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

R P Gray1, H McIntyre, D S Sheridan

  • 1Institute of Urology and Nephrology, University College London, 48 Riding House Street, London W1W 7EY, UK.

Pflugers Archiv : European Journal of Physiology
|May 26, 2001
PubMed

Insights

In left ventricular hypertrophy (LVH), the heart

Area of Science:

  • Cardiovascular Physiology
  • Cardiac Electrophysiology
  • Myocardial Biology

Background:

  • Left ventricular hypertrophy (LVH) is a cardiac condition associated with impaired contractility.
  • The force-frequency relationship (FFR) describes how heart muscle contraction changes with stimulation rate.
  • Intracellular sodium concentration ([Na+]i) plays a critical role in cardiac function.

Purpose of the Study:

  • To investigate the hypothesis that the positive force-frequency relationship is impaired in left ventricular hypertrophy (LVH).
  • To determine if impaired FFR in LVH is associated with elevated intracellular sodium concentration ([Na+]i).

Main Methods:

  • Human myocardial tissue from valve surgery patients and guinea-pig models of LVH induced by aortic constriction were studied.
  • Myocyte cross-section area, echocardiographic mass, and heart-to-body weight ratio quantified hypertrophy.
  • Force-frequency relationship was assessed by the tension ratio at 1.6 Hz and 0.8 Hz (T1.6/0.8).
  • Intracellular sodium ([Na+]i) was measured using ion-selective microelectrodes.

Main Results:

  • Both human and guinea-pig hypertrophied myocardium showed decreased T1.6/0.8 values, indicating an impaired positive force-frequency relationship.
  • Intracellular sodium concentration ([Na+]i) was significantly increased in hypertrophied myocardium.
  • A strong inverse correlation was observed between T1.6/0.8 and [Na+]i.
  • Recovery of [Na+]i after acidosis was slowed and stabilized at a higher level in hypertrophied hearts.

Conclusions:

  • Impaired positive force-frequency relationship in left ventricular hypertrophy is closely linked to elevated intracellular sodium.
  • Altered membrane mechanisms regulating intracellular sodium may be reset in hypertrophied myocardium.
  • These findings suggest a novel mechanism contributing to contractile dysfunction in LVH.

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