title: Myocardial work load is a major determinant of norepinephrine-induced left ventricular dysfunction.
abstract: This study was conducted to determine whether increased myocardial energy demand plays a role in norepinephrine (NE)-induced left ventricular (LV) dysfunction. A range of arterial pressure-heart rate (P-R) products (myocardial energy demand) was produced in both conscious and pentobarbital sodium-anesthetized rabbits with the same dose of NE (10 micrograms priming bolus plus 2.5 micrograms.kg-1 x min-1 for 2.5 h). After NE treatment, LV function was evaluated in vitro and found to be markedly diminished in the rabbits that had an elevated P-R product. In contrast, LV function was not significantly affected when the P-R product was maintained near control levels during NE treatment. In separate experiments, rabbit hearts were isolated and exposed to NE (10,000 or 50,000 pg/ml) for 2.5 h under low P-R product conditions. These hearts exhibited a dose-dependent decrease in LV function that was modest compared with that observed in rabbits that had elevated P-R products during in vivo NE treatment. Our results suggest that high concentrations of NE may cause modest degrees of LV dysfunction independently of increases in myocardial energy demand, but the LV dysfunction is exacerbated when myocardial energy demand is elevated.
authors.affiliation: Department of Physiology, Northeastern Ohio Universities College of Medicine, Rootstown 44272.
authors.forename: F J
authors.initials: FJ
authors.lastname: Bosso
authors.forename: F D
authors.initials: FD
authors.lastname: Allman
authors.forename: C F
authors.initials: CF
authors.lastname: Pilati
mesh_terms: D000768:Anesthesia, General; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003243:Consciousness; D003971:Diastole / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006339:Heart Rate / Q000187:drug effects*; D008955:Models, Cardiovascular; D009638:Norepinephrine / Q000494:pharmacology*; D010424:Pentobarbital; D011817:Rabbits; D013599:Systole / Q000187:drug effects; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects / Q000502:physiology*
chemical_list: D010424:Pentobarbital; D009638:Norepinephrine