title: Effect of beta-blockade on left atrial contribution to ventricular filling in dogs with moderate heart failure.
abstract: Abnormal left ventricular (LV) filling has been observed in patients with heart failure. One feature of this abnormality is a reduction in the left atrial (LA) contribution to filling, a feature that can adversely affect overall LV stroke output. In this study we examined the effects of early, long-term monotherapy with the beta-blocker, metoprolol, on LA contribution to ventricular filling in dogs with moderate heart failure. LV dysfunction (ejection fraction 30 percent to 40 percent) was produced in 14 dogs by multiple, sequential intracoronary microembolizations. Dogs were randomized to 3 months' therapy with metoprolol (25 mg twice daily; n = 7) or to no therapy at all (control; n = 7). Mitral inflow velocity was measured before randomization and after completion of therapy by using pulsed Doppler echocardiography. The percentage of LA contribution to LV filling was calculated as the ratio of the time-velocity integral of the LA component of mitral inflow velocity (Ai) to the time-velocity integral of total diastolic inflow velocity (Ti) times 100. In control dogs, the percentage of LA contribution to filling decreased after 3 months of follow-up compared with that before randomization (14 percent +/- 3 percent vs 23 percent +/- 5 percent; p = 0.02). In contrast, in dogs treated with metoprolol, the percentage of LA contribution to filling increased after 3 months of therapy compared with that before randomization (26 percent +/- 3 percent vs 21 percent +/- 2 percent; p = 0.001). Therapy with metoprolol produced a decrease in LV end-diastolic pressure, end-diastolic wall stress and stiffness, and an increase in LA fractional shortening compared with no therapy at all. We conclude that early, long-term therapy with metoprolol improves LA contribution to LV filling. This beneficial effect is likely caused by the ability of beta-blockers to reduce LA workload and consequently improve LA performance.
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and Vascular Institute, Detroit, MI 48202, USA.
authors.forename: H
authors.initials: H
authors.lastname: Shimoyama
authors.forename: H N
authors.initials: HN
authors.lastname: Sabbah
authors.forename: H
authors.initials: H
authors.lastname: Rosman
authors.forename: M
authors.initials: M
authors.lastname: Alam
authors.forename: S
authors.initials: S
authors.lastname: Goldstein
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002303:Cardiac Output, Low / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004285:Dogs; D018619:Echocardiography, Doppler, Pulsed; D006439:Hemodynamics / Q000187:drug effects; D008790:Metoprolol / Q000494:pharmacology*; D011897:Random Allocation; D016896:Treatment Outcome; D016277:Ventricular Function, Left / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D008790:Metoprolol