[A disorder of myocardial contractile function in acute experimental coronary failure: the submolecular mechanisms and the action of cardiac glycosides].

Abstract

Skinned and hybrid myocardial fibers were studied by methods of tensometry, determination of the ATP hydrolysis intensity, and resonance fluorescent energy transfer between highly selective labels bound to various amino acid residues. It was established that development of the early stage of heart failure in the case of acute myocardial ischemia caused by 15-min coronary artery occlusion (CAO) is related to a reversible damage or adaptive (functional) depression of the contractile protein system. As a result, the system features isolated submolecular post-translational variation in the properties of major proteins in a thin actin filament (myosin is not significantly damaged). This leads to a decrease in the force developed by the hybrid fibers (reconstructed using ghost myocardial fibers taken from ischemic area and normal myosin) and in the ATPase activity of actomyosin (ATP hydrolysis intensity) without any significant change in the Ca-sensitivity, cooperativity of the Ca-response of the actomyosin ensemble, and efficiency of the contractile process. In actin of the ischemic area, CAO results in a serious damage of the Lys61 and Cys374 regions and in a less pronounced damage of the Tyr69 and Cys10 regions. These results suggest that the Lys61 and, probably, Cys374-Lys61 regions are included in the actin monomer as a protomer, without adequate prepolymerization structural-conformational changes necessary to provide for the normal functioning of the filament. In the CAO-induced early stage of heart failure, cardiac glycosides (beta-acetyldigoxin, beta-methyldigoxin, and strophanthin K) produce a direct effect upon the intramolecular structure of myocardial actin, restore the generated force level, and increase the intensity of ATP hydrolysis by actomyosin ensemble. This is achieved by improving or normalizing the structural-conformational state and conformational mobility of the Lys61 and Cys374 region of actin.

• Authors: N V Karsanov, G V Sukoian, D R Tatulashvili, V N Karsanov, N E Guledani
• Journal: Eksperimental'naia i klinicheskaia farmakologiia (Eksp Klin Farmakol) 2000 Mar-Apr Vol. 63 Issue 2 Pg. 24-34 ISSN: 0869-2092 [Print] Russia (Federation)
• Vernacular Title: Narushenie sokratitel'noĭ funktsii miokarda pri ostroĭ éksperimental'noĭ koronarnoĭ nedostatochnosti: submolekuliarnye mekhanizmy, deĭstvie serdechnykh glikozidov.
• PMID: 10834090 (Publication Type: Comparative Study, English Abstract, Journal Article)

Chemical References

• Actins
• Cardiac Glycosides
• Fluorescent Dyes

Topics

• Actins (chemistry, drug effects)
• Acute Disease
• Animals
• Cardiac Glycosides (pharmacology, therapeutic use)
• Coronary Disease (complications, drug therapy, physiopathology)
• Dogs
• Drug Evaluation, Preclinical
• Fluorescent Dyes
• Heart (drug effects, physiopathology)
• Heart Failure (drug therapy, etiology, physiopathology)
• Hemodynamics (drug effects, physiology)
• Muscle Fibers, Skeletal (drug effects, physiology)
• Myocardial Contraction (drug effects, physiology)
• Protein Conformation (drug effects)