Myocardial pathologies are major causes of morbidity and mortality worldwide. Early detection of loss of cellular integrity and expansion in extracellular volume(ECV) in myocardium is critical to initiate effective tr...Myocardial pathologies are major causes of morbidity and mortality worldwide. Early detection of loss of cellular integrity and expansion in extracellular volume(ECV) in myocardium is critical to initiate effective treatment. The three compartments in healthy myocardium are: intravascular(approximately 10% of tissue volume), interstitium(approximately 15%) and intracellular(approximately 75%). Myocardial cells, fibroblasts and vascular endothelial/smooth muscle cells represent intracellular compartment and the main proteins in the interstitium are types Ⅰ/Ⅲ collagens. Microscopic studies have shown that expansion of ECV is an important feature of diffuse physiologic fibrosis(e.g., aging and obesity) and pathologic fibrosis [heart failure, aortic valve disease, hypertrophic cardiomyopathy, myocarditis, dilated cardiomyopathy, amyloidosis, congenital heart disease, aortic stenosis, restrictive cardiomyopathy(hypereosinophilic and idiopathic types), arrythmogenic right ventricular dysplasia and hypertension]. This review addresses recent advances in measuring of ECV in ischemic and non-ischemic myocardial pathologies. Magnetic resonance imaging(MRI) has the ability to characterize tissue proton relaxation times(T1, T2, and T2*). Proton relaxation times reflect the physical and chemical environments of water protons in myocardium. Delayed contrast enhanced-MRI(DE-MRI) and multi-detector computed tomography(DE-MDCT) demonstrated hyper-enhanced infarct, hypo-enhanced microvascular obstruction zone and moderately enhanced peri-infarct zone, but are limited for visualizing diffuse fibrosis and patchy microinfarct despite the increase in ECV. ECV can be measured on equilibrium contrast enhanced MRI/MDCT and MRI longitudinal relaxation time mapping. Equilibrium contrast enhanced MRI/MDCT and MRI T1 mapping is currently used, but at a lower scale, as an alternative to invasive sub-endomyocardial biopsies to eliminate the need for anesthesia, coronary catheterization and possibility of tissue sampling error. Similar to delayed contrast enhancement, equilibrium contrast enhanced MRI/MDCT and T1 mapping is completely noninvasive and may play a specialized role in diagnosis of subclinical and other myocardial pathologies. DE-MRI and when T1-mapping demonstrated sub-epicardium, sub-endocardial and patchy mid-myocardial enhancement in myocarditis, Behcet's disease and sarcoidosis, respectively. Furthermore, recent studies showed that the combined technique of cine, T2-weighted and DE-MRI technique has high diagnostic accuracy for detecting myocarditis. When the tomographic techniques are coupled with myocardial perfusion and left ventricular function they can provide valuable information on the progression of myocardial pathologies and effectiveness of new therapies.展开更多
Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction （MI）. Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is...Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction （MI）. Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is to examine in an acute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated with pump failure. Anterior MI was produced in dogs via ligation of left anterior descending （LAD） coronary artery, that resulted in an infract size of about 30% of the left ventricular wall. Measurements ofhemodynamic status, mitochondrial function, free radical production and mitochondrial uncoupling protein 3 （UCP3） expression were determined over 24 h period. Hemodynamic measurements revealed a 〉 50% reduction in cardiac output at 24 h post infarction when compared to baseline. Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction. ADP/O ratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to the ADP/O ratios within the same samples with and without palmitic acid （PA）. GTP inhibition of （PA）-stimulated state 4 respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarction respectively when compared to sham and pre-infarction samples. This would suggest that the mitochondria are uncoupled and this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsy samples. Blood samples from the coronary sinus measured by electron paramagnetic resonance （EPR） methods showed an increase in reactive oxygen species （ROS） over baseline at 6 h and 24 h post-infarction. In conclusion, mitochondrial bio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall. Mitochondria appear to be energetically uncoupled and this is associated with declining pump function. Free radical production may be associated with the induction of uncoupling proteins in the mitochondria.展开更多
Objectives: To study the effect of sulfotanshinone sodium (SS) injection in the treatment of non-ischemic retinal vein occlusion (RVO). Methods: Sixty-two RVO patients treated in our hospital between Jan. 2013 and Oct...Objectives: To study the effect of sulfotanshinone sodium (SS) injection in the treatment of non-ischemic retinal vein occlusion (RVO). Methods: Sixty-two RVO patients treated in our hospital between Jan. 2013 and Oct. 2014 were randomly divided into Control Group (30 patients;Bendazol tablets) and Treatment Group (32 patients, Bendazol tablets + SS injections), each with a follow-up period of 6 months. Statistical analysis was then performed on changes in visual acuity, central retinal thickness (CRT) and retinal circulation time (RCT) before and after the treatment. Results: After treatment, both Control Group and Treatment Group witnessed an improvement on visual acuity (Control Group: t = 2.103, p = 0.044;Treatment Group: t = 8.021, p = 0.000). Visual acuity could be greatly improved in Treatment Group when compared with Control Group, with significant differences (p < 0.01). Macular edema could be greatly relieved in Treatment Group measured by CRT (t = 2.571, p = 0.007) while the difference was of no statistical significance in Control Group (t = 1.016, p = 0.070). RCT were remarkably shortened in both groups (Control Group: t = 43.83, p = 0.000;Treatment Group: t = 27.34, p = 0.000), and when compared with Control group, the changes in Treatment Group were more significant (p < 0.05). Conclusion: SS injection could effectively improve the therapeutic effect in patients with non-ischemic retinal vein occlusion.展开更多
While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is ac...While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes(NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.展开更多
文摘Myocardial pathologies are major causes of morbidity and mortality worldwide. Early detection of loss of cellular integrity and expansion in extracellular volume(ECV) in myocardium is critical to initiate effective treatment. The three compartments in healthy myocardium are: intravascular(approximately 10% of tissue volume), interstitium(approximately 15%) and intracellular(approximately 75%). Myocardial cells, fibroblasts and vascular endothelial/smooth muscle cells represent intracellular compartment and the main proteins in the interstitium are types Ⅰ/Ⅲ collagens. Microscopic studies have shown that expansion of ECV is an important feature of diffuse physiologic fibrosis(e.g., aging and obesity) and pathologic fibrosis [heart failure, aortic valve disease, hypertrophic cardiomyopathy, myocarditis, dilated cardiomyopathy, amyloidosis, congenital heart disease, aortic stenosis, restrictive cardiomyopathy(hypereosinophilic and idiopathic types), arrythmogenic right ventricular dysplasia and hypertension]. This review addresses recent advances in measuring of ECV in ischemic and non-ischemic myocardial pathologies. Magnetic resonance imaging(MRI) has the ability to characterize tissue proton relaxation times(T1, T2, and T2*). Proton relaxation times reflect the physical and chemical environments of water protons in myocardium. Delayed contrast enhanced-MRI(DE-MRI) and multi-detector computed tomography(DE-MDCT) demonstrated hyper-enhanced infarct, hypo-enhanced microvascular obstruction zone and moderately enhanced peri-infarct zone, but are limited for visualizing diffuse fibrosis and patchy microinfarct despite the increase in ECV. ECV can be measured on equilibrium contrast enhanced MRI/MDCT and MRI longitudinal relaxation time mapping. Equilibrium contrast enhanced MRI/MDCT and MRI T1 mapping is currently used, but at a lower scale, as an alternative to invasive sub-endomyocardial biopsies to eliminate the need for anesthesia, coronary catheterization and possibility of tissue sampling error. Similar to delayed contrast enhancement, equilibrium contrast enhanced MRI/MDCT and T1 mapping is completely noninvasive and may play a specialized role in diagnosis of subclinical and other myocardial pathologies. DE-MRI and when T1-mapping demonstrated sub-epicardium, sub-endocardial and patchy mid-myocardial enhancement in myocarditis, Behcet's disease and sarcoidosis, respectively. Furthermore, recent studies showed that the combined technique of cine, T2-weighted and DE-MRI technique has high diagnostic accuracy for detecting myocarditis. When the tomographic techniques are coupled with myocardial perfusion and left ventricular function they can provide valuable information on the progression of myocardial pathologies and effectiveness of new therapies.
文摘Cardiogenic shock is the leading cause of death among patients hospitalized with acute myocardial infarction （MI）. Understanding the mechanisms for acute pump failure is therefore important. The aim of this study is to examine in an acute MI dog model whether mitochondrial bio-energetic function within non-ischemic wall regions are associated with pump failure. Anterior MI was produced in dogs via ligation of left anterior descending （LAD） coronary artery, that resulted in an infract size of about 30% of the left ventricular wall. Measurements ofhemodynamic status, mitochondrial function, free radical production and mitochondrial uncoupling protein 3 （UCP3） expression were determined over 24 h period. Hemodynamic measurements revealed a 〉 50% reduction in cardiac output at 24 h post infarction when compared to baseline. Biopsy samples were obtained from the posterior non-ischemic wall during acute infarction. ADP/O ratios for isolated mitochondria from non-ischemic myocardium at 6 h and 24 h were decreased when compared to the ADP/O ratios within the same samples with and without palmitic acid （PA）. GTP inhibition of （PA）-stimulated state 4 respiration in isolated mitochondria from the non-ischemic wall increased by 7% and 33% at 6 h and 24 h post-infarction respectively when compared to sham and pre-infarction samples. This would suggest that the mitochondria are uncoupled and this is supported by an associated increase in UCP3 expression observed on western blots from these same biopsy samples. Blood samples from the coronary sinus measured by electron paramagnetic resonance （EPR） methods showed an increase in reactive oxygen species （ROS） over baseline at 6 h and 24 h post-infarction. In conclusion, mitochondrial bio-energetic ADP/O ratios as a result of acute infarction are abnormal within the non-ischemic wall. Mitochondria appear to be energetically uncoupled and this is associated with declining pump function. Free radical production may be associated with the induction of uncoupling proteins in the mitochondria.
文摘Objectives: To study the effect of sulfotanshinone sodium (SS) injection in the treatment of non-ischemic retinal vein occlusion (RVO). Methods: Sixty-two RVO patients treated in our hospital between Jan. 2013 and Oct. 2014 were randomly divided into Control Group (30 patients;Bendazol tablets) and Treatment Group (32 patients, Bendazol tablets + SS injections), each with a follow-up period of 6 months. Statistical analysis was then performed on changes in visual acuity, central retinal thickness (CRT) and retinal circulation time (RCT) before and after the treatment. Results: After treatment, both Control Group and Treatment Group witnessed an improvement on visual acuity (Control Group: t = 2.103, p = 0.044;Treatment Group: t = 8.021, p = 0.000). Visual acuity could be greatly improved in Treatment Group when compared with Control Group, with significant differences (p < 0.01). Macular edema could be greatly relieved in Treatment Group measured by CRT (t = 2.571, p = 0.007) while the difference was of no statistical significance in Control Group (t = 1.016, p = 0.070). RCT were remarkably shortened in both groups (Control Group: t = 43.83, p = 0.000;Treatment Group: t = 27.34, p = 0.000), and when compared with Control group, the changes in Treatment Group were more significant (p < 0.05). Conclusion: SS injection could effectively improve the therapeutic effect in patients with non-ischemic retinal vein occlusion.
基金supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research (C) 20K08399 (to Yasuhiro Maejima)KAKENHI 19K18985,Grant-in-Aid for JSPS Fellows+1 种基金MSD Life Science FoundationPublic Interest Incorporated Foundation (to Yuka Shiheido-Watanabe)
文摘While several previous studies have indicated the link between periodontal disease (PD) and myocardial infarction (MI), theunderlying mechanisms remain unclear. Autophagy, a cellular quality control process that is activated in several diseases, includingheart failure, can be suppressed by Porphyromonas gingivalis (P.g.). However, it is uncertain whether autophagy impairment byperiodontal pathogens stimulates the development of cardiac dysfunction after MI. Thus, this study aimed to investigate therelationship between PD and the development of MI while focusing on the role of autophagy. Neonatal rat cardiomyocytes(NRCMs) and MI model mice were inoculated with wild-type P.g. or gingipain-deficient P.g. to assess the effect of autophagyinhibition by P.g. Wild-type P.g.-inoculated NRCMs had lower cell viability than those inoculated with gingipain-deficient P.g. Thisstudy also revealed that gingipains can cleave vesicle-associated membrane protein 8 (VAMP8), a protein involved in lysosomalsensitive factor attachment protein receptors (SNAREs), at the 47th lysine residue, thereby inhibiting autophagy. Wild-type P.g.-inoculated MI model mice were more susceptible to cardiac rupture, with lower survival rates and autophagy activity thangingipain-deficient P.g.-inoculated MI model mice. After inoculating genetically modified MI model mice (VAMP8-K47A) with wildtype P.g., they exhibited significantly increased autophagy activation compared with the MI model mice inoculated with wild-typeP.g., which suppressed cardiac rupture and enhanced overall survival rates. These findings suggest that gingipains, which arevirulence factors of P.g., impair the infarcted myocardium by cleaving VAMP8 and disrupting autophagy. This study confirms thestrong association between PD and MI and provides new insights into the potential role of autophagy in this relationship.
