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

We tested the hypothesis that in left ventricular myocardial hypertrophy (LVH) the positive stair-case effect is impaired and is related to a raised intracellular [Na(+)] ([Na(+)](i)). Human myocardial specimens were obtained from 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 area, echocardiographic mass (in humans) and heart-to-body weight ratio (in guinea-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 greater and less than 1.0 equate with positive and negative force/frequency relationships respectively, [Na(+)](i) was measured using ion-selective microelectrodes. 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) decreased 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 when the [Na(+)](i) was increased with strophanthidin in normal myocardium. The recovery of a raised [Na(+)](i) after an acute acidosis was slowed in hypertrophied myocardium and stabilised at a higher level, suggesting that the membrane mechanisms that regulate [Na(+)](i) are reset.