Differential structural remodeling of the left-atrial posterior wall in patients affected by mitral regurgitation with or without persistent atrial fibrillation: a morphological and molecular study.

INTRODUCTION: Atrial fibrillation (AF) in mitral regurgitation (MR) is a complex disease where multiple factors may induce left-atrial structural remodeling (SR). We explored the differential SR of the left-atrial posterior wall (LAPW) of patients affected by MR with or without persistent AF, and the expression of key proteins involved in its pathogenesis. METHODS AND RESULTS: Light microscopy of LAPW samples from 27 patients with MR and persistent AF (group 1), 33 with MR in sinus rhythm (group 2), and 15 autopsy controls (group 3) was used to measure myocyte diameter, percentage of myocytolytic myocytes, interstitial fibrosis, and capillary density; RT-PCR and Western blotting were used to assess the mRNA and protein levels of SOD-1, SOD-2, HO-1, calpain, MMP-2, MMP-9, TIMP-1, TIMP-2, and VEGF; immunofluorescence was used to locate these proteins. Myocyte diameter was similar in groups 1 and 2, but larger than controls. Compared to group 2, group 1 had more myocytolytic myocytes (20.8 ± 5.6% vs 14.7 ± 4.5%; P < 0.0001), increased interstitial fibrosis (10.4 ± 5.1% vs 7.5 ± 4.2%; P < 0.05), and decreased capillary density (923 ± 107 No/mm(2) vs 1,040 ± 100 No/mm(2); P < 0.0001). All of the proteins were more expressed in groups 1 and 2 than in controls. The protein and mRNA levels of SOD-1, SOD-2, MMP-2, and MMP-9 were higher in group 1 than in group 2. CONCLUSIONS: The LAPW of MR patients with or without AF shows considerable SR. The former has more severe histopathological changes and higher levels of proteins involved in SR, thereby reaching a threshold beyond which the sinus impulse cannot normally activate atrial myocardium.

[Effects of kavergal on indices of lipid peroxidation and the condition of the antioxidant system in patients with rheumatic heart disease presenting with circulatory insufficiency]. / Vliianie kavergala na pokazateli perikisnogo okisleniia lipidov i sostoianie antioksidantnoi sistemy u bol'nykh s revmaticheskim porokom serdtsa s nedostatochnost'iu krovoobrashcheniia.

132 patients with rheumatic heart disease presenting with circulatory insufficiency displayed increased LPO both in the blood plasma and red cells, decline in the antioxidant enzymes activity varying with the circulatory insufficiency functional class degree of severity. Basic therapy with making use of antiinflammatory drugs, cardiac glycosides, diuretics together with drugs endowed with an antiarrhythmic activity and nitroglycerin (where indicated) was found to have practically no effect on LPO level or activity of the antioxidant system. The use of the drug kavergal, 1 g three times daily (total daily dosage being 3 g) in the complex therapy, has been shown to significantly decrease hyperlipoperoxidation both in the blood plasma and red cells increasing the activity of enzymes of the antioxidant defence.