The protective effect of thalidomide on left ventricular function in a rat model of diabetic cardiomyopathy.
OBJECTIVE
To evaluate the protective effect of thalidomide, a potent anti-inflammatory drug, on the development of diabetic cardiomyopathy (DMCMP).


RESULTS
We induced type 1 diabetes using streptozocin in 8-week-old Sprague-Dawley rats, divided them into two groups-a thalidomide treatment group (DM-T, n = 15) and a non-treatment group (DM-N, n = 15)-and compared them with a normal control (n = 10). Ten weeks after diabetes induction, heart and lung mass indices were higher in the DM-N group compared with the control group. In the DM-T group, increases in heart and lung mass indices were attenuated compared with the DM-N group. On echocardiographic examination, systolic and diastolic mitral annulus velocities were impaired in the DM-N group, but they remained normal in the DM-T group. On haemodynamic analyses, left ventricular (LV) systolic function, represented by end-systolic elastance (0.35 ± 0.14 vs. 0.18 ± 0.07 mmHg/μl, P < 0.001) and preload-recruitable stroke work (90.5 ± 24.3 vs. 51.8 ± 22.0 mmHg, P < 0.001), was preserved in the DM-T group compared with the DM-N group. Likewise, deterioration of LV diastolic function was attenuated in the DM-T group. Increases in serum levels of TNF-α were attenuated in the DM-T group compared with the DM-N group. On histological analysis, thalidomide treatment lowered total myocardial collagen content and the expression of TNF-α, IL-1β, ICAM-1, and VCAM-1.


CONCLUSIONS
In an animal model of DMCMP, deterioration of LV systolic and diastolic function was partially prevented by thalidomide treatment.
Kim
Dae-Hee
DH
Department of Internal Medicine, Cardiovascular Center, Seoul National University Hospital, Seoul National University College of Medicine, Seoul, Korea.
Kim
Yong-Jin
YJ
Chang
Sung-A
SA
Lee
Hye-Won
HW
Kim
Ha-Na
HN
Kim
Hyung-Kwan
HK
Chang
Hyuk-Jae
HJ
Sohn
Dae-Won
DW
Park
Young-Bae
YB
D000704:Analysis of Variance; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D003094:Collagen / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1; D058065:Diabetic Cardiomyopathies / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005355:Fibrosis; D006352:Heart Ventricles / Q000000981:diagnostic imaging / Q000187:drug effects*; D006439:Hemodynamics; D017379:Hypertrophy, Left Ventricular / Q000188:drug therapy; D007166:Immunosuppressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D020780:Matrix Metalloproteinase 9; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013311:Streptozocin / Q000494:pharmacology; D013599:Systole; D013792:Thalidomide / Q000494:pharmacology* / Q000627:therapeutic use; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D013792:Thalidomide; D013311:Streptozocin; D003094:Collagen; D020780:Matrix Metalloproteinase 9