What is the clinical evidence from this study?

Study design: Other. Population: Normal feline left ventricle (n=12). Intervention: Potassium channel blockers (chromanol 293B and E-4031) vs. Baseline (control conditions). Primary outcome: Action potential duration at 90% repolarization (APD90) and transmural dispersion of repolarization.

January 1, 2003Open Access

Transmural Heterogeneity of the Action Potential Configuration in the Feline Left Ventricle

TATakeshi AibaElectrophysiology WSWataru ShimizuElectrophysiology MIMasashi InagakiNational Cerebral and Cardiovascular Center

Key Result

The feline left ventricle possesses an M cell layer with a longer action potential duration than epicardial and endocardial layers, demonstrating transmural electrical heterogeneity.

Structured PICO

Population

12 feline left ventricular wedge preparations studied to assess transmural electrophysiological heterogeneity and responses to potassium channel blockers.

Intervention

IKs blocker (chromanol 293B: 10 micromol/L) or IKr blocker (E-4031: 2 micromol/L)

Comparator

Baseline/control conditions without blockers

Outcome

Steady-state action potential duration at 90% repolarization (APD90) and its relation to cycle length (CL), and transmural dispersion of repolarization (TDR)surrogate

The feline left ventricle contains an M cell layer with distinct electrophysiological properties, but its homogeneous response to IKr blockade highlights important species differences compared to canine models.

Limitations

Did not directly record the IKr and IKs density of isolated feline ventricular myocytes in each region.
Contribution of other currents (especially INa, ICa,L, Ito, IK1) needs to be taken into account.
Did not observe early afterdepolarization and torsades de pointes in this preparation.

Abstract

There are M cells in the canine, rabbit, guinea pig, and human left ventricle (LV), but it is not known if they are present in the feline LV. Arterially perfused feline LV preparations were used for the recording of transmembrane action potentials from the epicardium (Epi), midmyocardium (M) and endomyocardium (Endo) under control conditions (n=12) and in the presence of I(Ks) blocker (chromanol 293B: 10 micromol/L, n=6) or I(Kr) blocker (E-4031: 2 micromol/L, n=6). The steady-state action potential duration at 90% repolarization and cycle length (APD90/CL) relation was obtained and fitted by the hyperbolic function APD(90) = CL/(a x CL) + b. In control, the shortest and longest action potential duration (APD) were observed in Epi and M, respectively, and the APD(90)/CL-relation curve was steeper in the M or Endo than in the Epi. Chromanol 293B prolonged APD in Epi, but not in M or Endo, resulting in no significant difference of the APD(90)/CL-relation curve among the 3 regions. E-4031 markedly, but homogeneously, prolonged APD in all regions, giving rise to decreased transmural dispersion of repolarization. In conclusion, there exists an M cell layer with a longer APD than the Epi and Endo layers and there is transmural electrical heterogeneity in the feline LV; however, the response to I(Kr) blocker is different from that of the canine LV probably because of species differences in the I(Kr) and I(Ks).

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