE concentration and the β3AR protein expression in the myocardial tissue of the left ventricular injury region were detected. Another 18 SD rats were randomly divided into a sham group, I/R groups, and I/R + BRL37344 group.ResultsCompared with the sham group, the serum NE concentration of rats in the I/R groups significantly increased at 6 hours (P < 0.001). The serum NE concentration and myocardial β3AR protein expression were both highest at 72 hours. Compared with the sham group, the expressions of the pro-apoptotic proteins Bax and cleaved caspase-3 after I/R were significantly increased (P < 0.01, P < 0.001, respectively), and the expression of anti-apoptotic protein Bcl-2 was significantly decreased (P < 0.01). Compared with I/R groups, the expressions of Bax and cleaved caspase-3 in the I/R + BRL37344 group were significantly decreased (P < 0.05, P < 0.01, respectively).ConclusionsWith the prolongation of myocardial I/R in rats, serum NE concentration and β3AR protein expression showed a significant increase trend and reached a peak at 72 hours. Specific β3AR agonist BRL37344 can reduce myocardial I/R injury in vivo in rats, alleviate apoptosis, reduce infarct size, and improve cardiac function.

scholarly journals Nrf2 Deficiency Unmasks the Significance of Nitric Oxide Synthase Activity for Cardioprotection

2018 ◽  
Vol 2018 ◽  
pp. 1-15 ◽  
Author(s):  
Ralf Erkens ◽  
Tatsiana Suvorava ◽  
Thomas R. Sutton ◽  
Bernadette O. Fernandez ◽  
Monika Mikus-Lelinska ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
De Novo ◽  
Ischemia Reperfusion Injury ◽  
Systolic Function ◽  
Ischemia Reperfusion ◽  
Systolic Dysfunction ◽  
Left Ventricular ◽  
Early Reperfusion ◽  
Myocardial Ischemia Reperfusion

The transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a key master switch that controls the expression of antioxidant and cytoprotective enzymes, including enzymes catalyzing glutathione de novo synthesis. In this study, we aimed to analyze whether Nrf2 deficiency influences antioxidative capacity, redox state, NO metabolites, and outcome of myocardial ischemia reperfusion (I/R) injury. In Nrf2 knockout (Nrf2 KO) mice, we found elevated eNOS expression and preserved NO metabolite concentrations in the aorta and heart as compared to wild types (WT). Unexpectedly, Nrf2 KO mice have a smaller infarct size following myocardial ischemia/reperfusion injury than WT mice and show fully preserved left ventricular systolic function. Inhibition of NO synthesis at onset of ischemia and during early reperfusion increased myocardial damage and systolic dysfunction in Nrf2 KO mice, but not in WT mice. Consistent with this, infarct size and diastolic function were unaffected in eNOS knockout (eNOS KO) mice after ischemia/reperfusion. Taken together, these data suggest that eNOS upregulation under conditions of decreased antioxidant capacity might play an important role in cardioprotection against I/R. Due to the redundancy in cytoprotective mechanisms, this fundamental antioxidant property of eNOS is not evident upon acute NOS inhibition in WT mice or in eNOS KO mice until Nrf2-related signaling is abrogated.

scholarly journals Ginsenoside Rg3 Improves Cardiac Function after Myocardial Ischemia/Reperfusion via Attenuating Apoptosis and Inflammation

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Li-ping Zhang ◽  
Yi-chuan Jiang ◽  
Xiao-feng Yu ◽  
Hua-li Xu ◽  
Min Li ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Caspase 3 ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
Ginsenoside Rg3 ◽  
Ventricular Ejection Fraction ◽  
Function Impairment ◽  
Myocardial Ischemia Reperfusion

Objectives. Ginsenoside Rg3 is one of the ginsenosides which are the main constituents isolated from Panax ginseng. Previous study demonstrated that ginsenoside Rg3 had a protective effect against myocardial ischemia/reperfusion- (I/R-) induced injury. Objective. This study was designed to evaluate the effect of ginsenoside Rg3 on cardiac function impairment induced by myocardial I/R in rats. Methods. Sprague-Dawley rats were subjected to myocardial I/R. Echocardiographic and hemodynamic parameters and histopathological examination were carried out. The expressions of P53, Bcl-2, Bax, and cleaved caspase-3 and the levels of TNF-α and IL-1β in the left ventricles were measured. Results. Ginsenoside Rg3 increased a left ventricular fractional shortening and left ventricular ejection fraction. Treatment with ginsenoside Rg3 also alleviated increases of left ventricular end diastolic pressure and decreases of left ventricular systolic pressure and ±dp/dt in myocardial I/R-rats. Ginsenoside Rg3 decreased apoptosis cells through inhibiting the activation of caspase-3. Ginsenoside Rg3 also caused significant reductions of the contents of TNF-α and IL-1β in left ventricles of myocardial I/R-rats. Conclusion. The findings suggested that ginsenoside Rg3 possessed the effect of improving myocardial I/R-induced cardiac function impairment and that the mechanism of pharmacological action of ginsenoside Rg3 was related to its properties of antiapoptosis and anti-inflammation.

Cardioprotective Effects of Saponins from Rhizoma Panacis Majoris on Myocardial Ischemia/Reperfusion Injury via Scavenging Excessive Reactive Oxygen Species

2014 ◽  
Vol 934 ◽  
pp. 165-172
Author(s):  
Cai Hong Bai ◽  
Hai Bo He ◽  
Fan Cheng ◽  
Jun Zhi Wang ◽  
Xiao Chen ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Antioxidant Activity ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Apoptotic Cell ◽  
Ischemia Reperfusion ◽  
Radical Scavenging ◽  
Protective Effects ◽  
Cardioprotective Effects ◽  
Myocardial Ischemia Reperfusion

Saponins from Rhizoma Panacis Majoris (SRPM), the bioactive component inRhizoma Panacis Majoris, were reported to possess protective effects on myocardial injury, but the underlying mechanisms remain poorly understood. This study was performed to investigate the protective effects and possible mechanism of SRPM on myocardial ischemia/reperfusion (I/R) injury in vivo. Cardioprotective effects of SPRM in I/R rats was evaluated by hemodynamic, infarct size, biochemical values, histopathological observations, antioxidative relative gene expressions; And the antioxidant activity of SPRM was studied using DPPH scavenging and β-carotene/linoleic acid tests. In the study, we found that SRPM possessed significant free radical-scavenging activity and considerable antioxidant activity, and significantly improved cardiac function, serum biochemical index and antioxidation level, decreased infarct size, reversed the down-regulated mRNA expressions of the SOD1, SOD2, SOD3 in I/R rats. The studies demonstrated that oxidative stress caused the overgeneration and accumulation of ROS, which was central of myocardial I/R injury. SPRM exerted beneficially cardioprotective effects on myocardial I/R injury, mainly scavenging oxidative stress-triggered overgeneration and accumulation of ROS, alleviating myocardial I/R injury and apoptotic cell death.

scholarly journals Effects on cardiac function, remodeling and inflammation following myocardial ischemia–reperfusion injury or unreperfused myocardial infarction in hypercholesterolemic APOE*3-Leiden mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Niek J. Pluijmert ◽  
Cindy I. Bart ◽  
Wilhelmina H. Bax ◽  
Paul H. A. Quax ◽  
Douwe E. Atsma
Keyword(s):  
Myocardial Infarction ◽  
Clinical Trials ◽  
Myocardial Ischemia ◽  
Cardiac Function ◽  
Infarct Size ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Apo E ◽  
Lv Remodeling ◽  
Myocardial Ischemia Reperfusion

Abstract Many novel therapies to treat myocardial infarction (MI), yielding promising results in animal models, nowadays failed in clinical trials for several reasons. The most used animal MI model is based on permanent ligation of the left anterior descending (LAD) coronary artery in healthy mice resulting in transmural MI, while in clinical practice reperfusion is usually accomplished by primary percutaneous coronary interventions (PCI) limiting myocardial damage and inducing myocardial ischemia–reperfusion (MI-R) injury. To evaluate a more similar murine MI model we compared MI-R injury to unreperfused MI in hypercholesterolemic apolipoprotein (APO)E*3-Leiden mice regarding effects on cardiac function, left ventricular (LV) remodeling and inflammation. Both MI-R and MI resulted in significant LV dilation and impaired cardiac function after 3 weeks. Although LV dilation, displayed by end-diastolic (EDV) and end-systolic volumes (ESV), and infarct size (IS) were restricted following MI-R compared to MI (respectively by 27.6% for EDV, 39.5% ESV, 36.0% IS), cardiac function was not preserved. LV-wall thinning was limited with non-transmural LV fibrosis in the MI-R group (66.7%). Two days after inducing myocardial ischemia, local leucocyte infiltration in the infarct area was decreased following MI-R compared to MI (36.6%), whereas systemic circulating monocytes were increased in both groups compared to sham (130.0% following MI-R and 120.0% after MI). Both MI-R and MI models against the background of a hypercholesterolemic phenotype appear validated experimental models, however reduced infarct size, restricted LV remodeling as well as a different distributed inflammatory response following MI-R resemble the contemporary clinical outcome regarding primary PCI more accurately which potentially provides better predictive value of experimental therapies in successive clinical trials.

A peptide inhibitor of c-Jun NH2-terminal kinase reduces myocardial ischemia-reperfusion injury and infarct size in vivo

2007 ◽  
Vol 292 (4) ◽  
pp. H1828-H1835 ◽  
Author(s):  
Giuseppina Milano ◽  
Sandrine Morel ◽  
Christophe Bonny ◽  
Michele Samaja ◽  
Ludwig K. von Segesser ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
P38 Mapk ◽  
Ischemia Reperfusion ◽  
Mapk Signaling ◽  
Left Ventricular ◽  
Mitogen Activated Protein Kinase ◽  
Peptide Inhibitor ◽  
Myocardial Ischemia Reperfusion

The c-Jun NH2-terminal kinase (JNK) pathway of the mitogen-activated protein kinase (MAPK) signaling cascade regulates cell function and survival after stress stimulation. Equally robust studies reported dichotomous results suggesting both protective and detrimental effects of JNK during myocardial ischemia-reperfusion (I/R). The lack of a highly specific JNK inhibitor contributed to this controversy. We recently developed a cell-penetrating, protease-resistant peptide inhibitor of JNK, d-JNKI-1. Here we report on the effects of d-JNKI-1 in myocardial I/R. d-JNKI-1 was tested in isolated-perfused adult rat hearts. Increased activation of JNK, p38-MAPK, and extracellular signal-regulated kinase-1/2 (ERK1/2), as assessed by kinase assays and Western blotting, occurred during I/R. d-JNKI-1 delivered before onset of ischemia prevented the increase in JNK activity while not affecting ERK1/2 and p38-MAPK activation. JNK inhibition reduced ischemic injury, as manifested by increased time to contracture ( P < 0.05) and decreased left ventricular end-diastolic pressure during ischemia ( P < 0.01), and enhanced posthypoxic recovery of systolic and diastolic function ( P < 0.01). d-JNKI-1 reduced mitochondrial cytochrome- c release, caspase-3 activation, and the number of apoptotic cells determined by terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling ( P < 0.05), indicating suppression of the mitochondrial machinery of apoptosis. d-JNKI-1 delivered at the time of reperfusion did not improve functional recovery but still prevented apoptosis. In vivo, d-JNKI-1 reduced infarct size after coronary artery occlusion and reperfusion by ∼50% ( P < 0.01). In conclusion, d-JNKI-1 is an important compound that can be used in preclinical models to investigate the role of JNK signaling in vivo. Inhibition of JNK during I/R is cardioprotective in anesthetized rats in vivo.

scholarly journals Cardioprotective Effect of the Aqueous Extract of Lavender Flower against Myocardial Ischemia/Reperfusion Injury

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Dong Wang ◽  
Xin Guo ◽  
Mingjie Zhou ◽  
Jichun Han ◽  
Bo Han ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Infarct Size ◽  
Aqueous Extract ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Myocardial Infarct Size ◽  
Myocardial Oxidative Stress ◽  
Myocardial Ischemia Reperfusion

This study was conducted to evaluate the cardioprotective property of the aqueous extract of lavender flower (LFAE). The myocardial ischemia/reperfusion (I/R) injury of rat was prepared by Langendorff retrograde perfusion technology. The heart was preperfused with K-H solution containing LFAE for 10 min before 20 minutes global ischemia, and then the reperfusion with K-H solution was conducted for 45 min. The left ventricular developed pressure (LVDP) and the maximum up/downrate of left ventricular pressure (±dp/dtmax) were recorded by physiological recorder as the myocardial function and the myocardial infarct size was detected by TTC staining. Lactate dehydrogenase (LDH) and creatine kinase (CK) activities in the effluent were measured to determine the myocardial injury degree. The superoxide anion dismutase (SOD) and malondialdehyde (MDA) in myocardial tissue were detected to determine the oxidative stress degree. The results showed that the pretreatment with LFAE significantly decreased the myocardial infarct size and also decreased the LDH, CK activities, and MDA level, while it increased the LVDP, ±dp/dtmax, SOD activities, and the coronary artery flow. Our findings indicated that LFAE could provide protection for heart against the I/R injury which may be related to the improvement of myocardial oxidative stress states.

scholarly journals Diabetes Upregulates Oxidative Stress and Downregulates Cardiac Protection to Exacerbate Myocardial Ischemia/Reperfusion Injury in Rats

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 679
Author(s):  
Chen-Yen Chien ◽  
Ting-Jui Wen ◽  
Yu-Hsiuan Cheng ◽  
Yi-Ting Tsai ◽  
Chih-Yao Chiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Myocardial Ischemia ◽  
Caspase 3 ◽  
Diastolic Pressure ◽  
Myocardial Dysfunction ◽  
Ischemia Reperfusion ◽  
Systolic Pressure ◽  
Left Ventricular ◽  
Microvascular Reactivity ◽  
Myocardial Ischemia Reperfusion

Diabetes exacerbates myocardial ischemia/reperfusion (IR) injury by incompletely understood mechanisms. We explored whether diabetes diminished BAG3/Bcl-2/Nrf-2/HO-1-mediated cardioprotection and overproduced oxidative stress contributing to exaggerated IR injury. Streptozotocin-induced diabetes enhanced hyperglycemia, cardiac NADPH oxidase p22/p67 expression, malondialdehyde amount and leukocyte infiltration, altered the mesenteric expression of 4-HNE, CaSR, p-eNOS and BAG3 and impaired microvascular reactivity to the vasoconstrictor/vasodilator by a wire myography. In response to myocardial IR, diabetes further depressed BAG3/Bcl-2/Nrf-2/HO-1 expression, increased cleaved-caspase 3/poly(ADP-ribose) polymerase (PARP)/TUNEL-mediated apoptosis and exacerbated IR-induced left ventricular dysfunction characterized by further depressed microcirculation, heart rate, left ventricular systolic pressure and peak rate of pressure increase/decrease (±dp/dt) and elevated left ventricular end-diastolic pressure (LVEDP) and Evans blue-2,3,5-triphenyltetrazolium chloride-stained infarct size in diabetic hearts. Our results implicated diabetes exacerbated IR-induced myocardial dysfunction through downregulated BAG3/Bcl-2/Nrf-2/HO-1 expression, increased p22/p67/caspase 3/PARP/apoptosis-mediated oxidative injury and impaired microvascular reactivity.

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