In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, ...In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, preserving left-ventricular systolic function and reducing the onset of heart failure. Within minutes after the restoration of blood flow, however, reperfusion itself results in additional damage, also known as myocardial ischemia-reperfusion injury. An improved understanding of the pathophysiological mechanisms underlying reperfusion injury has resulted in the identification ofseveral promising pharmacological(cyclosporin-A, exenatide, glucose-insulin-potassium, atrial natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and melatonin) therapeutic strategies for reducing the severity of myocardial reperfusion injury. Many of these agents have shown promise in initial proofof-principle clinical studies. In this article, we review the pathophysiology underlying myocardial reperfusion injury and highlight the potential pharmacological interventions which could be used in the future to prevent reperfusion injury and improve clinical outcomes in patients with coronary heart disease.展开更多
Objective: To investigate the expression of myocardium connexin 43(Cx43) in late exercise preconditioning(LEP) cardioprotection. Methods: Eight-week-old adult male Sprague Dawley rats were randomly assigned into four ...Objective: To investigate the expression of myocardium connexin 43(Cx43) in late exercise preconditioning(LEP) cardioprotection. Methods: Eight-week-old adult male Sprague Dawley rats were randomly assigned into four groups(n=8). Myocardial injury was judged in accordance with serum levels of c Tn and NT-pro BNP as well as hematoxylin basicfuchsin picric acid staining of myocardium. Cx43 m RNA was detected by in situ hybridization and qualified by real-time fluorescence quantitative PCR. Cx43 protein was localized by immunohistochemistry and its expression level was determined by western blotting. Results: The LEP obviously attenuated the myocardial ischemia/hypoxia injury caused by exhaustive exercise. There was no significant difference of Cx43 m RNA level between the four groups. Cx43 protein level was decreased significantly in group EE(P<0.05). However, LEP produced a significant increase in Cx43 protein level(P<0.05), and the decreased Cx43 protein level in exhaustive exercise was significantly up-regulated by LEP(P<0.05). Conclusions: LEP protects rat heart against exhaustive exercise-induced myocardial injury by up-regulating the expression of myocardial Cx43.展开更多
Objective: To establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles(MVs) from myocardial ischemic preconditioning(IPC) treated rats(IPC-MVs), and to i...Objective: To establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles(MVs) from myocardial ischemic preconditioning(IPC) treated rats(IPC-MVs), and to investigate the effects of IPC-MVs on ischemia/reperfusion(I/R) injury in rats. Methods: Myocardial IPC was elicited by three cycles of 5-min ischemia and 5-min reperfusion of the left anterior descending(LAD) coronary artery. Platelet-free plasma(PFP) was isolated through two steps of centrifugation at room temperature from the peripheral blood, and IPC-MVs were isolated by ultracentrifugation from PFP. PFP was incubated with anti-CD61, anti-CD144, anti-CD45 and anti-Erythroid Cells, and added 1, 2 μm latex beads to calibrate and absolutely count by flow cytometry. For functional research, I/R injury was induced by 30-min ischemia and 120-min reperfusion of LAD. IPC-MVs 7 mg/kg were infused via the femoral vein in myocardial I/R injured rats. Mean arterial blood pressure(MAP), heart rate(HR) and ST-segment of electrocardiogram(ECG) were monitored throughout the experiment. Changes of myocardial morphology were observed after hematoxylin-eosin(HE) staining. The activity of plasma lactate dehydrogenase(LDH) was tested by Microplate Reader. Myocardial infarct size was measured by TTC staining. Results: Total IPC-MVs and different phenotypes, including platelet-derived MVs(PMVs), endothelial cell-derived MVs(EMVs), leucocyte-derived MVs(LMVs) and erythrocyte-derived MVs(RMVs) were all isolated which were identified membrane vesicles(<1 μm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats(P<0.05, respectively). In addition, at the end of 120-min reperfusion in I/R injured rats, IPC-MVs markedly increased HR(P<0.01), decreased ST-segment and LDH activity(P<0.05, P<0.01). The damage of myocardium was obviously alleviated and myocardial infarct size was significantly lowered after IPC-MVs treatment(P<0.01). Conclusion: The method of flow cytometry was successfully established to detect the phenotypes and concentration alteration of IPC-MVs, including PMVs, EMVs, LMVs and RMVs. Furthermore, circulating IPC-MVs protected myocardium against I/R injury in rats.展开更多
BACKGROUND After cardiac and non-cardiac surgeries,elderly patients have a high probability of developing cardiac complications and postoperative delirium.Although several clinical trials have investigated whether per...BACKGROUND After cardiac and non-cardiac surgeries,elderly patients have a high probability of developing cardiac complications and postoperative delirium.Although several clinical trials have investigated whether perioperative intravenous dexmedetomidine can protect the heart and reduce postoperative complications such as delirium in elderly patients,the obtained results have been inconsistent.We conducted a meta-analysis to investigate the effects of dexmedetomidine on cardioprotection and other postoperative complications in elderly patients undergoing cardiac or non-cardiac surgery.AIM To investigate the effects of dexmedetomidine on cardiac complications and delirium in elderly patients undergoing cardiac or non-cardiac surgery.METHODS The PubMed,Cochrane Library,web of science,and other sources were comprehensively searched for all randomized controlled trials published before May 2021 that investigated the efficacy of dexmedetomidine in the prevention of cardiac and postoperative delirium(POD).RESULTS In total,18 studies involving 1025 patients were included in the meta-analysis.Intravenous dexmedetomidine significantly reduced cardiac troponin I(cTnI)and the inflammatory factor tumor necrosis factor-α(TNF-α)was comparable to the control group.Dexmedetomidine also reduced the POD and mortality rates.However,patients in the dexmedetomidine group were more likely to have a decreased heart rate(within the normal range)and hypotension during dexmedetomidine administration than those in the control group.There was no difference in the occurrence of myocardial infarction,bradycardia,or stroke between the two groups.Dexmedetomidine significantly shortened the time to extubate;however,it did not shorten the length of stay in the intensive care unit.CONCLUSION The administration of dexmedetomidine during cardiac and non-cardiac surgeries can provide myocardial protection by inhibiting inflammation and cTnI,which may be beneficial for the rapid recovery of patients.Meanwhile,the administration of dexmedetomidine reduced the incidence of POD and decreased mortality(in-hospital).展开更多
Cardiomyocytes comprise~70%to 85%of the total volume of the adult mammalian heart but only about 25%to 35%of its total number of cells.Advances in single cell and single nuclei RNA sequencing have greatly facilitated ...Cardiomyocytes comprise~70%to 85%of the total volume of the adult mammalian heart but only about 25%to 35%of its total number of cells.Advances in single cell and single nuclei RNA sequencing have greatly facilitated investigation into and increased appreciation of the potential functions of non-cardiomyocytes in the heart.While much of this work has focused on the relationship between non-cardiomyocytes,disease,and the heart's response to pathological stress,it will also be important to understand the roles that these cells play in the healthy heart,cardiac homeostasis,and the response to physiological stress such as exercise.The present review summarizes recent research highlighting dynamic changes in non-cardiomyocytes in response to the physiological stress of exercise.Of particular interest are changes in fibrotic pathways,the cardiac vasculature,and immune or inflammatory cells.In many instances,limited data are available about how specific lineages change in response to exercise or whether the changes observed are functionally important,underscoring the need for further research.展开更多
基金Supported by Framework of one research project of the Spanish Society of Cardiology for Clinical Research in Cardiology 2012
文摘In patients with an acute ST-segment elevation myocardial infarction, timely myocardial reperfusion using primary percutaneous coronary intervention is the most effective therapy for limiting myocardial infarct size, preserving left-ventricular systolic function and reducing the onset of heart failure. Within minutes after the restoration of blood flow, however, reperfusion itself results in additional damage, also known as myocardial ischemia-reperfusion injury. An improved understanding of the pathophysiological mechanisms underlying reperfusion injury has resulted in the identification ofseveral promising pharmacological(cyclosporin-A, exenatide, glucose-insulin-potassium, atrial natriuretic peptide, adenosine, abciximab, erythropoietin, metoprolol and melatonin) therapeutic strategies for reducing the severity of myocardial reperfusion injury. Many of these agents have shown promise in initial proofof-principle clinical studies. In this article, we review the pathophysiology underlying myocardial reperfusion injury and highlight the potential pharmacological interventions which could be used in the future to prevent reperfusion injury and improve clinical outcomes in patients with coronary heart disease.
基金supported by Chinese Postdoctoral Science Foundation(No.2014N560538)Hainan Province Colleges and Universities Scientific Research Project(No.Hnky2015-34)Project of Natural Science Foundation of Hainan Province(314090)
文摘Objective: To investigate the expression of myocardium connexin 43(Cx43) in late exercise preconditioning(LEP) cardioprotection. Methods: Eight-week-old adult male Sprague Dawley rats were randomly assigned into four groups(n=8). Myocardial injury was judged in accordance with serum levels of c Tn and NT-pro BNP as well as hematoxylin basicfuchsin picric acid staining of myocardium. Cx43 m RNA was detected by in situ hybridization and qualified by real-time fluorescence quantitative PCR. Cx43 protein was localized by immunohistochemistry and its expression level was determined by western blotting. Results: The LEP obviously attenuated the myocardial ischemia/hypoxia injury caused by exhaustive exercise. There was no significant difference of Cx43 m RNA level between the four groups. Cx43 protein level was decreased significantly in group EE(P<0.05). However, LEP produced a significant increase in Cx43 protein level(P<0.05), and the decreased Cx43 protein level in exhaustive exercise was significantly up-regulated by LEP(P<0.05). Conclusions: LEP protects rat heart against exhaustive exercise-induced myocardial injury by up-regulating the expression of myocardial Cx43.
基金supported by the Specialized Research Fund for the Doctoral Program of Higher Education of China(20101202110005)the Natural Science Foundation of Tianjin(11JCZDJC18300)the Research Foundation of Tianjin Municipal Education Commission(20110106)
文摘Objective: To establish a flow cytometric method to detect the alteration of phenotypes and concentration of circulating microvesicles(MVs) from myocardial ischemic preconditioning(IPC) treated rats(IPC-MVs), and to investigate the effects of IPC-MVs on ischemia/reperfusion(I/R) injury in rats. Methods: Myocardial IPC was elicited by three cycles of 5-min ischemia and 5-min reperfusion of the left anterior descending(LAD) coronary artery. Platelet-free plasma(PFP) was isolated through two steps of centrifugation at room temperature from the peripheral blood, and IPC-MVs were isolated by ultracentrifugation from PFP. PFP was incubated with anti-CD61, anti-CD144, anti-CD45 and anti-Erythroid Cells, and added 1, 2 μm latex beads to calibrate and absolutely count by flow cytometry. For functional research, I/R injury was induced by 30-min ischemia and 120-min reperfusion of LAD. IPC-MVs 7 mg/kg were infused via the femoral vein in myocardial I/R injured rats. Mean arterial blood pressure(MAP), heart rate(HR) and ST-segment of electrocardiogram(ECG) were monitored throughout the experiment. Changes of myocardial morphology were observed after hematoxylin-eosin(HE) staining. The activity of plasma lactate dehydrogenase(LDH) was tested by Microplate Reader. Myocardial infarct size was measured by TTC staining. Results: Total IPC-MVs and different phenotypes, including platelet-derived MVs(PMVs), endothelial cell-derived MVs(EMVs), leucocyte-derived MVs(LMVs) and erythrocyte-derived MVs(RMVs) were all isolated which were identified membrane vesicles(<1 μm) with corresponding antibody positive. The numbers of PMVs, EMVs and RMVs were significantly increased in circulation of IPC treated rats(P<0.05, respectively). In addition, at the end of 120-min reperfusion in I/R injured rats, IPC-MVs markedly increased HR(P<0.01), decreased ST-segment and LDH activity(P<0.05, P<0.01). The damage of myocardium was obviously alleviated and myocardial infarct size was significantly lowered after IPC-MVs treatment(P<0.01). Conclusion: The method of flow cytometry was successfully established to detect the phenotypes and concentration alteration of IPC-MVs, including PMVs, EMVs, LMVs and RMVs. Furthermore, circulating IPC-MVs protected myocardium against I/R injury in rats.
文摘BACKGROUND After cardiac and non-cardiac surgeries,elderly patients have a high probability of developing cardiac complications and postoperative delirium.Although several clinical trials have investigated whether perioperative intravenous dexmedetomidine can protect the heart and reduce postoperative complications such as delirium in elderly patients,the obtained results have been inconsistent.We conducted a meta-analysis to investigate the effects of dexmedetomidine on cardioprotection and other postoperative complications in elderly patients undergoing cardiac or non-cardiac surgery.AIM To investigate the effects of dexmedetomidine on cardiac complications and delirium in elderly patients undergoing cardiac or non-cardiac surgery.METHODS The PubMed,Cochrane Library,web of science,and other sources were comprehensively searched for all randomized controlled trials published before May 2021 that investigated the efficacy of dexmedetomidine in the prevention of cardiac and postoperative delirium(POD).RESULTS In total,18 studies involving 1025 patients were included in the meta-analysis.Intravenous dexmedetomidine significantly reduced cardiac troponin I(cTnI)and the inflammatory factor tumor necrosis factor-α(TNF-α)was comparable to the control group.Dexmedetomidine also reduced the POD and mortality rates.However,patients in the dexmedetomidine group were more likely to have a decreased heart rate(within the normal range)and hypotension during dexmedetomidine administration than those in the control group.There was no difference in the occurrence of myocardial infarction,bradycardia,or stroke between the two groups.Dexmedetomidine significantly shortened the time to extubate;however,it did not shorten the length of stay in the intensive care unit.CONCLUSION The administration of dexmedetomidine during cardiac and non-cardiac surgeries can provide myocardial protection by inhibiting inflammation and cTnI,which may be beneficial for the rapid recovery of patients.Meanwhile,the administration of dexmedetomidine reduced the incidence of POD and decreased mortality(in-hospital).
基金Supported by the NIH(R01AG061034(AR),R35HL15531(AR),R21AG077040(HL),and K08HL140200(JR))the American Heart Association(20CDA35310184(HL)and 19AMFDP34990046(JSG))+1 种基金Sarnoff Cardiovascular Research Foundation Fellowship award(LET and CS)Massachusetts General Hospital Sanchez-Ferguson Faculty Scholar Program(JSG)。
文摘Cardiomyocytes comprise~70%to 85%of the total volume of the adult mammalian heart but only about 25%to 35%of its total number of cells.Advances in single cell and single nuclei RNA sequencing have greatly facilitated investigation into and increased appreciation of the potential functions of non-cardiomyocytes in the heart.While much of this work has focused on the relationship between non-cardiomyocytes,disease,and the heart's response to pathological stress,it will also be important to understand the roles that these cells play in the healthy heart,cardiac homeostasis,and the response to physiological stress such as exercise.The present review summarizes recent research highlighting dynamic changes in non-cardiomyocytes in response to the physiological stress of exercise.Of particular interest are changes in fibrotic pathways,the cardiac vasculature,and immune or inflammatory cells.In many instances,limited data are available about how specific lineages change in response to exercise or whether the changes observed are functionally important,underscoring the need for further research.
