Impregnation of implantable cardiac pacemaker electrodes with dexamethasone sodium phosphate (dexamethasone) has been associated with reduced energy requirements for both atrial and ventricular stimulation. To determine whether cardiac cellular electrophysiologic effects of dexamethasone could in part account for lower stimulation thresholds, conventional microelectrode recording and stimulation techniques were used to assess both the immediate (acute) effects of dexamethasone (10-6 and 10-4 M) in superfused isolated rabbit right atrial and right ventricular preparations, and chronic effects in rabbit right ventricular tissue following 2 weeks of either daily parenteral dexamethasone (5 mg/kg, plasma concentration approximately 1 to 5 × 10-5 M) or saline placebo injections. In acute superfusion studies, dexamethasone resulted in a concentration dependent prolongation of spontaneous right atrial cycle length, but did not significantly affect right atrial transmembrane action potential characteristics or refractoriness. However, acute dexamethasone superfusion tended to increase right ventricular resting membrane potential and diminish stimulation threshold. On the other hand, compared to findings in saline-injected control rabbits, chronic dexamethasone injection had little effect on right ventricular stimulation threshold transmembrane action potential characteristics, or right ventricular refractoriness. Thus, the acute direct electrophysiologic effects of high-dose dexamethasone are compatible with the early reduction of cardiac stimulation thresholds associated with dexamethasone impregnated pacing electrodes. On the other hand, electrophysiologic findings in the presence of chronic dexamethasone exposure do not fully account for long-term reduction of stimulation energy requirements.
Bibliographical noteFunding Information:
This work was supported in part by National Research Service Award (IF32-HL06097) and grant-in-aid HL29460 from the National Institutes of Health, Bethesda, Maryland, and by a scholarship from the Veteran of Foreign Wars and administered by the American Heart Association-Minnesota Affiliate (CR). These studies were completed in part during Dr. Benditt’s tenure as an Established Investigator of the American Heart Association.
- Cardiac pacemaker
- Dexamethasone sodium phosphate
- Pacemaker electrodes
- Stimulation threshold
- Transmembrane action potential