Parameters of ventricular contractility in mice: influence of load and sensitivity to changes in inotropic state

Abstract

We examined the relative usefulness of parameters to determine left ventricular contractility in mice invasively. The optimal parameter must be sensitive to changes in inotropy and insensitive to changes in loading. Furthermore, it should be able to confirm or reject the hypothesis of altered myocardial contractility after a limited number of experiments. Left ventricular function was assessed in closed-chest mice using a microtip pressure-conductance catheter at baseline and after increases in preload, afterload, or contractility. The parameters are differentially influenced by loading conditions and inotropic state. Only those parameters that could differentiate between basal and increased contractility with a power of 0.85 in ten or less experiments were considered useful. Ejection fraction, preload-recruitable stroke work (PRSW), and dP/dt(max)/V (ed) could demonstrate the smallest changes in contractility. Stroke work, maximal power and dP/dt(max) were most influenced by preload. End-systolic elastance, ejection fraction, and stroke work were afterload-dependent. Dividing the magnitude of the effect of inotropic stimulation to that of load changes gives an index for the usefulness for each parameter. A high ratio indicates that the change in parameter reflects inotropic rather than load change. This ratio was highest for PRSW, which seems to be the best parameter for judging contractility differences in mice.

The relative value of strain and strain rate for defining intrinsic myocardial function

“…Finally, many invasive parameters have been proposed to accurately reflect myocardial contractile function. However, PRSW has recently been shown to be an optimal measure of contractility in mice as it is independent of preload and afterload (23). Although each of the parameters prospectively chosen to represent preload, afterload, and contractility have their limitations, they would seem the most appropriate independent approximations in this experimental setting.…”

“…Analysis of the pressure-volume loop data sets was performed with PVAN 3.2 software (Millar Instruments). The maximal rate of developed LV pressure (dP/dtmax), maximal value of time-varying elastance, end-systolic elastance (Ees), arterial elastance (Ea), and preload recruitable stroke work (PRSW) were measured as previously described (23). The maximal rate of pressure decay (dP/dt min) and time constant of isovolumic relaxation were also obtained.…”

Displacement-encoded and manganese-enhanced cardiac MRI reveal that nNOS, not eNOS, plays a dominant role in modulating contraction and calcium influx in the mammalian heart

“…Two studies have demonstrated enhanced ␤-adrenergic dP/dt max in eNOS Ϫ/Ϫ mice with Iso (10,19). However, dP/ dt max is known to be sensitive to afterload (44), suggesting that the innate hypertension in eNOS Ϫ/Ϫ mice may have influenced prior results (10,19). It is also possible that no differences were detected between eNOS Ϫ/Ϫ and WT mice as a result of the relatively low dose of Dob used.…”

Increased β-Adrenergic Inotropy in Ventricular Myocardium From Trpm4 −/− Mice

“…It is unclear how this arises because this effect is absent in isolated right atrium. Especially, the difference in preload recruitable stroke work is important because it is independent of the preload of the heart 21,22 and illustrates that the intrinsic inotropic status of the Trpm4 −/− muscle is enhanced compared with WT after β-adrenergic stimulation. In accordance with and sarcomere contraction strength (see for instance), 23 even a limited increase in the Ca 2+ transient will have a profound effect on contraction strength.…”