CONTRACTILE PROPERTIES OF MYOCARDIUM ARE ALTERED IN DYSTROPHIN-DEFICIENT MDX MICE

The objective of this study was to determine whether cardiac contracti le force is altered in the dystrophin-deficient mdr mouse model of mus cular dystrophy. Left atria from 12-14-week-old control and mdx mice w ere paced at 1 Hz in 1.25 mM external Ca2+ buffer. Twitch properties a nd effects of interposing intervals of 0.3 to 600 s on the force of su bsequent beats (force-interval curves) were examined. Peak force and t ime-to-peak force were similar in both groups, but half-relaxation tim e was significantly prolonged in mdx heart. In control hearts, force-i nterval curves increased to an inflection point at about 1 s; then ros e to a second peak near 60 s. In mdx heart, curves reached the early i nflection more quickly, the second peak was diminished in magnitude an d force was greatly depressed at long intervals. Curves were fitted to a four-parameter equation to quantify differences in shape. The param eter a, which reflects rate of rise to the first inflection, was signi ficantly increased in mdx atria, while the parameter B, which reflects amplitude of the late peak, was significantly reduced. These differen ces in force production were more marked when external Ca2+ was raised to 2.5 mM. Results show contractile properties are markedly altered i n atria from dystrophin-deficient mdx mice. These findings are consist ent with the hypothesis that dystrophin deficiency affects cardiac con tractile function, possibly through effects on SR function.