Diabetes mellitus reduces the antiarrhythmic effect of ion channel blockers.
We designed the present study to examine whether diabetes mellitus affects the antiarrhythmic effect of flecainide, a sodium channel blocker, E-4031, a potassium channel blocker, and verapamil, a calcium channel blocker, in diabetic rats. The experiments were performed in intact and diabetic rats 2, 4, and 6 wk after administration of streptozotocin. Rats were anesthetized with halothane and monitored continuously for arterial blood pressure and premature ventricular contractions. The arrhythmogenic dose of epinephrine was defined as the smallest dose producing 3 or more premature ventricular contractions within a 15-s period. The arrhythmogenic doses of epinephrine in the presence of flecainide were 8.2 +/- 2.2 (mean +/- sd), 7.4 +/- 6.1, 5.5 +/- 2.8, and 2.0 +/- 0.5 microg/kg in intact and diabetic rats 2, 4, and 6 wk after streptozotocin administration, respectively. Similarly, the arrhythmogenic doses of epinephrine in the presence of E-4031 were 7.7 +/- 2.6, 2.3 +/- 0.7, 2.0 +/- 0.7, and 1.2 +/- 0.5 microg/kg, and those in the presence of verapamil were 8.2 +/- 2.1, 3.1 +/- 1.2, 2.3 +/- 0.9, and 1.5 +/- 0.5 microg/kg. Insulin partially recovered the antiarrhythmic effect of the blockers. We concluded that diabetes mellitus reduces the antiarrhythmic effects of flecainide, E-4031, and verapamil.
Ito
Isao
I
Department of Anesthesiology, School of Allied Health Sciences, Osaka University Faculty of Medicine, Osaka, Japan.
Hayashi
Yukio
Y
Kawai
Yusuke
Y
Iwasaki
Mitsuo
M
Takada
Koji
K
Kamibayashi
Takahiko
T
Yamatodani
Atsushi
A
Mashimo
Takashi
T
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D003920:Diabetes Mellitus / Q000188:drug therapy*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D004837:Epinephrine / Q000494:pharmacology; D005424:Flecainide / Q000494:pharmacology*; D006221:Halothane / Q000494:pharmacology; D007473:Ion Channels / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D007473:Ion Channels; D010880:Piperidines; D026902:Potassium Channel Blockers; D011725:Pyridines; D026941:Sodium Channel Blockers; C063968:E 4031; D014700:Verapamil; D005424:Flecainide; D006221:Halothane; D004837:Epinephrine