The isolated working heart model in infarcted rat hearts.
Congestive heart failure (CHF) is one of the most common causes of death in western countries. The aim of this study was to establish and validate the working heart model in rat hearts with CHF. In the rat model the animals show parameters and symptoms that can be extrapolated to the clinical situation of patients with end-stage heart failure. The focus of attention was the evaluation of cardiodynamics (e.g.contractility) in the isolated 'working heart' model. The geometric properties of the left ventricle were measured by planimetry (stereology). Formulae available in the past for determining certain parameters in the working heart model (e.g.external heart work) have to be fitted to the circumstances of the infarcted rat hearts with its different organ properties.CHF was induced in Wistar Kyoto (WKY/NHsd) and spontaneously hypertensive rats (SHR/NHsd) by creating a permanent (8 week) occlusion of the left coronary artery, 2 mm distal to the origin from the aorta, by a modified technique (Itter et al. 2004). This resulted in a large infarction of the free left ventricular wall. We were able to establish and adapt a new and predictive working heart model in spontaneously hypertensive rat hearts with myocardial infarction (MI) 8-12 weeks after coronary artery ligation. At this stage the WKY rat did not show any symptoms of CHF. The SHR rat represented characteristic parameters and symptoms that could be extrapolated to the clinical situation of patients with end-stage heart failure (NYHA III-IV). Upon inspection, severe clinical symptoms of CHF such as dyspnoea, subcutaneous oedema, palebluish limbs and impaired motion were prominent. On necropsy the SHR showed lung oedema, hydrothorax, large dilated left and right ventricular chambers and hypertrophy of the septum. In the working heart model the infarcted animals showed reduced heart power, diminished contractility and enhanced heart work, much more so in the SHR/NHsd than in the Wistar Kyoto rat (WKY/NHsd). The aim for the future is to find a causal therapy of heart failure treatment. At present, only palliative therapy is possible for patients with heart failure. For this reason the working heart model in CHF rat hearts should provide a valuable method for early testing of new therapeutic approaches for patients with CHF.
Itter
G
G
Aventis Pharma Deutschland, LASW (H840), Zi. 140, DG Cardiovascular Diseases, D-65926 Frankfurt/ Main, Germany. Gabi.Itter@aventis.com
Jung
W
W
Schoelkens
B A
BA
Linz
W
W
D000818:Animals; D001794:Blood Pressure; D002302:Cardiac Output; D003331:Coronary Vessels / Q000473:pathology; D004195:Disease Models, Animal; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate; D008026:Ligation / Q000379:methods; D008297:Male; D009200:Myocardial Contraction / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D016276:Ventricular Function