Abstract 2872: Non-uniform Muscle Contraction Sustains and Facilitates Triggered Arrhythmias in Rat Cardiac Muscle
Background: Arrhythmias are benign or lethal depending on the sustainability and frequency of the arrhythmia, and lethal arrhythmias are prone to occur in diseased hearts with non-uniform muscle contraction. Thus, we investigated the effect of non-uniformity of muscle contraction on the sustainability and frequency of triggered arrhythmias.
Methods: In 21 rat trabeculae, force was measured with a strain gauge, sarcomere length with a laser diffraction technique, membrane potential with a ultracompliant microelectrode, and [Ca2+]i with microinjected fura-2 and a CCD camera. To produce non-uniform muscle contraction, a restricted region (~300 μm in length) of muscle was exposed to a jet of Hepes solution containing 20 mM 2,3-butanedione monoxime (BDM), which caused stretching of sarcomeres inside the region during twitches. Sustained arrhythmias (>10 s) were induced by 300 ms stimulus trains for 7.5 s (200 nM isoproterenol, [Ca2+]o=1.6±0.3 mM, 24°C). To modulate myofilament-Ca2+affinity inside the BDM jet region, SCH00013 (30 μM), a Ca2+sensitizer for myofilaments, was added, or muscle length was varied transiently from 2.0 to 2.2 or 1.9 μm during sustained arrhythmias. Streptomycin (100 μM) was added to eliminate the effect of stretch-activated channels.
Results: During sustained arrhythmias, Ca2+surges emerged within the border zone (BZ) around the BDM jet region during the relaxation phase, and were succeeded by synchronous increases in [Ca2+]i with action potentials (n=6). Stoppage of the BDM jet caused the Ca2+surge to become unclear and resulted in the arrest of sustained arrhythmias (n=6). The cycle length (CL) of sustained arrhythmias was shortened by SCH00013 (n=6, p<0.05). Sarcomere lengthening during sustained arrhythmias decreased the CL (n=7, p<0.05), and sarcomere shortening increased the CL (n=7, p<0.05). These changes in CLs were not suppressed by streptomycin (n=7, p<0.05). The maximum rate of force relaxation correlated inversely with the changes in CLs in the absence (n=14, r=0.73) and in the presence of streptomycin (n=10, r=0.89).
Conclusion: Non-uniform muscle contraction sustains and facilitates triggered arrhythmias through the increased amount of Ca2+dissociated from myofilaments within the BZ in cardiac muscle.