Changes in connexin 43, metalloproteinase and tissue inhibitor of metalloproteinase during tachycardia-induced cardiomyopathy in dogs

OBJECTIVE: To study changes in connexin, metalloproteinase and tissue inhibitor of metalloproteinase levels during tachycardia-induced cardiomyopathy (TIC). METHODS: Canine models of TIC were established by rapid right atrial pacing at 350-400 beats per min for 8 weeks in 11 dogs, six dogs acted as a sham operation group. Echocardiography, left ventricular pressure and its first derivation with time (positive and negative maximum, dp/dtmax, -dp/dtmax), and intracardiac electrograms were recorded before and after rapid pacing at 1, 4 and 8 weeks. Data were acquired in sinus rhythm. Ultrastructural changes in left ventricular tissue were observed by transmission electron microscope. Connexin 43 (Cx43) levels in the left ventricular myocardium were measured by confocal laser microscopy. The relative abundance of matrix metalloproteinase (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-2) were studied by immunoblotting. RESULT AND CONCLUSIONS: (1) Ventricular dilatation and systolic dysfunction occurred after 1 week of rapid right atrial pacing. (2) There was structural damage to the myofibrils, mitochondria, and the sarcoplasmic reticulum with intercalated disk discontinuity. (3) Levels of Cx43 decreased significantly and gap junction remodelling occurred during TIC. (4) TIC may result from several mechanisms, such as ultrastructural changes or gap junction and matrix remodelling.