title: Detrimental effects after dobutamine infusion on rat left ventricular function: mechanical work and energetics.
abstract: We have previously reported that continuous infusion of dobutamine into the coronary artery induces positive inotropic effects but induces no detrimental effects in cross-circulated, excised normal rat hearts and even in Ca2+ overload-induced contractile failing rat hearts. However, we hypothesized that some detrimental effects on left ventricular (LV) function are induced after continuous dobutamine infusion and the following clearance of blood dobutamine, as is the case after beta-adrenergic receptor stimulation. To test this hypothesis, we investigated LV mechanical work and energetics in the same type of preparations that underwent continuous dobutamine infusion and clearance of blood dobutamine. We found that both mean end-systolic pressure and systolic pressure-volume area (PVA; a measure of total mechanical energy per beat) at midrange LV volume were significantly (P < 0.01) decreased. The mean myocardial oxygen consumption per beat intercept, which is composed of for the total Ca2+ handling in excitation-contraction coupling and basal metabolism, of the and PVA linear relation was also significantly (P < 0.05) decreased (n=8). The mean slope of the linear relation was unchanged in such hearts. Post-dobutamine basal metabolism was unchanged (n = 5 of the 8 hearts). The moderate proteolysis of a cytoskeleton protein, alpha-fodrin was identified (n = 7 of the 8 hearts with the decreased intercept), after clearance of blood dobutamine. In agreement with our hypothesis, the detrimental effect of the post-beta-adrenergic receptor stimulation was induced by a moderate concentration of dobutamine; we found systolic dysfunction due to the impairment of Ca2+ handling in excitation-contraction coupling in the rat LV and proteolysis of a cytoskeleton protein, alpha-fodrin.
authors.affiliation: Department of Physiology II, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
authors.forename: Chikako
authors.initials: C
authors.lastname: Nakajima-Takenaka
authors.forename: Susumu
authors.initials: S
authors.lastname: Sakata
authors.forename: Satoshi
authors.initials: S
authors.lastname: Kato
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Ohga
authors.forename: Ken-ya
authors.initials: KY
authors.lastname: Murata
authors.forename: Shigeki
authors.initials: S
authors.lastname: Taniguchi
authors.forename: Miyako
authors.initials: M
authors.lastname: Takaki
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D015153:Blotting, Western; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D003427:Cross Circulation; D004280:Dobutamine / Q000008:administration & dosage / Q000633:toxicity*; D004562:Electrocardiography / Q000187:drug effects; D004591:Electrophoresis, Polyacrylamide Gel; D004734:Energy Metabolism / Q000187:drug effects*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007262:Infusions, Intravenous; D019344:Lactic Acid / Q000378:metabolism; D016014:Linear Models; D008297:Male; D008840:Microfilament Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D013318:Stroke Volume / Q000187:drug effects; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000503:physiopathology; D013049:Spectrin
chemical_list: D000318:Adrenergic beta-Agonists; D002118:Calcium; D002352:Carrier Proteins; D004280:Dobutamine; D019344:Lactic Acid; D008840:Microfilament Proteins; D013049:Spectrin