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 staircase 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 (T1.6/0.8); 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 T1.6/0.8 values decreased and [Na+]i increased with hypertrophy. For guinea-pig myocardium T1.6/0.8 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 T1.6/0.8 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.
Gray
R P
RP
Institute of Urology and Nephrology, University College London, 48 Riding House Street, London W1W 7EY, UK.
McIntyre
H
H
Sheridan
D S
DS
Fry
C H
CH
D000138:Acidosis / Q000139:chemically induced / Q000378:metabolism; D000643:Ammonium Chloride / Q000008:administration & dosage; D000818:Animals; D001011:Aorta; D001835:Body Weight; D003250:Constriction; D004558:Electric Stimulation; D006168:Guinea Pigs; D006801:Humans; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology*; D008297:Male; D008839:Microelectrodes; D009200:Myocardial Contraction; D009929:Organ Size; D012964:Sodium / Q000378:metabolism*
D000643:Ammonium Chloride; D012964:Sodium