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.

We investigated in conscious dogs (a) the effects of heart failure induced by chronic rapid ventricular pacing on the sequence of development of left ventricular (LV) diastolic versus systolic dysfunction and (b) whether the changes were load dependent or secondary to alterations in structure. LV systolic and diastolic dysfunction were evident within 24 h after initiation of pacing and occurred in parallel over 3 wk. LV systolic function was reduced at 3 wk, i.e., peak LV dP/dt fell by -1,327±105 mmHg/s and ejection fraction by -22±2%. LV diastolic dysfunction also progressed over 3 wk of pacing, i.e., r increased by +14.0±2.8 ms and the myocardial stiffness constant by +6.5±1.4, whereas LV chamber stiffness did not change. These alterations were associated with increases in LV endsystolic (+28.6±5.7 g/cm2) and LV end-diastolic stresses (+40.4±53 g/cm2). When stresses and heart rate were matched at the same-levels in the control and failure states, the increases in r and myocardial stiffness were no longer observed, whereas LV systolic function remained depressed. There were no increases in connective tissue content in heart failure. Thus, pacing-induced heart failure in conscious dogs is characterized by major alterations in diastolic function which are reversible with normalization of increased loading condition. (J.

The effects of exercise on regional myocardial blood flow and function were examined in the presence and absence of beta-adrenergic receptor blockade in 10 adult conscious dogs with severe left ventricular (LV) hypertrophy induced by aortic banding in puppies, which increased the LV weight/body weight ratio by 87%. Exercise at the most intense level studied increased LV systolic (+87 +/- 8 mm Hg) and end-diastolic (+28 +/- 5 mm Hg) pressures, systolic (+85 +/- 12 g/cm2) and diastolic (+49 +/- 11 g/cm2) wall stresses, and subepicardial wall thickening (+0.18 +/- 0.05 mm) but reduced subendocardial wall thickening (-0.45 +/- 0.12 mm) and full wall thickening (-0.42 +/- 0.13 mm). This was associated with a fall in the subendocardial/subepicardial (endo/epi) blood flow ratio to 0.87 +/- 0.06 from 1.24 +/- 0.08. Subendocardial dysfunction persisted during recovery, at a time when transmural blood flow distribution returned to baseline, suggesting myocardial stunning. At the least intense level of exercise studied, the endo/epi blood flow ratio did not fall (1.27 +/- 0.14), but increases in heart rate (+73 +/- 8 beats per minute) and LV systolic (+35 +/- 8 g/cm2) and diastolic (+27 +/- 3 g/cm2) wall stresses were observed, and subendocardial wall thickening fell significantly (-0.21 +/- 0.08 mm, p less than 0.05). With anticipation of exercise, subendocardial wall thickening was not changed. However, subendocardial dysfunction was even evident after 10 beats, i.e., the first 3 seconds of exercise, at a time when LV pressures and stresses had not increased. After beta-adrenergic receptor blockade with propranolol, the most intense level of exercise was associated with lesser increases in systolic and diastolic LV wall stresses, heart rate, and LV dP/dt, and the endo/epi blood flow ratio was no longer reduced below unity (1.17 +/- 0.09). In addition, there were no decreases in subendocardial or full wall thickening, and myocardial stunning was no longer observed. Thus, the subendocardial hypoperfusion and depression in subendocardial wall thickening observed during exercise in dogs with LV hypertrophy was prevented by pretreatment with beta-adrenergic receptor blockade. Furthermore, the subendocardial dysfunction occurred rapidly, before alterations in LV systolic or diastolic wall stress or an alteration in the endo/epi blood flow ratio.(ABSTRACT TRUNCATED AT 400 WORDS)