title: Acceleration of Ca2+ waves in monocrotaline-induced right ventricular hypertrophy in the rat.
abstract: BACKGROUND
  Triggered arrhythmias arise from delayed afterdepolarizations (DADs), with Ca(2+) waves playing an important role in their formation. In ventricular hypertrophy, however, it remains unclear how Ca(2+) waves change their propagation features and affect arrhythmogenesis. We addressed this important issue in a rat model of hypertrophy.
  
  
  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 Ca(2+) ([Ca(2+)](i)) was determined using microinjected fura-2. Reproducible Ca(2+) waves were induced by stimulus trains (2 Hz, 7.5s). MCT-rats showed a higher diastolic [Ca(2+)](i) and faster and larger Ca(2+) waves (P<0.01). The velocity and amplitude of Ca(2+) waves were correlated with the diastolic [Ca(2+)](i) both in the Ctr- and MCT-rats. The velocity of Ca(2+) waves in the MCT-rats was larger at the given amplitude of Ca(2+) waves than that in the Ctr-rats (P < 0.01). The amplitude of DADs was correlated with the velocity and amplitude of Ca(2+) waves in the Ctr- and MCT-rats.
  
  
  CONCLUSIONS
  The results suggest that an increase in diastolic [Ca(2+)](i) and an increase in Ca(2+) sensitivity of the sarcoplasmic reticulum Ca(2+) release channel accelerate Ca(2+) waves in ventricular hypertrophy, thereby causing arrhythmogenesis.
authors.affiliation: Department of Clinical Physiology, Health Science, Tohoku University Graduate School of Medicine, Sendai, Japan. mmiura@med.tohoku.ac.jp
authors.forename: Masahito
authors.initials: M
authors.lastname: Miura
authors.forename: Masanori
authors.initials: M
authors.lastname: Hirose
authors.forename: Hideaki
authors.initials: H
authors.lastname: Endoh
authors.forename: Yuji
authors.initials: Y
authors.lastname: Wakayama
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Sugai
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakano
authors.forename: Koji
authors.initials: K
authors.lastname: Fukuda
authors.forename: Chiyohiko
authors.initials: C
authors.lastname: Shindoh
authors.forename: Kunio
authors.initials: K
authors.lastname: Shirato
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D020013:Calcium Signaling; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007700:Kinetics; D008564:Membrane Potentials; D016686:Monocrotaline; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D016278:Ventricular Function, Right; D017725:Ventricular Pressure
chemical_list: D016686:Monocrotaline