TITLE:
Severity of Symptoms of Systemic Inflammatory Response Syndrome and Congestive Heart Failure Caused by Chronic Aortic Stenosis and Its Pharmacological Correction
AUTHORS:
G. V. Sukoyan, D. Iu. Ionov, P. A. Galenko-Iaroshevsky, A. V. Zelenskaya, V. V. Golovac
KEYWORDS:
Systemic Inflammatory Response Syndrome, Heart Failure, NAD-Containing Positive Inotropic Drug
JOURNAL NAME:
World Journal of Cardiovascular Diseases,
Vol.7 No.12,
December
20,
2017
ABSTRACT: Systemic inflammatory response syndrome (SIRS) is one of the key accompanied states that worsens severity of congestive heart failure (CHF) and leads refractory CHF to conventional therapy. We investigated whether the cessation of the symptoms and signs of SIRS prevents the progression of the CHF caused by chronic aortic stenosis in rabbits. 8 weeks after induced CHF by left descending coronary artery stenosis, all animals were randomly assigned into 3 groups: control (CG)—without therapy (infusion of 0.9% NaCl); main I— receive mg/kg of Adenocin® dissolved in water for injection i.v., once daily and main II—animals receive 0.25 mg/kg enalapril i.m, furosemide 1.0 mg/kg i.v. (bolus) and pimobendan 0.1 mg/kg i.v. once daily. All animals were euthanized after 14 days of the beginning of treatment. Long-term aortic stenosis leads to a simultaneously developing of CHF, diagnosed by developing cardiac hypertrophy, increased level of BNP and myocardial oedema and SIRS, confirmed by increasing markers and symptoms of endotoxemia, tissue dysoxia and decreasing reserve ability of intrinsic defense systems. Restoration of myocardium redox-potential and level of NAD under treatment with Adenocin® leads unlike combined treatment with enalapril, furosemide and pimobendan to restoration, the regulatory pathways of TNF-α synthesis, cessation of the hypoxic/ischemic, lysosomal dysfunction and free radical-induced damage in myocardium and symptoms of CHF. Potential important link between cellular metabolism (hypoxia/ischemia), endotoxemia and disturbances in intrinsic defense system is the level of redox-potentail, NAD/NADH in myocardium. Influence of oxidized form of NAD-containing positive inotropic drug Adenocin® leads to the decreasing symptoms of CHF and beneficial action occurs on all the key links of SIRS.