Influence of buffers on dV/dt(max) recovery kinetics with lidocaine in myocardium

Buffers are reported to modify electrical function of heart tissue. Since electrophysiological actions of antiarrhythmic drugs are examined in different buffer systems, we set out to examine the influence of buffers on lidocaine's electrophysiological actions by measuring recovery kinetics of maximum upstroke velocity (dV/dt(max)) in lidocaine solutions buffered with HCO 3 - -CO 2 , N-2-hydroxyethylpiperazine-N'-2-ethanesulfonic acid (HEPES), and tris(hydroxymethyl)aminomethane (Tris) at extracellular pH 7.4. Transmembrane potential and dV/dt(max) were recorded from guinea pig papillary muscle. Recovery kinetics were determined by introducing progressively earlier test stimuli during diastole. During lidocaine (1.5 x 10 -5 M) exposure, the time constant (τ(r)) of dV/dt(max) recovery significantly increased when 21 mM HCO 3 - -5% CO 2 was replaced by either 5 mM HEPES (38 ± 8%, mean ± SED) or 5 mM Tris (41 ± 6%). This potentiation of τ(r) was 1) reversed by increasing Tris to 20 mM, and 2) also abolished by restoring HCO 3 - -CO 2 to HEPES or Tris solutions. Decreasing HCO 3 - (21-4 mM) and CO 2 (5-1%) increased τ(r) by 27 ± 1%. We propose that the mechanism for the potentiation of τ(r) is therefore related to buffer concentration rather than to the lack of HCO 3 - -CO 2 . We speculate that, by reducing surface pH, lowered buffer capacity can slow the rate of dV/dt(max) recovery.

Duke Scholars

Author Augustus Oliver Grant Medicine, Cardiology