Ouabain pretreatment does not compromise the hemodynamic and myocardial energetic effects of CK‐3197, a selective positive inotropic agent, in dogs with propranolol‐induced heart failure

We examined the interaction between ouabain and CK‐3197, a new selective positive inotrope, on the hemodynamic and myocardial energetic parameters of anesthetized dogs with propranolol‐induced heart failure (PIHF). Mongrel dogs (13–18kg) of either sex were anesthetized with pentobarbital sodium (35mg/kg, i.v.) and instrumented for routine hemodynamic measurements using an open‐chest, artificially ventilated preparation. PIHF was produced by decreasing left ventricular (LV) dp/dt max by 50% from control values with an intial infusion of 0.5 mg/kg of propranolol followed by continuous infusion of 0.02 to 0.08 mg/kg of propranolol to maintain PIHF. This was followed by infusion of saline (2ml, i.v., n=8/group) or ouabain (25 μ/kg, i. v., n=8/group). Thirty minutes later one‐half of the saline and ouabain treated animals (Groups I and II;n =4/group) were given two increasing doses of saline or CK‐3197 (0.1 and 0.3 mg/kg, i. v.; n= Groups III and IV; n =4/group) 30 min apart. Hemodynamic paramters were monitored continuously, while myocardial oxygen consumption (MVO 2 ) was monitored 15 and 30 min after each dose of drug. CK‐3197 increased LV DP/dT max and LV dP/dT min by 41 and 78%, respectively. Mean arterial pressure increased by 16 and 6%. Heart rate decreased by 6 and 8%, while LV end diastolic pressure (LVEDP) decreased by 3mmHg after CK‐3197 (0.3 mg/Kg, i.v.). CK‐3197 increased LV work and LV contractile efficiency. Ouabain did not affect the hemodynamic and myocardial energetic profile of CK‐3197. These data support the conclusions that CK‐3197 is a selective positive inotrope which increases myocardial contractile efficiency in the dog with PIHF without any significant interaction with ouabain.