Length-dependent modulation of ANG II inotropism in rat myocardium: effects of myocardial infarction.
To determine whether changes in sarcomere length affect the inotropic response of the heart to angiotensin II (ANG II) differently in dilated and failing myocardium, papillary muscles were removed 2 days after infarction, and the effects of ANG II were studied at various muscle lengths. Myocardial infarction, which averaged 52% of the left ventricle inclusive of the interventricular septum, was characterized hemodynamically by left ventricular failure and right ventricular dysfunction. ANG II administration at 100% the muscle length where force development is maximal (Lmax) produced a 12% depression of developed tension in papillary muscles from noninfarcted ventricles and a 37% decrease in developed tension in the viable myocardium of infarcted rats. In contrast, at 85 and 92.5% Lmax and in the presence of ANG II, control muscles increased active tension by 16 and 1.0%, whereas muscles from coronary occluded hearts augmented developed tension by 13 and 22%, respectively. In conclusion, ANG II exerted a positive inotropic effect on rat myocardium at muscle lengths on the ascending limb of the Starling curve but a negative inotropic action at the muscle length normally associated with maximum force development. This phenomenon emphasizes that hormonal influences on the contractile state of the diseased heart may be modulated by the interaction of end-diastolic pressure, sarcomere length, and ventricular size and shape.
Li
P
P
Department of Medicine, New York Medical College, Valhalla 10595.
Sonnenblick
E H
EH
Anversa
P
P
Capasso
J M
JM
D000595:Amino Acid Sequence; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006801:Humans; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D008969:Molecular Sequence Data; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009203:Myocardial Infarction / Q000503:physiopathology*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology
D002316:Cardiotonic Agents; D000804:Angiotensin II