Biomedical subjects

P Nuutila

Publications and source records attributed to P Nuutila.

At least 19 recordsLinked to original sources

PubMed2001

Myocardial fatty acid oxidation in patients with impaired glucose tolerance.

AIMS/HYPOTHESIS: Fatty acids are an important source of energy in the myocardium. Abnormal myocardial fatty acid metabolism could contribute to the deterioration of cardiac function frequently observed in patients with Type II (non-insulin-dependent) diabetes mellitus. In our previous study, myocardial total uptake of non-esterified fatty acid (NEFA) was measured in patients with impaired glucose tolerance and found to be normal. This study aimed to investigate the subsequent metabolic steps and beta-oxidation of NEFA. METHODS: A total of 6 men with impaired fasting glucose (age 50 +/- 2 years, BMI 29 +/- 1 kg/m2, means +/- SEM) and 6 healthy men (50 +/- 1 years, 25 +/- 1 kg/ m2) were studied in the fasting state. Myocardial blood flow was measured with [15O]H2O and positron emission tomography and myocardial NEFA metabolism with [11C]palmitic acid. RESULTS: Myocardial blood flow was normal and not different between the impaired glucose tolerance and the control group (78 +/- 6 vs 73 +/- 13 ml/100 g/ min, NS). The [11C]palmitic acid uptake indices were similar between the groups (10.4 +/- 0.5 vs 11.2 +/- 0.8 ml/100 g/min, respectively, NS). The clearance of [11C]-palmitate from the myocardium, an index of NEFA beta-oxidation, was similar between the groups (half-times of activity 17.6 +/- 1.6 vs 19.5 +/- 2.3 min, respectively, NS) CONCLUSION/INTERPRETATION: The results indicate that myocardial NEFA uptake and beta-oxidation are not altered in patients with IGT. Thus, it is not likely that altered NEFA metabolism contributes to the deterioration of the cardiac function in patients with IGT or Type II diabetes.

Blood Glucose↗

PubMed2001

Perfusion heterogeneity in human skeletal muscle: fractal analysis of PET data.

Muscle blood flow has been shown to be heterogeneous at the voxel by voxel level in positron emission tomography (PET) studies using oxygen-15 labelled water. However, the limited spatial resolution of the imaging device does not allow direct measurement of true vascular flow heterogeneity. Fractal dimension (D) obtained by fractal analysis describes the relationship between the relative dispersion and the size of the region studied, and has been used for the assessment of perfusion heterogeneity in microvascular units. This study was undertaken to evaluate fractal characteristics of PET perfusion data and to estimate perfusion heterogeneity in microvascular units. Skeletal muscle blood flow was measured in healthy subjects using [15O]water PET and the fractal characteristics of blood flow in resting and exercising skeletal muscle were analysed. The perfusion heterogeneity in microvascular units was estimated using the measured heterogeneity (relative dispersion, RD = SD/mean) and D values. Heterogeneity due to methodological factors was estimated with phantoms and subtracted from the flow data. The number of aggregated voxels was inversely correlated with RD both in phantoms (Pearson r = -0.96-0.97) and in muscle (Pearson r = -0.94) when both parameters were expressed using a logarithmic scale. Fractal dimension was similar between exercising (1.13) and resting (1.14) muscles and significantly lower than the values in the phantoms with different activity levels (1.27-1.29). Measured flow heterogeneity values were 20% +/- 6% (exercise) and 27% +/- 5% (rest, P < 0.001), whereas estimated flow heterogeneity values in microvascular units (1 mm3) were 35% +/- 14% (exercise) and 49% +/- 14% (rest, P < 0.01). In conclusion, these results show that it is feasible to apply fractal analysis to PET perfusion data. When microvascular flow heterogeneity is estimated using fractals, perfusion appears to be more heterogeneous in microvascular units than when obtained by routine spatial analysis of PET data. Analysis of flow heterogeneity using PET and fractals could provide new insight into physiological conditions and diseases associated with changes in peripheral vascular function.

Adult↗

PubMed2001

Enhanced oxygen extraction and reduced flow heterogeneity in exercising muscle in endurance-trained men.

The aim of this study was to investigate the effects of endurance training on skeletal muscle hemodynamics and oxygen consumption. Seven healthy endurance-trained and seven untrained subjects were studied. Oxygen uptake, blood flow, and blood volume were measured in the quadriceps femoris muscle group by use of positron emission tomography and [15O]O2, [15O]H2O, and [15O]CO during rest and one-legged submaximal intermittent isometric exercise. The oxygen extraction fraction was higher (0.49 +/- 0.14 vs. 0.29 +/- 0.12; P = 0.017) and blood transit time longer (0.6 +/- 0.1 vs. 0.4 +/- 0.1 min; P = 0.04) in the exercising muscle of the trained compared with the untrained subjects. The flow heterogeneity by means of relative dispersion was lower for the exercising muscle in the trained (50 +/- 9%) compared with the untrained subjects (65 +/- 13%, P = 0.025). In conclusion, oxygen extraction is higher, blood transit time longer, and perfusion more homogeneous in endurance-trained subjects compared with untrained subjects at the same workload. These changes may be associated with improved exercise efficiency in the endurance-trained subjects.

Adult↗

PubMed2000

Muscle blood flow and flow heterogeneity during exercise studied with positron emission tomography in humans.

Blood flow is the main regulator of skeletal muscle's oxygen supply, and several studies have shown heterogeneous blood flow among and within muscles. However, it remains unclear whether exercise changes the heterogeneity of flow in exercising human skeletal muscle. Muscle blood flow and spatial flow heterogeneity were measured simultaneously in exercising and in the contralateral resting quadriceps femoris (QF) muscle in eight healthy men using H2(15)O and positron emission tomography. The relative dispersion (standard deviation/mean) of blood flow was calculated as an index of spatial flow heterogeneity. Average muscle blood flow in QF was 29 (10) ml x (kg muscle)(-1) x min(-1) at rest and 146 (54) ml x (kg muscle)(-1) x min(-1) during exercise (P = 0.008 for the difference). Blood flow was significantly (P < 0.001) higher in the vastus medialis and the vastus intermedius than in the vastus lateralis and the rectus femoris, both in the resting and the exercising legs. Flow was more homogeneous in the exercising vastus medialis and more heterogeneous (P < 0.001) in the exercising vastus lateralis (P = 0.01) than in the resting contralateral muscle. Flow was more homogeneous (P < 0.001) in those exercising muscles in which flow was highest (vastus intermedius and vastus medialis) as compared to muscles with the lowest flow (vastus lateralis and the rectus femoris). These data demonstrate that muscle blood flow varies among different muscles in humans both at rest and during exercise. Muscle perfusion is spatially heterogeneous at rest and during exercise, but responses to exercise are different depending on the muscle.

Exercise↗

PubMed2000

Use of positron emission tomography in the assessment of skeletal muscle and tendon metabolism and perfusion.

Positron emission tomography (PET) represents the most advanced scintigraphic imaging technology in humans, which allows non-invasive studies of metabolism and perfusion in vivo. PET has been employed for research of skeletal muscle physiology and pathophysiology as well as for studies of effects of training and exercise. PET is a functional research method, being a powerful tool, especially in studies of skeletal muscle perfusion in humans. It also provides a potential tool for studies of tendon physiology. In this review examples of recent studies of skeletal muscle in athletes and during exercise are given and potential applications of PET in the field of tendon studies discussed.

Coronary Circulation↗

PubMed2000

Lumped constant for [(18)F]fluorodeoxyglucose in skeletal muscles of obese and nonobese humans.

Quantitative 2-[(18)F]fluoro-2-deoxy-D-glucose ([(18)F]FDG) positron emission tomography (PET) has been widely used to calculate glucose utilization in skeletal muscle. FDG-PET results depend partly on the lumped constant (LC), which accounts for the differences in the transport and phosphorylation between [(18)F]FDG and glucose. In this study, we estimated the LC for [(18)F]FDG directly in normal and in insulin-resistant obese subjects by combining FDG PET with the microdialysis technique. Eight obese [age 29.4 +/- 1.0 yr, body mass index (BMI) 33.6 +/- 1.0 kg/m(2)] and eight nonobese (age 25.0 +/- 1.0 yr, BMI 23.1 +/- 1.0 kg/m(2)) males were studied during euglycemic hyperinsulinemia (1 mU. kg(-1).min(-1) for 150 min). Muscle blood flow was measured using (15)O-labeled water and PET. Muscle [(18)F]FDG uptake (rGU(FDG)) was calculated with Patlak graphic analysis. Interstitial glucose concentration of the quadriceps femoris muscle was measured simultaneously with [(18)F]FDG scanning using microdialysis. Muscle glucose uptake (by microdialysis, rGU(MD)) was calculated by multiplying glucose extraction by regional muscle blood flow. A significant correlation was found between rGU(MD) and rGU(FDG) (r = 0.78, P < 0.01). The LC was determined as the ratio of the rGU(FDG) to the rGU(MD). The LC averaged 1.16 +/- 0.16 and was similar in the obese and nonobese subjects (1.15 +/- 0.11 vs. 1.16 +/- 0.07, respectively, not significant). In conclusion, the microdialysis technique can be reliably combined with FDG PET to measure glucose uptake in skeletal muscle. Direct measurements with these two independent techniques suggest an LC value of 1.2 for [(18)F]FDG in human skeletal muscle during insulin stimulation, and the LC appears not to be sensitive to insulin resistance.

Blood Glucose↗

PubMed2000

Insulin-induced increment of coronary flow reserve is not abolished by dexamethasone in healthy young men.

Hyperinsulinemia is a risk factor for coronary artery disease. Previous studies have reported that hyperinsulinemia increases cardiac and skeletal muscle sympathetic nerve activity and skeletal muscle blood flow in normal subjects. However, little is known about insulin's effects on myocardial blood flow in humans. The purpose of this study was to investigate whether physiological hyperinsulinemia affects myocardial blood flow and flow reserve in healthy subjects. Additionally, the role of the sympathetic nervous system in regulating insulin's effects on coronary perfusion was tested. We used positron emission tomography and oxygen-15-labeled water to measure myocardial blood flow and coronary flow reserve in 16 healthy nonobese men (age, 34 +/- 4 yr; maximal aerobic capacity, 32 +/- 3 mL x g(-1) x min(-1); blood pressure, 118 +/- 10/65 +/- 8 mm Hg) at fasting and during euglycemic hyperinsulinemic clamp (1 mU x kg(-1) x min(-1) for 80 min). To study the role of the sympathetic nervous system, each subject was studied twice: once after administration of dexamethasone (dexa+) for 2 days (2 mg per day) and once without previous medication (dexa-). All studied subjects had normal left ventricular mass, function, and findings in stress echocardiography. Resting myocardial blood flow was 0.76 +/- 0.19 mL x g(-1) x min(-1), and a significant increase in flow was detected after adenosine infusion (140 microg/kg x min for 5 min i.v.), both in the basal fasting state (P < 0.001) and during hyperinsulinemia (P < 0.001). However, the flow response to adenosine was significantly higher during hyperinsulinemia, thus leading to a higher hyperemic flow (3.38 +/- 0.97 vs. 4.28 +/- 1.57 mL x g(-1) x min(-1), basal vs. hyperinsulinemic, P < 0.01) and higher coronary flow reserve (4.6 +/- 1.2 vs. 5.8 +/- 1.9, respectively, P < 0.05). Pretreatment with dexamethasone did not significantly change the resting blood flow [0.72 +/- 0.22 vs. 0.76 +/- 0.19 mL x g(-1) x min(-1), dexa+ vs. dexa-, not significant (NS)], the adenosine stimulated flow (3.56 +/- 1.49 vs. 3.38 +/- 0.97 mL x g(-1) x min(-1), respectively, NS), or the hyperinsulinemic adenosine-stimulated blood flow (4.68 +/- 1.74 vs. 4.28 +/- 1.57 mL x g(-1) x min(-1), respectively, NS). Coronary flow reserves in the basal state (5.3 +/- 2.7 vs. 4.6 +/- 1.2 mL x g(-1) x min(-1), dexa+ vs. dexa-, NS) and during hyperinsulinemia (6.8 +/- 2.9 vs. 5.8 +/- 1.9 mL x g(-1) x min(-1), respectively, NS) tended to be (but were not) significantly higher after dexamethasone treatment. These results demonstrate that insulin acts as a vasodilatory hormone also in the coronary vasculature. Because the insulin-induced increment of myocardial flow reserve remained unchanged by dexamethasone pretreatment, centrally mediated sympathetic activation seems not to play a major role in regulating insulin action on myocardial perfusion in healthy subjects.

Adenosine↗

PubMed2000

Enhanced stimulation of glucose uptake by insulin increases exercise-stimulated glucose uptake in skeletal muscle in humans: studies using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography.

In vitro studies have shown that insulin and exercise stimulate glucose uptake in part via distinct mechanisms. We determined whether a high rate of insulin-stimulated glucose uptake (good insulin sensitivity) is associated with an enhanced ability of exercise to increase glucose uptake in vivo in humans. In our study, 22 normal subjects performed one-legged isometric exercise for 105 min (45-150 min) under intravenously maintained euglycemic-hyperinsulinemic conditions (0-150 min). Rates of oxygen consumption, blood flow, and glucose uptake were quantitated simultaneously in skeletal muscle of both legs using [15O]O2, [15O]H2O, [18F]fluoro-deoxy-glucose, and positron emission tomography. The one-legged exercise, performed at an intensity of 11% of maximal isometric force, was designed to induce similar increases in oxygen consumption in both groups. In the entire group, exercise increased oxygen consumption from 2.3 +/- 0.3 ml x kg(-1) muscle x min(-1) (insulin) to 34.2 +/- 3. ml x kg(-1) muscle x min(-1) (insulin and exercise) (P < 0.001) and muscle glucose uptake from 60 +/- 6 pmol x kg(-1) muscle x min(-1) (insulin) to 220 +/- 22 micromol x kg(-1) muscle x min(-1) (insulin and exercise) (P < 0.001). The exercise-induced increase in glucose uptake was due to marked increases in blood flow (36 +/- 5 ml x kg(-1) muscle x min(-1) [insulin] vs. 262 +/- 20 ml x kg(-1) muscle x min(-1) [insulin and exercise], P < 0.001) rather than glucose extraction, which decreased from 2.0 +/- 0.2 mmol/l (insulin) to 1.0 +/- 0.1 mmol/1 (insulin and exercise) (P < 0.001). The subjects were classified according to their mean rate of whole-body insulin-stimulated glucose uptake into those with high (49 +/- 3 micromol x kg(-1) x min(-1)) and normal (27 +/- 2 micromol x kg(-1) x min(-1)) rates of insulin-stimulated glucose uptake. Both insulin-stimulated (2.4 +/- 1.1 vs. 2.3 +/- 1.2 ml x kg(-1) muscle x min(-1), normal vs. high insulin sensitivity) and exercise- and insulin-stimulated (33 +/- 6 vs. 34 +/- 4 ml x kg(-1) muscle x min(-1)) rates of oxygen consumption were comparable between the groups. Exercise increased glucose uptake more in the group with high insulin sensitivity (195 +/- 25 pmol x kg(-1) muscle x min(-1)) than in the group with normal insulin sensitivity (125 +/- 19 micromol x kg(-1) muscle x min(-1)) (P < 0.05). Muscle blood flow was closely correlated with the rate of oxygen consumption (r = 0.91, P < 0.0001), and insulin-stimulated (30 +/- 5 vs. 35 +/- 6 ml x kg(-1) muscle x min(-1)) and exercise-induced increments (222 +/- 31 vs. 228 +/- 23 ml x kg(-1) muscle x min(-1)) in muscle blood flow were similar between the groups. Glucose extraction remained higher in the group with high insulin sensitivity (1.2 +/- 0.2 mmol/l) than in the group with normal insulin sensitivity (0.7 +/- 0.1 mmol/l, P < 0.05). We conclude that whereas acute exercise per se increases glucose uptake via increasing glucose delivery, good insulin sensitivity modulates exercise-induced increases in glucose uptake by enhancing cellular glucose extraction.

Adult↗

PubMed1999

Sodium nitroprusside increases human skeletal muscle blood flow, but does not change flow distribution or glucose uptake.

1. The role of blood flow as a determinant of skeletal muscle glucose uptake is at present controversial and results of previous studies are confounded by possible direct effects of vasoactive agents on glucose uptake. Since increase in muscle blood flow can be due to increased flow velocity or recruitment of new capillaries, or both, it would be ideal to determine whether the vasoactive agent affects flow distribution or only increases the mean flow. 2. In the present study blood flow, flow distribution and glucose uptake were measured simultaneously in both legs of 10 healthy men (aged 29 +/- 1 years, body mass index 24 +/- 1 kg m-2) using positron emission tomography (PET) combined with [15O]H2O and [18F]fluoro-2-deoxy-D-glucose (FDG). The role of blood flow in muscle glucose uptake was studied by increasing blood flow in one leg with sodium nitroprusside (SNP) and measuring glucose uptake simultaneously in both legs during euglycaemic hyperinsulinaemia (insulin infusion 6 pmol kg-1 min-1). 3. SNP infusion increased skeletal muscle blood flow by 86 % (P < 0.01), but skeletal muscle flow distribution and insulin-stimulated glucose uptake (61.4 +/- 7. 5 vs. 67.0 +/- 7.5 micromol kg-1 min-1, control vs. SNP infused leg, not significant), as well as flow distribution between different tissues of the femoral region, remained unchanged. The effect of SNP infusion on blood flow and distribution were unchanged during infusion of physiological levels of insulin (duration, 150 min). 4. Despite a significant increase in mean blood flow induced by an intra-arterial infusion of SNP, glucose uptake and flow distribution remained unchanged in resting muscles of healthy subjects. These findings suggest that SNP, an endothelium-independent vasodilator, increases non-nutritive, but not nutritive flow or capillary recruitment.

Adult↗

PubMed1999

Myocardial oxygen consumption is unchanged but efficiency is reduced in patients with essential hypertension and left ventricular hypertrophy.

BACKGROUND: Patients with hypertension and left ventricular hypertrophy (LVH) are prone to develop heart failure. We tested the hypothesis that compensatory LVH is associated with normalization of myocardial oxygen consumption and that this occurs at the expense of a decrease in the ratio between cardiac work and oxygen consumption (efficiency). METHODS AND RESULTS: Nine hypertensive men with LVH (LVH+) (age 42+/-2 years), left ventricular mass index (LVMI) 161+/-8 g/m(2), blood pressure (BP) 145+/-16/88+/-10 mm Hg (mean+/-SD); 8 hypertensive men without LVH (LVH-) (age 39+/-5 years, LVMI 107+/-15 g/m(2), BP 140+/-15/90+/-11 mm Hg); and 10 normotensive men (CONT) were studied. Myocardial blood flow, oxygen consumption, and glucose uptake were measured during euglycemic hyperinsulinemia using PET techniques. LV dimensions, volumes, and workload were determined by echocardiography, and efficiency was calculated. Myocardial workload (2.5+/-0.8 versus 3.0+/-0.6 versus 2. 3+/-0.5 mm Hg. mL. min(-1). g(-1) for CONT versus LVH- versus LVH+; P<0.05, LVH- versus LVH+), myocardial blood flow (0.84+/-0.16 versus 1.06+/-0.22 versus 0.81+/-0.09 mL. g(-1). min, respectively; P<0.05, LVH- versus other groups) and oxygen consumption (0.09+/-0.02 versus 0.14+/-0.03 versus 0.11+/-0.01 ml. g(-1). min(-1), respectively; P<0. 05, LVH- versus other groups) were increased in the LVH- group. Myocardial efficiency was reduced in the LVH+ group (18.1+/-4.1% versus 15.1+/-2.3% versus 13.5+/-1.9%, respectively; P<0.05, LVH+ versus CONT). CONCLUSIONS: Myocardial oxygen consumption per unit weight is increased in hypertensive patients without LVH but is normal in those with LVH. The normalization of oxygen consumption via hypertrophy occurs at the expense of efficiency, which may predispose hypertensive patients with LVH to heart failure.

Adult↗

PubMed1999

Coronary flow reserve in young men with familial combined hyperlipidemia.

BACKGROUND: Familial combined hyperlipidemia (FCHL) is a common hereditary disorder of lipoprotein metabolism estimated to cause 10% to 20% of premature coronary heart disease. We investigated whether functional abnormalities exist in coronary reactivity in asymptomatic patients with FCHL. METHODS AND RESULTS: We studied 21 male FCHL patients (age, 34.8+/-5.4 years) and a matched group of 21 healthy control subjects. Myocardial blood flow (MBF) was measured at baseline and during dipyridamole-induced hyperemia with PET and 15O-labeled water. The baseline MBF was similar in patients and control subjects (0.79+/-0.19 versus 0.88+/-0.20 mL. g-1. min-1, P=NS). An increase in MBF was seen in both groups after dipyridamole infusion, but MBF at maximal vasodilation was lower in FCHL patients (3.54+/-1.59 versus 4.54+/-1.17 mL. g-1. min-1, P=0.025). The difference in coronary flow reserve (CFR) was not statistically significant (4.7+/-2.2 versus 5.3+/-1.6, P=NS, patients versus control subjects). Considerable variability in CFR values was detected within the FCHL group. Patients with phenotype IIB (n=8) had lower flow during hyperemia (2.5+/-1.2 versus 4.2+/-1.5 mL. g-1. min-1, P<0.05) and lower CFR (3.4+/-2.1 versus 5.4+/-2.0, P<0.05) compared with phenotype IIA (n=13). CONCLUSIONS: Abnormalities in coronary flow regulation exist in young asymptomatic FCHL patients expressing phenotype IIB (characterized by abnormalities in both serum cholesterol and triglyceride concentrations). This is in line with previous observations suggesting that the metabolic abnormalities related to the pathophysiology of FCHL are associated with the phenotype IIB.

Adult↗

PubMed1999

Decreased blood flow but unaltered insulin sensitivity of glucose uptake in skeletal muscle of chronic smokers.

Chronic cigarette smoking is associated with dysfunction of the vascular endothelium. Smokers have also been shown to be insulin-resistant, at least in some studies. Since insulin-induced vasodilation is dependent on endothelial cell nitric oxide (NO) synthesis, we tested the hypothesis that decreased skeletal muscle blood flow causes insulin resistance in smokers. We studied 37 young normotensive normolipidemic nondiabetic men, of which 14 were smokers and 23 lifelong nonsmokers. The groups were similar with respect to age, body mass index (BMI), and maximal oxygen uptake (VO2max). Basal and insulin-stimulated femoral muscle blood flow was measured using [(15)O]H2O and insulin-stimulated muscle glucose uptake using [18F]fluoro-2-deoxy-D-glucose ([18F]FDG) and positron emission tomography (PET). Whole-body glucose uptake was measured using the hyperinsulinemic (insulin infusion 5 mU/kg x min)-euglycemic clamp technique. In the basal state, muscle blood flow was 51% lower in smokers (17 +/- 3 mL/kg muscle x min) versus nonsmokers (35 +/- 17 mL/kg x min, P < .0001). Insulin increased muscle blood flow comparably in both groups; the mean rate of insulin-stimulated blood flow was 30 +/- 10 and 55 +/- 38 mL/kg x min (P = .049), respectively. Whole-body and skeletal muscle glucose uptake were similar in both groups during insulin infusion. We conclude that muscle blood flow is lower in chronic smokers compared with nonsmokers under both fasting and hyperinsulinemic conditions. The insulin-induced increase in muscle blood flow and insulin-stimulated glucose uptake appear normal, suggesting that the vasodilatory and metabolic effects of insulin are intact in smokers and the reduced muscle blood flow per se does not cause insulin resistance in these subjects.

Adult↗

PubMed1999

Insulin action on heart and skeletal muscle glucose uptake in weight lifters and endurance athletes.

There are no studies comparing myocardial metabolism between endurance- and resistance-trained athletes. We used 2-deoxy-2-[18F]fluoro-D-glucose and positron emission tomography combined with the euglycemic hyperinsulinemic clamp technique to compare the ability of insulin to stimulate myocardial, skeletal muscle, and whole body glucose uptake between weight lifters (n = 8), endurance athletes (n = 8), and sedentary men (n = 9). Maximal aerobic power (ml. kg- 1. min- 1) was higher in the endurance athletes (71 +/- 2, P < 0.001) than the weight lifters (42 +/- 2) and the sedentary men (42 +/- 2). Skeletal muscle glucose uptake (micromol. kg muscle- 1. min- 1) was enhanced in the endurance athletes (125 +/- 16, P < 0.01) but was similar in weight lifters (59 +/- 12) and sedentary (63 +/- 7) men. The rate of glucose uptake per unit mass of myocardium (micromol. kg- 1. min- 1) was similarly decreased in endurance athletes (544 +/- 50) and weight lifters (651 +/- 45) compared with sedentary men (1,041 +/- 78, P < 0.001 vs. endurance athletes and weight lifters). Both groups of athletes had increased left ventricular mass. Consequently, total left ventricular glucose uptake was comparable in all groups. These data demonstrate that aerobic but not resistance training is associated with enhanced insulin sensitivity in skeletal muscle. Despite this, cardiac changes are remarkably similar in weight lifters and endurance athletes and are characterized by an increase in left ventricular mass and diminished insulin-stimulated glucose uptake per heart mass.

Adult↗

PubMed1999

Myocardial blood flow, oxygen consumption, and fatty acid uptake in endurance athletes during insulin stimulation.

We have previously demonstrated reduced myocardial glucose uptake rates in hearts of endurance athletes, which could be due to increased use of alternative fuels or reduced energy demands. In the present study myocardial blood flow, oxygen consumption, and free fatty acid uptake were measured with [(15)O]H(2)O, [(15)O]O(2), [(18)F]FTHA, and positron emission tomography (PET) in 9 endurance athletes and 11 sedentary men during euglycemic hyperinsulinemia. Compared with sedentary men, athletes had 33% lower myocardial blood flow, 27% lower oxygen consumption, and 20% lower estimated myocardial work per gram of tissue. Myocardial fatty acid uptake rates were not significantly different in endurance athletes (0.83 +/- 0.29) and sedentary men (1.0 +/- 0.31 micromol. 100 g(-1). min(-1), P = 0.232). In conclusion, myocardial blood flow and oxygen consumption per unit mass of myocardium are reduced at rest in endurance athletes. This can be explained by reduced energy requirements per gram of tissue due to anatomic and physiological changes of the athlete's heart.

Adult↗

PubMed1999

Impaired free fatty acid uptake in skeletal muscle but not in myocardium in patients with impaired glucose tolerance: studies with PET and 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid.

Free fatty acids (FFAs) are an important substrate for myocardial and skeletal muscle metabolism, and increased availability and oxidation of FFA are suggested to be associated with insulin resistance. This study was undertaken to assess whether myocardial or muscle uptake of FFA is altered in patients with impaired glucose tolerance (IGT). Eight healthy men (control group; age 48+/-1 years, BMI 25+/-1 kg/m2, mean +/- SE) and eight men with IGT (glucose-intolerant group; age 49+/-1 years, BMI 29+/-1 kg/m2) were studied in the fasting state. Myocardial oxygen consumption and blood flow and myocardial and femoral muscle FFA uptake rates were measured with positron emission tomography (PET) and [15O]O2, [15O]H2O, [15O]CO, and 14(R, S)-[18F]fluoro-6-thia-heptadecanoic acid ([18F]FTHA), a fatty acid tracer trapped into the cell after undergoing initial steps of beta-oxidation. Serum glucose and insulin concentrations were higher in the glucose-intolerant group during the PET study, but FFA concentrations were comparable between the groups. No differences between the groups were observed in the myocardial blood flow, oxygen consumption, fractional FTHA uptake rates, or FFA uptake indices (5.6+/-0.4 vs. 5.2+/-0.4 pmol x 100 g(-1) x min(-1), glucose-intolerant versus control, NS). In the femoral muscle, fractional FTHA uptake (0.0062+/-0.0003 vs. 0.0072+/-0.0003 min(-1), P = 0.044) and FFA uptake indices (0.30+/-0.02 vs. 0.43+/-0.04 min(-1), P = 0.020) were significantly lower in the glucose-intolerant group than in the control group. In conclusion, when studied at the fasting state and normal serum FFA concentrations, subjects with IGT have similar myocardial but lowered femoral muscle FFA uptake. This finding argues against the hypothesis that an increased oxidation of serum FFA, via the competition of glucose and FFA as fuel sources, is the primary cause for impaired peripheral glucose utilization and insulin resistance commonly observed in IGT.

Coronary Circulation↗

PubMed1999

PET as a cardiovascular and metabolic research tool.

Positron emission tomography (PET) represents the most advanced scintigraphic imaging technology. It can be employed for cardiovascular research as well as for clinical applications in patients with various cardiovascular diseases. PET allows the noninvasive functional assessment of myocardial perfusion, substrate metabolism and cardiac innervation as well as the study of skeletal muscle metabolism and perfusion in vivo. The large number of existing tracers and the flexibility of the PET technique that allows it to be combined with many other methods, such as the insulin clamp technique, increase its potential as a research tool. In the detection of myocardial viability PET is regarded as the golden standard, and it is the only method available for the quantitative assessment of myocardial blood flow.

Blood Flow Velocity↗

PubMed1999

Iterative reconstruction based on median root prior in quantification of myocardial blood flow and oxygen metabolism.

UNLABELLED: The aim of this study was to compare reproducibility and accuracy of two reconstruction methods in quantification of myocardial blood flow and oxygen metabolism with 15O-labeled tracers and PET. A new iterative Bayesian reconstruction method based on median root prior (MRP) was compared with filtered backprojection (FBP) reconstruction method, which is traditionally used for image reconstruction in PET studies. METHODS: Regional myocardial blood flow (rMBF), oxygen extraction fraction (rOEF) and myocardial metabolic rate of oxygen consumption (rMMRO2) were quantified from images reconstructed in 27 subjects using both MRP and FBP methods. For each subject, regions of interest (ROIs) were drawn on the lateral, anterior and septal regions on four planes. To test reproducibility, the ROI drawing procedure was repeated. By using two sets of ROIs, variability was evaluated from images reconstructed with the MRP and the FBP methods. RESULTS: Correlation coefficients of mean values of rMBF, rOEF and rMMRO2 were significantly higher in the images reconstructed with the MRP reconstruction method compared with the images reconstructed with the FBP method (rMBF: MRP r = 0.896 versus FBP r = 0.737, P < 0.001; rOEF: 0.915 versus 0.855, P < 0.001; rMMRO2: 0.954 versus 0.885, P < 0.001). Coefficient of variation for each parameter was significantly lower in MRP images than in FBP images (rMBF: MRP 23.5% +/- 11.3% versus FBP 30.1% +/- 14.7%, P < 0.001; rOEF: 21.0% +/- 11.1% versus 32.1% +/- 19.8%, P < 0.001; rMMRO2: 23.1% +/- 13.2% versus 30.3% +/- 19.1%, P < 0.001). CONCLUSION: The MRP reconstruction method provides higher reproducibility and lower variability in the quantitative myocardial parameters when compared with the FBP method. This study shows that the new MRP reconstruction method improves accuracy and stability of clinical quantification of myocardial blood flow and oxygen metabolism with 15O and PET.

Adult↗

PubMed1998

Preserved relative dispersion but blunted stimulation of mean flow, absolute dispersion, and blood volume by insulin in skeletal muscle of patients with essential hypertension.

BACKGROUND: We examined the integrity of the effects of insulin on mean muscle blood flow, flow heterogeneity, and blood volume in essential hypertension. METHODS AND RESULTS: Positron emission tomography, combined with [15O]H2O and [15O]CO as tracers for direct measurement of blood flow and volume in skeletal muscle, and a new bayesian iterative reconstruction algorithm allowing pixel-by-pixel quantitation of blood flow and flow dispersion, were used. Measurements were performed basally after an overnight fast and under normoglycemic hyperinsulinemic conditions in 11 newly diagnosed, untreated mildly hypertensive men (age, 35 +/- 1 years; body mass index, 25.2 +/- 0.4 kg/m2, blood pressure 141 +/- 4/96 +/- 2 mm Hg, mean +/- SE) and 11 matched normotensive men. Insulin-stimulated whole body glucose uptake was significantly decreased in the hypertensive men (41 +/- 4 mumol/kg per minute) compared with the normotensive (59 +/- 4 mumol/kg per minute, P < 0.005) men. Mean blood flow in skeletal muscle was significantly lower in the hypertensive than the normal subjects basally (1.7 +/- 0.2 versus 2.7 +/- 0.4 mL/0.1 kg per minute, P < 0.05) and during hyperinsulinemia (2.3 +/- 0.2 versus 4.2 +/- 0.8, P < 0.05). The flow response to insulin (0.6 +/- 0.2 versus 1.9 +/- 0.5 mL/0.1 kg per minute, hypertensive versus normal subjects, P < 0.05) was also significantly blunted. Muscle blood volume was significantly lower in the hypertensive than in the normal subjects, both basally (3.0 +/- 0.2 versus 3.5 +/- 0.2 mL/0.1 kg, P < 0.05) and during hyperinsulinemia (3.1 +/- 0.2 versus 4.0 +/- 0.2 mL/0.1 kg muscle, P < 0.02). The increase in muscle blood volume by insulin was significant in the normal (P < 0.05) but not the hypertensive subjects. Regional pixel-by-pixel analysis within femoral muscles revealed significant spatial heterogeneity of blood flow. Insulin increased absolute dispersion of blood flow significantly more in the normal subjects than in the hypertensive subjects (P < 0.05). CONCLUSIONS: True flow heterogeneity, as judged from the coefficients of variation (relative dispersion), was comparable between the groups basally and during hyperinsulinemia. We conclude that mean flow, its absolute dispersion, and blood volume exhibit insulin resistance in patients with essential hypertension.

Adult↗