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Decreased contractility and altered responses to inotropic agents in myocytes from tachypacing-induced heart failure canines.
- Source :
-
Journal of pharmacological and toxicological methods [J Pharmacol Toxicol Methods] 2018 Sep - Oct; Vol. 93, pp. 98-107. Date of Electronic Publication: 2018 Jun 14. - Publication Year :
- 2018
-
Abstract
- Contractility measurements using primary isolated cardiac myocytes (CM) have commonly been used in understanding the physiology and pharmacology of cellular mechanics. In the majority of studies, CM from healthy animals were used, and fewer studies were performed with CM from diseased hearts. To better understand the translational value of contractility on the cellular level of a diseased animal model, myocytes were isolated from left ventricles of a tachypacing-induced heart failure (HF) canine model, and their contractility was measured by recording sarcomere shortening using an image-based IonOptix video system. A side-by-side comparison study was performed in myocytes isolated from 13 normal and 5 tachypacing-induced HF canines by evaluating both basal contractility and pharmacological responses to inotropic agents with different mechanisms, including dobutamine, isoproterenol, milrinone, levosimendan, pimobendan, diltiazem, and flecainide. Myocytes isolated from HF canines exhibited compromised contractility at the sarcomere level in comparison to normal myocytes, specifically, HF myocytes have smaller sarcomere contraction amplitude, longer resting sarcomere length, slower velocity of contraction and relaxation. In addition, they have altered pharmacological responses compared to that of normal canines, with much less potent effects observed in the application of classic inotropic agents, such as isoproterenol, dobutamine, and milrinone. These results indicate that myocytes isolated from tachy-paced HF canines have altered physiological and pharmacological properties, which could be utilized for understanding pathophysiology and developing pharmacological interventions for HF.<br /> (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cells, Cultured
Dogs
Dose-Response Relationship, Drug
Heart Failure pathology
Heart Failure physiopathology
Isoproterenol pharmacology
Male
Myocardial Contraction physiology
Myocytes, Cardiac physiology
Cardiac Pacing, Artificial adverse effects
Cardiotonic Agents pharmacology
Heart Failure etiology
Myocardial Contraction drug effects
Myocytes, Cardiac drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1873-488X
- Volume :
- 93
- Database :
- MEDLINE
- Journal :
- Journal of pharmacological and toxicological methods
- Publication Type :
- Academic Journal
- Accession number :
- 29908289
- Full Text :
- https://doi.org/10.1016/j.vascn.2018.06.001