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Chapter-20 Cardiotonic Drugs

BOOK TITLE: Drug Screening Methods

Author
1. Mohanty Ipseeta
ISBN
9788180613975
DOI
10.5005/jp/books/10243_20
Edition
1/e
Publishing Year
2004
Pages
14
Author Affiliations
1. MGM Medical College, Sector-16, Kamothe, Navi Mumbai 410 705, Maharashtra (India), All India Institute of Medical Sciences, New Delhi, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India
Chapter keywords
inadequate cardiac output, impaired contractility of heart, oxygen, isolated hamster cardiomyopathic heart, myocardial infarction, coronary artery ligation, heart failure, left ventricular dysfunction, myocardial failure, neurohumoral activation, increased myosin heavy chain mRNA, atrial natriuretic factor mRNA, left ventricular function, chronic instrumentation, chronic rapid pacing, ejection fraction, diastolic dysfunction, cardiac output, increased systemic vascular resistance, chronic experimental mitral regurgitation, closed chest dogs, disruption of mitral chordate

Abstract

The commonest feature of congestive heart failure (CHF) is inadequate cardiac output and impaired contractility of heart and as a result inability to meet body’s demand for oxygen. In vitro method discusses isolated hamster cardiomyopathic heart. Myocardial infarction following coronary artery ligation in Sprague-Dawley rats is a widely used rat model of heart failure. It is observed that in the control group the progression of left ventricular dysfunction and myocardial failure is associated with neurohumoral activation similar to that seen in patients with CHF. Heart failure is associated with increased myosin heavy chain mRNA and atrial natriuretic factor mRNA. Generally, dog and other large animal models of heart failure may allow the study of left ventricular function and volumes more accurately than rodent models. In particular, they allow better chronic instrumentation. Chronic rapid pacing is described. Heart failure is associated with a significant decrease in ejection fraction and diastolic dysfunction, followed by decreased cardiac output and increased systemic vascular resistance. Chronic experimental mitral regurgitation is produced in closed chest dogs by disruption of mitral chordae or leaflets using an arterially placed forceps. Chronic severe aortic regurgitation in rabbits, created by aortic valve perforation with a catheter, produces left ventricular hypertrophy, followed by systolic dysfunction and heart failure after period of months. Tachycardia pacing is discussed. Doxorubicin exhibits acute and chronic cardiotoxicity and is used to induce failure in various animal species. CHF in man is characterized by cardiac hypertrophy, peripheral edema, lung and liver congestion, dyspnea, hydrothorax, and ascites. The guinea pig model has similarities to human heart failure with respect to calcium cycling, myosin isoforms and myocardial function. Gene targeted disruption of the muscle protein (MLP) in mice is a new model of the heart failure. MLP is a regulator of myogenic differentiation.

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