Modifications of mechanoelectric feedback induced by 2,3-butanedione monoxime and Blebbistatin in Langendorff-perfused rabbit hearts.

AIM: Myocardial stretching is an arrhythmogenic factor. Optical techniques and mechanical uncouplers are used to study the mechanoelectric feedback. The aim of this study is to determine whether the mechanical uncouplers 2,3-butanedione monoxime and Blebbistatin hinder or modify the electrophysiological effects of acute mechanical stretch. METHODS: The ventricular fibrillation (VF) modifications induced by acute mechanical stretch were studied in 27 Langendorff-perfused rabbit hearts using epicardial multiple electrodes and mapping techniques under control conditions (n = 9) and during the perfusion of 2,3-butanedione monoxime (15 mM) (n = 9) or Blebbistatin (10 µm) (n = 9). RESULTS: In the control series, myocardial stretch increased the complexity of the activation maps and the dominant frequency (DF) of VF from 13.1 ± 2.0 Hz to 19.1 ± 3.1 Hz (P < 0.001, 46% increment). At baseline, the activation maps showed less complexity in both the 2,3-butanedione monoxime and Blebbistatin series, and the DF was lower in the 2,3-butanedione monoxime series (11.4 ± 1.2 Hz; P < 0.05). The accelerating effect of mechanical stretch was abolished under 2,3-butanedione monoxime (maximum DF = 11.7 ± 2.4 Hz, 5% increment, ns vs baseline, P < 0.0001 vs. control series) and reduced under Blebbistatin (maximum DF = 12.9 ± 0.7 Hz, 8% increment, P < 0.01 vs. baseline, P < 0.0001 vs. control series). The variations in complexity of the activation maps under stretch were not significant in the 2,3-butanedione monoxime series and were significantly attenuated under Blebbistatin. CONCLUSION: The accelerating effect and increased complexity of myocardial activation during VF induced by acute mechanical stretch are abolished under the action of 2,3-butanedione monoxime and reduced under the action of Blebbistatin.

Effects of chronic exercise on myocardial refractoriness: a study on isolated rabbit heart.

AIM: To determine whether chronic physical training increases atrial and ventricular refractoriness in isolated rabbit heart. METHODS: Trained rabbits were submitted to a protocol of treadmill running. The electrophysiological parameters of refractoriness investigated in an isolated heart preparation were: (1) atrial effective refractory period (AERP) and atrial functional refractory period and ventricular effective and functional refractory periods (VERP and VFRP) using the extrastimulus technique at four different pacing cycle lengths; (2) the dominant frequency (DF) of ventricular fibrillation (VF). A multi-electrode plaque containing 256 electrodes and a spectral method were used to obtain the mean, maximum and minimum DF of VF. Sinus cycle length of the isolated hearts was determined as an electrophysiological parameter of training. In vivo heart rate, myocardial heat shock proteins (HSP60) and inducible nitric oxide synthase were also determined in some animals as electrophysiological and biochemical markers of training respectively. RESULTS: VERP and VFRP were longer in the trained group than in the control group. The mean DF of VF was lower in the trained group than in the control group. Despite the fact that training did not significantly modify the AERP, it tended to be longer in the trained group (P = 0.09). CONCLUSION: Training seems to increase the electrical stability of ventricular myocardium. As the electrophysiological modifications were exhibited in hearts not submitted to extrinsic nervous system or humoral influences, they are, at least in part, intrinsic modifications. These electrophysiological data also suggest that training could protect against reentrant ventricular arrhythmias.