Published Online
on May 27, 2003

A more recent version of this article appeared on June 17, 2003

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Submitted on November 7, 2002
Revised on March 11, 2003
Accepted on March 13, 2003

Enhancement of Contractility With Sustained Afterload in the Intact Murine Heart. Blunting of Length-Dependent Activation

Maricela Reyes MS, Gregory L. Freeman MD, Daniel Escobedo , Shuko Lee MS, Mark E. Steinhelper PhD, and Marc D. Feldman MD^*

From the Department of Medicine (Division of Cardiology) and the Department of Physiology, University of Texas Health Science Center and the South Texas Veterans Health Care System, Audie L. Murphy Division, San Antonio, Tex.

^* To whom correspondence should be addressed. E-mail: feldmanm{at}uthscsa.edu.

Background--It has been hypothesized that because of its rapid heart rate, the intact murine heart functions near maximal contractility in the basal state. If this hypothesis is correct, then the fast and slow components of myocardial length-dependent activation should be blunted compared with larger mammals.

Methods and Results--Mice (n=24) were anesthetized, and via an open chest, LV pressure-volume relationships were determined by a dual-frequency conductance catheter system. Baseline pressure-volume relationships were determined during transient occlusion of the inferior vena cava, and repeat measurements were made after 1 (n=10) and 7 (n=21) minutes of sustained aortic occlusion. Control experiments were performed in a subset of mice (n=3). For baseline to 1 minute, an increase in afterload (maximal pressure 95±9 to 126±7 mm Hg; P<0.001) and effective arterial elastance (5.9±3.1 to 9.2±3.9 mm Hg/µl; P<0.001) resulted in an increase in end-diastolic volume (31±8 to 35±9 µL; P<0.001). The result was maintenance of stroke volume (17±6 to 15±6; P=NS) owing to an increase in contractility (leftward shift in V₁₀₀ [the volume of end-systolic elastance at 100 mm Hg], 24±9 to 16±5 µL; P<0.001). No additional augmentation of systolic function was found at 7 minutes.

Conclusions--This study demonstrates that the fast phase of length-dependent activation is intact but not the slow phase, consistent with murine myocardium functioning near maximal contractility in the basal state.

Key words: pressure • afterload • hemodynamics • contractility • diastole

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