A differential inotropic responsiveness to isoprenaline and ouabain in dogs with heart failure

We have previously shown that volume overload heart failure is associated with a depressed inotropic response to isoprenaline, noradrenaline, glucagon, and calcium. In these present experiments, the inotropic response of the failing heart to ouabain was examined because ouabain has a mechanism of action that is different from these other agents. The studies were conducted in dogs with heart failure resulting from an aortocaval fistula. The principal finding was that during heart failure the inotropic response to isoprenaline was markedly depressed while the inotropic response to ouabain was unaltered. These findings, coupled with our previous observations, suggest that heart failure is not associated with some common defect in the excitation-contraction coupling mechanism that reduces the response to inotropic agents. Additionally, we made the first measurements of plasma noradrenaline levels in this model of heart failure and found them to be elevated four-fold.