Myocardial region (right or left ventricle) and aetiology of heart failure can influence the inotropic effect of ouabain in failing human myocardium

Br J Clin Pharmacol. 1999 Nov;48(5):743-9. doi: 10.1046/j.1365-2125.1999.00064.x.

Abstract

Aims: To investigate whether the inotropic effect of ouabain in failing human myocardium varies according to the heart chamber tested (right or left ventricle) or the aetiology of the heart disease, i.e. ischaemic or idiopathic.

Methods: The inotropic effect of ouabain was measured, as the percentage change in baseline tension, in myocardial strips isolated from right (RV; n=21) and left ventricles (LV; n=21) of hearts explanted from patients with idiopathic (IDC; n=11) and ischaemic cardiomyopathy (CAD; n=10). Concentration-effect curves obtained with ouabain (0.05-1.6 micromol l-1 ) were analysed using the Emax sigmoidal model, and the following parameters were calculated: Emax, EC50, n and EC10 (threshold concentration). The influence of ventricular chamber and heart failure aetiology on these parameters was evaluated by means of a two-way anova.

Results: Age and baseline haemodynamic parameters did not differ between IDC and CAD patients. Baseline strip contractility was highly variable (range: 0.48-10.0 mN), but neither ventricular chamber nor aetiology could explain such variability. A two-way anova showed that EC10 was greater in CAD than in IDC preparations (0.097+/-0.013 micromol l-1 vs 0.059+/-0. 009 micromol l-1; 95% C.I. for difference 0.043, 0.071) and Emax was lower in RV than in LV (121+/-21% vs 250+/-38%; 95% C.I. -221, -36), while EC50 and n were not significantly different between groups.

Conclusions: The inotropic effect of ouabain in human myocardium may vary according to aetiology of heart failure and the ventricle being tested. Although our results do not support the hypothesis of increased sensitivity to cardiac glycosides in CAD patients, they may explain the diminished effect observed in patients with RV failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / physiology
  • Cardiomyopathy, Dilated / complications
  • Cardiomyopathy, Dilated / physiopathology
  • Cardiotonic Agents / pharmacology*
  • Female
  • Heart Failure / drug therapy
  • Heart Failure / etiology
  • Heart Failure / pathology*
  • Hemodynamics / drug effects
  • Humans
  • In Vitro Techniques
  • Male
  • Middle Aged
  • Myocardial Contraction / drug effects
  • Myocardial Ischemia / complications
  • Myocardial Ischemia / pathology
  • Myocardium / pathology*
  • Ouabain / pharmacology*
  • Ventricular Dysfunction, Left / drug therapy
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Dysfunction, Right / drug therapy
  • Ventricular Dysfunction, Right / pathology
  • Ventricular Dysfunction, Right / physiopathology

Substances

  • Cardiotonic Agents
  • Ouabain