[Functional activity of platelet guanylate cyclase and cardiac hemodynamics in patients with chronic heart failure and relevant changes after treatment with isosorbide-5-mononitrate].
OBJECTIVE
To study effects of long-term administration of isosorbide-5-mononitrate (monochinquare retard-MR) on functional activity of soluble guanylate cyclase (GC), cardiohemodynamics and exercise tolerance in patients with coronary heart disease (CHD) complicated by chronic cardiac failure (CCF).


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 indirect measurement of production of endothelial relaxing factor (NO)--by activation of platelet soluble GC in the presence of its activators: L-arginine, disulphide, sodium nitroprusside and protoporfirine IX. Hemodynamic parameters, morphofunctional condition of the heart, exercise tolerance test results 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 basal activity and low activity before the treatment with normalization of all the parameters after the treatment. Type II (n = 6): initially normal basal activity and GC activation with their lowering after the treatment. MR in a single daily dose 50 mg given for 12 weeks has improved morphofunctional cardiac parameters with a reduction of left ventricular volume, a 8.3% increase in the ejection fraction and a 117% increase in exercise tolerance. GC activity inhibition was recorded in some cases, in angina class III, in particular. In patients with normalization of GC activity the response was higher than in those who demonstrated inhibition of GC activity.


CONCLUSIONS
MR therapeutic action may be due to enhancement of soluble GC activity which was observed in 70% of the cases.
Ol'binskaia
L I
LI
Ushakova
A V
AV
Sizova
Zh M
ZhM
D000284:Administration, Oral; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001792:Blood Platelets / Q000187:drug effects / Q000201:enzymology*; D003692:Delayed-Action Preparations; D004562:Electrocardiography; D004730:Endothelium, Vascular / Q000201:enzymology; D017079:Exercise Tolerance / Q000187:drug effects; D005500:Follow-Up Studies; D006162:Guanylate Cyclase / Q000097:blood*; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007548:Isosorbide Dinitrate / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D016896:Treatment Outcome; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*
D015415:Biomarkers; D003692:Delayed-Action Preparations; D014665:Vasodilator Agents; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D007548:Isosorbide Dinitrate; C030397:isosorbide-5-mononitrate