Mechanical stimulation of endocardial Purkinje fibres can trigger ventricular arrhythmias

Acute ventricular dilation can evoke mechanically-induced arrhythmias, our study investigated whether Purkinje fibres (PFs) may play a role. Changes in left ventricular (LV) pressure and pseudo-ECGs were measured in isolated, Langendorff-perfused, male Wistar rat hearts in sinus rhythm. The LV endocardial surface was irrigated with experimental agents, via an indwelling catheter. Mechanically-induced arrhythmias were triggered by LV lumen inflation (100l in 2s) via an indwelling balloon. Arrhythmias occurred as the LV volume was increased and spontaneously ceased within 20s of the onset of LV inflation. Arrhythmias were indexed as an increase in the standard deviation of all R-R intervals (SDRR), the number of ectopic activations and the period of these activations. Following 10s LV endocardial irrigation with Lugols solution (IK/I2) to chemically ablate surface PFs or with 0 Na+ Tyrode, there was a statistically significant attenuation of mechanically-induced arrhythmias. Lugols reduced the mechanically-induced increase in SDRR (Tyrode pre-stretch 3.5{+/-}1.7ms to 113.8{+/-}15.1ms during stretch vs Lugol pre-stretch 3.3{+/-}0.5ms to 39.9{+/-}14.5ms during stretch n=8, P < 0.05). There was also a reduction in the number (21.2{+/-}2.0 to 1.5{+/-}0.7, P<0.001) and period (5.9{+/-}0.71s to 1.7{+/-}0.85s, P< 0.01) of ectopic activations. The experiment was repeated using LV lumen irrigation with either 1{micro}M GsMTx4, a peptide that blocks stretch-activated channels or 50{micro}M 9-Phenanthrol (9-Phen), a blocker of TRPM4 channels. GsMTx4 did not attenuate mechanically-activated arrhythmias while 9-Phen had a partial effect. 9-Phen statistically reduced the number and period of ectopic activations but did not attenuate the mechanically-induced increase in SDRR (n=6-11 for each intervention). In further studies, in situ focal mechanical stimulation of individual PFs, caused ectopic activations, in each of 4 sheep LV preparations (0.2{+/-}0.1 ectopics in 10s pre-mechanical stimulation vs 2.1{+/-}0.2 ectopics in 10s during mechanical stimulation, P<0.001). We interpret our observations in rat and sheep hearts as evidence for a role of PFs in the generation of some mechanically-induced arrhythmia.