Prevention of reoxygenation-induced arrhythmias in guinea pig papillary muscles.
Effects of various agents on reoxygenation-induced arrhythmias, action potentials, and tension of guinea pig papillary muscles were recorded to investigate the site of action. Triggered activities due to delayed afterdepolarizations (DADs) and aftercontractions were elicited on reoxygenation after 60-min substrate-free hypoxia. Low extracellular Ca2+ (0.1 mM) abolished arrhythmias, and high Ca2+ (4.9 mM) increased the amplitudes of DADs and aftercontractions. D-600 at the high concentration (20 microM) decreased the incidence of arrhythmias (p < 0.05 vs. no drug) and decreased the recovery of developed tension after reoxygenation (p < 0.001). Ryanodine (1 microM) abolished aftercontractions and arrhythmias but did not affect the recovery of developed tension. Tetrodotoxin (TTX 3 microM) and nicorandil (100 microM) decreased the incidence of arrhythmias (p < 0.05), but did not affect the recovery of developed tension or the amplitudes of aftercontractions. TTX caused only a slight decrease in Ca2+ transients in a fluo-3-loaded guinea pig ventricular myocyte. The Ca2+ entry through the Ca2+ channels apparently synchronized Ca2+ release from the sarcoplasmic reticulum, and D-600 at the high concentration apparently decreased the incidence of arrhythmias. TTX and nicorandil decreased arrhythmias, probably by decreasing the Na+ current or by increasing the ATP-sensitive K+ current, respectively.
Hayashi
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H
Photon Medical Research Center, Hamamatsu University School of Medicine, Japan.
Terada
H
H
Katoh
H
H
McDonald
T F
TF
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D005711:Gallopamil / Q000627:therapeutic use*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D020108:Nicorandil; D010210:Papillary Muscles / Q000187:drug effects* / Q000378:metabolism; D013779:Tetrodotoxin / Q000627:therapeutic use*
D000889:Anti-Arrhythmia Agents; D009536:Niacinamide; D020108:Nicorandil; D005711:Gallopamil; D013779:Tetrodotoxin; D002118:Calcium