EFFECTS OF LEFT-VENTRICULAR HYPERTROPHY ON FORCE AND CA2+ HANDLING INISOLATED RAT MYOCARDIUM

To study the effect of left ventricular (LV) hypertrophy on force and Ca2+ handling in isolated rat myocardium, LV hypertrophy was induced i n rats by banding of the abdominal aorta. After 16 wk, arterial pressu re was assessed by catheterization. LV trabeculae were isolated and lo aded with indo 1 salt by iontophoretic injection. Isometric force and intracellular free Ca2+ concentration ([Ca2+](i)) were measured at sti mulation frequencies between 0.25 and 3 Hz and rest intervals between 2 and 240 s. Sarcoplasmic reticulum (SR) Ca2+ content was also investi gated using rapid cooling contractures (RCC). Systolic and diastolic p ressure as well as heart weight-to-body weight ratios were significant ly elevated in banded compared with control animals (167 vs. 117 mmHg, 108 vs. 83 mmHg, and 4.6 vs. 4.0 mg/g, respectively). At high frequen cies, twitch relaxation and [Ca2+](i) decline rates were significantly slower in banded compared with control rats, and diastolic [Ca2+](i) was higher in the banded rat muscles (at 3 Hz, force half-time = 83 vs . 68 ms; time constant of [Ca2+](i) decline = 208 vs. 118 ms; and dias tolic [Ca2+](i) = 505 vs. 353 nM). These differences could not be ascr ibed to altered Na+/Ca2+ exchange, since twitch relaxation and Ca2+ ha ndling were not different between groups in the presence of caffeine ( or cyclopiazonic acid plus ryanodine), where relaxation depends primar ily on Na+/Ca2+ exchange. After long rest intervals (greater than or e qual to 120 s), control rats showed a significant rest potentiation of force and Ca2+ transients, whereas banded rats did not. In addition, RCC amplitudes increased with rest in control but were unaltered in ba nded rats. In summary, pressure-overload hypertrophy was associated wi th slower twitch relaxation and [Ca2+](i) decline but also with blunte d rest potentiation of twitches and SR Ca2+ content of LV trabeculae. The decrease in SR Ca2+-ATPase function in banded rats may contribute to the observed diastolic dysfunction associated with pressure-overloa d hypertrophy.