Effects of the antianginal drug trapidil on atrioventricular conduction disturbances during acute myocardial ischemia.
Adenosine and related compounds have been shown to produce atrioventricular (AV) conduction block during acute myocardial ischemia. We investigated the effects of the antianginal drug trapidil, which has been shown to inhibit phosphodiesterase, on AV conduction disturbances in a canine model of acute myocardial ischemia. In 35 anesthetized dogs, the AV node artery was cannulated and perfused with arterial blood. Adenosine (300 µg, 650 µg, or 1000 µg) was injected into the AV node artery. With administration of adenosine at 300 µg, 650 µg, or 1000 µg, the atrio-His (AH) interval was increased by 14.6 ms, 22.3 ms, and 29.7 ms, respectively. The effects of adenosine were potentiated by pretreatment with intravenous dipyridamole (250 µg/kg), an inhibitor of adenosine uptake, but the effects of adenosine were attenuated with intravenous trapidil (3 mg/kg), an inhibitor of phosphodiesterase. AV node artery occlusion resulted in prolongation of the AH interval in 4 of 12 dogs. The ischemia-induced AH prolongation was potentiated with intravenous dipyridamole and attenuated with intravenous trapidil. AV conduction disturbances associated with inferior myocardial infarction may be related in part to endogenously released adenosine, and trapidil may be useful in treating AV block associated with acute AV node ischemia.
Division of Cardiology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan.
Ichiro
I
Watanabe
Yasuo
Y
Okumura
Koichi
K
Nagashima
Masayoshi
M
Kofune
Kimie
K
Ohkubo
Hiroaki
H
Mano
Kazuyuki
K
Sonoda
Yuji
Y
Kasamaki
Atsushi
A
Hirayama
D000241:Adenosine / Q000494:pharmacology; D000787:Angina Pectoris / Q000503:physiopathology*; D000818:Animals; D054537:Atrioventricular Block / Q000503:physiopathology*; D001283:Atrioventricular Node / Q000187:drug effects* / Q000503:physiopathology*; D002036:Bundle of His / Q000187:drug effects / Q000503:physiopathology; D004176:Dipyridamole / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004562:Electrocardiography / Q000187:drug effects*; D007262:Infusions, Intravenous; D017202:Myocardial Ischemia / Q000503:physiopathology*; D012815:Signal Processing, Computer-Assisted; D014192:Trapidil / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D014665:Vasodilator Agents; D004176:Dipyridamole; D014192:Trapidil; D000241:Adenosine