Chronic right ventricular pressure overload increases myocardial glucose uptake and/or its phosphorylation in the right ventricular free wall, and alters the regional profiles of substrate use in the ventricular septum and left ventricular free wall despite the homogeneous blood flow distribution. The results of the acute right ventricular pressure overload study, in which only right ventricular 14C-BMHDA deposition was increased compared with controls, suggest that the findings obtained from chronic pulmonary artery constricted rats cannot be explained by increased right ventricular pressure alone.

Background-Several-(p-iodophenyl)-3-R,S-methylpentadecanoic acid (BMIPP) in 11 patients with atrial septal defect (ASD) and 11 control subjects. In the FDG study, we calculated myocardial metabolic rate of glucose (MMR) in interventricular septum (IVS) and left ventricular (LV) free wall. MMR was significantly increased in IVS compared with LV free wall in the ASD patients (420Ϯ35 versus 333Ϯ32 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ; PϽ0.05) but not in the control group (347Ϯ27 versus 357Ϯ25 mol ⅐ kg Ϫ1 ⅐ min Ϫ1 ). In both ASD and control groups, SPECT count was not significantly different between IVS and LV free wall in Tl (ASD, 160Ϯ11 versus 177Ϯ12; control, 141Ϯ12 versus 157Ϯ14 counts per 15 minutes) and BMIPP studies (ASD, 203Ϯ14 versus 212Ϯ18; control, 162Ϯ16 versus 176Ϯ16 counts per 15 minutes). MMR in the IVS/LV free wall ratio in the ASD group significantly correlated with indices related to RV volume overload. Conclusions-Given the assumption that long-term RV volume overload did not affect the lumped constant, the present study suggests that, unlike myocardial perfusion or fatty acid analogue uptake, myocardial glucose utilization in IVS relative to LV free wall is increased in relation to long-term RV volume overload in patients with ASD. (Circulation.

We have shown that myocardial glucose metabolism is heterogeneous in patients with hypertrophic cardiomyopathy. It is not known, however, whether glucose metabolism is impaired in patients with apical hypertrophic cardiomyopathy, which is fairly common in Japan. We studied 7 patients with apical hypertrophic cardiomyopathy and 5 normal subjects using fluoro-18 2-deoxyglucose (FDG) and positron emission tomography (PET). We calculated regional FDG fractional uptake and the inter-regional coefficient of variation (CV) of FDG fractional uptake in the interventricular septal, anteroapical, and posterolateral regions. The regional FDG fractional uptake was similar in the 2 groups and among the 3 different segments within each group. However, the inter-regional CV of FDG fractional uptake was increased in the anteroapical wall segment of the patient group compared with the control group and also with the other 2 regions in the patient group. The results did not differ when we studied another 5 patients and 6 normal control subjects with a PET scanner with higher spatial resolution. These data suggest that myocardial glucose metabolism may be impaired in the anteroapical wall segment of patients with apical hypertrophic cardiomyopathy.

To investigate the effects of endothelin blockade initiated immediately after the onset of myocardial infarction on survival and left ventricular remodeling, treatment with the nonselective receptor antagonist TAK-044 (n = 22) or saline (n = 19) for 3 weeks was initiated immediately after coronary ligation in rats. The 24-h survival rate was significantly lower in the TAK-044 group than in the saline group. The systolic blood pressure 24 h after the onset of myocardial infarction was similar in the saline and TAK-044 groups, although it was significantly lower in the TAK-044 group during the 3-week protocol. Heart weight/tibial length was significantly increased in the TAK-044 group compared with the saline group. As all deaths in the TAK-044 group occurred within 24 h after myocardial infarction, we performed additional experiments using a separate group of rats 12-16 h after myocardial infarction. Plasma and myocardial endothelin-1 levels were significantly increased, and a bolus injection of TAK-044 significantly reduced left ventricular dP/dtmax in these rats that had had a myocardial infarction compared with sham-operated rats. Endothelin receptor blockade initiated immediately after the onset of myocardial infarction may deteriorate acute-phase survival and left ventricular remodeling. Inhibition of the positive inotropic action of endothlin-1 may partially explain the increased 24-h mortality.

We determined whether spatial distributions of substrate uptake are heterogeneous within the area at risk during reperfusion. Quantitative autoradiography with imaging plates and two long-lived radioisotopes was applied to 15 open-chest, anesthetized rats subjected to 30 min of coronary artery ligation and 30 min of reperfusion. Regions showing increased β-methyl-[1-14C]heptadecanoic acid ([14C]BMHDA) uptake (166 ± 17% of that in the nonischemic area) appeared at the lateral borders and subepicardial layer within the area at risk, and 2-deoxy-d-[1-3H]glucose ([3H]DG) uptake was 103 ± 24% in these regions. Regions with decreased [14C]BMHDA uptake (28 ± 11%) occupied the midmyocardial layer except at the lateral borders within the area at risk, and [3H]DG uptake was 62 ± 18% in these regions. The percentage interregional coefficientsof variation (index of heterogeneity) in [14C]BMHDA uptake, [3H]DG uptake, and blood flow were higher in the area at risk than in the nonischemic area (76 ± 23 vs. 21 ± 7%, 39 ± 10 vs. 21 ± 7%, and 49 ± 19 vs. 14 ± 4%, respectively). Heterogeneous distributions of substrate uptake may explain the conflicting results concerning substrate metabolism during reperfusion.