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.