Pablo F. Soto

Impact of aging on substrate metabolism by the human heart.

BACKGROUND Results of studies in experimental animals have shown that, with age, myocardial fatty acid metabolism decreases, and glucose metabolism increases. Whether similar changes occur in humans is unknown. METHODS Seventeen healthy younger normal volunteers (six males, 26 +/- 5 years) and 19 healthy older volunteers (nine males, 67 +/- 5 years) underwent positron emission tomography (PET) under resting conditions in the fasted state. Myocardial blood flow (MBF), myocardial oxygen consumption (MVO(2)), myocardial fatty acid utilization (MFAU) and oxidation (MFAO), and myocardial glucose utilization (MGU) were quantified by PET with (15)O-water, (11)C-acetate, (11)C-palmitate, and(11)C-glucose, respectively. RESULTS Although MBF was similar between the groups, MVO(2) was higher in the older subjects (5.6 +/- 1.6 micromol/g/min) compared with younger subjects (4.6 +/- 1.0 micromol/g/min, p < 0.04). Rates of MFAU and MFAO (corrected for MVO(2)) were significantly lower in older subjects than in younger subjects (MFAU/MVO(2): 35 +/- 10 vs. 51 +/- 20 nmol free fatty acids (FFA)/nmol O(2) x 10(-3), p < 0.005, and MFAO/MVO(2): 33 +/- 10 vs. 48 +/- 18 nmol FFA/nmol O(2) x 10(-3), p < 0.004). In contrast, the rates of MGU corrected for MVO(2) did not differ between the groups. CONCLUSIONS With aging, humans exhibit a decline in MFAU and MFAO. Although absolute rates of MGU do not increase, by virtue of the decline in MFAU there is likely an increase in relative contribution of MGU to substrate metabolism. The clinical significance of this metabolic switch awaits further study.

Impact of Gender on the Myocardial Metabolic Response to Obesity

OBJECTIVES We sought to determine the gender-specific effects of obesity on myocardial metabolism, work, and efficiency. BACKGROUND Myocardial metabolism abnormalities may contribute to the development of obesity-related heart failure. Increased myocardial oxygen consumption (MVO(2)) and fatty acid (FA) metabolism and decreased efficiency occur with obesity in women. It is unknown whether similar changes occur with obesity in men. METHODS We quantified cardiac work, efficiency, myocardial blood flow (MBF), MVO(2), glucose, and FA metabolism with echocardiography and positron emission tomography in nonobese and obese men and women (N = 86). RESULTS There were significant differences between the obese (n = 35) and nonobese (n = 51) subjects in age, body composition, plasma lipids, and insulin resistance in addition to differences between the men (n = 30) and women (n = 56) in body composition and plasma lipids. Female gender independently predicted increased cardiac work (p < 0.001). Female gender also related to lower efficiency (p < 0.05). Obesity and female gender independently predicted greater MBF (p < 0.01, p < 0.0005, respectively) and MVO(2) (p < 0.0005, p < 0.0001). Myocardial glucose uptake was not different among the 4 subject groups, but obesity and gender interacted in predicting glucose uptake (p < 0.05). Lower myocardial glucose utilization was independently predicted by female gender (p < 0.05), and it independently predicted lower myocardial glucose utilization/plasma insulin (p < 0.05). Obesity and gender significantly interacted in the determination of glucose utilization/plasma insulin (p = 0.01). There were no differences in FA uptake among the 4 groups, and although increasing obesity correlated with greater myocardial FA utilization and oxidation; female gender (p < 0.005, p < 0.01) and plasma triglycerides (p < 0.05, p < 0.005) were their independent predictors. CONCLUSIONS Womens and mens myocardial metabolic responses to obesity are not exactly the same. Obesity and gender modulate MBF and MVO(2), are related to myocardial substrate metabolism, and sometimes interact in its prediction. Gender modifies efficiency. Gender-related differences in myocardial metabolism may affect the development of/adaptation to obesity-related cardiac disease.

Exercise training impacts the myocardial metabolism of older individuals in a gender-specific manner.

Aging is associated with decreases in aerobic capacity, cardiac function, and insulin sensitivity as well as alterations in myocardial substrate metabolism. Endurance exercise training (EET) improves cardiac function in a gender-specific manner, and EET has been shown to improve whole body glucose tolerance, but its effects on myocardial metabolism are unclear. Accordingly, we studied the effect of EET on myocardial substrate metabolism in older men and women. Twelve healthy older individuals (age: 60-75 yr; 6 men and 6 women) underwent PET with [(15)O]water, [(11)C]acetate, [(11)C]glucose, and [(11)C]palmitate for the assessment of myocardial blood flow (MBF), myocardial O(2) consumption (MVo(2)), myocardial glucose utilization (MGU), and myocardial fatty acid utilization (MFAU), respectively, at rest and during dobutamine infusion (10 microg.kg(-1).min(-1)). Measurements were repeated after 11 mo of EET. Maximal O(2) uptake (Vo(2max)) increased (P = 0.005) after EET. MBF was unaffected by training, as was resting MVo(2); however, posttraining dobutamine MVo(2) was significantly higher (P = 0.05), as was MGU (P < 0.04). Although overall dobutamine MFAU was unchanged, posttraining dobutamine MFAU increased in women (P = 0.01) but decreased in men (P = 0.03). Thus, EET in older individuals improves the catecholamine response of myocardial glucose metabolism. Moreover, gender differences exist in the myocardial fatty acid metabolic response to training. These findings suggest a role for altered myocardial substrate metabolism in modulating the cardiovascular benefits of EET in older individuals.

Effects of human immunodeficiency virus and metabolic complications on myocardial nutrient metabolism, blood flow, and oxygen consumption: a cross-sectional analysis

BackgroundIn the general population, peripheral metabolic complications (MC) increase the risk for left ventricular dysfunction. Human immunodeficiency virus infection (HIV) and combination anti-retroviral therapy (cART) are associated with MC, left ventricular dysfunction, and a higher incidence of cardiovascular events than the general population. We examined whether myocardial nutrient metabolism and left ventricular dysfunction are related to one another and worse in HIV infected men treated with cART vs. HIV-negative men with or without MC.MethodsProspective, cross-sectional study of myocardial glucose and fatty acid metabolism and left ventricular function in HIV+ and HIV-negative men with and without MC. Myocardial glucose utilization (GLUT), and fatty acid oxidation and utilization rates were quantified using 11C-glucose and 11C-palmitate and myocardial positron emission tomography (PET) imaging in four groups of men: 23 HIV+ men with MC+ (HIV+/MC+, 42 ± 6 yrs), 15 HIV+ men without MC (HIV+/MC-, 41 ± 6 yrs), 9 HIV-negative men with MC (HIV-/MC+, 33 ± 5 yrs), and 22 HIV-negative men without MC (HIV-/MC-, 25 ± 6 yrs). Left ventricular function parameters were quantified using echocardiography.ResultsMyocardial glucose utilization was similar among groups, however when normalized to fasting plasma insulin concentration (GLUT/INS) was lower (p < 0.01) in men with metabolic complications (HIV+: 9.2 ± 6.2 vs. HIV-: 10.4 ± 8.1 nmol/g/min/μU/mL) than men without metabolic complications (HIV+: 45.0 ± 33.3 vs. HIV-: 60.3 ± 53.0 nmol/g/min/μU/mL). Lower GLUT/INS was associated with lower myocardial relaxation velocity during early diastole (r = 0.39, p < 0.001).ConclusionMen with metabolic complications, irrespective of HIV infection, had lower basal myocardial glucose utilization rates per unit insulin that were related to left ventricular diastolic impairments, indicating that well-controlled HIV infection is not an independent risk factor for blunted myocardial glucose utilization per unit of insulin.Trial RegistrationNIH Clinical Trials NCT00656851