A newly proposed mathematical model accurately characterizes the time course of myocardial relaxation in canine papillary muscles under varying loading conditions and dobutamine administration.
Supports myocardial relaxation modeling in preclinical settings; leaves open human translation and clinical relevance.
OBJECTIVE: Study of myocardial relaxation (lusitropy) requires a lusitropic index that should reflect changes in the time course of relaxation, and is therefore ideally based on a model that encompasses the entire time course of relaxation. Since there is no such model, investigators could not evaluate and validate current measures of relaxation. A new model is therefore proposed and analysed here: X(t) = C(t/A)B(e)1-(t/A)B. X(t) is the time course of isometric force or isotonic shortening, t is time, and A, B and C are parameters. METHODS: The model was analysed and evaluated in nine in situ canine papillary muscles studied with a servo system which produced isometric and isotonic twitches. A, B and C were determined by Marquardt's algorithm. RESULTS: The new model is analytically sufficiently tractable to ascertain, for the first time, whether previous measures of relaxation reflect the time course of relaxation. It nonetheless fits observed data closely, the coefficients of determination being 0.995(SD 0.005) and 0.990(0.004) in isometric and isotonic switches. A and B showed little or no change, with alteration of preload and afterload states averaging 0.200(0.014) s and 0.21(0.022) s for A, and 1.87(0.099) and 2.15(0.158) for B in isometric and isotonic twitches respectively. Dobutamine decreased A but the change was significant only in isotonic twitches; it increased B significantly only in isometric twitches. Thus the lusitropic and chronotropic effects of dobutamine may depend on loading conditions. CONCLUSIONS: This model is uniquely useful because it permits the evaluation and reconciliation of previously proposed measures of myocardial relaxation. It also provides a convenient model of the time course of the mechanical activity of the myocardium under isometric and isotonic conditions and is successful in assigning physiological relevance to its parameters. Moreover it permits expeditious derivation of relations for its parameters, thus providing initial parameter estimates systematically.
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Obi N. Nwasokwa (1993) studied this question.
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