Masuko Satoh, MD; Nobumasa Ishide, MD; Tsuyoshi Shinozaki, MD; Yutaka Kagaya, MD; Kunio Shirato, MD

Abstract
Spontaneous asynchronous contractile activity caused by spontaneous release of calcium ions (Ca²⁺) from the sarcoplasmic reticulum (SR) is thought to be the cause of deterioration of ventricular function under conditions of calcium overload. We examined whether dantrolene sodium, which can inhibit Ca²⁺ release from the skeletal SR, improves the systolic and diastolic function of calcium-overloaded hearts. In isolated hamster left ventricles, the concentration of Ca²⁺ in the perfusate ([Ca²⁺]_o) was increased from 1 mmol/L to 7 mmol/L in 1-mmol/L steps in the absence (control, n=6) and presence of dantrolene sodium (11.8 µmol/L, n=5). Left ventricular developed pressure and its maximum rate of rise (max dP/dt) increased with an increase in [Ca²⁺]_o up to 4 mmol/L, and decreased with a further increase in [Ca²⁺]_o. In the presence of dantrolene sodium, developed pressure and max dP/dt increased up to 5 mmol/L [Ca²⁺]_o. Thus, dantrolene sodium improves Ca²⁺ tolerance. In isolated ventricles perfused with 1 mmol/L [Ca²⁺]_o, dantrolene sodium decreased developed pressure by 33.7±7.4% and max dP/dt by 37.4±5.6% (mean±SEM, n=8) at 1 mmol/L [Ca²⁺]_o. In contrast, at 5 mmol/L [Ca²⁺]_o ('calcium-overloaded state'), dantrolene sodium increased developed pressure by 6.8±2.6% and max dP/dt by 14.4±5.7%, and decreased the end-diastolic pressure by 5.3±1.9% (n=8). Dantrolene sodium partially suppressed the spontaneous contractile activities observed microscopically on the epicardium of ventricles perfused with 5 mmol/L [Ca²⁺]_o. Dantrolene sodium improved the Ca²⁺ tolerance of left ventricles and exerted positive inotropic effects and decreased diastolic stiffness in calcium-overloaded hamster left ventricles by suppressing spontaneous contractile activity.
(Jpn Circ J 1997; 61: 855-863)

Key Words: Hamster left ventricles; Sarcoplasmic reticulum; Calcium oscillation; Ventricular function; Fura-2

Mailing address: Nobumasa Ishide, First Department of Internal Medicine, Tohoku University School of Medicine, 1-1, Seiryo-machi, Aoba-ku, Sendai, 980-77, Japan