title: Isoproterenol-induced alterations in myocardial blood flow, systolic and diastolic function in conscious dogs with heart failure.
abstract: The effects of isoproterenol were examined in 10 conscious, chronically instrumented adult dogs with left ventricular (LV) failure after pressure overload hypertrophy induced by aortic banding at 8-10 weeks of age (LV free wall plus septum-to-body weight ratio, 8.6 +/- 0.5 g/kg) and also in eight control dogs (LV free wall plus septum-to-body weight ratio, 5.1 +/- 0.3 g/kg). Baseline values of heart rate, LV end-diastolic pressure, LV end-diastolic stress, and LV systolic wall stress were greater in the LV failure dogs (p less than 0.01), whereas the ejection phase index, rate of change of LV short-axis diameter, LV dD/dt, was depressed compared with control animals. In the control animals, isoproterenol infusion increased Vcf and LV dD/dt significantly (p less than 0.05), whereas LV systolic wall stress did not change. In the LV failure dogs, the increases in Vcf and LV dD/dt were less (p less than 0.01), and LV systolic wall stress increased (p less than 0.01). In the control animals, LV end-diastolic pressure, LV end-diastolic stress, LV end-diastolic stress-dimension ratio, diastolic radial myocardial stiffness, and the time constant of isovolumic relaxation decreased (p less than 0.05), whereas in the LV failure dogs, LV end-diastolic pressure, LV end-diastolic stress, diastolic radial myocardial stiffness, and the LV end-diastolic stress-dimension ratio increased. In the LV failure group, the endocardial to epicardial blood flow ratio fell to 0.59 +/- 0.06 during isoproterenol infusion, that is, significantly lower than in control dogs (0.93 +/- 0.06). These data support the concept that potent sympathomimetic amines exert deleterious effects on systolic and diastolic function in the failing heart, potentially related to subendocardial hypoperfusion.
authors.affiliation: Department of Medicine, Harvard Medical School, Brigham and Women's Hospital, Boston, Massachusetts.
authors.forename: L
authors.initials: L
authors.lastname: Hittinger
authors.forename: R P
authors.initials: RP
authors.lastname: Shannon
authors.forename: S
authors.initials: S
authors.lastname: Kohin
authors.forename: A S
authors.initials: AS
authors.lastname: Lader
authors.forename: W T
authors.initials: WT
authors.lastname: Manders
authors.forename: T A
authors.initials: TA
authors.lastname: Patrick
authors.forename: P
authors.initials: P
authors.lastname: Kelly
authors.forename: S F
authors.initials: SF
authors.lastname: Vatner
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000209:etiology / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects*; D003971:Diastole / Q000187:drug effects*; D004195:Disease Models, Animal; D004285:Dogs; D005260:Female; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000187:drug effects / Q000503:physiopathology; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D013599:Systole / Q000187:drug effects*; D014851:Wakefulness / Q000187:drug effects* / Q000502:physiology
chemical_list: D007545:Isoproterenol