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Am J Physiol Heart Circ Physiol 282: H2190-H2197, 2002. First published February 7, 2002; doi:10.1152/ajpheart.00759.2001
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Vol. 282, Issue 6, H2190-H2197, June 2002

Heart size-independent analysis of myocardial function in murine pressure overload hypertrophy

Hideyuki Takaoka1, Giovanni Esposito1, Lan Mao1, Hiroyuki Suga2, and Howard A. Rockman1

1 Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710; and 2 National Cardiovascular Center Research Institute, Osaka 565-8565, Japan

Pressure overload cardiac hypertrophy may be a compensatory mechanism to normalize systolic wall stress and preserve left ventricular (LV) function. To test this concept, we developed a novel in vivo method to measure myocardial stress (sigma )-strain (varepsilon ) relations in normal and hypertrophied mice. LV volume was measured using two pairs of miniature omnidirectional piezoelectric crystals implanted orthogonally in the endocardium and one crystal placed on the anterior free wall to measure instantaneous wall thickness. Highly linear sigma -epsilon relations were obtained in control (n = 7) and hypertrophied mice produced by 7 days of transverse aortic constriction (TAC; n = 13). Administration of dobutamine in control mice significantly increased the load-independent measure of LV contractility, systolic myocardial stiffness. In TAC mice, systolic myocardial stiffness was significantly greater than in control mice (3,156 ± 1,433 vs. 1,435 ± 467 g/cm2, P < 0.01), indicating enhanced myocardial contractility with pressure overload. However, despite the increased systolic performance, both active (time constant of LV pressure decay) and passive (diastolic myocardial stiffness constant) diastolic properties were markedly abnormal in TAC mice compared with control mice. These data suggest that the development of cardiac hypertrophy is associated with a heightened contractile state, perhaps as an early compensatory response to pressure overload.

systolic myocardial stiffness; contractility; cardiac mechanics; transgenic mice


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