Nonlinear biphasic relationship between the time constant tau and load

Dear Editor, We read with great interest the article by Prabhu [1]. This author studied left ventricular (LV) relaxation during transient vena cava occlusion in normal and failing hearts. He described the LV relaxation-systolic load relationship as non-linear and biphasic. Prabhu concluded that ‘this biphasic relationship between tau and systolic load had not been reported previously’ (Discussion, subsection 4.1, right column, 3rd paragraph, lines 5-6). This statement, on this otherwise interesting and careful study, could be challenged: In a similar canine model a biphasic relationship between tau and load had already been the subject of a detailed analysis [2]. This relationship fitted in an updated framework on the regulation of myocardial relaxation by load [3]. To summarise, increases in afterload not exceeding 81–84% (in dogs) or 73–76% (in rabbits) of peak isovolumetric load (i.e. relative load) accelerate LV relaxation. Yet, when the systolic load exceeds this limit, then LV relaxation is delayed to the extent that it may even cause incomplete myocardial relaxation and diastolic heart failure [4]. Delayed myocardial relaxation may occur in the normal heart because of excessive load but may also occur in the failing heart because of low peak isovolumetric load [3]. Vena cava occlusions, as performed by Prabhu, decrease simultaneously preload and afterload. When compared to selective afterload changes, caval occlusions are more complex to explain in terms of underlying mechanisms. A key confounding factor is length dependent activation of myocardial function (i.e. Frank-Starling's law), hence peak isovolumetric pressure and relative load. In addition, venous return may affect both systolic and diastolic function in a way which is far from being predictable as evidenced by recent observations in cardiac patients [5,6]. In conclusion, the effects of Prabhu's study are presumably related to the combination of afterload dependence of myocardial relaxation (relative load) and length dependent activation of myocardial function (Frank-Starling). It nevertheless appears that the biphasic relationship between tau and load described by Prabhu is the mirror image of the ‘J-shaped’ biphasic relationship between tau and afterload previously described by our group [2–4].