TY - JOUR

T1 - The antiarrhythmic peptide analog ZP123 prevents atrial conduction slowing during metabolic stress.

AU - Haugan, Ketil

AU - Olsen, Kristine Boisen

AU - Hartvig, Line

AU - Petersen, Jørgen Søberg

AU - Hennan, James K

AU - Nielsen, Morten Schak

AU - Holstein-Rathlou, N.-H.

N1 - Keywords: Animals; Dose-Response Relationship, Drug; Electrophysiologic Techniques, Cardiac; Heart Atria; Heart Conduction System; Ion Channels; Male; Myocardial Contraction; Oligopeptides; Rats; Rats, Sprague-Dawley

PY - 2005

Y1 - 2005

N2 - OBJECTIVE: As atrial conduction slowing is important in the pathogenesis of atrial reentry arrhythmias, a drug that increases atrial conduction or prevents atrial conduction slowing could serve to prevent atrial reentry arrhythmias. In this study, we investigated whether the novel stable antiarrhythmic peptide analog, ZP123, was able to prevent atrial conduction slowing. METHODS: We examined the effect of ZP123 on metabolic stress-induced changes in conduction velocity (CV) and on dynamic CV restitution in isolated left atria from male Sprague-Dawley rats. We performed binding of ZP123 to a broad panel of 80 different cardiac and noncardiac ion channels and receptors and examined the effect of ZP123 on HERG channel conductance. RESULTS: ZP123 dose-dependently prevented metabolic stress-induced atrial CV slowing at doses ranging from 1 nM to 10 microM. ZP123 did not affect CV during physiological conditions nor did it affect dynamic CV restitution. ZP123 had no effect on atrial contractility. ZP123 showed no or low affinity binding to all ion channels and receptors examined. ZP123 had no effects on HERG channel activity in concentrations that affected atrial conduction. The concentration of ZP123 giving maximal effect on atrial conduction (100 nM) inhibited the outward K(+)-current by 2.7 +/- 0.1%. CONCLUSION: ZP123 has no effects on atrial conduction during physiological conditions, but it selectively prevents atrial conduction slowing during metabolic stress.

AB - OBJECTIVE: As atrial conduction slowing is important in the pathogenesis of atrial reentry arrhythmias, a drug that increases atrial conduction or prevents atrial conduction slowing could serve to prevent atrial reentry arrhythmias. In this study, we investigated whether the novel stable antiarrhythmic peptide analog, ZP123, was able to prevent atrial conduction slowing. METHODS: We examined the effect of ZP123 on metabolic stress-induced changes in conduction velocity (CV) and on dynamic CV restitution in isolated left atria from male Sprague-Dawley rats. We performed binding of ZP123 to a broad panel of 80 different cardiac and noncardiac ion channels and receptors and examined the effect of ZP123 on HERG channel conductance. RESULTS: ZP123 dose-dependently prevented metabolic stress-induced atrial CV slowing at doses ranging from 1 nM to 10 microM. ZP123 did not affect CV during physiological conditions nor did it affect dynamic CV restitution. ZP123 had no effect on atrial contractility. ZP123 showed no or low affinity binding to all ion channels and receptors examined. ZP123 had no effects on HERG channel activity in concentrations that affected atrial conduction. The concentration of ZP123 giving maximal effect on atrial conduction (100 nM) inhibited the outward K(+)-current by 2.7 +/- 0.1%. CONCLUSION: ZP123 has no effects on atrial conduction during physiological conditions, but it selectively prevents atrial conduction slowing during metabolic stress.

U2 - 10.1111/j.1540-8167.2005.40687.x

DO - 10.1111/j.1540-8167.2005.40687.x

M3 - Journal article

C2 - 15877626

VL - 16

SP - 537

EP - 545

JO - Journal of Cardiovascular Electrophysiology

JF - Journal of Cardiovascular Electrophysiology

SN - 1045-3873

IS - 5

ER -