Myocardial Ischemia-reperfusion In Rats Research Articles

MiR-451 on Myocardial Ischemia-Reperfusion in Rats by Regulating AMPK Signaling Pathway.

Myocardial infarction is the main cause of death in patients with coronary heart disease. At present, the main method to treat cardiovascular disease is perfusion therapy. Myocardial ischemia-reperfusion will inevitably lead to reperfusion injury, which is also a major problem in the treatment of cardiovascular diseases. It has been reported that mir-451 in microRNA family participates in the protection of myocardial ischemia-reperfusion by regulating AMPK. The aim of this study was to investigate the effect of mir-451 on myocardial ischemia-reperfusion in rats by regulating AMPK signaling pathway. Sixty adult male rats were selected to establish myocardial ischemia-reperfusion animal model by ligating and loosening coronary artery. The expression level of mir-451 was regulated by injection of mir-451 virus vector and antibody, and the effect of increased or decreased mir-451 expression level on the activity of AMPK signaling pathway was detected. The myocardial infarct area and apoptosis rate of myocardial tissue were detected after 75 min ischemia-reperfusion. The results showed that when the expression level of mir-451 decreased by 15.7%, the activity index of AMPK signaling pathway was increased by 18.3%, the infarct area was reduced by 22.4%, and the apoptosis rate of myocardial cells was decreased by 25.2%. At the same time, the pathological structure of myocardial tissue was improved. Therefore, mir-451 is an inhibitor gene of AMPK signaling pathway. Reducing the expression of mir-451 can enhance the activity of AMPK signal pathway, and the increase of AMPK signal pathway activity is beneficial to reduce myocardial ischemia-reperfusion injury.

Cannabidiol-mediated RISK PI3K/AKT and MAPK/ERK pathways decreasing reperfusion myocardial damage.

Myocardial ischemia continues to be the first cause of morbimortality in the world; the definitive treatment is reperfusion; however, this action causes additional damage to ischemic myocardial tissue; this forces to seek therapies of cardioprotection to reduce this additional damage. There are many cardioprotective agents; within these, cannabinoids have shown to have beneficial effects, mainly cannabidiol (CBD). CBD is a non psychoactive cannabinoid. To evaluate the effect in experimental models of CBD in myocardial ischemia reperfusion in rats, twelve‐week‐old male rats have been used. The animals were divides in 3 groups: control(C), ischemia reperfusion (IR) and CBD pretreatment (1/day/5mg/kg /10days). Langendorff organ isolate studies were performed, and the area of infarction was assessed with triphenyl tetrazolium, in addition to molecular analysis of AT1 and AT2 receptors and Akt and Erk proteins and their phosphorylated forms related to RISK pathways. It was observed that there is an improvement with the use of CBD increasing inotropism and cardiac lusitropism, improving considerably the cardiovascular functionality. These could be related to the reduction of the area of infarction and activation of the AT2 receptor and the RISK pathway with absence of activation of the AT2 receptor (these could relate the reduction of the infarct area and the restoration of cardiovascular function with the activation of the AT2 receptor and the RISK pathway with the absence of activation of the AT2 receptor). The use of cannabinoids was shown to have beneficial effects when used as a treatment for myocardial reperfusion damage.

Cardioprotective efficiency of pharmacological postconditioning using lactic acid in ischemia-reperfusion of the myocardium in rats with transitional hypercholesterolemia

Cardiovascular disease is the leading cause of death all over the world: for no other reason as many people die every year as from the cardiovascular disease. Taking into account the high medical and social significance of the problem of treating patients with coronary heart disease and acute myocardial infarction, the search for new effective methods of preventing or weakening ischemic myocardial damage and revealing the mechanisms of their implementation is an urgent task of modern experimental and clinical medicine. The aim of the study was to experimentally test the cardioprotective efficiency of pharmacological postconditioning with lactic acid in myocardial ischemia-reperfusion in rats with transient hypercholesterolemia.In the course of the study, it was found that remote ischemic postconditioning (RIPostC) during myocardial ischemia-reperfusion leads to an increase in the level of lactate in the blood and has an infarction-limiting effect in rats. It was revealed that lactate, after injection into the bloodstream of animals at a dose of 10 mg/kg 25 minutes after the start of reperfusion, like RIPostC, leads to a decrease in the necrosis area in the left ventricular of the myocardium. Pharmacological postconditioning with lactate is ineffective in the limiting necrosis area in the myocardium of the left ventricle of rats with transient hypercholesterolemia. The presence of such a risk factor for cardiovascular diseases as hypercholesterolemia can serve as a criterion for excluding the use of pharmacological postconditioning with lactate as a way to reduce ischemic and reperfusion damage to the myocardium in patients with acute myocardial infarction.

Ischemic Postconditioning-Mediated DJ-1 Activation Mitigate Intestinal Mucosa Injury Induced by Myocardial Ischemia Reperfusion in Rats Through Keap1/Nrf2 Pathway.

Intestinal mucosal barrier dysfunction induced by myocardial ischemia reperfusion (IR) injury often leads to adverse cardiovascular outcomes after myocardial infarction. Early detection and prevention of remote intestinal injury following myocardial IR may help to estimate and improve prognosis after acute myocardial infarction (AMI). This study investigated the protective effect of myocardial ischemic postconditioning (IPo) on intestinal barrier injury induced by myocardial IR and the underlying cellular signaling mechanisms with a focus on the DJ-1. Adult SD rats were subjected to unilateral myocardial IR with or without ischemic postconditioning. After 30 min of ischemia and 120 min of reperfusion, heart tissue, intestine, and blood were collected for subsequent examination. The outcome measures were (i) intestinal histopathology, (ii) intestinal barrier function and inflammatory responses, (iii) apoptosis and oxidative stress, and (iv) cellular signaling changes. IPo significantly attenuated intestinal injury induced by myocardial IR. Furthermore, IPo significantly increased DJ-1, nuclear Nrf2, NQO1, and HO-1 expression in the intestine and inhibited IR-induced apoptosis and oxidative stress. The protective effect of IPo was abolished by the knockdown of DJ-1. Conversely, the overexpression of DJ-1 provided a protective effect similar to that of IPo. Our data indicate that IPo protects the intestine against myocardial IR, which is likely mediated by the upregulation of DJ-1/Nrf2 pathway.

Neohesperidin alleviated pathological damage and immunological imbalance in rat myocardial ischemia-reperfusion injury via inactivation of JNK and NF-κB p65.

Neohesperidin (NEO) exerts antiviral, antioxidant, anti-inflammation, and antitumor effects in some diseases. The purpose of this study was to investigate the effect and mechanism of NEO on myocardial ischemia-reperfusion (I/R) injury. Results indicated that NEO suppressed the levels of serum inflammatory cytokines, myocardial damage markers, and oxidative stress markers, and increased the levels of antioxidant in myocardial I/R rats. NEO also inhibited cell apoptosis. Besides, NEO also inhibited the phosphorylation of c-Jun N-terminal kinases (JNK) and nuclear factor kappa B (NF-κB) p65. Furthermore, the protective effects of NEO on myocardial tissue damage, inflammatory cytokines, myocardial injury markers, oxidative stress markers, cell apoptosis, spleen, thymus and liver indices, and phagocytic indices were reversed by JNK activator and NF-κB activator, respectively. In conclusion, NEO alleviates myocardial damage, oxidative stress, cell apoptosis, and immunological imbalance in I/R injury via the inactivation of JNK and NF-κB, making NEO a potential agent for myocardial I/R therapy.

Corrigendum] Sevoflurane post‑conditioning reduces rat myocardial ischemia reperfusion injury through an increase in NOS and a decrease in phosphorylated NHE1 levels.

Following the publication of the above article, an interested reader drew to the authors' attention that the data shown for the I/R and L‑NAME experiments in Fig.2A appeared to be strikingly similar. After having re‑examined their raw data, the authors realized that the data panel of the L‑NAME group was inadvertently loaded incorrectly, resulting in a duplication of the I/R data in the Figure. The revised version of Fig. 2, containing the correct data for the L‑NAME group in Fig.2A, is shown below. The authors are grateful to the Editor of International Journal of Molecular Medicine for granting them the opportunity to publish this Corrigendum, and stress that this error did not significantly affect either the results or the conclusions of the paper. All the authors agree with the publication of this Corrigendum, and apologize to the readership for any inconvenience caused. [the original article was published in International Journal of Molecular Medicine 36: 1529-1537, 2015; DOI: 10.3892/ijmm.2015.2366].

Protective action of the ginsenoside Rh3 in a rat myocardial ischemia-reperfusion injury model by inhibition of apoptosis induced via p38 mitogen-activated protein kinase/caspase-3 signaling.

ObjectiveTo investigate the protective effects of the ginsenoside Rh3 on rats subjected to myocardial ischemia-reperfusion (MIR) via its impact on caspase-3 and the p38 mitogen-activated protein kinase (MAPK) pathway.MethodsFifteen male Sprague-Dawley rats were randomly categorized into the MIR group (MY group, n = 5), sham surgery group (SS group, n = 5), and ginsenoside Rh3 group (GR group, n = 5).ResultsThe MY group exhibited the largest myocardial infarctions compared with the GR and SS groups. The GR group exhibited significantly higher cell viability of cardiomyocytes and significantly decreased apoptosis compared with the MY group. Fibrils of infarcted tissue in the GR group were disordered but less swollen, with a more organized fibril orientation than those in the MY group. The GR group showed reduced p-p38 MAPK protein and caspase-3 mRNA expression levels compared with the MY and SS groups.ConclusionsRh3 significantly improved myocardial necrosis and caspase-3 levels in myocardial tissues by suppressing the p38 MAPK pathway, thereby inhibiting caspase-3 involvement in apoptosis. Thus, Rh3 was effective in inhibiting the escalated apoptotic pathway in myocardial infarction and can potentially serve as a useful therapeutic agent to rescue myocardial infarction.

On the significance of hyperlactatemia in the implementation of the infarct-limiting effect of remote ischemic postconditioning in myocardial ischemia-reperfusion in the experiment

Modern medicine faces the problem of the growth of cardiovascular pathology. Given the high medical and social significance of the problem of treating patients with coronary heart disease and acute myocardial infarction, the search for new effective methods to prevent or weaken ischemic myocardial damage and mechanisms for their implementation is an urgent task of modern experimental and clinical medicine. The aim of the study was to determine the significance of hyperlactatemia in the realization of the infarct-limiting effect of remote ischemic postconditioning (RIPostC) in rat myocardial ischemia-reperfusion in the experiment. The study revealed that after 15-minute RIPostC, which was performed 10 minutes after 30-minute acute myocardial ischemia followed by 120-minute reperfusion, the plasma lactate level in rats increased 1.87 times (87.7 %, p < 0.05) compared with intact animals. It was established that the introduction of L-lactate into the left common jugular vein at a dose of 10 μg/kg, which was carried out 25 minutes after the onset of reperfusion under the conditions of myocardial ischemia (30 minutes) and next reperfusion (120 minutes) and RIPostC (10 minutes after the onset of reperfusion), which was reproduced by ischemia of these limbs, have a heart attack-limiting effect. The increase of the level of blood lactate (hyperlactatemia) after RIPostC in myocardial ischemia-reperfusion is of significance in the implementation of its infarct-limiting effect.

The Regulation of AMPKα1/Nrf2/ HO-1 Pathway Mediated by Galantamine Hydrobromide Lycoremine in Myocardial Ischemia Reperfusion Rats

To investigate the effects of AMPKα1/Nrf2/heme oxygenase-1 (HO-1) pathway mediated by galantamine hydrobromide lycoremine (Gal) on endoplasmic reticulum stress apoptosis, myocardial apoptosis and fibrosis in rats with myocardial ischemia reperfusion (I/R). A myocardial ischemia reperfusion injury rat model was established, and the rats were randomly divided into 5 groups: Control group, I/R model group, Gal 1 mg/kg group, Gal 2 mg/kg group and Gal 4 mg/kg group. Left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV), left ventricular wall thickness (LVWT), and left ventricular short-axis shortening rate (FS) were detected by doppler ultrasound. Hematoxylin eosin staining was used to detect the pathological damage of myocardial tissue. The expression of Caspase-3 was detected by immunohistochemistry. Protein expression levels of CCAAT/enhancer-binding protein homologous protein (CHOP), cleaved Caspase-12, growth arrest and DNA damageinducible protein 34 (GADD34), immunoglobulin heavy-chain-binding protein (BiP), α-smooth muscle actin (α-SMA), Collagen Ⅰ, AMPKα1, Nrf2, and HO-1 were measured by western blot, and AMPK inhibitor Compound C was added for verification. Compared with the I/R model group, the grade of pathological damage of myocardial tissue in each group of Gal was improved, and cleaved Caspase-3 positive expression rate and Caspase-3 mRNA level were significantly reduced ( P<0.05) as well. The results showed that LVWT, FS and LVEF in Gal 2 mg/kg and Gal 4 mg/kg groups were significantly increased ( P<0.05), LVEDV and LVESV were significantly reduced ( P<0.05) compared with I/R model group. CHOP, cleaved Caspase-12, α-SMA, Collagen Ⅰ, AMPKα1, Nrf2, HO-1 protein levels were significantly reduced ( P<0.05), and GADD34 and BiP protein levels were significantly increased ( P<0.05) in Gal 2 mg/kg and Gal 4 mg/kg groups. The regulation of AMPKα1/Nrf2/HO-1 pathway mediated by Gal on endoplasmic reticulum stress apoptosis, myocardial apoptosis and fibrosis in myocardial ischemia reperfusion rats.

MiR-19a suppress apoptosis of myocardial cells in rats with myocardial ischemia/reperfusion through PTEN/Akt/P-Akt signaling pathway.

To detect differentially expressed micro ribonucleic acids (miRNAs) in rats with myocardial ischemia/reperfusion (MIR), and to explore the influence of miR-19a on MIR rats and its mechanism. Firstly, the Sprague-Dawley (SD) rats were used to prepare MIR models, RNAs were extracted, and miRNA sequencing analysis was carried out to determine differentially expressed miRNAs related to MIR. Secondly, the predicted target genes of miR-19a were collected, and WebGestalt was applied to analyze gene ontology (GO) and pathway enrichment. Thirdly, the expression of the related proteins and the apoptosis of myocardial cells in MIR rats were detected via Western blotting. Fourthly, the interaction between miR-19a and the target gene phosphatase and tensin homolog (PTEN) was examined through Luciferase reporter assay. Compared with that in the Sham operation (Sham) group, the miR-19a expression in rat myocardial tissues in the MIR group was significantly increased (p<0.05). Compared with those in the miR-negative control (miR-NC) group, the messenger RNA (mRNA) and protein expressions of PTEN in the miR-19a group were notably decreased (p<0.05). In comparison with the miR-NC group, miR-19a group had elevated expression of phosphorylated protein kinase B (p-Akt) (p<0.05). The Luciferase reporter gene assay manifested the direct binding of miR-19a to PTEN mRNA. MiR-19a inhibits the PTEN expression by directly binding to the 3'-UTR of PTEN mRNA, thus activating the Akt/p-Akt signaling pathway to suppress the apoptosis of myocardial cells in MIR injury.

Resveratrol Nanoparticle Complex: Potential Therapeutic Applications in Myocardial Ischemia Reperfusion Injury.

Resveratrol (RES) is a natural non-flavonoid polyphenol with cardioprotective activities, antioxidant, antiplatelet, and antiinflammatory. However, its low aqueous solubility, chemical stability, and oral bioavailability, as well as a short circulation half-life greatly limit its clinical applications. To overcome these limitations of RES, we synthesized a methoxy poly(ethylene glycol)-b-oligomerization(D, L-Leucine) (mPEG-b-O(D, L-Leu)) nanoparticle (NP) as the carrier of RES and evaluated the myocardial-protective effectiveness of this RES/NP complex in rat myocardial ischemia-reperfusion injury models. We gauged the characterization of the NP through proton nuclear magnetic resonance spectroscopy, gel permeation chromatography, transmission electron microscope, and Fourier transform infrared spectroscopy and then loaded RES on the nanocarrier by hydrophobic interactions under physiological pH to extend the release time of RES and prolong its circulation half-life. Subsequently, we used rat cardiomyocytes (H9C2 cells) and rat MI/RI model to investigate the relationship between drug composition and myocardial preservation properties. It was found that RES was encapsulated quickly and efficiently, and displayed an effectual loading-capacity and in vitro sustained-release. Anti-MI/RI effect of the RES/NP complex was found satisfactory in rat models in vivo using free RES as the control. This study suggested that NP may prove to be a potent nanocarrier to augment the pharmacotherapy of RES against MI/RI.

Effects of propofol on LC3II and mTOR/p-mTOR expression during ischemia-reperfusion myocardium injury in rats with type 2 diabetes mellitus.

To investigate the effects of propofol on myocardial ischemia reperfusion in rats with type 2 diabetes, male adult rats were divided into five groups: Sham-operation (CC), ischemia-reperfusion (CI), low-dose propofol (LP), moderate-dose propofol (MP) and high-dose propofol (HP). The LP, MP and HP groups were administered with 6, 12 and 24 mg/kg/h propofol, respectively, prior to occlusion. Heart rate (HR), left ventricular systolic pressure (LVSP) and the rate (dp/dt max) of left ventricular pressure rise in early systole (±dp/dt max) were recorded. The role of autophagy was also studied by measuring the levels of superoxide dismutase (SOD), malondialdehyde (MDA), autophagy marker protein LC3II, mammalian target of rapamycin (mTOR)/phosphorylate (p)-mTOR and cardiac troponin T (cTnT). The myocardial morphological features were assessed using light and electron microscopy. The present results demonstrated that the HR, LVSP, +dp/dt and -dp/dt levels in the propofol groups (LP, MP and HP) were significantly increased (P<0.05) when compared with the CI group. The myocardial cells in the MP group showed mild edematous changes and partially dissolved mitochondrial cristae and membrane rupture. SOD, cTnT and MDA levels were significantly decreased (P<0.05), mTOR expression decreased significantly (P<0.05) and p-mTOR expression increased significantly in the MP group (P<0.05). The present study demonstrated the protective effects of propofol in T2DM rats exhibiting MIRI, with an optimal protective effect at an infusion rate of 12 mg/kg/h. Additionally, the results revealed that propofol led to significant reductions in LC3II and mTOR serum levels and the inhibition of autophagy in myocardial cells.

Downregulation of P300/CBP-Associated Factor Attenuates Myocardial Ischemia-Reperfusion Injury Via Inhibiting Autophagy.

Cardiomyocyte autophagy plays an important role in myocardial ischemia-reperfusion injury (MIRI). P300/CBP-associated factor (PCAF) was involved in the regulation of autophagy. However, the role of PCAF in MIRI is currently unknown. This study was to investigate whether downregulation of PCAF attenuate MIRI. The results showed that the expression of PCAF was significantly increased in MIRI in vivo and in vitro. Downregulation of PCAF not only inhibited autophagy and damage of H9c2 cells induced by hypoxia-reoxygenation, but also reduced autophagy and myocardial infarct size during myocardial ischemia-reperfusion in rats. In addition, downregulation of PCAF promoted activation of PI3K/Akt/mTOR signaling pathway in cardiomyocytes during hypoxia-reoxygenation. Wortmannin, a PI3K/Akt inhibitor, could abrogate the effects of downregulation of PCAF on cardiomyocytes autophagy. These results demonstrated that downregulation of PCAF alleviated MIRI by inhibiting cardiomyocyte autophagy through PI3K/Akt/mTOR signaling pathway. Thus, PCAF may be a potential target for prevention and treatment of MIRI.

Acanthopanax senticosus Protects Against Myocardial Ischemia Reperfusion Injury in Rats

The protective effects of Acanthopanax senticosus on myocardial ischemia reperfusion injury in rats was explored. A total of 60 male Sprague Dawley rats were randomly divided into the sham operated group (group C), the ischemia reperfusion group (group IR), the Acanthopanax senticosus plus blocker group (group ASS+Z), and the Acanthopanax senticosus group (group ASS). The rat myocardial ischemia reperfusion injury models were established through ligating left anterior descending branches of coronary artery in rats. TUNEL assay and Western Blot was used to detect the apoptotic index of myocardial cells and the expression levels of extracellular regulating kinase 1/2 (ERK1/2) and phosphorylation ERK1/2 (p-ERK1/2). Meanwhile, a total of 30 rats were randomly selected and divided into 5 groups; the control group (group c) was the simple ischemia reperfusion group, while groups P1, P2, P3, and P4 were given different dosage concentrations of Acanthopanax senticosus for pre-adaptation. The Langendorff isolated heart perfusion model was used to record the dynamic changes in cardiac functions and coronary artery flow in each group. The results have shown that the Acanthopanax senticosus had certain protective effects on the ischemia reperfusion injury of rat myocardium, as well as the pre-adaptive effects on the systolic functions of left ventricles after reperfusion, which would increase coronary flow and resist the arrhythmia, thereby reducing the apoptosis rates of myocardial cells and protecting the myocardium through activating the ERK1/2 pathway.

Protective effect of FBXL10 in myocardial ischemia reperfusion injury via inhibiting endoplasmic reticulum stress.

The aim of the study was to investigate the mechanism and effect of FBXL10 in myocardial ischemia reperfusion injury in vivo and in vitro. The myocardial ischemia reperfusion (I/R) model was established by 30min of coronary occlusion followed by 2h of reperfusion in rats. Western blot and TUNEL assay were used to measure the apoptosis during I/R. The expression levels of endoplasmic reticulum related proteins in myocardial tissues and H9c2 cells were detected by immunohistochemistry staining and immunofluorescence staining. Flow cytometry and CCK-8 were used to detect the apoptosis and viability of H9c2 cells. The results revealed that FBXL10 significantly reduced myocardial infarction, improved the pathological morphology of myocardium, markedly reduced inflammatory response in the myocardial ischemia reperfusion rats. Moreover the expressions of endoplasmic reticulum stress key proteins were caused by I/R were suppressed significantly by FBXL10 treatment, including CHOP, GRP78, ATF4 and p-PERK. Additionally FBXL10 inhibited the expression of endoplasmic reticulum stress key proteins in H/R H9c2 cells. Furthermore, FBXL10 reduced the levels of apoptotic cells and inflammatory response compared with I/R and H/R group. Taken together, we found that FBXL10 could attenuate I/R injury through inhibiting endoplasmic reticulum stress (ERs).

Retracted: Cardioprotective Effect of Isosorbide Dinitrate Postconditioning Against Rat Myocardial Ischemia-Reperfusion Injury In Vivo

The Fig 4C and 4D are the same, but the author showed them as two parallel groups. Reference: Cardioprotective Effect of Isosorbide Dinitrate Postconditioning Against Rat Myocardial Ischemia-Reperfusion Injury In Vivo Xinwen Zhao, Mengjuan Wang, Mei Li, Na Wu, Dalin Song Med Sci Monit 2019;25: 1629-1636 10.12659/MSM.912814.

Bone marrow mesenchymal stem cell-derived exosomes protect against myocardial infarction by promoting autophagy.

Exosomes have been demonstrated to be effective in the treatment of a variety of cardiac disorders. However, the effects of mesenchymal stem cell (MSC) exosomes on myocardial infarction is yet to be determined. The current study aimed to investigate the potential therapeutic effects of MSC exosomes on myocardial injuries that are caused by myocardial infarction. MSCs were isolated from rat bone marrow and were used for exosome enrichment using culture medium. Confirmation that MSCs and exosomes had been successfully extracted was performed using flow cytometry, electron microscopy and western blot analysis. A rat myocardial ischemia reperfusion (I/R) model was established by ligation of the left anterior descending coronary artery. Rat myocardial injuries were determined using 2,3,5-triphenyltetrazolium chloride, Masson and TUNEL staining. H9c2 cell proliferation, apoptosis and migration were analyzed using 5-ethynyl-2′-deoxyuridine, Hoechst staining, flow cytometry and Transwell assays. Marker gene expression was evaluated using reverse transcription-quantitative PCR, western blot analysis and immunofluorescence. Rat MSC exosomes were revealed to suppress myocardial injury and the myocardiocyte functions that were induced by I/R. The results also demonstrated decreased apoptotic protease activating factor-1 and increased autophagy-related protein 13 expression. The H9c2 cell proliferation and migration inhibition, as well as cell apoptosis during hypoxia-reoxygenation (H/R), were suppressed by rat MSC exosomes, with an alteration of the expression of apoptotic and autophagic genes also being demonstrated. The application of autophagy inhibitor 3-methyladenine significantly mitigated the effect of exosomes on H9c2 cell proliferation and apoptosis, which were induced by H/R. Rat MSC exosomes inhibited myocardial infarction pathogenesis, possibly by regulating autophagy.

LncRNA CASC7 inhibits myocardial apoptosis in myocardial ischemia-reperfusion rats by regulating MiR-21 expression.

LncRNA CASC7 inhibits myocardial apoptosis in myocardial ischemia-reperfusion rats by regulating MiR-21 expression.

Evaluation of Coronary Flow Reserve After Myocardial Ischemia Reperfusion in Rats.

Coronary artery disease is the leading cause of death worldwide. After an acute myocardial infarction, early and successful myocardial intervention via recanalization of the coronary artery is the most effective strategy for reducing the size of ischemic myocardium. The coronary microvasculature cannot be visualized and imagedin vivo, but there are several invasive and noninvasive techniques that can be used to assess parameters which depend directly on coronary microvascular function. The endothelial function after ischemia reperfusion can be assessed also at the level of the coronary circulation via the coronary flow reserve (CFR).In this study, peak velocity of left anterior descending (LAD) coronary arteries was measured in rats in vivo via Transthoracic Doppler Echocardiography during resting and stress challenge (induced by Dobutamine). A normal heart can increase its coronary blood flow up to four times above the resting values during stress induction. Following ischemia reperfusion, we found a significantly diminished CFR, which can be used as a marker of coronary microvascular dysfunction. CFR has opened a window on the importance of microvascular dysfunction and has been shown to predict cardiovascular risk independent of whether the severe obstructive disease is present.

Influences of remifentanil on myocardial ischemia-reperfusion injury and the expressions of Bax and Bcl-2 in rats.

To investigate the influences of remifentanil on myocardial ischemia-reperfusion injury in rats and the expressions of b-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax) and other apoptosis-related proteins. A total of 60 Sprague-Dawley (SD) rats were randomly divided into sham operation (S) group, model (M) group, low-dose remifentanil (L) group and high-dose remifentanil (H) group, with 15 rats in each group. The rat model of myocardial ischemia-reperfusion injury was established by the ligation of the left anterior descending branch (LAD). After ischemia for 30 min and reperfusion for 24 h, the cardiac function of rats in each group was measured by an ultrasonic instrument. Triphenyl tetrazolium chloride (TTC) staining was used to detect the myocardial infarction area of rats in each group. The activity of myocardial enzymes in the serum of rats in each group was detected. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was adopted to examine the apoptosis level of rat cardiomyocytes in each group. Quantitative polymerase chain reaction (qPCR) and Western blotting were applied to detect the expression levels of apoptosis-related proteins and messenger ribonucleic acids (mRNAs) in rat cardiomyocytes in each group. Compared with those in S group, left ventricular internal dimension in systole (LVIDs) and left ventricular internal dimension in diastole (LVIDd) were markedly increased (p<0.01), while left ventricular ejection fraction (LVEF) and left ventricular fractional shortening (LVFS) were notably decreased in M group (p<0.01). LVIDs and LVIDd in L group and H group were lower than those in M group (p<0.05, p<0.01), whereas LVEF and LVFS were higher than those in M group (p<0.05, p<0.01). The myocardial infarction area in M group was significantly larger than that in S group (p<0.01), and those in L group and H group were remarkably smaller than that in M group (p<0.05, p<0.01). The activities of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase-muscle/brain (CK-MB) in the serum of rats in M group were evidently higher than those in S group (p<0.01), and compared with those in M group, those in L group and H group were significantly decreased (p<0.05, p<0.01). The apoptosis level of myocardial cells in M group was significantly higher than that in S group (p<0.01), while those in L group and H group were markedly lower than that in M group (p<0.05, p<0.01). Compared with those in S group, the expression levels of cleaved caspase-3 and its mRNAs in myocardial cells in M group were remarkably increased (p<0.01), while those of Bcl-2/Bax and it mRNAs were significantly decreased (p<0.01). The expression levels of cleaved caspase-3 and its mRNAs in myocardial cells in L group and H group were significantly lower than those in M group (p<0.05, p<0.01), but those of Bcl-2/Bax and its mRNAs were significantly higher than those in M group (p<0.05, p<0.01). Remifentanil can effectively reduce myocardial cell injury caused by myocardial ischemia-reperfusion in rats, improve cardiac function, reduce the myocardial infarction area, decrease cleaved caspase-3 in myocardial cells, and increase Bcl-2/Bax.