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Multi-scale modeling of cardiac excitation-contraction coupling in the normal and failing heart

McCulloch, A (UC, San Diego)
Tuesday 21 July 2009, 13:30-14:15

Seminar Room 1, Newton Institute


The excitation-contraction coupling properties of cardiac myocytes isolated from different regions of the mammalian left ventricular wall have been shown to vary considerably, with uncertain effects on ventricular function. We developed a detailed model of excitation-contraction coupling model with region-dependent parameters for epicardial, mid-myocardial and endocardial myocytes, and then embedded it within a fully coupled finite element model of ventricular electromechanics coupled to a lumped parameter model of the circulation. Comparing this model with one in which heterogeneous myocyte parameters were assigned randomly throughout the mesh while preserving the total amount of each cell subtype, we observed similar transmural patterns of fiber and cross-fiber strains at end systole, but clear differences in fiber strain distributions at earlier times during systole. Hemodynamic function, including peak left ventricular pressure, maximum rate of left ventricular pressure development, and stroke volume were essentially identical in the two models.

We also modeled ventricular electromechanics in the dyssynchronous failing dog heart and examined the relative roles of dilation, negative inotropy, negative lusitropy and electrical dyssynchrony on global and regional function. The analysis suggested that there is significant interactions between dilation and dyssynchrony especially on regional mechanics.

Finally, we present initial findings on a preliminary clinical study to test the ability of such multi-scale models of electromechanics in the failing heart to predict clinical outcomes of cardiac resynchronization therapy.

Supported by : NIH, NSF, UC Discovery, Medtronic


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