Effect of chronic treatment with bovine recombinant growth hormone on cardiac dysfunction and lesion progression in UM-X7.1 cardiomyopathic hamsters.
In view of the potentially beneficial effect of GH on ventricular function of humans suffering from idiopathic dilated cardiomyopathy, we undertook a study to evaluate the optimal time to initiate treatment with GH and its duration in UM-X7.1 cardiomyopathic hamsters (CMH). GH (1 mg/kg.d) therapy was initiated either in the early or late (30 and 160 d old, respectively) phases of the disease and continued until death at 240 d of age. Age- and sex-matched Golden Syrian hamsters (GSH) were used as controls. Basal IGF-1 levels in serum were reduced by nearly half in CMH compared with GSH but were increased within a physiological range in male hamsters. In contrast, female hamsters presented elevated basal serum IGF-1 levels that were not further elevated by GH administration, as reported in experimental models and humans. Accordingly, the present study will focus on the effects of GH therapy on cardiac performance in male hamsters. GH did not improve ventricular function when starting at a late stage of the disease compared with CMH controls. Maximum rate of left ventricular pressure development decreased by approximately 64% in CMH treated early with recombinant bovine GH. Ventricular dysfunction was associated with morphologic indices of hypertrophy, ventricular dilatation, and extensive fibrosis. Mortality was strikingly increased in GH-treated CMH for 210 d (four males and eight females), as opposed to four females (and no male) in the vehicle-treated group. These results suggest that chronic treatment with recombinant bovine GH in CMH, starting at an early stage of lesion development, is associated with a reduced cardiac performance at the terminal stage of the disease.
Marleau
Sylvie
S
Faculty of Pharmacy, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada H3C 3J7.
Lapointe
Nathalie
N
Massicotte
Julie
J
Céméus
Catia
C
Jasmin
Gaëtan
G
Dumont
Louis
L
Sirois
Martin G
MG
Rouleau
Jean-Lucien
JL
Du Souich
Patrick
P
Ong
Huy
H
D000818:Animals; D006332:Cardiomegaly / Q000209:etiology; D009202:Cardiomyopathies / Q000401:mortality / Q000473:pathology / Q000503:physiopathology*; D006224:Cricetinae; D003971:Diastole; D005260:Female; D013006:Growth Hormone / Q000008:administration & dosage* / Q000009:adverse effects*; D007334:Insulin-Like Growth Factor I / Q000032:analysis; D008297:Male; D008647:Mesocricetus; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D015996:Survival Rate; D013599:Systole; D018487:Ventricular Dysfunction, Left / Q000209:etiology
C073294:growth hormone, bovine; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone