EFFECT OF TRIMETAZIDINE AND VERAPAMIL ON THE CARDIOMYOPATHIC HAMSTER MYOSIN PHENOTYPE

1 In this study we investigated whether long-term trimetazidine (anti- ischaemic drug) therapy alters the ventricular myosin heavy chain (MHC ) isoform composition in a model of cardiomyopathy. 2 MHC isoforms wer e analysed in the native state by electrophoresis in a pyrophosphate b uffer. Myosin isoform patterns were studied in cardiac muscle from car diomyopathic hamsters (CMH) of the BIO 14:6 strain during the time cou rse of the disease and compared with those of healthy golden hamsters (FIB). The correlation between myosin profile and Ca2+ activated ATPas e activity was determined from 220 days. 3 At the stage of insufficien cy (350 days), CMH presented the most abnormal phenotype with 53% V1-2 4% V3 compared to 79% V1-7% V3 (P<0.001), in F1B. Trimetazidine was ad ministered to cardiomyopathic hamsters from the early stage of active disease (30 days) to the congestive stages (220-350 days). Within 65 d ays, trimetazidine treatment, in CMH and F1B, reduced V1 to a low leve l (53% and 62%, respectively), which remained constant throughout the treatment. This level was similar to that in 220 and 350 days-old untr eated-CMH. In sharp contrast, a standard calcium blocker, verapamil, a dministered to CMH in the same conditions resulted in a higher V1 (abo ut 70%) and higher global myosin ATPase activity from 220 days. 4 Prev ious results in terms of hypertrophy and survival, compared to these r esults, suggest that verapamil and trimetazidine treatments reveal a d isssociation between ventricular hypertrophy and isomyosin distributio n. In addition, the shift in favour of V3 may not necessarily be an ag gravating factor of the disease but an adaptative compensatory event.