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(Circulation. 2003;107:2962.)
© 2003 American Heart Association, Inc.

Basic Science Reports

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; 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.

Correspondence to Marc D. Feldman, MD, Room 5.642 U, University of Texas Health Science Center in San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229-3900. 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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