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.


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.
Zhong
Jing-quan
JQ
Cardiology Department, Qilu Hospital of Shandong University, 107 Wen Hua Xi Lu, Jinan 250012, Shandong Province, China.
Zhang
Wei
W
Gao
Haiqing
H
Li
Yan
Y
Zhong
Ming
M
Li
Duoling
D
Zhang
Cheng
C
Zhang
Yun
Y
D000818:Animals; D006328:Cardiac Catheterization; D009202:Cardiomyopathies / Q000503:physiopathology*; D018031:Connexin 43 / Q000378:metabolism*; D004195:Disease Models, Animal; D004285:Dogs; D004562:Electrocardiography; D005260:Female; D006325:Heart Atria / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D045726:Metalloproteases / Q000378:metabolism*; D018613:Microscopy, Confocal; D009206:Myocardium / Q000648:ultrastructure; D013599:Systole; D013610:Tachycardia / Q000150:complications*; D019714:Tissue Inhibitor of Metalloproteinases / Q000378:metabolism*; D018754:Ventricular Dysfunction
D018031:Connexin 43; D019714:Tissue Inhibitor of Metalloproteinases; D045726:Metalloproteases