Intracellular sodium and contractile function in hypertrophied human and guinea-pig myocardium

We tested the hypothesis that in left ventricular myocardial hypertrophy (L VH) the positive stair-case effect is impaired and is related to a raised i ntracellular [Na+] ([Na+](i)). Human myocardial specimens were obtained fro m patients undergoing mitral and aortic valve surgery, the latter group had LVH. LVH was induced in guinea-pigs by ascending aortic constriction. The extent of hypertrophy was quantified by measuring myocyte cross-section are a, echocardiographic mass (in humans) and heart-to-body weight ratio (in gu inea-pigs). The response to increasing stimulation frequency was expressed as the ratio of tension generated at 1.6 and 0.8 Hz (T-1.6/0.8); ratios gre ater and less than 1.0 equate with positive and negative force/frequency re lationships respectively, [Na+](i) was measured using ion-selective microel ectrodes. In human and guinea-pig myocardium T-1.6/0.8 values decreased and [Na+](i) increased with hypertrophy. For guinea-pig myocardium T-1.6/0.8 d ecreased from 1.39 +/-0.05 to 1.02 +/-0.05 and [Na+](i) increased from 7.3 +/-1.4 to 12.1 +/-1.3 mM in LVH. There was a close relationship between the reduction of T-1.6/0.8 and increase of [Na+](i) which was also observed wh en the [Na+](i) was increased with strophanthidin in normal myocardium. The recovery of a raised [Na+](i) after an acute acidosis was slowed in hypert rophied myocardium and stabilised at a higher level, suggesting that the me mbrane mechanisms that regulate [Na+](i) are reset.