Minocycline attenuates ischemia-induced ventricular arrhythmias in rats.
Minocycline has been shown to protect against myocardial ischemia-reperfusion injury. This study investigated the effects of minocycline on ischemia-induced ventricular arrhythmias in rats. Anesthetized male rats were once treated with minocycline (45mg/kg, i.p.) 1h before ischemia in the absence and/or presence of 2-(4-morpholinyl)-8-phenyl-1(4H)-benzopyran-4-one hydrochloride (LY294002, 0.3mg/kg, i.v., a PI3K inhibitor) and 5-hydroxydecanoic acid [5-HD, 10mg/kg, i.v., a specific inhibitor of mitochondrial ATP-sensitive potassium (K(ATP)) channels] which were once injected 10min before ischemia and then subjected to ischemia for 30min. Ventricular arrhythmias were assessed. L-type Ca(2+) current was measured by the patch-clamp technique. During the 30-minute ischemia, minocycline significantly reduced the incidence of ventricular fibrillation (VF) (P<0.05). The duration of VT+VF, the number of VT+VF episodes and the severity of arrhythmias were all significantly reduced by minocycline compared to those in myocardial ischemia group (P<0.05 for all). Administration of LY294002 or 5-HD abolished the protective effects of minocycline on VF incidence, the duration of VT+VF, the number of VT+VF episodes and the severity of arrhythmias (P<0.05 for all). In addition, minocycline inhibited L-type Ca(2+) currents of normal myocardial cell membrane in a dose-dependent manner. This study suggested that minocycline could attenuate ischemia-induced ventricular arrhythmias in rats in which PI3K/Akt signaling pathway, mitochondrial K(ATP) channels and L-type Ca(2+) channels may be involved.
Department of Cardiology, Renmin Hospital of Wuhan University, Cardiovascular Research Institute of Wuhan University, Wuhan, China.
Xiaorong
X
Hu
Bing
B
Wu
Xin
X
Wang
Changwu
C
Xu
Bo
B
He
Bo
B
Cui
Zhibing
Z
Lu
Hong
H
Jiang
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D008911:Minocycline / Q000494:pharmacology*; D017202:Myocardial Ischemia / Q000150:complications*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D015221:Potassium Channels / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
D000900:Anti-Bacterial Agents; D010750:Phosphoproteins; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D008911:Minocycline; D002118:Calcium