查看更多>>摘要：The acute myocardial infarction(AMI)and sudden cardiac death(SCD),both associated with acute cardiac ischemia,are one of the leading causes of adult death in economically developed countries.The development of new approaches for the treatment and prevention of AMI and SCD remains the highest priority for medicine.A study on the cardiovascular effects of chronic hypoxia(CH)may contribute to the development of these methods.Chronic hypoxia exerts both positive and adverse effects.The positive effects are the infarct-reducing,vasoprotective,and antiarrhythmic effects,which can lead to the improvement of cardiac contractility in reperfusion.The adverse effects are pulmonary hypertension and right ventricular hypertrophy.This review presents a comprehensive overview of how CH enhances cardiac tolerance to ischemia/reperfusion.It is an in-depth analysis of the published data on the underlying mechanisms,which can lead to future development of the cardioprotective effect of CH.A better understanding of the CH-activated protective signaling pathways may contribute to new therapeutic approaches in an increase of cardiac tolerance to ischemia/reperfusion.
Leonid N.MaslovNatalia V.NaryzhnayaMaria SirotinaAlexandr V.Mukhomedzyanov...
255-267页
查看更多>>摘要：The role of reactive oxygen species(ROS)in ischemic and reperfusion(I/R)injury of the heart has been discussed for more than 40 years.It has been demonstrated that reperfusion triggers a multiple increase in free radical generation in the isolated heart.Antioxidants were found to have the ability to mitigate I/R injury of the heart.However,it is unclear whether their cardioprotective effect truly depends on the decrease of ROS levels in myocardial tissues.Since high doses and high concentrations of antioxidants were experimentally used,it is highly likely that the cardioprotective effect of antioxidants depends on their interaction not only with free radicals but also with other molecules.It has been demonstrated that the antioxidant N-2-mercaptopropionyl glycine or NDPH oxidase knockout abolished the cardioprotective effect of ischemic preconditioning.Consequently,there is evidence that ROS protect the heart against the I/R injury.
Leonid N.MaslovNatalia V.NaryzhnayaSergey V.PopovAlexandr V.Mukhomedzyanov...
268-289页
查看更多>>摘要：The analysis of experimental data demonstrates that platelets and neutrophils are involved in the no-reflow phenomenon,also known as microvascular obstruction(MVO).However,studies performed in the isolated perfused hearts subjected to ischemia/reperfusion(I/R)do not suggest the involvement of microembolization and microthrombi in this phenomenon.The intracoronary administration of alteplase has been found to have no effect on the occurrence of MVO in patients with acute myocardial infarction.Consequently,the major events preceding the appearance of MVO in coronary arteries are independent of microthrombi,platelets,and neutrophils.Endothelial cells appear to be the target where ischemia can disrupt the endothelium-dependent vasodilation of coronary arteries.However,reperfusion triggers more pronounced damage,possibly mediated by pyroptosis.MVO and intra-myocardial hemorrhage contribute to the adverse post-infarction myocardial remodeling.Therefore,pharmacological agents used to treat MVO should prevent endothelial injury and induce relaxation of smooth muscles.Ischemic conditioning protocols have been shown to prevent MVO,with L-type Ca2+channel blockers appearing the most effective in treating MVO.
查看更多>>摘要：Sepsis-induced myocardial dysfunction is primarily accompanied by severe sepsis,which is associated with high morbidity and mortality.11β-hydroxysteroid dehydrogenase type 1(11β-HSD1),encoded by Hsd11b1,is a reductase that can convert inactive cortisone into metabolically active cortisol,but the role of 11β-HSD1 in sepsis-induced myocardial dysfunction remains poorly understood.The current study aimed to investigate the effects of 11β-HSD1 on a lipopolysaccharide(LPS)-induced mouse model,in which LPS(10 mg/kg)was administered to wild-type C57BL/6J mice and 11β-HSD1 global knockout mice.We asscessed cardiac function by echocardiography,performed transmission electron microscopy and immunohistochemical staining to analyze myocardial mitochondrial injury and histological changes,and determined the levels of reactive oxygen species and biomarkers of oxidative stress.We also employed polymerase chain reaction analysis,Western blotting,and immunofluorescent staining to determine the expression of related genes and proteins.To investigate the role of 11β-HSDl in sepsis-induced myocardial dysfunction,we used LPS to induce lentivirus-infected neonatal rat ventricular cardiomyocytes.We found that knockdown of 11β-HSD1 alleviated LPS-induced myocardial mitochondrial injury,oxidative stress,and inflammation,along with an improved myocardial function;furthermore,the depletion of 11β-HSD1 promoted the phosphorylation of adenosine 5'-monophosphate-activated protein kinase(AMPK),peroxisome proliferator-activated receptor gamma coactivator 1α(PGC-1α),and silent information regulator 1(SIRT1)protein levels both in vivo and in vitro.Therefore,the suppression of 11β-HSD1 may be a viable strategy to improve cardiac function against endotoxemia challenges.
查看更多>>摘要：To investigate the feasibility and effectiveness of establishing porcine ischemia-reperfusion models by ligating the left anterior descending(LAD)coronary artery,we first randomly divided 16 male Bama pigs into a sham group and a model group.After anesthesia,we separated the arteries and veins.Subsequently,we rapidly located the LAD coronary artery at the beginning of its first diagonal branch through a mid-chest incision.Then,we loosened and released the ligation line after five minutes of pre-occlusion.Finally,we ligated the LAD coronary artery in situ two minutes later and loosened the ligature 60 min after ischemia.Compared with the sham group,electrocardiogram showed multiple continuous lead ST-segment elevations,and ultrasound cardiogram showed significantly lower ejection fraction and left ventricular fractional shortening at one hour and seven days post-operation in the model group.Twenty-four hours after the operation,cardiac troponin T and creatine kinase-MB isoenzyme levels significantly increased in the model group,compared with the sham group.Hematoxylin and eosin staining showed the presence of many inflammatory cells infiltrating the interstitium of the myocardium in the model group but not in the sham group.Masson staining revealed a significant increase in infarct size in the ischemia/reperfusion group.All eight pigs in the model group recovered with normal sinus heart rates,and the survival rate was 100％.In conclusion,the method can provide an accurate and stable large animal model for preclinical research on ischemia/reperfusion with a high success rate and homogeneity of the myocardial infarction area.
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