Jy. Zhang et al., BIOENERGETIC ABNORMALITIES ASSOCIATED WITH SEVERE LEFT-VENTRICULAR HYPERTROPHY, The Journal of clinical investigation, 92(2), 1993, pp. 993-1003
Transmurally localized P-31-nuclear magnetic resonance spectroscopy (N
MR) was used to study the effect of severe pressure overload left vent
ricular hypertrophy (LVH) on myocardial high energy phosphate content.
Studies were performed on 8 normal dogs and 12 dogs with severe left
ventricular hypertrophy produced by banding the ascending aorta at 8 w
k of age. Spatially localized P-31-NMR spectroscopy provided measureme
nts of the transmural distribution of myocardial ATP, phosphocreatine
(CP), and inorganic phosphate (P(i)); spectra were calibrated from mea
surements of ATP content in myocardial biopsies using HPLC. Blood flow
was measured with microspheres. In hypertrophied hearts during basal
conditions, ATP was decreased by 42%, CP by 58%, and the CP/ATP ratio
by 32% in comparison with normal. Increasing myocardial blood flow wit
h adenosine did not correct these abnormalities, indicating that they
were not the result of persistent hypoperfusion. Atrial pacing at 200
and 240 beats per min caused no change in high energy phosphate conten
t in normal hearts but resulted in further CP depletion with P(i) accu
mulation in the inner left ventricular layers of the hypertrophied hea
rts. These changes were correlated with redistribution of blood flow a
way from the subendocardium in LVH hearts. These findings demonstrate
that high energy phosphate levels and the CP/ATP ratio are significant
ly decreased in severe LVH. These abnormalities are proportional to th
e degree of hypertrophy but are not the result of persistent abnormali
ties of myocardial perfusion. In contrast, depletion of CP and accumul
ation of P(i) during tachycardia in LVH are closely related to the pac
ing-induced perfusion abnormalities and likely reflect subendocardial
ischemia.