Abstract-Ca2ϩ waves underlying triggered propagated contractions (TPCs) are initiated in damaged regions in cardiac muscle and cause arrhythmias. We studied Ca 2ϩ waves underlying TPCs in rat cardiac trabeculae under experimental conditions that simulate the functional nonuniformity caused by local mechanical or ischemic local damage of myocardium. A mechanical discontinuity along the trabeculae was created by exposing the preparation to a small jet of solution with a composition that reduces excitation-contraction coupling (ECC) in myocytes within that segment. The jet solution contained either caffeine (5 mmol/L), 2,3-butanedione monoxime (BDM; 20 mmol/L), or low Ca 2ϩ concentration ([Ca 2ϩ ]; 0.2 mmol/L). Force was measured with a silicon strain gauge and sarcomere length with laser diffraction techniques in 15 trabeculae. Simultaneously, [Ca 2ϩ ] i was measured locally using epifluorescence of Fura-2. The jet of solution was applied perpendicularly to a small muscle region (200 to 300 m) at constant flow. When the jet contained caffeine, BDM, or low [Ca 2ϩ ], during the stimulated twitch, muscle-twitch force decreased and the sarcomeres in the exposed segment were stretched by shortening normal regions outside the jet. Typical protocols for TPC induction (7.5 s-2.5 Hz stimulus trains at 23°C; [Ca 2ϩ ] o ϭ2.0 mmol/L) reproducibly generated Ca 2ϩ waves that arose from the border between shortening and stretched regions. Such Ca 2ϩ waves started during force-relaxation of the last stimulated twitch of the train and propagated (0.2 to 2.8 mm/sec) into segments both inside and outside of the jet. Arrhythmias, in the form of nondriven rhythmic activity, were induced when the amplitude of the Ca Key Words: rat trabeculae Ⅲ nonuniformity Ⅲ troponin C Ⅲ Ca 2ϩ waves Ⅲ arrhythmias I schemic and failing hearts are both prone to ventricular arrhythmias and commonly show regional differences in contractile strength caused by heterogeneous impairment of excitation-contraction coupling (ECC). It is generally accepted that lethal arrhythmias are frequently associated with alterations of the excitation step of ECC. 1 It is less well known what role nonuniform ECC 2 plays in initiating arrhythmias. 3,4 We have previously investigated the triggered propagated contractions (TPCs) phenomenon in rat cardiac trabeculae. TPCs probably result from local damage and the ensuing nonuniform ECC. 4 TPCs consist of local sarcomere shortening 5-7 associated with a [Ca 2ϩ ] i transient that propagates in a wave-like manner along the muscle. 8 -10 Ca 2ϩ waves underlying TPCs cause delayed after-depolarizations (DADs) and triggered arrhythmias. 6,7,10 In the model of damaged muscle, TPCs and underlying Ca 2ϩ waves started invariably in regions located near the dissected end of the muscle or near cut branches. 4,5 The regions bordering the damaged areas exhibit elevated cytosolic and sarcoplasmic reticulum (SR)-Ca 2ϩ and constitute a source of nonuniformity in ECC. 6 However, a detailed study of the role of these ...

Rapid shortening of active cardiac muscle [quick release (QR)] dissociates Ca2+ from myofilaments. We studied, using muscle stretches and QR, whether Ca2+ dissociation affects triggered propagated contractions (TPCs) and Ca2+ waves. The intracellular Ca2+ concentration was measured by a SIT camera in right ventricular trabeculae dissected from rat hearts loaded with fura 2 salt, force was measured by a silicon strain gauge, and sarcomere length was measured by laser diffraction while a servomotor controlled muscle length. TPCs (n = 27) were induced at 28 degrees C by stimulus trains (7.5 s at 2.65 +/- 0.13 Hz) at an extracellular Ca2+ concentration ([Ca2+]o) = 2.0 mM or with 10 microM Gd3+ at [Ca2+]o = 5.2 +/- 0.73 mM. QR during twitch relaxation after a 10% stretch for 100-200 ms reduced both the time between the last stimulus and the peak TPC (PeakTPC) and the time between the last stimulus and peak Ca2+ wave (PeakCW) and increased PeakTPC and PeakCW (n = 13) as well as the propagation velocity (Vprop; n = 8). Active force during stretch also increased Vprop (r = 0.84, n = 12, P < 0.01), but Gd3+ had no effect (n = 5). These results suggest that Ca2+ dissociation by QR during relaxation accelerates the initiation and propagation of Ca2+ waves.