Impact of Coronary Plaque Composition on Cardiac Troponin Elevation After Percutaneous Coronary Intervention in Stable Angina Pectoris : A Computed Tomography Analysis

ObjectivesThe authors used multidetector computed tomography (MDCT) to study the relation between culprit plaque characteristics and cardiac troponin T (cTnT) elevation after percutaneous coronary intervention (PCI).BackgroundPercutaneous coronary intervention is often complicated by post-procedural myocardial necrosis manifested by elevated cardiac biomarkers.MethodsStable angina patients (n = 107) with normal pre-PCI cTnT levels underwent 64-slice MDCT before PCI to evaluate plaque characteristics of culprit lesions. Patients were divided into 2 groups according to presence (group I, n = 36) or absence (group II, n = 71) of post-PCI cTnT elevation ≥3 times the upper limit of normal (0.010 ng/ml) at 24 h after PCI.ResultsComputed tomography attenuation values were significantly lower in group I than in group II (43.0 [26.5 to 75.7] HU vs. 94.0 [65.0 to 109.0] HU, p 1.05; odds ratio: 4.54; 95% confidence interval: 1.36 to 15.9; p = 0.014) and spotty calcification (odds ratio: 4.27; 95% confidence interval: 1.30 to 14.8; p = 0.016) were statistically significant independent predictors for cTnT elevation. For prediction of cTnT elevation, the presence of all 3 variables (CT attenuation value 1.05, and spotty calcification) showed a high positive predictive value of 94%, and their absence showed a high negative predictive value of 90%.ConclusionsMDCT may be useful in detecting which lesions are at high risk for myocardial necrosis after PCI

Rev-erb agonist improves adverse cardiac remodeling and survival in myocardial infarction through an anti-inflammatory mechanism

Rev-erb α, known as nuclear receptor 1D1 (NR1D1), regulates circadian rhythm, modulates glucose and lipid metabolism, and inflammatory response. However, little is known about the effect of Rev-erb agonist on the progression of myocardial infarction (MI) and heart failure. To investigate it, wild-type male mice underwent sham-operation or permanent ligation of the left anterior descending coronary artery to create MI model. Rev-erb agonist SR9009 (100 mg/kg/day) or vehicle was intraperitoneally administered. Echocardiography was performed to evaluate cardiac function 1 week after surgery. The gene and protein expression levels in the left ventricles (LVs) were determined with real-time PCR, western blotting, and immunofluorescence. Moreover, immune cell infiltration into the LVs was analyzed by flow cytometry. Survival rate and reduced LV function were significantly improved by the treatment with SR9009 after MI. The expression level and plasma concentration of brain natriuretic peptide were significantly lower in MI mice treated with SR9009 (MI+SR) than in MI mice treated with vehicle (MI+V). Moreover, the mRNA expression levels of inflammatory-related molecules such as Il6, Mcp1, Ly6g, Cd11b, matrix metallopeptidase (Mmp)9, and the protein expression levels of phosphorylated NF-κB p65, phosphorylated ERK, and phosphorylated p38 were also significantly lower in MI+SR than in MI+V. Immunofluorescence intensity for MMP-9 was enhanced in the LVs, but was less so in MI+SR than in MI+V. Furthermore, infiltrations of neutrophils and proinflammatory macrophages in the LVs were dramatically increased in MI+V and were significantly suppressed in MI+SR. Rev-erb agonist SR9009 treatment inhibited post-MI mortality and improved cardiac function through modulating inflammation and remodeling process

Enhancing endogenous adenosine A2A receptor signaling induces slow-wave sleep without affecting body temperature and cardiovascular function

Insomnia is one of the most common sleep problems with an estimated prevalence of 10%–15% in the general population. Although adenosine A2A receptor (A2AR) agonists strongly induce sleep, their cardiovascular effects preclude their use in treating sleep disorders. Enhancing endogenous A2AR signaling, however, may be an alternative strategy for treating insomnia, because adenosine levels in the brain accumulate during wakefulness. In the present study, we found that 3,4-difluoro-2-((2-fluoro-4-iodophenyl)amino)benzoic acid, denoted A2AR positive allosteric modulator (PAM)-1, enhanced adenosine signaling at the A2AR and induced slow wave sleep (SWS) without affecting body temperature in wild-type male mice after intraperitoneal administration, whereas the SWS-inducing effect of this benzoic acid derivative was abolished in A2AR KO mice. In contrast to the A2AR agonist CGS 21680, the A2AR PAM-1 did not affect blood pressure or heart rate. These findings indicate that enhancing A2AR signaling promotes SWS without cardiovascular effects. Therefore, small molecules that allosterically modulate A2ARs could help people with insomnia to fall asleep

Exercise training reduces ventricular arrhythmias through restoring calcium handling and sympathetic tone in myocardial infarction mice

Exercise can improve morbidity and mortality in heart failure patients; however, the underlying mechanisms remain to be fully investigated. Thus, we investigated the effects of exercise on cardiac function and ventricular arrhythmias in myocardial infarction (MI) induced heart failure mice. Wild‐type male mice underwent sham‐operation or permanent left coronary artery ligation to induce MI. MI mice were divided into a sedentary (MI‐Sed) and two intervention groups: MI‐Ex (underwent 6‐week treadmill exercise training) and MI‐βb (oral bisoprolol treatment (1 mg/kg/d) without exercise). Cardiac function and structure were assessed by echocardiography and histology. Exercise capacity and cardiopulmonary function was accepted as oxygen consumption at peak exercise (peak VO2). Autonomic nervous system function and the incidence of spontaneous ventricular arrhythmia were evaluated via telemetry recording. mRNA and protein expressions in the left ventricle (LV) were investigated by real‐time PCR and Western blotting. There were no differences in survival rate, MI size, cardiac function and structure, while exercise training improved peak VO2. Compared with MI‐Sed, MI‐Ex, and MI‐βb showed decreased sympathetic tone and lower incidence of spontaneous ventricular arrhythmia. By Western blot, the hyperphosphorylation of CaMKII and RyR2 were restored by exercise and β‐blocker treatment. Furthermore, elevated expression of miR‐1 and decreased expression of its target protein PP2A were recovered by exercise and β‐blocker treatment. Continuous intensive exercise training can suppress ventricular arrhythmias in subacute to chronic phase of MI through restoring autonomic imbalance and impaired calcium handling, similarly to that for β‐blockers

持続性心房細動における心房内異常電位の成因と機序の解明

科学研究費助成事業 研究成果報告書：基盤研究(C)2014-2016課題番号 : 2646105