[Experimental study of effect of carvedilol on myocardial collagen network remodeling after acute myocardial infarction in rats].
OBJECTIVE
To investigate the effects of carvedilol, irbesartan and their combination on myocardial collagen network remodeling after acute myocardial infarction (AMI) in rats.


METHODS
Twenty-four hours after ligating left anterior descending coronary artery, 35 surviving AMI male Sprague-Dawley rats were randomly assigned to control (n=8), carvedilol (n=9, 10 mg.kg(-1).d(-1)), irbesartan (n=9, 45 mg.kg(-1).d(-1)), and carvedilol (10 mg.kg(-1).d(-1)) plus irbesartan (45 mg.kg(-1).d(-1), n=9) groups. Sham operating group was comprised of 8 rats without coronary artery ligation as controls. After 8 weeks of administration of the drug by gastric gavage, hemodynamics and left ventricular function were measured, then the rat hearts were fixed, sectioned, and stained with Sirius red, and pathologically analyzed using polarized light. The total collagen volume density fraction (CVF) and type I and III CVF in the infarcted and noninfarcted zone (IZ/NIZ) were measured by computer-assisted image analysis system.


RESULTS
There were no significant differences in myocardial infarction size among the four AMI groups (40.02%-44.70%, P>0.05). Compared with the sham operation group, left ventricular (LV) end diastolic pressure (LVEDP), left and right ventricular relative weight (LVRW/RVRW), the total CVF and the CVF of type I and III in the IZ and NIZ were all significantly higher (P<0.05 or P<0.01), and in contrast, blood pressure, left ventricular systolic pressure (LVSP), the left ventricular pressure maximal rate of rise and fall (+/-dp/dt max) and their adjustment by LVSP (+/-dp/dt max/LVSP) were significantly decreased (P<0.05 or P<0.01). Compared with the control group, LVEDP, LVRW, RVRW, the total CVF and the CVF of type I and III in the NIZ were all significantly decreased (P<0.05 or P<0.01), while +/-dp/dt max and +/-dp/dt max/LVSP were all significantly increased (all P<0.01) in the carvedilol, irbesartan and their combination therapy groups.


CONCLUSIONS
Carvedilol, irbesartan and their combination can all effectively decrease collagen deposition in the NIZ of left ventricle, prevent left ventricular remodeling after AMI in rats, improve hemodynamics and LV function.
Liu
Hong-bin
HB
Department of Cardiological Laboratory, General Hospital of PLA, Beijing 100853, China. liuhbin301@sohu.com
Bian
Su-yan
SY
Yang
Ting-Shu
TS
Wang
Li
L
Yi
Jun
J
Yang
Xia
X
D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology*; D000077261:Carvedilol; D003094:Collagen / Q000378:metabolism*; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D000077405:Irbesartan; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology*; D011412:Propanolamines / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects*
D001713:Biphenyl Compounds; D002227:Carbazoles; D011412:Propanolamines; D013777:Tetrazoles; D000077261:Carvedilol; D003094:Collagen; D000077405:Irbesartan