effects of doxycycline on Cx43 distribution and cardiac arrhythmia susceptibility of rats after myocardial infarction

ABSTRACT

This study aims to observe the effects of doxycycline [DOX] on gap junction remodeling after MI and the susceptibility of rats to cardiac arrhythmia. The proximal left anterior descending coronary artery of rats was ligated to establish a myocardial infarction animal model. DOX, methylprednisolone [MP], or vehicle was intraperitoneally injected into the animals for two weeks. Then, the heart size and heart function of all animals were determined through echocardiography. The experimental animals were sacrificed after the electrophysiologic study. Myocardial tissues were sampled to analyze the distribution of Cx43 using immunofluorescence; the Cx43 content was analyzed using western blot analysis; and the MMP-2 and MMP-9 activity in the myocardium was analyzed using gelatin zymography. The distribution of Cx43 in the border of the infarcted myocardia in the MI and MP groups was clearly disrupted and the Cx43 content was significantly reduced. In addition, the distribution of Cx43 in the border of the infarct in the DOX group was relatively regular, whereas two weeks of DOX treatment significantly inhibited MMP activity. Meanwhile, the induction rate of arrhythmia in the rats after DOX treatment was lower than those in the MI and MP groups. The results show that DOX treatment after myocardial infarction improves gap junction remodeling in the myocardial tissue near the infarcted area by inhibiting MMP activity and reducing susceptibility to cardiac arrhythmia