Rebuttal from Yellin and Nikolic

We are pleased that Kovacs' group has raised the importance of clarifying the relation between diastolic suction and ventricular equilibrium volume. There is, indeed, a need to translate experimental studies of diastolic suction into the clinical realm. Zhang et al. (10) and Shmuylovich et al. (9) argue as follows: 1) on the basis of the Katz criterion (5) onset of filling is caused by suction; 2) when flow ceases in diastasis, the equilibrium volume is reached; 3) therefore, “every ventricle approaches diastasis [and equilibrium volume] by suction-initiated filling” (9). This statement is true, but trivial. Think on it: if X occurs at t = 0 and Y occurs at t > 0, then of course it follows that X precedes Y, but this does not imply causality between Y and X.

Kovacs' group fails to separate the roles of elastic recoil and relaxation and fails also to understand the role of elastic recoil and its relation to the Brecher/Nikolic definition of chamber equilibrium volume, Vo (1, 7). The analogy to cardiac muscle mechanics should help the reader understand our approach. Every inactive unloaded muscle has a rest length, Lo, analogous to Vo. Both are physical properties. When stimulated at Lo a muscle will shorten, and when deactivated it will return to Lo due to elastic restoring forces. It has been clearly demonstrated that the restoring forces are due to the sarcomere protein Titin and arise at muscle contraction below Lo (2, 4). Figure 2 in a later paper by Granzier and Labeit (3) is of particular interest because it shows the relation between passive force and sarcomere length that includes the negative portion, i.e., L < Lo, directly analogous to ESV < 0 in the chamber P-V relation. Note also that Nikolic et al. (7) relates the chamber volumes above and below Vo to in vivo sarcomere lengths above and below Lo. Further corroboration in canine and human studies can be found in Opdahl et al. (8) where caval constriction acutely decreased volume and the ventricle contracted below Vo, and in Levine et al. (6) where bed rest chronically changed Vo.

We believe that Kovacs' group (9, 10) has failed to justify their definition of ventricular equilibrium volume and its relation to diastolic suction. The reader will, of course, make the final decision.