Mechanics of contraction and relaxation of the ventricle in experimental heart failure produced by rapid ventricular pacing in the conscious dog.
A model of heart failure produced by rapid ventricular pacing in the conscious dog instrumented with a conductance catheter to monitor instantaneous left ventricular volume has been developed. This experimental model is capable of analysis of the left ventricular pressure-volume relationship on a beat-to-beat basis, and has been used to assess ventricular function serially in the progress of heart failure and effects of pharmacological intervention. In seven dogs the magnitude of cardiotonic effects were significantly attenuated after development of heart failure. These findings support the concept that in the failing heart there is subsensitivity to beta-adrenergic stimulation in proportion to the severity. The failing heart was characterized by incomplete left ventricular relaxation. Dobutamine improved left ventricular early relaxation but did not affect chamber distensibility. In contrast new phosphodiesterase inhibitor, E-1020, improved ventricular distensibility with less marked changes in active relaxation; improved left ventricular relaxation appeared to be mediated by increased systolic shortening with enhancement of internal restoring forces, and improved distensibility by accelerated function of sarcoplasmic reticulum through increased intracellular cyclic AMP.
2nd Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
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Sasayama
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Asanoi
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Ishizaka
D000818:Animals; D002304:Cardiac Pacing, Artificial; D004280:Dobutamine / Q000627:therapeutic use; D004285:Dogs; D006333:Heart Failure / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D007093:Imidazoles / Q000627:therapeutic use; D009200:Myocardial Contraction / Q000502:physiology*; D010726:Phosphodiesterase Inhibitors / Q000627:therapeutic use; D011728:Pyridones / Q000627:therapeutic use; D016277:Ventricular Function, Left / Q000502:physiology*
D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D004280:Dobutamine; C059498:olprinone