Effect of Nonuniform Muscle Contraction on Sustainability and Frequency of Triggered Arrhythmias in Rat Cardiac Muscle

Abstract

Background-Arrhythmias are benign or lethal, depending on their sustainability and frequency. To determine why lethal arrhythmias are prone to occur in diseased hearts, usually characterized by nonuniform muscle contraction, we investigated the effect of nonuniformity on sustainability and frequency of triggered arrhythmias.

Effect of Carbenoxolone on Arrhythmogenesis in Rat Ventricular Muscle

“…Such regional differences in contractile strength may produce paradoxical stretching and shortening of the impaired muscle by contractions of the more viable neighboring muscle, thereby inducing Ca 2+ waves and triggered arrhythmias. 3, 44 The findings of the present study show that in the myocardium with non-uniform contraction, Cx43 plays some role in Ca 2+ wave propagation and the occurrence of arrhythmias, probably under the modulation of mitochondrial KATP channels, making Cx43 an attractive therapeutic target for suppressing triggered arrhythmias in such diseased hearts. 45,46 In conclusion, the present study suggests that Cx43 plays an affects ∆Ψm.…”

Acceleration of Ca2+ Waves in Monocrotaline-Induced Right Ventricular Hypertrophy in the Rat

“…Membrane potential was measured using ultracompliant glass microelectrodes and sarcomere length (SL) was measured using laser diffraction techniques, as previously described. 13 [Ca 2+ ]i was measured as previously described. 13, 15 Briefly, fura-2 pentapotassium salt was microinjected electrophoretically into each trabecula.…”

Effect of myofilament Ca2+ sensitivity on Ca2+ wave propagation in rat ventricular muscle

“…Muscle stretch increases myofilament Ca 2+ sensitivity and increases Ca 2+ binding to the myofilaments [12], thereby increasing the developed force [13][14][15]. Recently, it has been reported that muscle stretch increases the frequency of Ca 2+ sparks [16,17] due to production of reactive oxygen species (ROS) by the activation of NADPH oxidase in cardiac muscle [18].…”

“…Ca 2+ wave propagation is deeply involved in the occurrence of arrhythmias [14,19]. Ca 2+ waves are initiated not only by Ca 2+ leak from the sarcoplasmic reticulum (SR) under Ca 2+ overload [20] but also by Ca 2+ dissociation from the myofilaments under nonuniform contraction [15,21].…”

“…Thus, the velocity of Ca 2+ waves is one of the important determinants of the occurrence of triggered arrhythmias. Therefore, in the present study we focused on myofilament Ca 2+ sensitivity, investigating how the velocity of arrhythmogenic Ca 2+ waves changes in response to increased myofilament Ca 2+ sensitivity by muscle stretch or by the addition of SCH00013, a myofilament Ca 2+ sensitizer [14,26,27]. We further investigated whether ROS production may play a role in changes in the velocity of these waves.…”