Functional activity of platelet guanylate cyclase and cardiohemodynamics in patients with chronic heart failure and relevant changes after treatment with isosorbide-5-mononitrate

Aim. To study effects of long-term administration of isosorbide-5-mononitra te (monochinquare retard - MR) on functional activity of soluble guanylate cyclase (GC), cardiohemodynamics and exercise tolerance in patients with co ronary heart disease (CHD) complicated by chronic cardiac failure (CCF). Materials and methods. The trial included 20 males aged 58 to 77 years with CHD, effort angina (NYHA class II-III), CCF (NYHA class I-II). Endothelial function was assessed before the treatment and 12 weeks after it by indire ct measurement of production of endothelial relaxing factor (NO) - by activ ation of platelet soluble GC in the presence of its activators: L-arginine, disulphide, sodium nitroprusside and protoporfirine IX. Hemodynamic parame ters, morphofunctional condition of the heart, exercise tolerance test resu lts were compared with changes in GC functional activity after 12 weeks of MR monotherapy. Results. Two types of the changes were revealed Type I (n=14): high GC basa l activity and low activity before the treatment with normalization of all the parameters after the treatment Type II (n=6): initially normal basal ac tivity and GC activation with their lo,cering after the treatment. MR in a single daily dose 50 mg given for 12 weeks has improved morphofunctional ca rdiac parameters with a reduction of left ventricular volume, a 8.3% increa se in the ejection fraction and a 117% increase in exercise tolerance. GC a ctivity inhibition was recorded in some cases, in angina class III, in part icular. In patients with normalization of GC activity the response was high er than in those who demonstrated inhibition of GC activity. Conclusion. MR therapeutic action may be due to enhancement of soluble GC a ctivity which was observed in 70% of the cases.