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 he...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.展开更多
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 radi...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.展开更多
Acute myocardial infarction(AMI)is one of the main reasons of cardiovascular disease-related death.The introduction of percutaneous coronary intervention to clinical practice dramatically decreased the mortality rate ...Acute myocardial infarction(AMI)is one of the main reasons of cardiovascular disease-related death.The introduction of percutaneous coronary intervention to clinical practice dramatically decreased the mortality rate in AMI.Adverse cardiac remodeling is a serious problem in cardiology.An increase in the effectiveness of AMI treatment and prevention of adverse cardiac remodeling is difficult to achieve without understanding the mechanisms of reperfusion cardiac injury and cardiac remodeling.Inhibition of pyroptosis prevents the development of postinfarction and pressure overload-induced cardiac remodeling,and mitigates cardiomyopathy induced by diabetes and metabolic syndrome.Therefore,it is reasonable to hypothesize that the pyroptosis inhibitors may find a role in clinical practice for treatment of AMI and prevention of cardiac remodeling,diabetes and metabolic syndrome-triggered cardiomyopathy.It was demonstrated that pyroptosis interacts closely with apoptosis and autophagy.Pyroptosis could be inhibited by nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 inhibitors,caspase-1 inhibitors,microRNA,angiotensin-converting enzyme inhibitors,angiotensinⅡreceptor blockers,and traditional Chinese herbal medicines.展开更多
基金supported by the Russian Science Foundation(Grant No.23-65-10017)The mini-chapter on treatment of MVO was supported by state assignment 122020300042-4.
文摘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.
文摘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.
基金supported by Russian Foundation of Basic Research(Grant No.21-515-53003)
文摘Acute myocardial infarction(AMI)is one of the main reasons of cardiovascular disease-related death.The introduction of percutaneous coronary intervention to clinical practice dramatically decreased the mortality rate in AMI.Adverse cardiac remodeling is a serious problem in cardiology.An increase in the effectiveness of AMI treatment and prevention of adverse cardiac remodeling is difficult to achieve without understanding the mechanisms of reperfusion cardiac injury and cardiac remodeling.Inhibition of pyroptosis prevents the development of postinfarction and pressure overload-induced cardiac remodeling,and mitigates cardiomyopathy induced by diabetes and metabolic syndrome.Therefore,it is reasonable to hypothesize that the pyroptosis inhibitors may find a role in clinical practice for treatment of AMI and prevention of cardiac remodeling,diabetes and metabolic syndrome-triggered cardiomyopathy.It was demonstrated that pyroptosis interacts closely with apoptosis and autophagy.Pyroptosis could be inhibited by nucleotide-binding oligomerization domain-like receptor with a pyrin domain 3 inhibitors,caspase-1 inhibitors,microRNA,angiotensin-converting enzyme inhibitors,angiotensinⅡreceptor blockers,and traditional Chinese herbal medicines.
