Echocardiographic assessment of cardiac morphology and function in mutant dwarf rats.
Although the mutant dwarf rat has been proposed as a model of growth hormone (GH) deficiency, few studies have addressed its cardiovascular abnormalities. Therefore, the aim of the present study was to investigate cardiac structure and function in mutant dwarf rats in vivo before and after chronic GH administration, by means of transthoracic Doppler echocardiography. To this purpose, forty 90-day-old female dwarf rats were randomized to receive either GH treatment or placebo. Twenty age-and sex-matched Lewis rats (200-250 g) served as the control group. All rats underwent echocardiograms before receiving any drug and after 3 weeks of therapy. Echocardiographically detected left ventricular mass indexed to tibial length was reduced by 41% in dwarf rats compared to the control group. Such relative cardiac atrophy was also evident at the myocyte level, and was fully reversible after GH therapy. In contrast to the control group, dwarf rats also showed a reduction of left ventricular diastolic volumes normalized to tibial length and impaired cardiac performance as suggested by the reduction of cardiac index, abnormal stress-shortening relations, and a significant elevation of total peripheral vascular resistance. All these abnormalities were reversible upon GH therapy for 3 weeks. In conclusion, GH plays an important role in maintaining a normal cardiac structure and function. Since the observed changes are similar to those seen in GH-deficient men, the mutant dwarf rat represents a faithful animal model of GH deficiency.
Longobardi
S
S
Cardiovascular Division, Department of Medicine, Charles A. Dana Research Institute and the Harvard-Thorndike Laboratory, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, USA.
Cittadini
A
A
Strömer
H
H
Katz
S E
SE
Grossman
J D
JD
Clark
R G
RG
Morgan
J P
JP
Douglas
P S
PS
D000818:Animals; D004392:Dwarfism / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology*; D004452:Echocardiography / Q000187:drug effects; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006720:Homozygote; D019382:Human Growth Hormone / Q000097:blood / Q000627:therapeutic use*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D011922:Rats, Mutant Strains; D012016:Reference Values; D015203:Reproducibility of Results
D019382:Human Growth Hormone; D007334:Insulin-Like Growth Factor I