HIGH-ENERGY PHOSPHATE RESPONSES TO TACHYCARDIA AND INOTROPIC STIMULATION IN LEFT-VENTRICULAR HYPERTROPHY

Spatially localized nuclear magnetic resonance (NMR) spectroscopy was used to examine the effect of tachycardia and inotropic stimulation on myocardial ATP, creatine phosphate (CrP), and inorganic phosphate (P- i) in animals with left ventricular hypertrophy (LVH). Studies were pe rformed in eight normal dogs and seven dogs with moderate LVH produced by banding the ascending aorta. P-31-NMR spectra were obtained from f ive layers across the LV wall, while blood flow (BF) was measured with microspheres during control conditions, pacing at 200 and 240 beats/m in, and during dobutamine infusion (Dob). Myocardial ATP and CrP level s were normal in the LVH hearts during control conditions. Pacing did not alter the transmural distribution of perfusion or the levels of Cr P, ATP, and P-i in normal hearts. In contrast, in four of seven LVH he arts, pacing decreased the subendocardial/subepicardial (ENDO/EPI) BF ratio and caused depletion of CrP and appearance of P-i characteristic of ischemia in the subendocardium. Dob produced greater increases in the heart rate x LV systolic pressure product (RPP) and greater increa ses of P-i and decreases of CrP in LVH than in normal hearts; however, at comparable elevations of RPP the alterations of P-i and CrP were s imilar in both groups. Although Dob decreased the ENDO/EPI in LVH hear ts, Dob-induced alterations in CrP and P-i were uniform across the LV wall. Increasing myocardial BF with adenosine or carbochromen did not reverse the alterations in P-i or CrP produced by Dob. We conclude tha t 1) ENDO perfusion abnormalities during tachycardia in LVH do produce ENDO subendocardial ischemia; 2) when the degree of augmentation of m echanical performance is considered, the metabolic changes induced by Dob were similar in normal and LVH hearts; 3) Dob-induced alterations in P-i and CrP were not related to inadequate perfusion, since increas ing coronary BF did not reverse these changes; and 4) alterations of P -i and CrP during Dob infusion were not more prominent in the ENDO, in dicating that the decreased ENDO/EPI how did not cause ENDO ischemia b ut may reflect relatively lower O-2 demands in this region during inot ropic stimulation.