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- Title
Effects of Thalidomide on Isoprenaline-Induced Acute Myocardial Injury: A Haemodynamic, Histopathological and Ultrastructural Study.
- Authors
Loh, Harish K.; Sahoo, Kanhei C.; Kishore, Kamal; Ray, Ruma; Nag, Tapas C.; Kumari, Santosh; Arya, Dharamvir S.
- Abstract
In the present study, we investigated the cardioprotective effects of thalidomide in a rat model of acute myocardial injury, induced by subcutaneous injection of isoprenaline hemisulphate (85 mg/kg per day for 2 days). Thalidomide (75/150/300 mg/kg) or vehicle (dimethylsulphoxide) or saline (0.9% NaCl) was administered orally for 14 days and isoprenaline injection on the 12th and 13th days. Cardiovascular responses (arterial and left ventricular haemodynamic parameters and heart rate) were obtained in anaesthetized rats on the 14th day. Histopathological and electronmicroscopical analysis of myocardial injury was done. The results showed that thalidomide 300 mg/kg per day orally caused significant improvement in isoprenaline-induced reduction of cardiac function with increases in maximum rate of pressure development (+LVdP/dt, P < 0.001) and maximum rate of pressure decline (–LVdP/dt, P < 0.001) and decreases in left ventricular end-diastolic pressure (P < 0.01), systolic arterial pressure (P < 0.001), diastolic arterial pressure (P < 0.001), mean arterial pressure (P < 0.001) and heart rate (P < 0.001). The myocardial injury caused by isoprenaline was significantly reduced by thalidomide treatment as judged by the reduction of myocardial necrosis, ultrastructural changes such as mitochondria and myofibril damage, 300 mg/kg being the most effective dose. In conclusion, oral administration of thalidomide is able to ameliorate isoprenaline-induced myocardial injury and impaired myocardial function in spite of decreases in systolic arterial pressure, diastolic arterial pressure and mean arterial pressure, which may be due to its depressant effect on the sino-atrial node and sedative action.
- Subjects
THALIDOMIDE; PHTHALIC acid; MEDICAL research; LABORATORY rats; LABORATORY animals; MYOCARDIAL depressants; CARDIOVASCULAR agents; PHYSIOLOGY
- Publication
Basic & Clinical Pharmacology & Toxicology, 2007, Vol 100, Issue 4, p233
- ISSN
1742-7835
- Publication type
Article
- DOI
10.1111/j.1742-7843.2007.00022.x