Acceleration of Ca2+ waves in monocrotaline-induced right ventricular hypertrophy in the rat

Masahito Miura, Masanori Hirose, Hideaki Endoh, Yuji Wakayama, Yoshinao Sugai, Makoto Nakano, Koji Fukuda, Chiyohiko Shindoh, Kunio Shirato, Hiroaki Shimokawa

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

Abstract

Background: Triggered arrhythmias arise from delayed afterdepolarizations (DADs), with Ca2+ waves playing an important role in their formation. In ventricular hypertrophy, however, it remains unclear how Ca2+ waves change their propagation features and affect arrhythmogenesis. We addressed this important issue in a rat model of hypertrophy. Methods and Results: Rats were given a subcutaneous injection of 60 mg/kg monocrotaline (MCT-rats) or solvent (Ctr-rats). After 4 weeks, MCT-rats showed high right ventricular (RV) pressure and RV hypertrophy. Trabeculae were dissected from 36 right ventricles. The force was measured using a silicon strain gauge and regional intracellular Ca2+ ([Ca2+]i) was determined using microinjected fura-2. Reproducible Ca2+ waves were induced by stimulus trains (2 Hz, 7.5 s). MCT-rats showed a higher diastolic [Ca2+]i and faster and larger Ca2+ waves (P<0.01). The velocity and amplitude of Ca2+ waves were correlated with the diastolic [Ca2+]i both in the Ctr- and MCT-rats. The velocity of Ca2+ waves in the MCT-rats was larger at the given amplitude of Ca2+ waves than that in the Ctr-rats (P<0.01). The amplitude of DADs was correlated with the velocity and amplitude of Ca2+ waves in the Ctr- and MCT-rats. Conclusions: The results suggest that an increase in diastolic [Ca2+]i and an increase in Ca2+ sensitivity of the sarcoplasmic reticulum Ca2+ release channel accelerate Ca2+ waves in ventricular hypertrophy, thereby causing arrhythmogenesis.

Original languageEnglish
Pages (from-to)1343-1349
Number of pages7
JournalCirculation Journal
Volume75
Issue number6
DOIs
Publication statusPublished - 2011 Jun

Keywords

  • Ca waves
  • Monocrotaline
  • Ventricular hypertrophy

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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