Stretch-activated receptors mediate cardiac memory.
BACKGROUND
Cardiac memory refers to long-lasting T-wave changes that follow an episode of altered ventricular activation sequence. Memory-induced alterations in repolarizing ion channel activity have been characterized. However, the mechanism by which changes in activation sequence produce these effects is unknown. We hypothesized that cardiac memory is mediated by the response of stretch-activated receptors (SARs) to a change in mechanical activation sequence.


METHODS
In anesthetized, closed-chest dogs, coronary sinus leads were used to pace the posterolateral left ventricle (LV) continuously for 1 hour at a rate of 120 bpm. The surface vectorcardiogram was used to quantify cardiac memory by measuring T-wave displacement after pacing. Streptomycin, which has been shown to block SARs, was given at a dose of 4 g intramuscularly 1 hour before experimental LV pacing sessions. T-wave displacement after control sessions of LV pacing in the absence of drug (n = 12) was compared to that produced by pacing after streptomycin administration (n = 10 sessions).


RESULTS
There was a distinct and consistent cardiac memory seen after 1 hour of LV pacing under control conditions, with T-wave displacement of 1.28 +/- 0.43 mV (P < 0.001 vs baseline). Pretreatment with streptomycin had no direct effect on the electrocardiogram or hemodynamics, but decreased pacing-induced T-wave displacement to 0.50 +/- 0.28 mV (P < 0.001 vs control sessions).


CONCLUSIONS
Streptomycin, a SAR blocker, dramatically attenuated the development of cardiac memory following epicardial pacing. These data suggest that SARs are a critical link between mechanical sequence of activation and regional modulation of action potential duration that is responsible for cardiac memory.
Kooshkabadi
Mohammad
M
Section of Cardiac Electrophysiology, Emory University, 1342 Clifton Road, Atlanta, GA 30322, USA. mkooshk@emory.edu
Whalen
Patrick
P
Yoo
Dale
D
Langberg
Jonathan
J
D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D004285:Dogs; D005260:Female; D006329:Heart Conduction System / Q000502:physiology*; D006352:Heart Ventricles / Q000294:innervation*; D008297:Male; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008568:Memory / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology*; D011311:Pressoreceptors / Q000502:physiology*; D016276:Ventricular Function / Q000502:physiology*