Loading sequence is a major determinant of afterload-dependent relaxation in intact canine heart

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Abstract
To elucidate the role of loading sequence in afterload-dependent slowed relaxation in hearts in situ, the time constants (Texp from best exponential fitting method and TL from semilogarithmic method) of isovolumetric left ventricular (LV) pressure decay were studied in nine anesthetized open-chest dogs under the pharmacological blockade of autonomic nerve activity. An afterload change was imposed by clamping the ascending or descending aorta to make the peak LV pressure early or late in systole. During afterload interventions, in contractions with the peak LV pressure in late systole Texp and TL were significantly (P less than 0.05) larger than in those with the peak LV pressure in early systole in any comparable peak LV pressure range. Moreover, both time constants were directly correlated (P less than 0.01) with the time of peak LV pressure irrespective of peak LV pressure and clamp mode of aorta. In another protocol, marked differences both in Texp and TL were also observed between each of 25 pairs of contractions with different loading sequence but with comparable peak LV pressure and LV dimension (segment length). Thus afterload-dependent slowed relaxation in hearts in situ could not be attributed to an increased total load but to the altered loading sequence associated with an increase in afterload.