The responses to hypertrophic stimuli are not always homogeneously distributed across the ventricular wall (e.g. Shipsey et al. 1997). We have recently shown that myocytes from spontaneously hypertensive rats (SHR) show less cellular hypertrophy (when compared with myocytes from normotensive Wistar-Kyoto rats, WKY) in the mid-myocardial region (MID) than the sub-epicardial (EPI) or subendocardial (ENDO) regions (McCrossan & White, 2000). We have now tested the hypothesis that transmural heterogeneity is also present in the electrical response of these cells.

Rats were humanely killed at 20 weeks of age (by UK Home Office Schedule 1 methods) and hearts removed and weighed. Single myocytes were isolated from EPI, MID and ENDO regions of SHR and WKY left ventricles. Action potentials were recorded under perforated patch conditions at a stimulation frequency of 1 Hz and a temperature of 37 °C. Data are expressed as means ± S.E.M.

Action potential duration was dependent upon both region and strain at 25 % repolarisation (APD₂₅) and strain at 75 % repolarisation (APD₇₅) (P < 0.05, two-way ANOVA, n = 6-16 cells in each of the 6 groups). Consistent with previous reports, APD was longer in ENDO vs. EPI cells and SHR vs. WKY cells. However, the extent of the prolongation of the action potential in SHR vs. WKY was smaller in MID cells than either EPI or ENDO cells at both APD₂₅ and APD₇₅ (P < 0.05, x² test, see Fig. 1).Cardiac hypertrophy in response to isoprenaline (Shipsey et al. 1997) or voluntary exercise (Natali et al. 2000) has been shown to cause greatest prolongation of the late APD in EPI cells such that the difference between EPI and ENDO APD is significantly reduced. However, in the SHR model we observed that the EPI to ENDO difference was maintained (APD₇₅: WKY EPI 73 ± 10 ms, n = 6, ENDO 91 ± 11 ms, n = 6; SHR EPI 108 ± 11 ms, n = 11, ENDO 126 ± 12 ms, n = 9).

The reduced electrical response of SHR MID cells reflects the absence of hypertrophy in these cells (McCrossan & White, 2000). Such hypertrophy-induced alterations in transmural gradients can have serious consequences for ventricular repolarisation and may contribute to the higher incidence of arrhythmias observed in cardiac hypertrophy.Z.A.M. is supported by the MRC.

Figure 1. Prolongation in mean action potential duration in SHR vs. WKY cells from ENDO, MID and EPI regions (hypertrophy-induced prolongation was significantly different between regions, P < 0.05, x2 test).

McCrossan, Z.A. & White, E. (2000). J. Physiol. 526.P, 88P.

Natali, A.J., Harrison, S.M., Turner, D.L. & White, E. (2000). J. Physiol. 526.P, 83P.

Shipsey, S.J., Bryant, S.M. & Hart, G. (1997). Circulation 96, 2061-2068.