956.
Background: Patients may receive more than one positive inotropic drug to improve myocardial function and cardiac output, with the assumption that the effects of two drugs are additive. The authors hypothesized that combinations of dobutamine and epinephrine would produce additive biochemical and hemodynamic effects.
Methods: The study was performed in two parts. Phase 1 used human lymphocytes in an in vitro model of cyclic adenosine monophosphate (cAMP) generation in response to dobutamine (10-8 to 10-4 M) or epinephrine (10-9 M to 10-5 M), and dobutamine and epinephrine together. Phase 2 was a clinical study in patients after aortocoronary artery bypass in which isobolographic analysis compared the cardiotonic effects of dobutamine (1.25, 2.5, or 5 [micro sign]g [middle dot] kg-1 [middle dot] min-1) or epinephrine (10, 20, or 40 ng [middle dot] kg-1 [middle dot] min-1), alone or in combination.
Results: In phase 1, dobutamine increased cAMP production 41%, whereas epinephrine increased cAMP concentration [almost equal to] 200%. However, when epinephrine (10-6 M) and dobutamine were combined, dobutamine reduced cAMP production at concentrations between 10-6 to 10-4 M (P = 0.001). In patients, 1.25 to 5 [micro sing]g [middle dot] kg-1 [middle dot] min-1 dobutamine increased the cardiac index (CI) 15-28%. Epinephrine also increased the CI with each increase in dose. However, combining epinephrine with the two larger doses of dobutamine (2.5 and 5 [micro sign]g [middle dot] kg-1 [middle dot] min-1) did not increase the CI beyond that achieved with epinephrine and the lowest dose of dobutamine (1.25 [micro sign]g [middle dot] kg-1 [middle dot]-1 min (-1)). In addition, the isobolographic analysis for equieffective concentrations of dobutamine and epinephrine suggests subadditive effects. 相似文献