Influence of positive inotropic agents on intracellular calcium transients. Part II. Cardiomyopathic hamster hearts.
To study the mechanism of dobutamine on end-stage heart failure, we assessed hemodynamic responses, high-energy phosphates (31P-NMR), and free intracellular calcium ([Ca2+]i) transients (surface fluorometry) during perfusion with 10(-6) mol/L dobutamine in Syrian cardiomyopathic hamsters with severe heart failure. These results were compared to perfusion of the heart with 10(-6) mol/L norepinephrine and 10(-6) mol/L isoproterenol. With the positive inotropic agents the rate-pressure product increased immediately (p less than 0.01 with dobutamine, norepinephrine; p less than 0.003 with isoproterenol); after 10 to 15 minutes of perfusion the rate-pressure product remained relatively stable with norepinephrine and isoproterenol but decreased with dobutamine (p = NS vs control values). [Ca2+]i-transients increased significantly in all groups. The end-diastolic [Ca2+]i decreased continuously with norepinephrine and isoproterenol (p less than 0.008; p less than 0.005) but increased during dobutamine by 19%. Alterations in coronary flow, pHi, high-energy phosphates, and the phosphorylation potential were not significantly different among the three catecholamines. In conclusion, in contrast to norepinephrine and isoproterenol, dobutamine depressed myocardial performance and increased end-diastolic [Ca2+]i in late heart failure.
Stefenelli
T
T
Department of Medicine (Cardiology), University of California, San Francisco 94143.
Wu
S T
ST
Parmley
W W
WW
Mason
D T
DT
Wikman-Coffelt
J
J
D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism*; D002303:Cardiac Output, Low / Q000503:physiopathology; D009202:Cardiomyopathies / Q000378:metabolism*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D006224:Cricetinae; D004280:Dobutamine / Q000494:pharmacology; D005453:Fluorescence; D006321:Heart / Q000503:physiopathology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D008647:Mesocricetus; D009206:Myocardium / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D010710:Phosphates / Q000378:metabolism
D002316:Cardiotonic Agents; D010710:Phosphates; D004280:Dobutamine; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine