Production of cardiac lesions with tyramine in intact rats
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The authors performed an experimental study on myocardial injury induced by tyramine. For this purpose Sprague-Dawley male rats received multiple dose levels of tyramine hydrochloride. The drug exerts its sympathomimetic effects chiefly by the release of catecholamines stored in nerve endings. Myocardial lesions were documented on the basis of serum creatinkinase isoenzyme (MB-CK) changes and creatinkinase activity (CK) depletion in homogenate of cardiac tissue in animals sacrificed at different time intervals from tyramine injection.
Accordingly, MB-CK values expressed as IU/l×103 (mean±standard error of the mean, [SEM]) assessed at the 2nd and 4th hours from 50, 100, or 150 mg i.p. tyramine/100 g body weight were 0.99±0.23 or 0.85±0.30 (50 mg), 1.75±0.24 or 8.50±0.41 (100 mg), 2.07±0.60 or 8.40±0.39 (150 mg), respectively. Values in control animals were 0.51±0.07. As shown, the most marked increase in MB-CK levels is obtained at the 4th hour in 100 mg/100 g b.w. tyramine-treated rats. Thus MB-CK values were also explored at the 6th (7.43±0.15) and 12th (2.24±0.23) hours from drug administration. A significant (p<0.001) rise in serum MB-CK levels can be observed reaching the peak at the 4th hour after tyramine (100 mg/100 g b.w.).
Moreover, the CK myocardial content (IU/mg of protein) in the same tyramine-animals at the 2nd or 4th hours from 50, 100 or 150 mg of the i.p. drug/100 g b.w. were (mean ± SEM) 11.10±0.05 or 9.26±0.57 (50 mg), 9.42±0.81 or 8.57±0.22 (100 mg), 8.92±2.17 or 6.70±0.04 (150 mg), respectively. At the 6th or 12th hours from i.p. tyramine (100 mg/100 g b.w.) CK values were 9.60±0.48 or 9.99±0.56. Control values showed 13.50±0.68. A significant (p<0.001) decrease in CK myocardial content in the rats treated by the drug was achieved with the most marked CK depletion 4 hours after receiving tyramine (100 mg/100 g b.w.).
On these bases, the ultrastructural changes were investigated in tyramine-treated rats (100 mg/100 g b.w.) at the 4th hours from the drug administration. The finding included mitochondrial and myofibrillar damage.
In conclusion, this experimental model accounts for the possibility to induce myocardial damagein vivo in tyramine-treated rats.
Key wordstyramine myocardial lesions myocardial ultrastructure creatinkinase isoenzyme creatinkinase activity Sprague-Dawley rats
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