Objective: Mechanoelectric Feedback, a mechanical intervention inducing an electrical change, is gaining credence as a cause of cardiac arrhythmia in the clinical situation. However, the precise mechanism is unknown. To elucidate this we investigated mechanical and chemical modulation of stretch-induced premature ventricular beats. Methods: We positioned a balloon in the left ventricle of an isolated heart (New Zealand White rabbit), perfused by the Langendorff technique. Balloon inflation regularly produces premature ventricular beats. Monophasic action potentials, ECG's and pressure recordings monitored changes during mechanical intervention. The hearts were subjected to (i) variations in the degree of preload and duration of inflation, and (ii) cytoskeletal disrupters, colchicine and cytochalasin-B. Results: Mechanical dilation of the left ventricle can not only induce premature ventricular beats, but also induce a period during which premature beats cannot be re-induced on a subsequent inflation, i.e. a mechanoelectric adaptation period. The trigger for the mechanoelectric adaptation period seems to occur immediately on balloon inflation and required up to 60 s to recover. This period started with an undershoot in the diastolic component of the monophasic action potential as well as in the peak systolic pressure, with return to control levels within the period. Deflation produced an overshoot (rather than undershoot) in the monophasic action potential duration, but this also returned to control levels within the period. Changes in preload, duration of inflation and disruption of the cytoskeleton failed to modulate the mechanically induced premature beats, or the mechanoelectric adaptation period. Conclusions: Transient ventricular stretch produces arrhythmia, followed by an antiarrhythmic adaptive period. Possible mechanisms are related to a mechanical influence on stretch-activated channels, changes in ionic concentration or diffusion, or second messenger systems, which influence membrane potential. The arrhythmic adaptation does not appear to be related to the mechanical properties of the cytoskeleton. Final elucidation of the mechanism of the mechanoelectric adaptation period demonstrated, may prove important in determining the mechanism of stretch-induced premature ventricular beats and consequently arrhythmia management. (C) 1998 Elsevier Science B.V.
