ABSTRACT
Objective To test whether cardiosphere-derived cells(CDCs)were sufficient to decrease manifestations of heart failure with preserved ejection fraction(HFpEF)in hypertensive rats.Methods DS rats(Charles River,Wilmington,Massachusetts)were fed 0.3% NaCl(low-salt)diet until 7 weeks of age.At that time,the diet was switched to an 8% NaCl(high-salt)diet in rats by random assignment.DS rats fed the low-salt diet constituted the control group(n=20).At 13 to 14 weeks of age,rats with the high-salt diet were randomized to receive allogeneic rat CDCs or PBS.Echocardiography long-axis images of the left ventricular systolic and diastolic dimensions.Sirius red was used to assess fibrosis and proliferation.Results E/A ratio increased in the PBS-treated group compared with the control group and the CDCs-treated group [(1.20±0.30)vs.(1.70±0.20)or(1.80±0.16),t=0.782,0.844,all P<0.001].LAA kept increasing in the PBS-treated group[(27.20±1.10)mm2 vs.(19.80±0.76)mm2 or(17.80±0.82)mm2,t=0.892,0.774,all P<0.001].The time constant of isovolumic LV pressure fall was prolonged in placebo-treated animals compared with CDCs-treated animals and control rats[(6.2±0.3)×103 mmHg/s vs.(9.4±0.4)×103 mmHg/s,t=0.382,P=0.024;(6.2±0.3)×103 mmHg/s vs.(9.1±0.5)×103 mmHg/s,t=0.883,P=0.022].LVEDP was 2-fold higher in placebo-treated group than in CDC-treated and control animals[(17±10)mmHg vs.(8±3)mmHg,t=0.922,P=0.003;(17±10)mmHg vs.(9±4)mmHg,t=0.922,P=0.004].A dramatic improvement of survival was observed in CDC-treated rats(Kaplan-Meier survival curves)(P=0.027).Cardiac myofibroblasts increased dramatically in PBS-treated(110/field vs.46/field,P<0.001).Inflammatory cytokines expression siginficantly increased in PBS-treated group.Conclusion CDCs improves survival in a rat model of HFpEF through reducing inflammation and fibrosis.
ABSTRACT
Objective To investigate whether cardiosphere-derived cells (CDCs)can protect ischemia-reperfusion in acute myocardial infarction,and to explore its mechanism.Methods 7 -10 week-old female Wistar-Kyoto (WKY)rats were used for all in vivo experiment.Ischemia was induced for 45 min to allow reperfusion. Twenty minutes (or two hours)later,CDCs (or PBS control)were injected into the LV cavity with an aortic cross-clamp.After 48 hours and 2 weeks,representative echocardiography long-axis images of the left ventricular (LV) systolic and diastolic dimensions,the protein level of activated caspase-3 were observed,the apoptosis rate of myo-cardial cells and the infarct area of the heart were determined in those groups.Results Rats underwent 45 minutes of ischemia,followed by either 20 minutes or 120 minutes (delayed injection)of reperfusion prior to infusion of CDCs (cells per 100μL)or PBS control (100μL)into the LV cavity during aortic cross-clamp.Ejection fraction,as meas-ured by echocardiography,was significantly preserved in CDCs-treated animals at 48 hours with a 20 -minute,but not a 120-minute,delay of infusion(28.0% vs 38.0%,χ2 =7.340,P=0.008).CDCs-treated animals reduced percentage of infarct mass(6.2% vs 13.4%,χ2 =4.226,P=0.002;6.2% vs 13.5%,χ2 =1.853,P=0.003), infarct mass(6.2% vs 13.4%,χ2 =2.220,P=0.002;6.2% vs 13.5%,χ2 =3.119,P=0.003)treated with PBS control.CDC-treated animals reduced infarct size,relative to those of animals treated with PBS control(45.0% vs 24.0%,χ2 =4.825,P=0.008),less thinning of the LV anterior wall(1.96mm vs 1.45mm,t=0.897,P=0.028). Protein expressions of MMP-8 and CXGL7 were elevated in the infarct zone of hearts treated with CDCs(MMP-8:0.74 vs 0.56,t=0.657,P=0.014;CXGL7:0.44 vs 0.81,t=0.791,P=0.010).Conclusion CDCs is suggested to be a promising cell source to repair acute myocardial infarction through inhibiting apoptosis and reduce proinflam-matory cytokine expression.
ABSTRACT
Objective To study the feasibility of using fractional flow reserve (FFR) to guide whether to perform coronary revascularization of non-culprit moderate stenosis in patients with unstable angina and estimate their clinical prognosis. Methods This study enrolled unstable angina patients with multivessel disease. First successful stenting of the culprit artery, then the other non-culprit moderate coronary stenosis were randomized into PCI guided by angiography or guided by FFR measurements. Death from any cause, nonfatal myocardial infarction, unplanned hospitalization leading to urgent revascularization and clinical manifestations with angina were followed during the first year. Results 71 patients were included, among them 35 patiens were randomly assigned to angiography-guided PCI and 36 patients to FFR-guided PCI. In FFR-guided PCI group, FFR was successfully measured in all of non-culprit moderate coronary stenosis. In 23 stenosis, the FFR was greater than 0.80, and stents were not placed in these stenosis. In 13 stenosis with FFR<0.8, stent were inplant and FFR was raised≥0.95 after stenting. The percentage of patients who had a primary end-point event was higher in the angiography-guided PCI group than the FFR-guided PCI group (P<0.05). Neither the rate of mortelity from any cause nor the rate of non-fatal myocardial infarction had significant difference between the 2 groups. Related to the target vessels rates of nonfatal myocardial infarction (5.6%vs. 28.6%) and target lesion revascularization (5.6%vs. 31.4%) were statistically different (P<0.01 and P<0.05, respectively). Conclusions In patients with unstable angina, it is safe to use FFR values to guide decisions on the revascularization of angiographically moderate non-culprit stenosis. Routine measurement of FFR in addition to angiographic guidance, as compared with PCI guided by angiography alone, results in a significant reduction in major adverse events at 1 year, particularly in urgent revascularization, and clinical manifestations with angina get better.