TGF-β1 attenuates myocardial ischemia-reperfusion injury via inhibition of upregulation of MMP-1

2003 ◽  
Vol 284 (5) ◽  
pp. H1612-H1617 ◽  
Author(s):  
Hongjiang Chen ◽  
Dayuan Li ◽  
Tom Saldeen ◽  
Jawahar L. Mehta
Keyword(s):  
Myocardial Ischemia ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Necrosis ◽  
Left Ventricular ◽  
Blue Staining ◽  
Control Group ◽  
Dependent Manner ◽  
Arterial Blood ◽  
Group I

Ischemia-reperfusion (I/R) is thought to upregulate the expression and activity of matrix metalloproteinases (MMPs), which regulate myocardial and vascular remodeling. Previous studies have shown that transforming growth factor-β1 (TGF-β1) can attenuate myocardial injury induced by I/R. TGF-β1 is also reported to suppress the release of MMPs. To study the modulation of MMP-1 by TGF-β1 in I/R myocardium, Sprague-Dawley rats were given saline and subjected to 1 h of myocardial ischemia [total left coronary artery (LCA) ligation] followed by 1 h of reperfusion ( n = 9). Parallel groups of rats were pretreated with recombinant TGF-β1(rTGF-β1, 1 mg/rat, n = 9) before reperfusion or exposure to sham I/R (control group). I/R caused myocardial necrosis and dysfunction, indicated by decreased first derivative of left ventricular pressure, mean arterial blood pressure, and heart rate (all P < 0.01 vs. sham-operated control group). Simultaneously, I/R upregulated MMP-1 ( P < 0.01). Treatment of rats with rTGF-β1 reduced the extent of myocardial necrosis and dysfunction despite I/R (all P < 0.01). rTGF-β1 treatment also inhibited the upregulation of MMP-1 in the I/R myocardium ( P < 0.05). To determine the direct effect of MMP-1 on the myocardium, isolated adult rat myocytes were treated with active MMP-1, which caused injury and death of cultured myocytes, measured as lactate dehydrogenase release and trypan blue staining, in a dose- and time-dependent manner ( P < 0.05). Pretreatment with PD-166793, a specific MMP inhibitor, attenuated myocardial injury and death induced by active MMP-1. The present study for the first time shows that MMP-1 can directly cause myocyte injury or death and that attenuation of myocardial I/R injury by TGF-β1 may, at least partly, be mediated by the inhibition of upregulation of MMP-1.

Endothelin A and B receptor antagonist bosentan reduces postischemic myocardial injury in the rat: critical timing of administration

2005 ◽  
Vol 83 (3) ◽  
pp. 259-266 ◽  
Author(s):  
Zhengyuan Xia ◽  
Kuo-Hsing Kuo ◽  
John H McNeill ◽  
David M Ansley
Keyword(s):  
Myocardial Ischemia ◽  
Myocardial Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Control Treatment ◽  
Control Group ◽  
Myocardial Infarct Size ◽  
Early Reperfusion ◽  
Endothelin 1

The purpose of this study was to investigate the effects of bosentan, a mixed endothelin receptor A and B subtype antagonist, on myocardial ischemia-reperfusion injury and to explore the influence of the timing of bosentan administration on its cardioprotective effects. Adult rat hearts were perfused by the Langendorff technique with Krebs-Henseleit solution (KH) at a constant flow rate at 10 mL/min. Global myocardial ischemia was induced by stopping KH perfusion for 40 min, and this was followed by 60 min of reperfusion. Hearts were randomized to 1 of 3 experimental groups (n = 7 each): untreated control; treatment with bosentan 1 µmol/L 10 min prior to, during 40 min global ischemia, and for 15 min of reperfusion (BOS); or treatment with bosentan 1 µmol/L after 15 min of reperfusion (BOS-R). We observed that BOS-R, but not the BOS treatment regimen, significantly reduced the release of cardiac-specific creatine kinase and postischemic myocardial infarct size (P < 0.05 vs. control) without affecting myocardial contractility. Left ventricular developed pressure in the BOS group was significantly (P < 0.01) lower than that in the control group throughout reperfusion. It is concluded that pharmacologically delayed antagonism of endothelin-1 during reperfusion attenuates postischemic myocardial injury. Endothelin-1 antagonist application during early reperfusion may exacerbate postischemic myocardial dysfunction.Key words: bosentan, ischemia, heart, rat, endothelin-1 antagonist.

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 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 Hydrogen sulfide preconditions the db/db diabetic mouse heart against ischemia-reperfusion injury by activating Nrf2 signaling in an Erk-dependent manner

2013 ◽  
Vol 304 (9) ◽  
pp. H1215-H1224 ◽  
Author(s):  
Bridgette F. Peake ◽  
Chad K. Nicholson ◽  
Jonathan P. Lambert ◽  
Rebecca L. Hood ◽  
Hena Amin ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Hydrogen Sulfide ◽  
Myocardial Ischemia ◽  
Reperfusion Injury ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Heme Oxygenase 1 ◽  
Dependent Manner

Hydrogen sulfide (H2S) therapy protects nondiabetic animals in various models of myocardial injury, including acute myocardial infarction and heart failure. Here, we sought to examine whether H2S therapy provides cardioprotection in the setting of type 2 diabetes. H2S therapy in the form of sodium sulfide (Na2S) beginning 24 h or 7 days before myocardial ischemia significantly decreased myocardial injury in db/db diabetic mice (12 wk of age). In an effort to evaluate the signaling mechanism responsible for the observed cardioprotection, we focused on the role of nuclear factor E2-related factor (Nrf2) signaling. Our results indicate that diabetes does not alter the ability of H2S to increase the nuclear localization of Nrf2, but does impair aspects of Nrf2 signaling. Specifically, the expression of NADPH quinine oxidoreductase 1 was increased after the acute treatment, whereas the expression of heme-oxygenase-1 (HO-1) was only increased after 7 days of treatment. This discrepancy was found to be the result of an increased nuclear expression of Bach1, a known repressor of HO-1 transcription, which blocked the binding of Nrf2 to the HO-1 promoter. Further analysis revealed that 7 days of Na2S treatment overcame this impairment by removing Bach1 from the nucleus in an Erk1/2-dependent manner. Our findings demonstrate for the first time that exogenous administration of Na2S attenuates myocardial ischemia-reperfusion injury in db/db mice, suggesting the potential therapeutic effects of H2S in treating a heart attack in the setting of type 2 diabetes.

Differential contribution of necrosis and apoptosis in myocardial ischemia-reperfusion injury

2004 ◽  
Vol 286 (5) ◽  
pp. H1923-H1935 ◽  
Author(s):  
James D. McCully ◽  
Hidetaka Wakiyama ◽  
Yng-Ju Hsieh ◽  
Mara Jones ◽  
Sidney Levitsky
Keyword(s):  
Infarct Size ◽  
Reperfusion Injury ◽  
Myocardial Injury ◽  
Caspase 3 ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Parp Cleavage ◽  
Control Group ◽  
Early Reperfusion

Necrosis and apoptosis differentially contribute to myocardial injury. Determination of the contribution of these processes in ischemia-reperfusion injury would allow for the preservation of myocardial tissue. Necrosis and apoptosis were investigated in Langendorff-perfused rabbit hearts ( n = 47) subjected to 0 (Control group), 5 (GI-5), 10 (GI-10), 15 (GI-15), 20 (GI-20), 25 (GI-25), and 30 min (GI-30) of global ischemia (GI) and 120 min of reperfusion. Myocardial injury was determined by triphenyltetrazolium chloride (TTC) staining, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL), bax, bcl2, poly(ADP)ribose polymerase (PARP) cleavage, caspase-3, -8, and -9 cleavage and activity, Fas ligand (FasL), and Fas-activated death domain (FADD). The contribution of apoptosis was determined separately ( n = 42) using irreversible caspase-3, -8, and -9 inhibitors. Left ventricular peak developed pressure (LVPDP) and systolic shortening (SS) were significantly decreased and infarct size and TUNEL-positive cells were significantly increased ( P < 0.05 vs. Control group) at GI-20, GI-25, and GI-30. Proapoptotic bax, PARP cleavage, and caspase-3 and -9 cleavage and activity were apparent at GI-5 to GI-30. Fas, FADD, and caspase-8 cleavage and activity were unaltered. Irreversible inhibition of caspase-3 and -9 activity significantly decreased ( P < 0.05) infarct size at GI-25 and GI-30 but had no effect on LVPDP or SS. Myocardial injury results from a significant increase in both necrosis and apoptosis ( P < 0.05 vs. Control group) evident by TUNEL, TTC staining, and caspase activity at GI-20. Intrinsic proapoptotic activation is evident early during ischemia but does not significantly contribute to infarct size before GI-25. The contribution of necrosis to infarct size at GI-20, GI-25, and GI-30 is significantly greater than that of apoptosis. Apoptosis is significantly decreased by caspase inhibition during early reperfusion, but this protection does not improve immediate postischemic functional recovery.

scholarly journals Histological changes of the arterial bed of the hind limbs of the rats under condition of the acute ischemia-reperfusion and correction with the carbacetam

2020 ◽  
Vol 26 (2) ◽  
pp. 5-11
Author(s):  
T.O. Veresiuk ◽  
P.R. Selskyy ◽  
A.T. Televiak
Keyword(s):  
Histological Examination ◽  
Ischemia Reperfusion ◽  
Control Group ◽  
Acute Ischemia ◽  
Histological Changes ◽  
Arterial Blood ◽  
Vascular Bed ◽  
Hind Limbs ◽  
Group I ◽  
Ischemic Period

The ischemic-reperfusion lesion is a complex multifactorial damage of the primary ischemic tissues as a result of restoration of the arterial blood circulation in them, which is accompanied by local morpho-functional reorganization of the vascular bed of the hind limbs of the rats. One of the promising means in the treatment and prevention of the reperfusion disorders is a carbacetam, which smooths the phenomena of hypo- and hyperperfusion in the post-ischemic period. The aim of the study was to established the manifestations of the morpho-functional remodeling of the vascular bed of the hind limbs of the rats in ischemia-reperfusion and under conditions of correction with carbacetam. Histological examination of the vascular bed of the hind limbs of 30 rats under conditions of ischemia-reperfusion (group I) and 30 rats in the simulation of ischemia-reperfusion, which in the post-ischemic period administered carbacetam once a day (5 mg/kg) for 14 days (group II) were done. There were 6 intact animals in the control group. Simulation of ischemia was performed by applying SWAT rubber tourniquets on the hind limbs for 2 hours, and reperfusion – by removing of the tourniquet. The animals of the experimental groups were divided into 5 subgroups with reperfusion terms after 1, 2 hours and 1 day, as well as after 7 and 14 days. Histological examination was performed according to generally accepted methods. The vascular bed in the middle third of the thigh and the shin below the tourniquet was examined using a Bresser Trino Researcher 40x–1000x microscope. Analyzing of the obtained results, was established that after 1 hour of the reperfusion the histological changes became a systemic, and after 1 day it were more significant. It should be noted that the thickness of the vessel walls increased, and the elastic membranes were partially eligned, thinned and torned. The stepwise clarity of the arterials walls structure was lost. The edema acquired a total nature. The histological examination of the vessels after 7 days revealed that the swelling of the walls decreased and the condition of the elastic frame was improved. There was a proliferation of collagen fibers in the adventitia, which was a response to ischemic effects. It is noted that after 14 days in all wall membranes the proliferative activity of fiboblasts was remained. Under the conditions of the correction with the carbacetam after 2 hours, the structural positive dynamics became more pronounced and increased to a maximum level after 7 days of the experiment. The number of the modified and exfoliated endothelial cells decreased, and the condition of smooth myocytes increased. Histologically, the gradual restoration of endothelial coverage of the intima was established. As follows, ischemia and reperfusion cause vascular remodeling after 1 hour with a peak of the manifestations after 1 day of the reperfusion, which includes edematous syndrome, dystrophic-degenerative changes with an inflammatory response to the damage, and in the late reperfusion period increased a fibroblasts activity. Gradual return of morphological changes occurs after 14 days of the experiment. Under the conditions of correction, the acceleration of the remodeling with stabilization of the process and the most possible structural restoration after 7 days of the study was noted.

scholarly journals Histological and biochemical serum effects of alpha-tocopherol on ischemia/reperfusion-related injuries induced in the pelvic limb of rats

2005 ◽  
Vol 20 (5) ◽  
pp. 375-381 ◽  
Author(s):  
Marcelo Gomes da Silva ◽  
Aldemar Araújo Castro ◽  
Eduardo Antonio Gonçalves Ramos ◽  
Ediriomar Peixoto ◽  
Fausto Miranda Jr ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Creatine Phosphokinase ◽  
Ischemia Reperfusion ◽  
Alpha Tocopherol ◽  
Male Rats ◽  
Control Group ◽  
Infrarenal Aorta ◽  
Arterial Blood ◽  
Group I ◽  
Group Ii

PURPOSE: To evaluate the protective action of alpha-tocopherol in ischemia/reperfusion injuries of pelvic member of rats. METHODS: Thirty adult male rats of the Wistar strain were randomized into three experimental groups of 10: Group I - control group with no ischemia or reperfusion. Groups II and III - four hours of ischemia and of hours of reperfusion by means of clamping of the infrarenal aorta. The animals of Group II were treated with saline and those of Group III were treated with i.v. alpha-tocopherol (50 mg/kg). Parameters studied were biopsies of the soleus muscle, dosing of creatine phosphokinase, lactate dehydrogenase, potassium, calcium and arterial blood gasometry. RESULTS: The results of biopsies of the soleus muscles studied by optical microscopy, were not significant in terms of presence of edema among the three groups studied. Variables inflammation and necrosis were not observed, therefore cannot be statistically analyzed. As to dosing of calcium and lactate dehydrogenase, the pH, pO2 and pCO2 values were not significant for all groups studied. We observed that the levels of potassium (Group II > Group I, Fcalculated = 5.84; Fcritical = 3.33), creatine phosphokinase (Group II > Groups I and III, Hcalculated = 13.92; Hcritical = 5.99) and bicarbonate (Groups I and III > Group II, Hcalculated = 11.98; Hcritical = 5.99) presented significant results among groups. CONCLUSION: From the serum biochemical perspective, the treatment with alpha-tocopherol has attenuated the metabolic injuries in the ischemia/reperfusion syndrome in this experimental model.

Insulin attenuates myocardial ischemia/reperfusion injury via reducing oxidative/nitrative stress

2010 ◽  
Vol 298 (4) ◽  
pp. E871-E880 ◽  
Author(s):  
Lele Ji ◽  
Feng Fu ◽  
Lihua Zhang ◽  
Wenchong Liu ◽  
Xiaoqing Cai ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Ischemia Reperfusion ◽  
Left Ventricular ◽  
Cardioprotective Effect ◽  
Male Rats ◽  
No Production ◽  
Arterial Blood ◽  
Nitrative Stress ◽  
Enos Phosphorylation ◽  
Myocardial Ischemia Reperfusion

It is well known that insulin possesses a cardioprotective effect and that insulin resistance is closely related to cardiovascular diseases. Peroxynitrite (ONOO−) formation may trigger oxidative/nitrative stress and represent a major cytotoxic effect in heart diseases. This study was designed to investigate whether insulin attenuates ONOO− generation and oxidative/nitrative stress in acute myocardial ischemia/reperfusion (MI/R). Adult male rats were subjected to 30 min of myocardial ischemia and 3 h of reperfusion. Rats randomly received vehicle, insulin, or insulin plus wortmannin. Arterial blood pressure and left ventricular pressure were monitored throughout the experiment. Insulin significantly improved cardiac functions and reduced myocardial infarction, apoptotic cell death, and blood creatine kinase/lactate dehydrogenase levels following MI/R. Myocardial ONOO− formation was significantly attenuated after insulin treatment. Moreover, insulin resulted in a significant increase in Akt and endothelial nitric oxide (NO) synthase (eNOS) phosphorylation, NO production, and antioxidant capacity in ischemic/reperfused myocardial tissue. On the other hand, insulin markedly reduced MI/R-induced inducible NOS (iNOS) and gp91phox expression in cardiac tissue. Inhibition of insulin signaling with wortmannin not only blocked the cardioprotection of insulin but also markedly attenuated insulin-induced antioxidative/antinitrative effect. Furthermore, the suppression on ONOO− formation by either insulin or an ONOO− scavenger uric acid reduced myocardial infarct size in rats subjected to MI/R. We concluded that insulin exerts a cardioprotective effect against MI/R injury by blocking ONOO− formation. Increased physiological NO production (via eNOS phosphorylation) and superoxide anion reduction contribute to the antioxidative/antinitrative effect of insulin, which can be reversed by inhibiting phosphatidylinositol 3′-kinase. These results provide important novel information on the mechanisms of cardiovascular actions of insulin.

The Protective Effects of Preconditioning With Dioscin on Myocardial Ischemia/Reperfusion-Induced Ventricular Arrhythmias by Increasing Connexin 43 Expression in Rats

2018 ◽  
Vol 24 (3) ◽  
pp. 262-268 ◽  
Author(s):  
Jin Cheng ◽  
Chuang Sun ◽  
Jingyu Zhang ◽  
Qing Zou ◽  
Qimeng Hao ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Infarct Size ◽  
Ventricular Arrhythmias ◽  
Connexin 43 ◽  
Ischemia Reperfusion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Dependent Manner ◽  
Protective Effects ◽  
Arterial Blood ◽  
Myocardial Ischemia Reperfusion

Myocardial ischemia–reperfusion (IR) injury is associated with high disability and mortality worldwide. This study was to explore the roles of dioscin in the myocardial IR rats and discover the related molecular mechanisms. Rats were divided into 5 groups: sham, IR, IR + 15 mg/kg dioscin, IR + 30 mg/kg dioscin, and IR + 60 mg/kg dioscin. Heart rate (HR), mean arterial blood pressure (MAP), and rate pressure product (RPP) were evaluated at 10 minutes before ischemia, immediately after ischemia, and at the beginning, middle, and end of reperfusion. Arrhythmia score and myocardial infarct size were examined in rats of all groups. The serum creatine kinase-muscle/brain (CKMB) and cardiac troponin I (cTnI) levels were analyzed via enzyme-linked immunosorbent assay. Protein amount of total connexin 43 (T-Cx43) and phosphorylated connexin 43 (P-Cx43) was evaluated by Western blot. Ischemia reperfusion significantly decreased HR, MAP, and RPP of rats compared to the sham group. However, dioscin significantly attenuated the above phenomena in a dose-dependent manner. Dioscin markedly inhibited IR-induced increase in arrhythmias score, infarct size, and serum CKMB and cTnI levels. In addition, dioscin strikingly induced IR-repressed expression of T-Cx43 and P-Cx43. Our results suggested that dioscin pretreatment exhibited protective effects against myocardial IR injury. Moreover, we found that dioscin attenuated myocardial IR-induced ventricular arrhythmias via upregulating Cx43 expression and activation.

scholarly journals Efficacy and Mechanism of Preoperative Simvastatin Therapy on Myocardial Protection after Extracorporeal Circulation

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Ping Hua ◽  
Jianyang Liu ◽  
Jun Tao ◽  
Rongjun Zou ◽  
Xifeng Lin ◽  
...  
Keyword(s):  
Ejection Fraction ◽  
Myocardial Injury ◽  
Ischemia Reperfusion ◽  
Assisted Ventilation ◽  
Left Ventricular ◽  
Beclin 1 ◽  
Left Ventricular Ejection ◽  
Control Group ◽  
Ventricular Ejection Fraction ◽  
Statin Group

Background. Cardiopulmonary bypass (CPB) causes systemic inflammatory response and ischemia-reperfusion (IR) injury. Objective. To investigate the effect and mechanism of simvastatin on myocardial injury in cardiac valve surgery with CPB. Methods. One hundred thirty patients were randomly assigned to the statin group (n=65) or control group (n=65). Simvastatin was administered preoperatively and postoperatively. Duration of intensive care unit stay, duration of assisted ventilation, and left ventricular ejection fraction were recorded. Plasma was analysed for troponin T (cTnT), isoenzyme of creatine kinase (CK-MB), tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), and interleukin-8 (IL-8). Ultrastructure of the myocardium and autophagosomes were observed. Beclin-1, LC3-II/I, P62, AMPK, and the phosphorylation of AMPK in cardiomyocytes were detected. Results. Simvastatin significantly reduced the duration of assisted ventilation (P=0.030) and ejection fraction was significantly higher in the statin group (P=0.024). Simvastatin significantly reduced the levels of cTnT, CK-MB, TNF-α, IL-6, and IL-8 (P<0.05), reduced the expression of LC3-II/LC3-I and Beclin 1, and increased the expression of phosphorylation of AMPK. Simvastatin reduced the generation of autophagosomes and the ultrastructural injuries to myocardium. Conclusion. Perioperative statin therapy reduced myocardial injury by regulating myocardial autophagy and activating the phosphorylation of AMPK. The registration number of this study is ChiCTR-TRC-14005164.

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