Amiodarone protection against myocardial injury and fibrosis induced by isoprenaline is abolished by thyroid hormone.
OBJECTIVE
Catecholamines induce myocyte necrosis and myocardial fibrosis. These effects are probably related to beta adrenergic receptor stimulation and to thyroid hormonal status. The aim of the study was to test the hypothesis that amiodarone prevents myocardial damage induced by isoprenaline and that these effects are not observed when thyroid hormone is administered.


METHODS
Myocardial injury was assessed in the first experiment. Isoprenaline (1 mg.kg-1 subcutaneously once) was given to two groups of rats which received monoclonal antimyosin. Group 1 (n = 5) was pretreated with amiodarone and group 2 (n = 6) received only isoprenaline. In the second experiment, the effects of amiodarone on isoprenaline induced myocardial fibrosis and of supplementary triiodothyronine (T3) were examined. Group 3 (n = 10) received only isoprenaline for 4 d. Group 4 (n = 10) received amiodarone for 14 d and isoprenaline during 4 d. Group 5 (n = 8) received amiodarone and isoprenaline like group 4, plus T3. Untreated rats served as controls (group 6; n = 10). Collagen volume fraction (CVF) was measured in each heart.


RESULTS
No rats pretreated with amiodarone showed antimyosin labelling, while the mean score of rats receiving only isoprenaline was 2.8 (p < 0.05), indicating the presence of significant myocyte injury. In group 3, CVF was significantly higher than in controls, at 7.63(SEM 0.89)% v 1.74(0.07)%, p < 0.001, whereas rats pretreated with amiodarone (group 4) showed significantly less fibrosis [CVF 2.96(0.19)%]. This protective effect was lost when amiodarone and T3 were given together [CVF 7.92(1.8)%, p < 0.005 between groups 4 and 6].


CONCLUSIONS
By preventing isoprenaline induced myocardial injury and fibrosis, amiodarone may have a cardioprotective role. This effect is completely abolished by thyroid hormone.
Dussaillant
G
G
Pontificia Universidad Catolica de Chile, Department of Cardiovascular Disease, Santiago.
Jalil
J E
JE
Cespedes
C
C
D000638:Amiodarone / Q000627:therapeutic use*; D000818:Animals; D005355:Fibrosis; D005455:Fluorescent Antibody Technique; D006321:Heart / Q000187:drug effects*; D007545:Isoproterenol / Q000009:adverse effects*; D008297:Male; D009206:Myocardium / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D007545:Isoproterenol; D000638:Amiodarone