In vivo and in vitro evidence that endurance exercise training attenuates enhanced cardiac β2-adrenoreceptor responsiveness and prevents ventricular fibrillation in animals susceptible to sudden death

the infarct border zone is thought to facilitate reentry and contribute to ventricular tachycardias (VT). Using a microcontact printing approach, we created an 8mm 4mm island of cell strands having a rectangular zig-zag pattern in the center of 22mm diameter monolayers of neonatal rat ventricular myocytes. The zig-zag pattern had an aspect ratio of 1:9 (width of cell strand 100 m, separation between strands 300 m, length between neighboring transverse connections 2700 m, number of transverse connections either greater on the right side or on the left side of the island). Cells outside the central island were confluent and randomly oriented. After day 5 of culture, transmembrane potentials were optically mapped from 253 sites (1mm resolution) using the voltage-sensitive dye di-4-ANEPPS. The cell monolayers (n 6) were paced from one edge using a point stimulus (trains of 30 pulses at increasing repetition rates starting at 3 Hz). At pacing rates up to 9 Hz, the wavefront passed symmetrically around both sides of the central island. The central island exhibited slowed transverse conduction (4.1 0.9 cm/s at 3Hz pacing) but normal longitudinal conduction (28.1 2.2 cm/s) compared with the surrounding region (27.2 4.3 cm/s). At high pacing rates (11.2 1.2 Hz), the wave passing around the side of the island that had the greater number of transverse connections (dominant side) had a slightly higher conduction velocity compared with the wave on the other side (weak side), so that the point of collision advanced towards the weak side. With successive beats the collision point advanced even more, until conduction failure and unidirectional block developed on the weak side. Consequently, a reentrant wave could be initiated that revolved around either the distal edge or proximal edge of the central island (forming a line of block). Reentry was stable and persisted for at least 10 minutes (10.7 1.4 Hz cycle length). In conclusion, sustained functional reentry around a line of block can be readily induced by rapid pacing in cell monolayers containing a central island of zig-zag conduction.