Differential effects of growth hormone on cardiomyocyte and extracellular matrix protein remodeling following experimental myocardial infarction.
OBJECTIVE
Growth hormone (GH) causes cardiomyocyte hypertrophy without development of fibrosis in the normal rat heart. The aim of this study was to evaluate the effects of GH on cardiac remodeling following experimental myocardial infarction (MI).


METHODS
Following ligation of the left coronary artery or sham operation, rats were randomized to receive 2 IU GH/kg/day or vehicle for four weeks (n = 140). Extracellular matrix proteins were assessed in the non-infarcted myocardium of the posterior wall using immunohistochemistry and automatic image analysis. In addition, cardiomyocyte size was measured.


RESULTS
Compared to sham, vehicle-treated rats with moderate (20-40%) and large (> 40%) infarct size showed left ventricular (LV)-dilatation, reduced fractional shortening as well as increases in LV end-diastolic and right atrial pressures, LV/body weight (BW) ratio and LV posterior wall thickness. Compared to vehicle-treated MI-rats, treatment with GH considerably increased fractional shortening and attenuated LV-dilatation. Vehicle-treated MI-rats displayed progressive increases in cardiomyocyte width and deposition of collagen I, compared to sham rats. Treatment with GH nearly doubled the increase in cardiomyocyte width and reduced collagen I accumulation by 50%.


CONCLUSIONS
Our study demonstrates that GH, given early after large MI, elicits a unique pattern of structural effects characterized by enhanced cardiomyocyte hypertrophy and reduced adaptive fibrosis. This attenuation of pathological remodeling translates into a significant improvement in systolic and diastolic LV-function.
Grimm
D
D
Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Germany.
Cameron
D
D
Griese
D P
DP
Riegger
G A
GA
Kromer
E P
EP
D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology; D048429:Cell Size / Q000187:drug effects; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D013006:Growth Hormone / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D007150:Immunohistochemistry; D008297:Male; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D020257:Ventricular Remodeling / Q000187:drug effects*
D016326:Extracellular Matrix Proteins; D013006:Growth Hormone