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Comparison of hearts with 2 types of pressure-overload left ventricular hypertrophy
K W Saupe1, C C Lim, J S Ingwall
1Cardiac Muscle Research Laboratory, Whitaker Cardiovascular Institute, Boston University School of Medicine, MA 02118, USA. ksaupe@aol.com
Insights
Left ventricular hypertrophy (LVH) from hypertension protects against heart ischemia-induced diastolic dysfunction. This occurs because hypertensive LVH minimizes severe acidosis regions in the myocardium during low-flow ischemia.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
- Medical Imaging
Background:
- Left ventricular hypertrophy (LVH) is a common cardiac response to pressure overload.
- Hypertension and aortic constriction are the primary causes of LVH, but their effects on myocardial function during ischemia are not fully understood.
Purpose of the Study:
- To compare myocardial remodeling and function in response to pressure overload from hypertension versus aortic constriction.
- To investigate the impact of different LVH origins on myocardial energetics and diastolic stiffness during low-flow ischemia.
Main Methods:
- Isolated hearts from Dahl salt-sensitive rats with controlled LVH (hypertension or aortic constriction) and control groups were studied.
- (31)P nuclear magnetic resonance spectroscopy was used to assess myocardial energetics and pH.
- Isovolumic cardiac function and stiffness were measured under low-flow ischemia.
Main Results:
- Hearts with hypertensive LVH exhibited significantly lower end-diastolic pressure (a measure of stiffness) during ischemia compared to controls and aortic-banded hearts.
- Low-flow ischemia induced distinct regions of moderate (pH 6.9) and severe (pH 6.2) acidosis in all groups.
- The size of the severely acidotic region was smallest in hypertensive LVH hearts and correlated with reduced LV stiffening.
Conclusions:
- LVH secondary to hypertension offers protection against ischemia-induced diastolic dysfunction in Dahl rats.
- This protection is mediated by minimizing the extent of severe myocardial acidosis during ischemic events.
- Understanding these differences is crucial for developing targeted therapies for pressure overload-induced heart conditions.
Abstract:
Comparisons of myocardium remodeled by the 2 most common causes of left ventricular hypertrophy (LVH), hypertension and aortic constriction, are limited. We hypothesized that important differences may exist in the myocardium of hearts with these 2 origins of "pressure overload" LVH. Accordingly, we studied isolated hearts from 3 groups of Dahl salt-sensitive rats, controls, and hearts with matched amounts of LVH secondary to either hypertension or aortic constriction. Isovolumic LV function and myocardial energetics ((31)P nuclear magnetic resonance spectroscopy) were measured as coronary flow was lowered to 16% of baseline for 48 minutes. During this low-flow ischemia, isovolumic end-diastolic pressure, a measure of LV stiffness, increased to 52+/-4 mm Hg in controls and 51+/-6 mm Hg in aortic banded hearts but to only 35+/-5 mm Hg in hearts with hypertensive LVH. In all hearts, the P(i) resonance in the (31)P nuclear magnetic resonance spectrum, whose position indicates myocardial pH, split into 2 peaks during low-flow ischemia, which indicates distinct regions of pH 6.9 (moderate acidosis) and pH 6.2 (severe acidosis). Concentrations of ATP, PCr, P(i), and H(+) of the moderately acidotic region were not different among groups. However, the size of the severely acidotic region was smallest in the hypertensive LVH hearts, and in all 3 groups, the size of this region correlated (r(2)=0.65 to 0.80) with the degree of LV stiffening. We conclude that in Dahl rats, LVH secondary to hypertension protects against ischemia-induced diastolic dysfunction by minimizing the size of the region of severe acidosis.