Does Cl-/HCO3- exchange play an important role in reperfusion arrhythmias in rats?
The protective effects of Cl(-)/HCO(3)(-) exchange inhibitors, 4,4'-diisothiocyano-stilbene-2,2'-disulfonic acid (DIDS) and 4-acetamido-4'isothiocyanato-stilbene-2,2'-disulfonic acid (SITS), against reperfusion-induced arrhythmias were investigated in anesthetized rats. Rats were subjected to 5-min occlusion of the left coronary artery followed by 10-min reperfusion. All drugs were intravenously administered 5 min before the onset of occlusion. DIDS (75 mg/kg) reduced the incidence of ventricular fibrillation and mortality to 0%, whereas SITS (75 mg/kg) only decreased these parameters to 60%. DIDS simultaneously decreased the mean blood pressure and heart rate, and prolonged PQ and QRS intervals, whereas SITS produced a weaker effect on these parameters and no change in QRS interval. Mexiletine (5 mg/kg), which had been demonstrated to suppress the arrhythmias and reduce the heart rate and mean blood pressure in this model, was shown to prolong PQ and QRS intervals. Verapamil (0.5 mg/kg) or diltiazem (0.4 mg/kg) suppressed the arrhythmias, simultaneously decreasing the heart rate and mean blood pressure and prolonging PQ interval. The results indicate that the protective effect of DIDS on reperfusion arrhythmias in the anesthetized rats is unlikely to be attributed to the inhibitory action on Cl(-)/HCO(3)(-) exchange, but possibly mediated by its blocking effects on cardiac ion channels, such as Na(+) or Ca(2+) channels.
Zhu
Bing-Mei
BM
Department of Pharmacology, University of Yamanashi, Faculty of Medicine, Tamaho-cho, Nakacoma-gun, Yamanashi 409-3898, Japan. hs99d09@stu.yamanashi-med.ac.jp
Miyamoto
Shigeki
S
Nagasawa
Yoshinobu
Y
Saitoh
Masaki
M
Komori
Sadayoshi
S
Hashimoto
Keitaro
K
D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology / Q000627:therapeutic use; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology / Q000627:therapeutic use; D001145:Arrhythmias, Cardiac / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D027963:Chloride-Bicarbonate Antiporters / Q000037:antagonists & inhibitors / Q000502:physiology*; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000889:Anti-Arrhythmia Agents; D027963:Chloride-Bicarbonate Antiporters; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid