Introduction: Diabetic cardiomyopathy (DMCMP) is an important cause of heart failure in DM patients. We investigated the effect of thalidomide, a strong anti-inflammatory and anti-fibrotic drug, on LV dysfunction in an animal model of DMCMP.
Method: DMCMP animal model: DM was induced in 10 SD-rats by streptozocin injection. At week 10, development of DMCMP was confirmed by pressure-volume analyses using conductance catheter. Treatment with thalidomide: DM rats were treated with thalidomide (n=12) or placebo (n=12) for 10 weeks after DM induction. LV function was assessed using echocardiography and hemodynamic analyses. Myocardial tissue was analyzed for the expression of inflammatory cytokines, adhesion molecules and total collagen contents. Serum TNF-慣levels were measured by ELISA.
Results: LV dysfunction was documented by reduced endsystolic elastance (Ees,0.19짹0.08 vs 0.53짹0.18 mmHg/關l, p=0.001) and preload recruitable stroke work in DM rat compared with normal controls. This was accompanied by a significant increase of total collagen contents, expression of ICAM-1, VCAM-1 and inflammatory cytokines including TNF-��, IL-1棺. Treatment with thalidomide attenuated LV dysfunction (Ees: 0.44짹0.15 vs 0.19짹0.18 mmHg/關l, p=0.001) decreasing cardiac fibrosis, the levels of inflammatory cytokines and adhesion molecules compared with non-treated DM controls.
Conclusion: Thalidomide attenuated LV dysfunction by decreasing cardiac inflammation and fibrosis in STZ-induced DMCMP animal model.