title: Myocardial perfusion dependent and independent mechanisms of regional myocardial dysfunction in hypertrophy.
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.
authors.affiliation: Department of Medicine, Harvard Medical School, Brigham & Women's Hospital, Boston, Massachusetts.
authors.forename: S F
authors.initials: SF
authors.lastname: Vatner
authors.forename: L
authors.initials: L
authors.lastname: Hittinger
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology*; D003326:Coronary Circulation; D004195:Disease Models, Animal; D004285:Dogs; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics; D017202:Myocardial Ischemia / Q000503:physiopathology*; D009206:Myocardium / Q000378:metabolism*; D005082:Physical Exertion; D011433:Propranolol / Q000494:pharmacology; D012039:Regional Blood Flow
chemical_list: D011433:Propranolol