The evaluation of drug-induced changes in left ventricular function in pentobarbital-anesthetized dogs.

Abstract Introduction The goal of this study was to determine whether assessment of myocardial contractility and hemodynamics in an anesthetized dog model, could consistently detect drug-induced changes in the inotropic state of the heart using drugs known to have clinically relevant positive and negative effects on myocardial contractility. Methods Derived parameters included: diastolic, systolic and mean arterial BP, peak systolic LVP, HR, end-diastolic LVP, and LVdP/dt max as the primary contractility index. Results These results demonstrate that statistically significant increases (amrinone and pimobendan) and decreases (atenolol and itraconazole) in left ventricular dP/dt max were observed at clinically relevant exposures. Discussion The analysis from the current study supports the strategic use of the anesthetized dog model early in the drug Discovery process for a comprehensive cardiovascular evaluation that can include left ventricular dP/dt max with good translation to human.