title: An analytical method to separate inotropic and vasodilatory drug effects in patients with heart failure.
abstract: A recently proposed analytical technique to determine whether an inotropic agent improves cardiac pumping performance via its vasodilatory or its positive inotropic effects was adopted to evaluate the pharmacological properties of a positive inotropic agent, dobutamine, and a vasodilatory calcium antagonist, felodipine, in patients with severe heart failure. This technique used a new principle of pump-load interaction, which states that for a given change in vascular input impedance unaccompanied by any direct alteration in the pumping characteristics all possible values of pump power output due to the change in impedance per se are confined within two calculated limits. When dobutamine was infused at 10 micrograms.kg-1.min-1 seven out of 10 patients had power output values above the defined limits, implying that the technique can identify correctly in vivo the direct positive inotropic effects of dobutamine in the presence of its vasodilating activity. In contrast, when 5-10 mg of felodipine was given to 10 patients the consequent power outputs were all within the defined limits, implying that the effects can be explained by vasodilatation alone. In conclusion, this study showed that the analytical technique can be applied clinically to detect the presence of drug induced positive inotropic effects in the midst of vasodilatation and therefore may be useful in determining whether inotropic agents actually improve cardiac function via their positive inotropic effects.
authors.affiliation: Department of Cardiovascular Medicine, University of Birmingham, East Birmingham Hospital.
authors.forename: L B
authors.initials: LB
authors.lastname: Tan
authors.forename: R G
authors.initials: RG
authors.lastname: Murray
authors.forename: W A
authors.initials: WA
authors.lastname: Littler
mesh_terms: D000368:Aged; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004280:Dobutamine / Q000494:pharmacology; D015736:Felodipine; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006334:Heart Function Tests / Q000379:methods*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D009568:Nitrendipine / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D002316:Cardiotonic Agents; D014665:Vasodilator Agents; D004280:Dobutamine; D009568:Nitrendipine; D015736:Felodipine