COMPARISON OF TWITCH FORCE AND CALCIUM HANDLING IN PAPILLARY-MUSCLES FROM RIGHT-VENTRICULAR PRESSURE-OVERLOAD HYPERTROPHY IN WEANLING AND JUVENILE FERRETS

Objective: The aim was to compare differences in peak twitch force occ urring despite similar degrees of right ventricular hypertrophy in fer rets with pulmonary artery banding at either weanling or juvenile age. Methods: After inducing pressure overload hypertrophy by banding the pulmonary artery of weanling and juvenile age ferrets, mechanical func tion (that is, isometric twitch force and passive stiffness), intracel lular [Ca2+] using the calcium indicator aequorin, markers of myocardi al energy supply, and quantified connective tissue content were studie d. Results: It was previously found that there was a reduced peak isom etric twitch force despite normal [Ca2+](i) in juvenile banded ferrets age 10-12 weeks with right ventricular pressure overload hypertrophy (POHj). In the present study we report findings in banded weanling fer rets (POHw) age 7 weeks. POHw animals showed a similar degree of hyper trophy to that found in the POHj. However, there was a greater peak tw itch force in hypertrophied muscles at higher [Ca2+](o). There was no difference in peak [Ca2+](i): -3.1(SEM 0.1) v -3.1(0.3) (log fractiona l luminescence) at 16 mM [Ca2+](o) for control and POHw, respectively. Connective tissue content for control animals was 10(1)% versus 10(2) % in POHw. Despite a lack of quantitative change in connective tissue content or resting [Ca2+](i) in POHw, passive stiffness in papillary m uscles was increased. Retrospective analysis of tissue from POHj revea led a connective tissue content of 24(6.8)% (P << 0.001). Thus the dec reased peak twitch force reported in POHj might in part be due to an i ncrease in fibrous connective tissue. In this study, lactate dehydroge nase was significantly higher (38%) in POHw animals. In contradistinct ion, total creatine kinase activity and total creatine content were si gnificantly less (22%) in hearts from POHj animals, indicating differe nces in myocyte remodelling despite similar degrees and durations of h ypertrophy. Conclusions: Comparison of POHw and POHj showed that, when there is restructuring of the extracellular space in terms of increas ed fibrosis, there is also molecular remodelling in the myocyte, as de monstrated by a decrease in the creatine kinase system.