title: Exhaustion of Frank-Starling mechanism in conscious dogs with heart failure.
abstract: The goal of this study was to elucidate the ability of the left ventricle to accommodate an increase in preload (Frank-Starling mechanism) in the presence of congestive heart failure (CHF) but in the absence of the complicating effects of hypertrophy and fibrosis. To accomplish this, the effects of volume loading were examined in eight conscious dogs during the control state and after 3 wk of right ventricular pacing (240 beats/min). CHF increased heart rate (by 16 +/- 5 from 92 +/- 5 beats/min), left ventricular (LV) end-diastolic pressure (by 17 +/- 2 from 10 +/- 1 mmHg), and LV end-diastolic volume (EDV; by 23 +/- 4 from 57 +/- 3 ml). Despite reduced LV ejection fraction (from 54 +/- 3 to 31 +/- 3%), there was no significant change in cardiac output (2.5 +/- 0.3 l/min) compared with control (2.7 +/- 0.2 l/min). Stroke volume was preserved (control 19 +/- 2 ml; CHF 18 +/- 2 ml) at a constant heart rate by a shift to the right in the relationship between LV stroke volume and EDV, indicating the importance of chronic ventricular dilatation in maintaining pump performance. In the control state, acute volume load increased LV EDV (by 17 +/- 2 ml) and stroke volume (by 11 +/- 2 ml), whereas in CHF it did not increase LV EDV or stroke volume. Scanning electron microscopy revealed areas of reduced collagen weave pattern surrounding myofibers. Myocyte cross-sectional area by transmission electron microscopy was significantly reduced, and there were multiple electron-dense expansions of the Z lines with disruption of the normal lateral sarcomere alignment. These morphological findings suggest that chronic ventricular dilatation utilized in CHF results from myocyte stretch and morphological intracellular rearrangement. Furthermore, the failing heart cannot further augment stroke volume by acutely increasing EDV in CHF, suggesting that the Frank-Starling reserve is essentially exhausted.
authors.affiliation: Department of Medicine, Harvard Medical School, Brigham & Women's Hospital, Boston, Massachusetts.
authors.forename: K
authors.initials: K
authors.lastname: Komamura
authors.forename: R P
authors.initials: RP
authors.lastname: Shannon
authors.forename: T
authors.initials: T
authors.lastname: Ihara
authors.forename: Y T
authors.initials: YT
authors.lastname: Shen
authors.forename: I
authors.initials: I
authors.lastname: Mirsky
authors.forename: S P
authors.initials: SP
authors.lastname: Bishop
authors.forename: S F
authors.initials: SF
authors.lastname: Vatner
mesh_terms: D000818:Animals; D001794:Blood Pressure; D001810:Blood Volume; D002302:Cardiac Output; D003971:Diastole; D004285:Dogs; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006333:Heart Failure / Q000473:pathology / Q000503:physiopathology*; D006439:Hemodynamics; D008297:Male; D008854:Microscopy, Electron; D008955:Models, Cardiovascular; D009206:Myocardium / Q000648:ultrastructure; D012016:Reference Values; D013318:Stroke Volume; D016277:Ventricular Function, Left