The effect of pinacidil on postshock activation and ventricular defibrillation threshold in canine hearts.
OBJECTIVE
To determine the postshock activation patterns with both successful and failed shocks in a canine model of ventricular fibrillation, and whether piniacidil, an early after-depolarization (EAD) inhibitor, altered the defibrillation threshold (DFT) and postshock activation patterns.


METHODS
In 6 beagles, a basket catheter with 64 unipolar electrodes was placed in the LV for global endocardial mapping, a monophasic action potential catheter was inserted into the LV apex, and a catheter with the negative electrode in the right ventricle and the positive electrode in the superior vena cava was inserted for defibrillation. The DFT, 90% action potential duration (APD(90)) and activation recovery interval (ARI) were evaluated before and after pinacidil administration (loading dosage 0.5 mg/kg and maintenance dosage 0.5 mg·kg(-1)·h(-1), iv). Electrical heterogeneities were defined with the dispersion of ARI. After successful and failed shocks with near-DFT strength, the earliest postshock activation patterns (focal or nonfocal endocardial activation), interval and location were detected.


RESULTS
Pinacidil significantly decreased APD(90) (from 178±16 ms to 168±18 ms) and ARI from (152±10 ms to 143±10 ms) at pacing cycle length of 300 ms. The drug significantly increased VF activation rate (from 10.0±1.9 Hz to 10.8±2.0 Hz). The drug did not affect the dispersion of ARI, neither it changed DFT (baseline: 480±110 V; pinacidil: 425±55 V, P>0.05). The earliest postshock activation arose locally on the LV apical endocardium before and after the drug treatment. Pinacidil significantly prolonged the postshock cycle length of cycles 2 to 5 for the successful episodes but not for the failed episodes.


CONCLUSIONS
Pinacidil increases the postshock cycle length suggesting that EAD may play a role in postshock activation, while it fails to alter DFT suggesting that EAD produced by shock does not determine a defibrillation success or failure.
Department of Cardiology, Shanghai Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
Qi
Q
Jin
Ning
N
Zhang
Jian
J
Zhou
Chang-jian
CJ
Lin
Yang
Y
Pang
Gang
G
Gu
Wei-feng
WF
Shen
Li-Qun
LQ
Wu
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D004056:Differential Threshold / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004554:Electric Countershock / Q000009:adverse effects; D004562:Electrocardiography; D004566:Electrodes; D006339:Heart Rate / Q000187:drug effects; D010496:Pericardium / Q000503:physiopathology; D020110:Pinacidil / Q000008:administration & dosage / Q000494:pharmacology*; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology; D014693:Ventricular Fibrillation / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*
D020110:Pinacidil