ALTERED EXPRESSION OF TROPONIN-T ISOFORMS IN MILD LEFT-VENTRICULAR HYPERTROPHY IN THE RABBIT

Alterations in troponin T (TnT) isoforms have been reported in severe human and experimental heart failure (HF), and may play a role in the depressed myofibrillar ATPase activity observed in this condition, It is unclear whether these alterations reflect very severe hemodynamic d erangement or are a component of mild hypertrophic stress, Therefore, we studied the expression of TnT isoforms (SDS-PAGE, Western blots), m yosin isoforms, myofibrillar ATPase activity, and left ventricular (LV ) mechanoenergetics (rbc perfused, isovolumically contracting isolated heart) in a rabbit model of mild hypertrophy (LVH) due to gradual hyp ertension caused by 12 weeks of cellophane wrap of the kidneys (n=12), LV/body weight ratio increased by 28% in LVH compared to shams (P<0.0 01); no animals had evidence of HF. In LVH, the percentage of TnT(2) w as modestly but significantly increased compared to shams [6.2 +/- 1.9 (+/-S.D.) v 3.7 +/- 1.0%, P<0.05], mainly as a consequence of a paral lel decrease in TnT, (P=0,07). Sham hearts ranged from 75-100% V-3 iso myosin, whereas all LVH hearts had 100% of the V-3 form, There were no significant differences in myofibrillar ATPase activity or mechanical variables, including contraction and relaxation rates, The slope of t he VO2-pressure-volume-area relation (a measure of the energy conversi on efficiency of the contractile machinery) was also unchanged, We con clude that in the rabbit, shifts in TnT isoforms toward a more ''fetal '' pattern occur during mild LVH and, therefore, are likely to be a ge neral feature of the response to hemodynamic stress, rather than a phe nomenon confined to end-stage disease, These modest shifts are not ass ociated with major alterations in LV myofibrillar ATPase activity or m echanoenergetics. (C) 1997 Academic Press Limited.