Hypertrophied (H) cardiac cells are longer and there are more sarcomeres in series than normal (N); we predicted there would be less than N shortening per sarcomere in contracting H cardiac fibres. Using laser diffraction analysis we demonstrated less auxotonic sarcomere shortening in isometric twitches and reduced isotonic sarcomere shortening in trabeculae from right ventricles of rabbits with pulmonary artery constriction as compared with N; the sarcomere length (SL) at the peak of the twitch, peak total tension relationship is symmetrically shifted to longer than N SL in the H muscles. In cardiac H, shortening velocity and myosin ATPase activity are less than N. Therefore, crossbridge cycling rate may be decreased and the probability of crossbridge attachment increased when compared with N, and with less sarcomere shortening in H compensation may occur as follows: 1) less deactivation due to less than N sarcomere shortening during contraction; 2) greater than N probability of crossbridge attachment; and 3) less than N rate of calcium release and uptake by the sarcoplasmic reticulum (observed by others). The above will be manifest in H as: prolonged contraction (1,2,3); enhanced active tension development (1,2,3 (slower uptake)); and enhanced muscle shortening (1,3(slower uptake)). There are findings in skeletal muscle (SM) similar to the above and an identical line of reasoning is appropriate for changes from N in SM H. I plan to study the above with SL clamped and controlled twitches in cardiac muscle (CM) using a servo-controlled motor and laser diffraction. Relative number of attached crosbridges (an index of activation level) and their turnover rate are assessed with tension responses to rapid shortening transients (about 0.2 ms) during controlled sarcomere or muscle shortening. Myocyte size is assessed from enzymatically dispersed, Ca++ resistant cells. H will be induced in rabbit soleus muscle by excising a portion and used as N in comparison with fibres will be prepared from the excised portion and used as N in comparison with fibres prepared subsequently from the H remaining muscle and from a contralateral sham-operated muscle. The amount excised and the duration of overload are adjusted to produce the same extent of H as in CM. Experiments similar to that in CM will be carried out in single SM fibres but with the advantage of tetanic contractions and control of myofilament pCA in the latter. The instantaneous level of activation during contraction in hypertrophic heart disease may be important for compensation. The comparison of CM with SM hypertrophy optimizes the match of a specific question with the preparation needed for a definitive experiment.
| Hamrell, B B; Huber, S A; Leslie, K O (1995) Depressed unloaded sarcomere shortening velocity in acute murine coxsackievirus myocarditis: myocardial remodelling in the absence of necrosis or hypertrophy. Eur Heart J 16 Suppl O:31-5 |
| Hamrell, B B; Huber, S A; Leslie, K O (1994) Reduced unloaded sarcomere shortening velocity and a shift to a slower myosin isoform in acute murine coxsackievirus myocarditis. Circ Res 75:462-72 |
| Hamrell, B B; Roberts, E T; Carkin, J L et al. (1986) Myocyte morphology of free wall trabeculae in right ventricular pressure overload hypertrophy in rabbits. J Mol Cell Cardiol 18:127-38 |
| Hultgren, P B; Hamrell, B B (1985) Decreased auxotonic sarcomere shortening in hypertrophied rabbit myocardium. Am J Physiol 249:H820-6 |
