Genetically altered mice have become an increasingly important tool for the
study of mechanisms of cardiac function, and therefore it is vital to char
acterize the basic contractile properties of the mouse heart. As a first ap
proach to this goal, we first optimized perfusion conditions and characteri
zed the effect of incremental left ventricular balloon inflation on end-dia
stolic, systolic and developed pressures in the isovolumically-contracting
mouse heart. Under constant loading conditions, we determined developed pre
ssure in response to changing perfusate calcium (1.25, 2.5, 3.75 and 5.0 mM
) and perfusate temperature (30 and 37 degrees C). We then compared the int
rinsic inotropic responsiveness to changes in extracellular calcium of left
ventricular myocardium from mouse to that from the rat. In the baseline st
ate (1.25 mM extracellular calcium; [Ca2+](o)), both isometric contraction
duration and normalized active force at the peak of the active force-length
relationship (L-max) were less in mouse than in rat myocardium. Under isot
onic conditions, temporal parameters of shortening and the relative shorten
ing were less in mouse vs rat myocardium. Increasing [Ca2+](o) from 1.25 to
2.5 mM markedly increased active isometric force and rate of force develop
ment (+ dF/dt) in the mouse. However, rat myocardium responded to a lesser
extent. Under isotonic conditions, peak shortening and the rate of shorteni
ng also increased to a greater extent in mouse relative to rat myocardium.
Increasing the bath calcium concentration to 5.0 mM increased isometric for
ce and + dF/dt further in the rat but not the mouse, suggesting that two sp
ecies operate at different points on the force vs [Ca2+](o) relationship. W
e conclude that mouse myocardium exhibits increased sensitivity to changes
in [Ca2+](o) within the physiologic range in comparison to rat. These diffe
rences do not appear to be due to differences in loading conditions. The da
ta suggest that differences in inotropic responsiveness to calcium may refl
ect intrinsic differences in myocardial calcium sensitivity between species
. (C) 1999 Elsevier Science Inc. All rights reserved.