Effect of dantrolene sodium on calcium-overloaded heart

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

Research output: Contribution to journalArticle

7 Citations (Scopus)

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 l 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.

Original languageEnglish
Pages (from-to)855-863
Number of pages9
JournalJAPANESE CIRCULATION JOURNAL
Volume61
Issue number10
DOIs
Publication statusPublished - 1997 Oct

Keywords

  • Calcium oscillation
  • Fura-2
  • Hamster left ventricles
  • Sarcoplasmic reticulum
  • Ventricular function

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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