Effects of hypoxia and digitalis glycosides on myocardial stiffness

The influences of hypoxia and of the interactions of hypoxia with digoxin and ouabain on myocardial stiffness were studied at two extracellular calcium concentrations (2.5 mM and 4.0 mM) in isolated, isometrically contracting cat papillary muscles. Stiffness (delta T/delta L), defined as a change in tension (delta T) in response to an imposed length change (delta L), was measured during contraction and during rest by use of a sinusoidal forcing function. Neither digoxin, ouabain, nor increased extracellular calcium altered contraction or resting stiffness in the well-oxygenated environment. Resting stiffness was increased at the end of hypoxia only in the presence of digoxin in both 2.5 mM and 4.0 mM Ca. Contraction stiffness was increased in 2.5 mM Ca by hypoxia alone and by hypoxia in the presence of digoxin or ouabain, but was not increased in experiments carried out in 4.0 mM Ca. Thus it appears that hypoxia per se increases contraction stiffness, but increasing extracellular calcium from 2.5 mM to 4.0 mM prevents the increase elicited by hypoxia; resting stiffness, however, is increased by hypoxia only in the presence of digoxin, and this occurs in both 2.5 mM and 4.0 mM Ca.