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Myocardial perfusion dependent and independent mechanisms of regional myocardial dysfunction in hypertrophy
1Department of Medicine, Harvard Medical School, Brigham & Women's Hospital, Boston, Massachusetts.
Insights
Ventricular hypertrophy impairs coronary blood flow during exercise, causing subendocardial dysfunction. Beta-blockers prevent this dysfunction by reducing cardiac stress and improving blood flow, highlighting key mechanisms in hypertrophied hearts.
Area of Science:
- Cardiology
- Physiology
- Exercise Science
Background:
- Ventricular hypertrophy is associated with reduced coronary reserve.
- This reduction can impair left ventricular (LV) function during stress, like exercise.
- Increased metabolic demand during exercise may exceed coronary blood flow capacity in hypertrophied hearts.
Purpose of the Study:
- To investigate the mechanisms of subendocardial dysfunction during exercise in hypertrophied hearts.
- To assess the role of hemodynamic changes and beta-adrenergic blockade in exercise-induced myocardial dysfunction.
Main Methods:
- Studied dogs with left ventricular hypertrophy during exercise.
- Measured LV pressures, wall stress, heart rate, and LV dP/dt.
- Assessed subendocardial perfusion and wall thickening using the endo/epi blood flow ratio.
- Administered beta-adrenergic blockade (propranolol) to evaluate its effects.
Main Results:
- Subendocardial dysfunction occurred rapidly during exercise, even before significant increases in LV wall stress or perfusion deficits.
- More severe exercise led to persistent subendocardial dysfunction and reduced perfusion.
- Beta-adrenergic blockade attenuated increases in LV wall stress and heart rate, preventing subendocardial hypoperfusion and dysfunction.
Conclusions:
- Subendocardial dysfunction during exercise in hypertrophied hearts is mediated by both perfusion-dependent and independent mechanisms.
- Rapid onset of dysfunction suggests early involvement of factors beyond elevated wall stress.
- Beta-adrenergic blockade offers a protective effect by mitigating hemodynamic stress and preserving subendocardial perfusion.
Abstract:
Reduced coronary reserve is one of the hallmarks of ventricular hypertrophy. Although this reduced coronary reserve may not affect baseline left ventricular (LV) function, it could be of greater importance during periods of stress such as occurs during exercise where increased metabolic demands induced by the stress may not be fully met by increases in coronary blood flow. The impaired subendocardial coronary reserve is caused not only by the hypertrophy but also by the hemodynamic changes, e.g., the LV subendocardial wall stress, which increases markedly upon exercise. In the severely hypertrophied heart during exercise there is impaired subendocardial wall function even after 10 beats, i.e., the first 3 s of exercise, at a time when LV pressures and stresses had not increased, and subendocardial perfusion was still preserved. During more severe exercise, subendocardial dysfunction persisted and was associated with reduced subendocardial perfusion. After beta-adrenergic receptor blockade with propanolol, the most intense level of exercise was associated with lesser increase in systolic and diastolic LV wall stresses, heart rate, and LV dP/dt, and the endo/epi blood flow ratio, an index of adequacy of subendocardial perfusion, was no longer reduced below unity, and there were no decreases in subendocardial wall thickening. Thus, the subendocardial dysfunction occurred rapidly, before alterations in LV systolic or diastolic wall stress or an alteration in the endo/epi blood flow ratio. However, the subendocardial hypoperfusion and depression in subendocardial wall thickening observed during more severe exercise in dogs with LV hypertrophy was prevented by pretreatment with beta-adrenergic receptor blockade. Therefore, myocardial perfusion dependent and independent mechanisms mediate regional myocardial dysfunction during exercise in the hypertrophied heart.