Daiya Takeyama

Effects of long-term pressure overload on regional myocardial glucose and free fatty acid uptake in rats. A quantitative autoradiographic study.

To investigate the effects of long-term pressure overload on regional myocardial substrate use, we performed quantitative autoradiography using 2-deoxy-D-[U-14C]glucose (14C-DG) and beta-methyl[1-14C]heptadecanoic acid (14C-BMHDA) in conscious rats with a 10-week ascending aortic constriction. Heart weight/body weight ratio increased by 27% in aortic-constricted rats as compared with sham-operated rats (p less than 0.01). Myocardial 14C-DG uptake increased (258 +/- 63 vs. 144 +/- 41 nCi/g, p less than 0.01, n = 6 for each group); however, 14C-BMHDA extraction decreased (251 +/- 69 vs. 342 +/- 75 nCi/g, p less than 0.05, n = 7 for each group) in aortic-constricted rats as compared with sham-operated rats. In sham-operated rats, both 14C-DG and 14C-BMHDA uptakes were higher in the left ventricular anterior and lateral walls as compared with the posterior wall or the interventricular septum. In aortic-constricted rats, 14C-DG uptake also increased in the interventricular septum, as well as in the left ventricular anterior and lateral walls, as compared with the posterior wall. There was, however, no regional difference in 14C-BMHDA extraction among these four regions. Myocardial blood flow distribution determined by 4-[N-methyl-14C]iodoantipyrine or myocyte width showed no regional variations among the four regions, either in aortic-constricted or sham-operated rats. Regional interstitial fibrosis was small in either group. The present study suggests that myocardial substrate uptake is altered nonhomogeneously, and that the nonhomogeneity is not because of regional variations in blood flow distribution, myocyte hypertrophy, or interstitial fibrosis. The results of angiotensin II-induced acute pressure overloading in other sham-operated rats, in which a remarkable increase in myocardial 14C-BMHDA extraction (n = 3, p less than 0.01) and no difference in 14C-DG uptake (n = 3) as compared with normotensive sham-operated rats were elicited, suggest that the findings in aortic-constricted rats are not direct responses to increased left ventricular pressure itself but rather should be explained by still unknown factors related to prolonged pressure overload.

Effects of chronic right ventricular pressure overload on myocardial glucose and free fatty acid metabolism in the conscious rat

OBJECTIVE The aim was to investigate the effects of chronic right ventricular pressure overload on myocardial glucose and free fatty acid metabolism in the right ventricular free wall, ventricular septum, and left ventricular free wall. METHODS Using a glucose analogue, 14C-2-deoxyglucose (14C-DG), and a fatty acid analogue, 14C-beta methylheptadecanoic acid (14C-BMHDA), quantitative autoradiography was performed in conscious rats with 4 week pulmonary artery constriction. RESULTS In rats with chronic pulmonary artery constriction, right ventricular peak systolic pressure and right ventricular weight to body weight ratio increased by 88% and 127%, respectively, compared with sham operated rats (P < 0.01 for each). In the right ventricular free wall, 14C-DG deposition increased but 14C-BMHDA accumulation did not differ in the chronic pulmonary artery constricted rats compared with sham operated rats [212(SEM 27), n = 6 v 101(15) nCi.g-1, n = 4, P < 0.01, and 406(40), n = 6, v 333(48) nCi.g-1, n = 4, NS, respectively]. In sham operated rats, 14C-DG and 14C-BMHDA deposition did not differ between the ventricular septum and the left ventricular free wall. In contrast, 14C-DG and 14C-BMHDA accumulations were lower in the ventricular septum compared with the left ventricular free wall wall in chronic pulmonary artery constricted rats. Myocardial blood flow assessed by 14C-iodoantipyrine was homogeneously distributed throughout both ventricles. CONCLUSIONS 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.

Differences in myocardial fluoro-18 2-deoxyglucose uptake in young versus older patients with hypertrophic cardiomyopathy

The purpose of this study was to determine whether regional myocardial glucose use in patients diagnosed as having hypertrophic cardiomyopathy (HC) at a younger age differs from that in those diagnosed at middle to old age. Sixteen patients with HC (group 1 aged less than 40 years (n = 8); group 2 aged greater than 40 (n = 8) were studied using positron emission tomography and fluoro-18 2-deoxyglucose (FDG). All patients were diagnosed as having HC within 6 years of the study. Contiguous regions of interest were selected circumferentially on each cross-sectional image of the left ventricular wall. In each region of interest, % FDG fractional uptake was calculated. In each patient, % left ventricular FDG fractional uptake was determined as a mean value of % FDG fractional uptake in each region of interest. Moreover, as a measure of nonhomogeneity, the % interregional coefficient of variation in FDG fractional uptake was calculated in each patient. Whereas % left ventricular FDG fractional uptake did not differ between the 2 groups, the % interregional coefficient of variation in FDG fractional uptake was increased in group 1 compared with that in group 2 (11.5 +/- 3.6 vs 7.4 +/- 1.6%; p less than 0.02). Interventricular septum/left ventricular posterior wall thickness ratio and total counts in cross-sectional image did not differ between the 2 groups. These data suggest that patients diagnosed as having HC at a younger age have more nonhomogeneous myocardial metabolic characteristics than do patients diagnosed at middle or old age, and support the notion that HC in the young may be different from that in the middle-aged or elderly.

Heterogeneous fatty acid uptake early after reperfusion in rat hearts

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 beta-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 coefficients of 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.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.