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 were analysed in the native state by electrophoresis in a pyrophosphate buffer. Myosin isoform patterns were studied in cardiac muscle from cardiomyopathic hamsters (CMH) of the BIO 14:6 strain during the time course of the disease and compared with those of healthy golden hamsters (F1B). The correlation between myosin profile and Ca2+-activated ATPase activity was determined from 220 days. 3. At the stage of insufficiency (350 days), CMH presented the most abnormal phenotype with 53% V1-24% V3 compared to 79% V1-7% V3 (P<0.001), in F1B. Trimetazidine was administered to cardiomyopathic hamsters from the early stage of active disease (30 days) to the congestive stages (220-350 days). Within 65 days, trimetazidine treatment, in CMH and F1B, reduced V1 to a low level (53% and 62%, respectively), which remained constant throughout the treatment. This level was similar to that in 220 and 350 days-old untreated-CMH. In sharp contrast, a standard calcium blocker, verapamil, administered to CMH in the same conditions resulted in a higher V1 (about 70%) and higher global myosin ATPase activity from 220 days. 4. Previous results in terms of hypertrophy and survival, compared to these results, suggest that verapamil and trimetazidine treatments reveal a dissociation between ventricular hypertrophy and isomyosin distribution. In addition, the shift in favour of V3 may not necessarily be an aggravating factor of the disease but an adaptative compensatory event.
D'hahan
N
N
Laboratoire de Biologie, Ecole Centrale Paris, Châtenay-Malabry, France.
Taouil
K
K
Janmot
C
C
Morel
J E
JE
D000818:Animals; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D009202:Cardiomyopathies / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics; D006224:Cricetinae; D004591:Electrophoresis, Polyacrylamide Gel; D008647:Mesocricetus; D009218:Myosins / Q000235:genetics* / Q000302:isolation & purification; D010641:Phenotype; D014292:Trimetazidine / Q000627:therapeutic use*; D014665:Vasodilator Agents / Q000627:therapeutic use*; D014700:Verapamil / Q000627:therapeutic use*
D002121:Calcium Channel Blockers; D014665:Vasodilator Agents; D014700:Verapamil; D009218:Myosins; D000252:Calcium-Transporting ATPases; D014292:Trimetazidine