Effects of thalidomide on isoprenaline-induced acute myocardial injury: a haemodynamic, histopathological and ultrastructural study.
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.
Loh
Harish K
HK
Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India.
Sahoo
Kanhei C
KC
Kishore
Kamal
K
Ray
Ruma
R
Nag
Tapas C
TC
Kumari
Santosh
S
Arya
Dharamvir S
DS
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004699:Endocardium / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006335:Heart Injuries / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D006339:Heart Rate / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007279:Injections, Subcutaneous; D007545:Isoproterenol / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D046529:Microscopy, Electron, Transmission; D008929:Mitochondria, Heart / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D009206:Myocardium / Q000473:pathology / Q000648:ultrastructure; D009210:Myofibrils / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D013792:Thalidomide / Q000008:administration & dosage / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D007166:Immunosuppressive Agents; D013792:Thalidomide; D007545:Isoproterenol