title: Effects of commonly used inotropes on myocardial function and oxygen consumption under constant ventricular loading conditions.
abstract: Inotropic medications are routinely used to increase cardiac output and arterial blood pressure during critical illness. However, few comparative data exist between these medications, particularly independent of their effects on venous capacitance and systemic vascular resistance. We hypothesized that an isolated working heart model that maintained constant left atrial pressure and aortic blood pressure could identify load-independent differences between inotropic medications. In an isolated heart preparation, the aorta and left atrium of Sprague Dawley rats were cannulated and placed in working mode with fixed left atrial and aortic pressure. Hearts were then exposed to common doses of a catecholamine (dopamine, epinephrine, norepinephrine, or dobutamine), milrinone, or triiodothyronine (n = 10 per dose per combination). Cardiac output, contractility (dP/dtmax), diastolic performance (dP/dtmin and tau), stroke work, heart rate, and myocardial oxygen consumption were compared during each 10-min infusion to an immediately preceding baseline. Of the catecholamines, dobutamine increased cardiac output, contractility, and diastolic performance more than clinically equivalent doses of norepinephrine (second most potent), dopamine, or epinephrine (P < 0.001). The use of triiodothyronine and milrinone was not associated with significant changes in cardiac output, contractility or diastolic function, either alone or added to a baseline catecholamine infusion. Myocardial oxygen consumption was closely related to dP/dtmax (r(2) = 0.72), dP/dtmin (r(2) = 0.70), and stroke work (r(2) = 0.53). In uninjured, isolated working rodent hearts under constant ventricular loading conditions, dobutamine increased contractility and cardiac output more than clinically equivalent doses of norepinephrine, dopamine, and epinephrine; milrinone and triiodothyronine did not have significant effects on contractility.
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts;
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: DeWitt
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts;
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Black
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts;
authors.forename: Ravi R
authors.initials: RR
authors.lastname: Thiagarajan
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts; and.
authors.forename: James A
authors.initials: JA
authors.lastname: DiNardo
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts;
authors.forename: Steven D
authors.initials: SD
authors.lastname: Colan
authors.affiliation: Department of Anesthesiology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.
authors.forename: Francis X
authors.initials: FX
authors.lastname: McGowan
authors.affiliation: Department of Cardiology, Boston Children's Hospital, Boston, Massachusetts; john.kheir@childrens.harvard.edu.
authors.forename: John N
authors.identifier: 0000-0001-6080-8739
authors.initials: JN
authors.lastname: Kheir
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002395:Catecholamines / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects* / Q000378:metabolism; D020105:Milrinone / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014284:Triiodothyronine / Q000494:pharmacology; D014655:Vascular Resistance / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D002316:Cardiotonic Agents; D002395:Catecholamines; D014284:Triiodothyronine; D020105:Milrinone
keywords: contractility; inotropy; oxygen consumption