Left ventricular hypertrophy (LVH) is associated with an enhanced risk of cardiac arrhythmias (Levy et al. 1987) but the fundamental mechanism is unknown. Several factors have been proposed to exacerbate re-entrant excitation, including anisotropic conduction and small-scale discontinuities in the conduction pathway (Spach et al. 1981). We have shown recently that LVH is associated with an altered degree of anisotropic conduction (Carey et al. 2001), although it is unknown whether local conduction discontinuities are more prevalent in hypertrophied myocardium. We have examined this possibility by plotting three-dimensional current flow in myocardium from hearts with LVH.

Left ventricular hypertrophy was induced in guinea-pigs by placing a plastic clip (2 mm diameter) around the ascending aorta under anaesthesia (0.22 ml kg^-1 sodium pentobarbitone, followed by inhalation of a 49 %-49 %-2 %, N₂O-O₂-halothane mixture). Sham-operated animals served as a control. After 40-100 days the heart was removed after Schedule 1 killing and papillary muscles superfused in Tyrode solution at 37 °C. Dual microelectrode impalements were used to pass current and record the consequent change of membrane potential.

In control myocardium subthreshold current pulses spread homogeneously up to 2 mm, and could be described adequately by three-dimensional cable theory indicating few discontinuities of current flow on this scale. Averaged action potential conduction velocity (CV) was 22.4 ± 2.7 cm s^-1 (mean ± S.E.M., n = 6). In hyper-trophied myocardium, averaged CV was 18.1 ± 2.3 cm s^-1 (P > 0.05 vs. control). However, the average resistance to electrotonic current flow was significantly greater in hypertrophied myocardium (3.1 times sham, P < 0.05, Mann-Whitney U test) and the occurrence of abrupt discontinuities in the spread of action potentials or electrotonic pulses was more prevalent in hypertrophied myocardium.

These measurements are consistent with the concept that in hypertrophied left ventricular myocardium abrupt discontinuities of current flow are present on a millimetre scale, and are sufficient to increase the susceptibility to re-entrant excitation.

Carey, P.A., Turner, M., Fry, C.H. & Sheridan, D.J. (2001). J. Cardiovasc Electrophysiol. (in the Press).

Levy, D., Anderson, K.M., Savage, D.D., Balkus, S.A., Kannel, W.B. & Castelli, W.P. (1987). Am. J. Cardiol. 60, 560-565.

Spach, M.S., Miller, W.T., Geselowitz, D.B., Barr, R.C., Kootsey, J.M. & Johnson, E.A. (1981). Circ. Res. 48, 39-54.