Isolated annular dilation does not usually cause important functional mitral regurgitation Comparison between patients with lone atrial fibrillation and those with idiopathic or ischemic cardiomyopathy

AbstractObjectivesWe sought to test whether isolated mitral annular (MA) dilation can cause important functional mitral regurgitation (MR).BackgroundMitral annular dilation has been considered a primary cause of functional MR. Patients with functional MR, however, usually have both MA dilation and left ventricular (LV) dilation and dysfunction. Lone atrial fibrillation (AF) can potentially cause isolated MA dilation, offering a unique opportunity to relate MA dilation to leaflet function.MethodsMid-systolic MA area, MR fraction, LV volumes and papillary muscle (PM) leaflet tethering length were compared by echocardiography among 18 control subjects, 25 patients with lone AF and 24 patients with idiopathic or ischemic cardiomyopathy (ICM).ResultsPatients with lone AF had a normal LV size and function, but MA dilation (isolated MA dilation) significant and comparable to that of patients with ICM (MA area: 8.0 ± 1.2 vs. 11.6 ± 2.3 vs. 12.5 ± 2.9 cm2[control vs. lone AF vs. ICM]; p < 0.001 for both lone AF and ICM). However, patients with lone AF had only modest MR, compared with that of patients with ICM (MR fraction: −3 ± 8% vs. 3 ± 9% vs. 36 ± 25%; p < 0.001 for patients with ICM). Multivariate analysis identified PM tethering length, not MA dilation, as an independent primary contributor to MR.ConclusionsIsolated annular dilation does not usually cause moderate or severe MR. Important functional MR also depends on LV dilation and dysfunction, leading to an altered force balance on the leaflets, which impairs coaptation

Effect of a Large Dose of Di (2-ethylhexyl) phthalate (DEHP) on Hepatic Peroxisome in Cynomolgus Monkeys (Macaca Fascicularis)

To elucidate the effect of a large dose of di (2-ethylhexyl) phthalate (DEHP), a plasticizer and peroxisome proliferator-activated receptor-α (PPARα) agonist, on hepatic peroxisomes, we orally administered 1,000 mg/kg/day, once daily, to 3 male and 4 female cynomolgus monkeys for 28 days consecutively. Light-microscopic and electron microscopic examinations of the liver were carried out in conjunction with measurement of the hepatic fatty acid β-oxidation system (FAOS), carnitine acetyltransferase (CAT) and carnitine palmitoyltransferase (CPT) activities, which are peroxisomal and/or mitochondrial enzyme activities. Electron microscopically, enlargement of the mitochondria was observed with lamellar orientation of the cristae along the major axis. Although the number of peroxisomes showed a tendency to increase when compared with those in a biopsied specimen before treatment, no abnormality in morphology was observed. A slight increase in CPT activity was noted at termination. No changes were noted in hepatic FAOS or CAT activity. In conclusion, although repeated oral treatment of cynomolgus monkeys with a large dose of DEHP induced a subtle increase in the numbers of peroxisomes with slight enlargements of the mitochondria, this low-sensitivity response to peroxisome proliferators in cynomolgus monkeys was considered to be closer to the response in humans than that in rodents