ObjectiveTo investigate the spontaneous premature cardiac aging in SHJH^hr mice. MethodsA comparative study was conducted between SHJH^hr mice (SHJH^hr group) and wild-type ICR mice (WT group) at different ages (10 and 24 weeks). Cardiac function was analyzed using a small animal in vivo ultrasound imaging system. After euthanasia, organs were collected and weighed to assess the extent of cardiac atrophy. Cardiac pathological damage was observed using hematoxylin-eosin (HE) staining. Cardiac fibrosis was analyzed using Masson staining. Myocardial cell area was analyzed after wheat germ agglutinin (WGA) staining. The activities of oxidative damage indicators in myocardial tissue, including superoxide dismutase (SOD), glutathione peroxidase (GPX), and catalase (CAT), as well as the content of 8-hydroxy-2'-deoxyguanosine (8-OHdG), were measured using enzyme-linked immunosorbent assay. Real-time fluorescence quantitative PCR was used to measure the mRNA expression levels of factors associated with inflammation, fibrosis, and oxidative stress. Colorimetric assay was used to measure malondialdehyde (MDA) levels. ResultsCompared to WT group mice of the same age, 10-week-old mice in the SHJH^hr group showed no significant differences in stroke volume (SV), ejection fraction (EF), fractional shortening (FS), or heart and lung weights. However, at 24 weeks of age, mice in the SHJH^hr group had significantly lower SV, EF, and FS values compared to mice of the same age in the WT group (P<0.05), with no significant change in lung weight but a significant reduction in heart weight (P<0.05). Histological analysis of heart tissue from 24-week-old mice revealed no significant difference in cardiac fibrosis levels between SHJH^hr and WT groups, but WGA staining showed a significant reduction in myocardial cell area in mice in the SHJH^hr group (P<0.05). PCR analysis revealed a significant downregulation of mRNA levels of oxidative stress factors Sod2, Gpx1, and Cat genes (P<0.05). Biochemical assays indicated significantly reduced activities of oxidative damage-related enzymes SOD, GPX, and CAT in myocardial tissue (P<0.05), while the levels of oxidative damage markers 8-OHdG and MDA significantly increased (P<0.05). ConclusionMice in the SHJH^hr group exhibit premature cardiac aging, which may be associated with oxidative stress damage in myocardial tissue.

BACKGROUND: Salvianolate is a compound mainly composed of salvia magnesium acetate, which is extracted from the Chinese herb Salvia miltiorrhiza . In recent years, salvianolate injection has been widely used in the treatment of cardiovascular diseases, but the mechanism of how it can alleviate cardiotoxicity remains unclear. METHODS: The cardiac injury model was constructed by treatment with doxorubicin (Dox) or azithromycin (Azi) in zebrafish larvae. Heart phenotype, heart rate, and cardiomyocyte apoptosis were observed in the study. RNA-sequencing (RNA-seq) analysis was used to explore the underlying mechanism of salvianolate treatment. Moreover, cardiomyocyte autophagy was assessed by in situ imaging. In addition, the miR-30a/becn1 axis regulation by salvianolate was further investigated. RESULTS: Salvianolate treatment reduced the proportion of pericardial edema, recovered heart rate, and inhibited cardiomyocyte apoptosis in Dox/Azi-administered zebrafish larvae. Mechanistically, salvianolate regulated the lysosomal pathway and promoted autophagic flux in zebrafish cardiomyocytes. The expression level of becn1 was increased in Dox-induced myocardial tissue injury after salvianolate administration; overexpression of becn1 in cardiomyocytes alleviated the Dox/Azi-induced cardiac injury and promoted autophagic flux in cardiomyocytes, while becn1 knockdown blocked the effects of salvianolate. In addition, miR-30a, negatively regulated by salvianolate, partially inhibited the cardiac amelioration of salvianolate by targeting becn1  directly. CONCLUSION This study has proved that salvianolate reduces cardiomyopathy by regulating autophagic flux through the miR-30a/becn1 axis in zebrafish and is a potential drug for adjunctive Dox/Azi therapy.
Animals ; Zebrafish ; MicroRNAs/genetics* ; Autophagy/drug effects* ; Myocytes, Cardiac/metabolism* ; Cardiomyopathies/metabolism* ; Beclin-1/genetics* ; Apoptosis/drug effects* ; Plant Extracts/therapeutic use* ; Doxorubicin

Objective To measure and analyze biological characteristics and aging phenotype of SHJH^hr mice and provide basic data for the application of the mouse model in aging mechanisms research and antiaging drug development. MethodsWith ICR mice of the same age as control group, the body mass growth data of SHJH^hr mice at the age of 3 to 16 weeks, the reproduction ability of 1 to 4 fetuses and the life cycle of SHJH^hr mice were measured. Blood routine (30 items) and serum biochemical indexes (25 items) of 6-week-old SHJH^hr mice were measured. The venous blood of 8-week-old SHJH^hr mice was collected for flow cytometry analysis to determine the content of immune cells. The aging bone structure of the cancellous bone and bone mineral density of SHJH^hr mice aged 4, 8 and 26 weeks were measured by micro-CT. Histopathological changes of bone and joint of 8-week-old mice were observed. ResultsCompared with ICR mice, the female and male body mass of SHJH^hr mice were significantly lower at the age of 16 weeks (P < 0.05), and the reproductive performance of female mice was low (P < 0.01) or did not have normal reproductive capacity. The shortest survival time of SHJH^hr mice was 57 weeks and the longest was 71 weeks, which was shorter than those of normal ICR mice, showing obvious rapid aging phenomenon. At the same time, some physiological and biochemical indexes of blood and pathological changes of bone and cartilage tissues also showed the accelerated aging and abnormality of animal physiological functions. ConclusionSHJH^hr mice have some biological characteristics of rapid aging as well as some physiological and pathological changes caused by aging.

Coronary heart disease (CHD) treatment methods are changing rapidly, and new drugs are constantly entering the clinic. Antiplatelet drugs are the basis for the treatment of CHD, but there are currently no new drugs that can challenge the status of aspirin and P2Y

Objective Myocardial bridging is a congenital anomaly.However,little data is available for patients with myocardial bridging (MB) associated with acute myocardial infarction (AMI).The goals of this study are to evaluate characteristics of MB in patients with AMI.Methods From March 1999 to February 2006,137 patients with both MB and AMI,were identified by coronary angiography,including 117 men and 20 women with an average age of 60.77±12.01 years (range 30-83 years) were enrolled in the present study.Results There were 119 patients with MB at the middle segment of left anterior descending artery (LAD),15 patients at distal segment of LAD,2 patients at middle segment of left circumflex (LCX),and 1 at the proximal segment of the obtuse marginal branch (OM) of LCX.There are 36 patients with non-ST elevation acute myocardial infarction (NSTEAMI),38 patients with anterior ST elevation AMI (STEAMI),40 patients with inferior STEAMI and 23 patients with inferior-posterior STEAMI.Risk factors such as hypertension,diabetes,hyperlipidemia and smoking were not different among four groups.Patients with anterior AMI included 8 patients who showed no stenosis at the segment of MB.Conclusion Patients with MB and ST elevation AMI were mainly inferior AMI.MB might be one of the causes of AMI.

Objective: To investigate the safety and efficacy of rotational atherectomy in the interventional treatment of coronary chronic total occlusion lesions. Methods: In this retrospective study,a total of 31 consecutive patients with coronary chronic total occlusion(CTO) lesions underwent rotational atherectomy in our hospital from February 2004 to December 2016 were enrolled,and the clinical features were analyzed. Coronary atherectomy was performed if balloon failed to cross the CTO lesions or balloon could not be fully dilated in the CTO lesions after wire crossing. The definition of procedure success was defined as residual stenosis less than 20% after implantation of drug eluting stent and rotational atherectomy. After the procedure, the patients were followed up to observe major adverse cardiac and cerebral vascular events which including cardiogenic death, myocardial infarction, cerebrovascular accident, and target lesion revascularization. Results: The 1.25 mm diameter burr was firstly selected in 80.6% (25/31) patients,and 96.8%(30/31) patients used only 1 burr to complete the rotational atherectomy procedure. The complication rate was 9.8% (3/31) including 1 patient with coronary dissection and 3 patients with slow flow or no flow. There was 1 patent with both coronary dissection and slow flow. The procedure success rate was 96.8%(30/31). Interventional treatment related myocardial infarction occurred in 3 patients during hospitalization.The 30 patients with procedure success were followed up 36(11, 96) months. The incidence rate of major adverse cardiac and cerebral vascular events was 13.3% (4/30), of which the cardiogenic death rate was 3.3% (1/30), the myocardial infarction rate was 6.7% (2/30), cerebrovascular accident rate was 3.3%(1/30),and the target lesion revascularization rate was 6.7% (2/30). Conclusion Rotational atherectomy is safe and effective in the interventional treatment of coronary CTO lesions.

Objective To observe the efficacy of antithrombotic treatment of acute ST-segment elevation myocardial infarction patients with failure primary percutaneous coronary intervention because of high thrombus burden,and its effect on elective percutaneous coronary intervention.Methods Eight acute ST-segment elevation myocardial infarction patients were enrolled,who suffered from failure of primary percutaneous coronary intervention because of high thrombus burden.Summarize the antithrombotic strategies in perioperative and postoperative period,the operative strategies and the follow-up coronary intervention were recorded and reviewed.Results All the patients were male and most of them had acute inferior myocardial infarction with right coronary occluded because of high thrombus burden.Four patients received thrombus aspiration and balloon dilation.One patient received thrombus aspiration and the other three patients did not receive coronary intervention.Tirofiban were given in perioperative period to all the patients.Low molecular weight heparin was given to 6 patients.Dual antiplatelet therapy was given to 6 patients (aspirin 100 mg/day plus clopidogrel 75 mg/day) and 1 patient required up-titration of aspirin to 200 mg/day.Coronary angiography were repeated (29.00 ± 23.25) days later,and the thrombus in the culprit vessels disappeared in two patients,and coronary stent implantation was performed in three patients.Conclusions The routine antithrombotic strategies play limited roles in thrombus clearance in acute ST segment elevation myocardial infarction patients with failure primary percutaneous coronary intervention because of high thrombus burden.The time for the thrombus to be totally organized and the timing of elective percutaneous coronary intervention are still uncertain and need to be further studied.

OBJECTIVE: To assess magnetic resonance imaging (MRI) features of coronary microembolization in a swine model induced by small-sized microemboli, which may cause microinfarcts invisible to the naked eye. MATERIALS AND METHODS: Eleven pigs underwent intracoronary injection of small-sized microspheres (42 microm) and catheter coronary angiography was obtained before and after microembolization. Cardiac MRI and measurement of cardiac troponin T (cTnT) were performed at baseline, 6 hours, and 1 week after microembolization. Postmortem evaluation was performed after completion of the imaging studies. RESULTS: Coronary angiography pre- and post-microembolization revealed normal epicardial coronary arteries. Systolic wall thickening of the microembolized regions decreased significantly from 42.6 +/- 2.0% at baseline to 20.3 +/- 2.3% at 6 hours and 31.5 +/- 2.1% at 1 week after coronary microembolization (p < 0.001 for both). First-pass perfusion defect was visualized at 6 hours but the extent was largely decreased at 1 week. Delayed contrast enhancement MRI (DE-MRI) demonstrated hyperenhancement within the target area at 6 hours but not at 1 week. The microinfarcts on gross specimen stained with nitrobluetetrazolium chloride were invisible to the naked eye and only detectable microscopically. Increased cTnT was observed at 6 hours and 1 week after microembolization. CONCLUSION: Coronary microembolization induced by a certain load of small-sized microemboli may result in microinfarcts invisible to the naked eye with normal epicardial coronary arteries. MRI features of myocardial impairment secondary to such microembolization include the decline in left ventricular function and myocardial perfusion at cine and first-pass perfusion imaging, and transient hyperenhancement at DE-MRI.
Animals ; Coronary Angiography/*methods ; Coronary Vessels/*pathology ; Disease Models, Animal ; Embolism/*pathology ; Female ; Heart/radiography ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging/*methods ; Microspheres ; Myocardial Contraction/physiology ; Myocardial Infarction/*pathology ; Myocardium/pathology ; Nitroblue Tetrazolium ; Staining and Labeling ; Swine ; Troponin T/blood ; Ventricular Function, Left

Objective To evaluate the application of multi-slice computed tomographic coronary angiography in diagnosis of chronic total occlusion (CTO) of coronary artery.Methods Six hundred and thirty eight patients were diagnosed as CTO disease with coronary angiography (CAG) from June 2011 to December 2012 in Zhongshan Hospital;236 of them received multi-slice computed tomographic coronary angiography in 60 days before.Results In total 708 vessels of the 236 patients,244 vessels were proved totally occluded,128 (52.5％) of which were located in left anterior descending artery,31 (12.7％) were located in left circumflex coronary artery and 85 (34.8％) located in right coronary artery.Multi-slice computed tomographic coronary angiography was superior to CAG in judgment of stump anatomy (64.3％ vs.52.5％,F =7.09,P =0.010),plaque calcification (40.2％ vs.26.2％,F =10.68,P =0.001) and distal vessel interpretability (93.9％ vs.74.6％,F =34.06,P ＜ 0.001).There was no significant difference in judging side branch,tortuosity and lesion length between multi-slice computed tomographic coronary angiography and CAG (all P ＞ 0.05).Conclusion Multi-slice computed tomographic coronary angiography provides more detailed anatomy information of CTO lesions and is of value in diagnosis and treatment of CTO lesions.

Objective To assess the MR characterization of coronary microembolization (CME)in an animal model as well as the evolution using MR cardiac cine,first-pass perfusion,and delay enhancement imaging.Methods Coronary microembolization models were established through intracoronary infusion of 120 000 microspheres (42 μm)into the left anterior descending artery in 1 1 pigs. Coronary angiography was performed at baseline and immediately after the injection of microspheres.MR imaging was carried out at baseline,6 hours,and 1 week after microembolization.Then,postmortem evaluation was performed using NBT and HE staining.Re-sults Coronary angiography after the injection of microspheres showed normal-appearing epicardial arteries in all animals.Coronary microembolization caused a significant decline in systolic wall thickening of the microembolized myocardial segments on cine MR ima-ges [from (42.6±2.0)% at baseline to (20.3±2.3)% at 6 hours and (31.5±2.1)% at 1 week after CME;P < 0.001 for both]. First-pass perfusion deficit was visualized at 6 hours after microembolization,and was less pronounced at 1 week.Hyperenhanced myocardium was found on delay enhancement MRI at 6 hours after microembolization in microembolized segments,but was not shown at 1 week. The microinfarcts were detectable microscopically through HE staining but invisible for the naked eye on gross NBT specimen.Con-clusion Coronary microembolization may cause a persistent decline in myocardial contraction and its MR characterization may vary with different stages.A combined use of different cardiac MRI techniques and follow-up examinations may be helpful for evaluating myocardial impairment due to coronary microembolization.