Superiority of mitral valve replacement with preservation of subvalvular structure to conventional replacement in severe rheumatic mitral valve disease: a modified technique and results of one-year follow up.

BACKGROUND AND AIM OF THE STUDY: Mitral valve replacement with preservation of the subvalvular apparatus (MRVP) has been proven superior to conventional mitral valve replacement (MVR). We devised a simple modified MVRP method in this prospective, randomized study to investigate the clinical effects and one-year follow up echocardiographic results of MVRP compared with MVR in patients with severe rheumatic mitral insufficiency (MI). METHODS: Sixty-eight patients with severe rheumatic MI with or without stenosis were randomized to MVRP (n = 35) and MVR (n = 33) groups. In MVRP patients, the preserved tissue was pulled back posteriorly to the posterior wall of the left ventricle, then plicated and reaffixed to one-fourth of the annular circumference in the posterior annulus, in order to prevent left ventricular outflow tract (LVOT) obstruction. Clinical data including cumulative ventricular arrhythmias and use of inotropes were collected. Echocardiography examination was performed before surgery, and at five days, three months and one year thereafter. RESULTS: There were no preoperative differences patient data. The cross-clamp time was 2.2 min longer in MVRP patients. The one-month mortality rate after surgery was lower in MVRP patients (2.9% versus 15.2%, p = 0.074). Mechanical ventilation and ICU times were shorter in the MVRP group (17.6 versus 24.8 and 52.5 versus 70.6 h, p = 0.001 and 0.1, respectively). There were fewer ventricular arrhythmias and less need for inotropic support in this group. One year follow up echocardiography data showed better preserved left ventricular ejection fraction (LVEF) and better recovery of heart size after MRVP. There was no indication that preserved valvular tissue interfered with mechanical valve function, or caused LVOT obstruction. CONCLUSION: This modified MVRP technique is simple, effective and without risk of LVOT obstruction. In severe rheumatic MI patients the outcome of MVRP is superior to that of conventional MVR in term's of mortality, postoperative care needs, left ventricular function and heart dimensions.

Cyanide-induced neurotoxicity involves nitric oxide and reactive oxygen species generation after N-methyl-D-aspartate receptor activation.

To study oxidative mechanisms in cyanide toxicity, cyanide-induced generation of intracellular oxidant species was determined by microfluorescence in cerebellar granule cells loaded with the oxidant-sensitive fluorescence dye 2,7-dichlorofluorescin. KCN produced a concentration-dependent (25-200 microM) generation of intracellular oxidant species that was blocked by N-methyl-D-aspartate receptor antagonists (MK-801 or AP5) or by removal of extracellular Ca++ from the incubation medium. To determine the relative contribution of NO and reactive oxygen species (ROS) to the increase of cellular fluorescence after KCN, a selective inhibitor of nitric oxide synthase, a NO scavenger and enzymes that metabolize ROS were added to the incubation medium. Interference with the nitric oxide system (reduced hemoglobin as a NO scavenger or [N(G)-nitro-L-arginine methyl ester [L-NAME] reduced fluorescence by 50%). Addition of enzymes that metabolize peroxide (catalase or superoxide dismutase [SOD]) also reduced fluorescence by nearly 50%. Combination of SOD with hemoglobin or L-NAME provided additional attenuation of the fluorescence and it was concluded that both NO and ROS are generated concurrently after KCN. Furthermore a correlation was observed between NO and ROS formation and levels of malonaldehyde (MDA), a marker of lipid peroxidation. Pretreatment with MK-801 blocked KCN-induced MDA formation, whereas L-NAME partially diminished MDA production. Treatment with a combination of SOD/catalase and L-NAME blocked the KCN-induced lipid peroxidation. In cytotoxicity studies cyanide-induced cell death was blocked by MK-801, whereas partial attenuation was produced by L-NAME; SOD/catalase treatments did not protect the cells. However, significant protection from cyanide-induced cytotoxicity was observed when L-NAME was combined with SOD/catalase. It is concluded that cyanide activates N-methyl-D-aspartate receptors to simultaneously generate both NO and ROS, which may lead to formation of the cytotoxic peroxynitrite anion.