Interactions between changes in the intensity and duration of the active state in the characterization of inotropic stimuli on heart muscle.

The responses of isolated cat papillary muscles and left atrial strips to a variety of procedures were classified systematically according to the induced changes in peak tension (T), mean rate of tension development (AT/At), and time to peak tension (TTP). Increasing temperature from 25° to 37°C augmented AT/At but reduced TTP reciprocally so that T remained constant. Increased frequency of contraction, thyroid hormone, and increased temperature markedly augmented AT/At but shortened TTP, with relatively little alteration in T. Norepinephrine, tyramine, paired electrical stimulation, strophanthidin, and calcium increased T by augmenting AT/At proportionately more than they reduced TTP. Acetylcholine and serotonin augmented T by raising AT/At with relatively little effect on TTP. Strontium increased T by causing both a prolongation of TTP and an augmentation of AT/At. Depression of T in muscles from failing hearts occurred primarily by a reduction of AT/At, and the negative inotropic effects of hypoxia or pentobarbital resulted from reductions in both AT/At and TTP. In muscles from hypothyroid cats, depression of AT/At was partially compensated for by prolongation of TTP. Since AT/At is related to the intensity of the active state and TTP to its duration, such analysis of these variables should provide a framework for the characterization and quantitative comparison of various types of inotropic stimuli. ADDITIONAL