Comparative influence of load versus inotropic states on indexes of ventricular contractility: experimental and theoretical analysis based on pressure-volume relationships.

Abstract

We examined the quantitative influence of carefully controlled alterations in enddiastolic volume and afterload resistance on multiple simultaneously determined ejection and isovolumetric phase indexes of left ventricular contractile function in 23 isolated supported canine ventricles. The influence of load change on each index was compared with its sensitivity to inotropic stimulation, and this sensitivity was in turn contrasted to the response of the end-systolic pressure-volume relationship (ESPVR). Experimental data demonstrated various degrees of load sensitivity among the indexes, with a generally curvilinear relationship between load and index response for both preload and afterload alterations. The curvilinear nature of these relationships meant that over a select range of loading, many indexes demonstrated relative load independence. They also often displayed greater sensitivity to inotropic change than the ESPVR, and both factors help explain their enduring clinical utility. To further explore the influence of load and contractile state on several of the indexes, we developed a theoretical analysis, using variables common to pressure-volume relationships, in which these dependencies could be derived. The theoretical models fit very well with the experimental data, and reaffirmed the frequently curvilinear nature of the relationships. We conclude that while many clinical indexes of ventricular contractile function show significant load dependence, the information they provide can be reasonably interpreted within defined ranges of load and inotropic alteration. Any advantage of the ESPVR will derive not from the magnitude of its response to inotropic change, which is smaller than most other indexes, but from its relative insensitivity to load alteration over a wider range of load.

Vascular ventricular coupling in patients with malignant phase hypertension: the West Birmingham malignant hypertension project

“…16,18 It is well recognized that changes in contractile performance alter Ees, but Ees is also influenced by chamber geometry and by factors that alter the passive stiffness of the myocardium. 11,18,19 The values for the Ea/Ees ratio obtained in both study groups are within the above range and …”

Multiscale model of the human cardiovascular system: Description of heart failure and comparison of contractility indices

“…A good index of cardiac contractility should vary only with the inotropic state of the heart and be perfectly loadindependent. Many cardiac indices have been proposed to assess ventricular contractile state [32,33,34] and here we compare some of these with our model.…”

“…Another contractility index with a relatively weak afterloaddependence is the peak first derivative of left ventricular pressure, (dP/dt) max [32]. In clinic, it is however easier to assess the arterial pressure than the ventricular pressure, so the arterial (dP/dt) max was also proposed as a cardiac contracility index [34].…”

Laterality in Direct and Indirect Inotropic Effects of Sympathetic Stimulation in Isolated Canine Heart.

“…In an isolated cross-circulated canine heart, we can precisely measure left ventricular volume and pressure and therefore estimate E es , which has been known to be a load insensitive index of left ventricular contractility [5][6][7][8][9]. Although direct actions of pharmacological agents on the heart can be investigated without autonomic nerves, indirect actions of pharmacological agents on the heart through the modulation of the autonomic nervous system cannot be analyzed by ordinary isolated canine heart preparation.…”

“…Although previous studies investigated sympathetic regulation of left ventricular function and HR [1][2][3][4], the load dependency of the indexes of ventricular contractility used in these studies, such as dP/dt (the first derivative of pressure waveform), ejection fraction, and stroke volume, makes it difficult to quantitatively compare the relative contribution of the direct and indirect inotropic effects. On the other hand, left ventricular end-systolic elastance (E es ), which is the slope of the end-systolic pressurevolume relationship, has been shown to be a load-insensitive index of ventricular contractility [5][6][7][8][9]. Although the precise estimation of E es can be achieved in an isolated cross-circulated canine heart preparation, because the heart was denervated during the isolation procedure makes this preparation inappropriate for investigating its autonomic regulation.…”