TY - JOUR
T1 - Cardiac electrophysiologic effects of orally administered DPI 201-106 in conscious canines
T2 - Effects of pharmacologic autonomic blockade or cardiac transplantation
AU - Walker, Michael J.
AU - Tuna, Ishik C.
AU - Gornick, Charles C.
AU - Goldenberg, Irvin F.
AU - Almquist, Adrian
AU - Milstein, Simon
AU - Benditt, David G
PY - 1989/9
Y1 - 1989/9
N2 - This study assessed the cardiac electrophysiologic effects of DPI 201-106 (DPI), a novel orally absorb-able positive inotropic agent, the administration of which has been associated with electrocardiographic (ECG) QT and T-wave changes. In the intact conscious dog, oral administration of both 8 and 16 mg/kg DPI produced marked sinus cycle length prolongation (8 mg/kg, + 11%; 16 mg/kg, +9%) within 60 min of DPI administration (p <0.05 vs. baseline). DPI also tended to prolong right atrial refractory periods, and increase sinus node recovery time. In addition, DPI exhibited a negative dromotropic effect on the atrioventricular (AV) node, prolonging both AV node effective and functional refractory periods and tending to increase the minimum atrial paced cycle length at which AV conduction of 1:1 was maintained. DPI also significantly increased right ventricular effective refractory period (ERP) at both doses studied and increased ventricular functional refractory period (FRP) at the 16-mg/kg dose. Finally, although DPI administration was associated with QT interval prolongation, this effect was slight when corrected for sinus cycle length (SCL) (QTc, + 3%). When administered concomitantly with propranolol and atropine or after surgical cardiac denervation, DPI-induced electrophysiologic changes were largely attenuated or abolished. Thus, findings in this study indicate that the apparent cardiac electrophysiologic effects of DPI are predominantly of neurally mediated origin in this animal model.
AB - This study assessed the cardiac electrophysiologic effects of DPI 201-106 (DPI), a novel orally absorb-able positive inotropic agent, the administration of which has been associated with electrocardiographic (ECG) QT and T-wave changes. In the intact conscious dog, oral administration of both 8 and 16 mg/kg DPI produced marked sinus cycle length prolongation (8 mg/kg, + 11%; 16 mg/kg, +9%) within 60 min of DPI administration (p <0.05 vs. baseline). DPI also tended to prolong right atrial refractory periods, and increase sinus node recovery time. In addition, DPI exhibited a negative dromotropic effect on the atrioventricular (AV) node, prolonging both AV node effective and functional refractory periods and tending to increase the minimum atrial paced cycle length at which AV conduction of 1:1 was maintained. DPI also significantly increased right ventricular effective refractory period (ERP) at both doses studied and increased ventricular functional refractory period (FRP) at the 16-mg/kg dose. Finally, although DPI administration was associated with QT interval prolongation, this effect was slight when corrected for sinus cycle length (SCL) (QTc, + 3%). When administered concomitantly with propranolol and atropine or after surgical cardiac denervation, DPI-induced electrophysiologic changes were largely attenuated or abolished. Thus, findings in this study indicate that the apparent cardiac electrophysiologic effects of DPI are predominantly of neurally mediated origin in this animal model.
KW - Cardiac electrophysiology
KW - DPI 201-106
KW - Inotropic drugs
KW - QT interval
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U2 - 10.1097/00005344-198909000-00005
DO - 10.1097/00005344-198909000-00005
M3 - Article
C2 - 2476616
AN - SCOPUS:0024386639
SN - 0160-2446
VL - 14
SP - 381
EP - 388
JO - Journal of Cardiovascular Pharmacology
JF - Journal of Cardiovascular Pharmacology
IS - 3
ER -