Nonlinear biphasic relationship between the time constant tau and load

To the Editor, On the other hand, the effects of length-dependent activation on myocardial function manifest significantly later, I appreciate the excellent points raised by Leite-Moreira et occurring several minutes after the initial change in muscle al. regarding my manuscript examining the load sensitivity length [6,7]. This is well beyond the time period examined of left ventricular (LV) relaxation in heart failure [1], and in my study, in which transient caval occlusion was only welcome the opportunity to respond. As has been detailed performed for 10 seconds. Furthermore, an exaggerated by these authors and others previously, relaxation behavior biphasic response of tau to load was noted in heart failure, is complex and can be influenced by multiple factors a pathophysiologic state characterized by attenuation of including the magnitude of load, the timing of load, and length-dependent activation [8,9]. Thus, it is unlikely that the manner in which the load is applied. This study length-dependent activation significantly influenced the examined the effect of load on LV relaxation in the intact results reported. state during transient reductions in preload while controlIn summary, studies examining the influence of load on ling such variables as heart rate and neurohumoral reflexes. left ventricular relaxation have utilized several types of These experimental conditions are quite different than interventions to alter load: long-term steady-state changes, those used by the authors in their previous studies describshort-term transient changes (as with caval occlusion in my ing a J-shaped tau-load relation [2,3], which examined the study), and single beat changes (as performed by Leiteeffect of single beat elevations in afterload on LV relaxaMoreira and coworkers). When considered together, these tion. Prior studies examining the influence of transient studies provide a complementary and comprehensive aschanges in preload on tau [4,5], including one recently sessment of the complex influence of load on LV relaxapublished by the authors [5] have reported a direct linear tion. Unlike steady-state changes, the time course of relationship between load and tau. It is in this context that transient caval occlusion precludes a significant impact of the finding of a biphasic relationship between tau and load length-dependent activation on myocardial function. during preload reduction is novel. As outlined in the paper, differences between my results and these prior studies may be secondary to differences in experimental design (e.g. References heart rate and reflex effects) and the degree of load reduction achieved. Thus, I would view my study and [1] Prabhu SD. Load sensitivity of left ventricular relaxation in normal those by Leite-Moreira, Gillebert, and coworkers [2,3] as and failing hearts: evidence of a biphasic response. Cardiovasc Res 1999;43:354–363. describing complementary but not identical phenomena [2] Leite-Moreira AF, Gillebert TC. Nonuniform course of left ventricuregarding the influence of load on LV relaxation. lar pressure fall and its regulation by load and contractile state. I agree with Leite-Moreira et al. that transient caval Circulation 1994;90:2481–2491. occlusion alters both preload and afterload (an expected [3] Gillebert TC, Leite-Moreira AF, De Hert SG. Relaxation-systolic occurrence in the intact state when a series of beats is pressure relation. A load independent assessment of left ventricular assessed following an isolated initial load change), and contractility. Circulation 1997;95:745–752. [4] Ishizaka S, Asanoi H, Wada O, Kameyama T, Inoue H. Loading invokes the first phase of the myocardial stretch response. sequence plays an important role in enhanced load sensitivity of left ventricular relaxation in conscious dogs with tachycardia-induced *Tel.: 11-502-852-7959; fax: 11-502-852-7147. cardiomyopathy. Circulation 1995;92:3560–3567. E-mail address: [email protected] (S.D. Prabhu) [5] De Hert SG, Gillebert TC, Ten Broecke PW, Moulijn AC. Length-