Biomedical subjects

R A Neese

Publications and source records attributed to R A Neese.

At least 55 records · Page 3Linked to original sources

PubMed1993

Measurement of endogenous synthesis of plasma cholesterol in rats and humans using MIDA.

We used the mass isotopomer distribution analysis (MIDA) technique to measure endogenous synthesis of plasma cholesterol in vivo in rats and normal human subjects. Sodium [1-13C]- or [2-13C]acetate was infused, and plasma free cholesterol was analyzed by gas chromatography-mass spectrometry. Frequencies of mass isotopomers M0-M4 (mass-to-charge ratio 368-372) were quantified. The enrichment of the true precursor for cholesterol synthesis (acetyl-coenzyme A in contributing tissues) was determined using the MIDA method. This technique remains mathematically valid even if more than one tissue contributes to circulating free cholesterol. The fractional contribution (f) from endogenous synthesis to free cholesterol in normal women (n = 5) was 2.48 +/- 0.39% after 7 h in the postabsorptive state and 1.27 +/- 0.41% after 8 h of refeeding. In ad libitum-fed rats (n = 12), f was 2.89 +/- 0.44% after 12 h, whereas administration of recombinant tumor necrosis factor increased this value fourfold. Next, the rate constant (k) for removal of labeled free cholesterol from plasma was calculated. Higher masses (M2-M4) were followed to avoid the problem of persistent label incorporation. During the 60 h after cessation of [13C]acetate infusions, k was 0.02490 +/- 0.00298/h in humans. Using these values of k and f, absolute cholesterogenesis was 568 +/- 55 mg/day in normal women (follicular menstrual phase), similar to prior estimates based on whole body sterol balances. Women also exhibited a diurnal variation for endogenous cholesterol synthesis (34.6 +/- 5.4 mg/h nighttime vs. 15.9 +/- 5.2 mg/h daytime) consistent with current knowledge about rhythms in cholesterogenesis. Checks on the model were internally consistent (e.g., comparisons among different isotopomers for calculating precursor enrichment). We conclude that fractional and absolute endogenous cholesterol synthesis can be measured using stable isotopes in vivo by the MIDA technique.

Adult↗

PubMed1993

Model for measuring absolute rates of hepatic de novo lipogenesis and reesterification of free fatty acids.

We have previously presented a precursor-product stable isotopic technique for measuring in vivo the fraction of very low-density lipoprotein-fatty acids (VLDL-FA) derived from de novo lipogenesis (fractional DNL). Here, we propose a technique for converting fractional DNL into absolute rates of DNL and describe its explicit underlying assumptions. The technique combines the fractional DNL method with a modification of the method of S. Klein, V. R. Young, G. L. A. Blackburn, B. R. Bistrain, and R. R. Wolfe (J. Clin. Invest. 78: 928-933, 1986), for estimating hepatic reesterification of free fatty acids (FFA). Infusions of [1,2,3,4-13C]palmitate and [1-13C]acetate are performed concurrently with indirect calorimetry in human subjects. Fractional DNL (based on mass isotopomer distribution analysis of VLDL-FA), the rate of appearance of plasma FFA (Ra of FFA), and net fat oxidation in the whole body are measured. Equations from the hepatic reesterification model, modified to include the contribution from DNL, allow calculation of absolute DNL (= fractional DNL x [Ra of FFA - net whole body fat oxidation], when respiratory quotient < 1.0). Sample results from human subjects with different dietary energy intakes are presented, with calculations of absolute DNL, absolute reesterification, and absolute fat oxidation rates. The assumptions of this technique (in particular, that all fat oxidized is derived at steady state from circulating FFA and that DNL and reesterification of FFA both occur exclusively in liver) are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetates↗

PubMed1993

Anabolic effects of recombinant human growth hormone in patients with wasting associated with human immunodeficiency virus infection.

Body wasting, characterized by disproportionate loss of body cell mass, is a feature of many chronic diseases, including infection with the human immunodeficiency virus (HIV). Therapies that merely increase energy intake do not consistently restore body cell mass in patients with the wasting syndrome. Because treatment with GH has induced nitrogen (N) retention in catabolic patients after surgery, burns, cancer, and hypocaloric feeding, we designed this study to determine whether GH could also produce an anabolic response in persons with HIV-associated weight loss. Six HIV-positive (HIV+) men with an average weight loss of 19% and six healthy weight-stable controls (HIV-) were hospitalized on a metabolic ward, where they consumed a constant metabolic diet during successive 5-day precontrol, 7-day baseline, and 7-day treatment [recombinant human GH (rhGH), 0.1 mg/kg.day] periods. The effects of rhGH on body weight, N and electrolyte excretion, energy expenditure, substrate oxidation, and integrated lipid and carbohydrate metabolism were assessed. Body weight increased promptly and progressively during treatment (2.0 +/- 0.3 and 1.6 +/- 0.2 kg in HIV+ and HIV-, respectively). Urinary N excretion decreased by 288 +/- 17 and 287 +/- 42 mmol/day in HIV+ and HIV-, respectively. Resting energy expenditure increased by 7.5% in both groups. Protein oxidation decreased, whereas lipid oxidation increased significantly. Glucose flux increased, and modest increases in fasting plasma triglyceride, glucose, and insulin levels were observed. Thus, short term rhGH treatment increased both protein anabolism and protein-sparing lipid oxidation, effects that should increase body cell mass if sustained during chronic therapy.

Adult↗

PubMed1992

Mass isotopomer distribution analysis: a technique for measuring biosynthesis and turnover of polymers.

Mass isotopomer distribution analysis (MIDA) is a technique for measuring biosynthesis and turnover of polymers in vivo. A stable isotopically enriched precursor is administered, and the relative abundances of different mass isotopomers in the polymer of interest are measured by mass spectrometry (MS). By comparison of statistical distributions predicted from the binomial or multinomial expansion to the pattern of excess isotopomer frequencies observed in the polymer, the enrichment of the biosynthetic precursor subunits (p) for newly synthesized polymers is calculated. MIDA thereby provides a solution to the problem of determining the isotope content in the actual precursor molecules that entered a particular polymeric product (the "true" precursor). The fraction of polymer molecules in a mixture that were newly synthesized during an isotopic experiment (fractional synthesis) can then be calculated. We describe some mathematical characteristics of MIDA and point out certain advantageous features. For example, mathematical estimates of p remain valid even if there does not exist a single anatomic or functional precursor pool. The interpretation of decay curves of endogenously labeled polymers may be improved by the use of higher mass isotopomers, which better fulfill the assumption of flash labeling. By combining fractional synthesis values with rate constants of decay, absolute endogenous synthesis rates can be calculated. Thus, by using probability logic combined with MS analysis, MIDA allows dynamic measurements to be made through analyses on a polymer alone during both isotopic incorporation and decay phases. The method has been applied to fatty acids, cholesterol, and glucose and is potentially applicable to nucleic acids, porphyrins, perhaps proteins, and many other classes of polymers.

Indicator Dilution Techniques↗

PubMed1992

Effects of high arterial oxygen tension on function, blood flow distribution, and metabolism in ischemic myocardium.

BACKGROUND: Although oxygen inhalation therapy has long been used in the treatment of acute myocardial ischemia, experimental evidence that increased arterial PO2 has any beneficial effect in the absence of hypoxemia is equivocal. In this study, we used a swine model of subendocardial myocardial ischemia to determine the effects of arterial hyperoxia on regional myocardial contractile function (sonomicrometry), myocardial blood flow distribution (microspheres), and regional myocardial glycolytic metabolism (carbon isotope-labeled substrates). METHODS AND RESULTS: In 10 domestic swine, the left anterior descending coronary artery was cannulated and flow to this artery was strictly controlled via a roller pump in the perfusion circuit. Arterial PO2 was controlled by manipulating inspired oxygen concentration (FIO2). Low-flow myocardial ischemia was induced by reducing pump flow to 50% of the control value, which diminished regional endocardial systolic shortening to 30-50% of normal. After a 15-minute period of flow stability, each animal was exposed in randomized order to two additional 15-minute experimental periods: coronary normoxia (PO2 = 90-110 mm Hg) and coronary hyperoxia (PO2 greater than 400 mm Hg). At each level of oxygenation, we measured regional myocardial function, regional myocardial blood flow and metabolism, and hemodynamic indexes of myocardial oxygen demand. Myocardial ischemia during normoxia reduced systolic shortening to 10.9 +/- 5.3% in the ischemic zone. Hyperoxia increased ischemic zone systolic shortening substantially to 15.2 +/- 4.6%. During myocardial ischemia, endocardial blood flow was decreased to 0.26 +/- 0.06 ml.g-1.min-1 in the ischemic zone. During hyperoxia, endocardial blood flow rose to 0.34 +/- 0.10 ml.g-1.m-1. The endocardial: epicardial flow ratio was 0.45 +/- 0.18 in the initial ischemia period and rose to 0.61 +/- 0.23 in the hyperoxic period. Myocardial ischemia increased regional uptake of glucose, conversion of glucose to released lactate, and net myocardial lactate release. In the ischemic myocardium, coronary hyperoxia decreased both chemically measured lactate production and isotopically measured lactate release and decreased glucose extraction and the conversion of glucose to lactate. CONCLUSIONS: These data demonstrate for the first time that increasing arterial PO2 to high levels during acute low-flow myocardial ischemia improves both function and flow distribution in the ischemic myocardium and decreases glycolytic metabolism in the ischemic zone. The degree of improvement in contractile function (5% absolute increase in systolic shortening or 25% change normalized to preischemic values) is consistent with the observed increase in subendocardial blood flow.

Animals↗

PubMed1990

Myocardial metabolism during hypoxia: maintained lactate oxidation during increased glycolysis.

In the intact animal, myocardial lactate utilization and oxidation during hypoxia are not well understood. Nine dogs were chronically instrumented with flow probes on the left anterior descending coronary artery and with a coronary sinus sampling catheter. [14C]lactate and [13C]glucose tracers, or [13C]lactate and [14C]glucose were administered to quantitate lactate and glucose oxidation, lactate conversion to glucose, and simultaneous lactate extraction and release. The animals were anesthetized and exposed to 90 minutes of severe hypoxia (PO2 = 25 +/- 4 torr). Hypoxia resulted in significant increases in heart rate, cardiac output and myocardial blood flow, but no significant change in myocardial oxygen consumption. The arterial/coronary sinus differences for glucose and lactate did not change from normoxia to hypoxia; however, the rate of glucose uptake increased significantly due to the increase in myocardial blood flow. Tracer-measured lactate extraction did not decrease with hypoxia, despite a 250% increase in lactate release. During hypoxia, 90% +/- 4% of the extracted 14C-lactate was accounted for by the appearance of 14CO2 in the coronary sinus, compared with 88% +/- 4% during normoxia. Thus, in addition to the expected increase in glucose uptake and lactate production, we observed an increase in lactate oxidation during hypoxia.

Acetates↗

PubMed1990

Tracer mixing: sites of tracer infusion and sampling.

Controversy exists in the literature concerning the correct infusion and sampling sites in studies measuring substrate turnover rates. To investigate this problem, we examined the results obtained with various infusion and sampling sites in 7 anesthetized dogs. [1-14C]lactate was infused by a primed continuous infusion method in three different sites (the left ventricle, ascending aorta, and the aortic arch) in a sequential fashion; samples were obtained simultaneously from five sites (femoral artery, carotid artery, pulmonary artery, superior vena cava and inferior vena cava) for each of the three different infusion sites. [U-13C]lactate was also infused in a femoral vein and simultaneous samples were obtained in the carotid artery and femoral artery for analysis of the stable isotope. [14C]lactate analysis demonstrated that infusion of the tracer into the left ventricular chamber resulted in a uniform distribution in the systemic circulation. Infusion into the ascending aorta near the aortic valve resulted in uniform distribution of tracer in four out of five experiments. Tracer infusion into the aortic arch resulted in nonuniform systemic distribution of tracer. The [U-13C]lactate results showed that infusion into the femoral vein gives uniform systemic distribution, similar to that observed with left ventricular infusion. The pulmonary artery lactate specific activities varied from those in the superior vena cava. Thus, this study shows that the tracer must be infused in the left ventricle or upstream from this chamber to obtain optimal systemic distribution. Vena caval sampling, especially superior vena caval sampling, will not give a consistent mixed venous concentration of the lactate tracer. Therefore, aortic tracer infusion with vena caval sampling may lead to errors in determining substrate turnover values.

Animals↗

PubMed1990

Increased lactate appearance and reduced clearance during hypoxia in dogs.

In order to assess the effects of severe hypoxia on whole body glucose and lactate kinetics, nine experiments were performed on anesthetized, ventilated mongrel dogs. [U-13C]glucose and [1-14C]lactate (n = 5), or [6-14C]glucose and [U-13C]lactate (n = 4) were infused using the primed-continuous infusion method. Cardiac output was measured by thermodilution. After a control period with 21% O2, inspired O2 was reduced for 90 minutes. Three of the experiments resulted in unstable hemodynamics and lactate levels, and are excluded from the mean data. Arterial PO2 fell from a control level of 106.8 +/- 11.9 to 24.2 +/- 3.5 mmHg during the last 45 minutes of hypoxia, and O2 transport fell to 52% of normoxic values. Arterial lactate concentration and the rate of appearance increased by 428% and 182%, respectively, from control to hypoxia. The metabolic clearance rate for lactate fell by 34%. Arterial glucose levels did not change significantly with hypoxia, but the rate of glucose disappearance rose by 70%, and the rate of glucose conversion to lactate increased 3-fold. It is concluded that acute severe hypoxia in anesthetized dogs causes 1) a large increase in arterial lactate levels, but no significant change in glycemia, 2) a large increase in the rate of lactate disappearance and only a small increase in the rate of glucose disappearance and 3) a fall in the metabolic clearance rate of lactate.

Animals↗

PubMed1990

Myocardial lactate release during ischemia in swine. Relation to regional blood flow.

To determine the relation between regional myocardial blood flow, contractile function, and myocardial lactate release during mild-to-moderate regional myocardial ischemia, nine open-chest swine were instrumented for measurement of regional myocardial blood flow (microsphere method), contractile function (sonomicrometry), and hemodynamics. L-[1-14C]Lactate or L-[U-13C]lactate was infused intravenously using a primed continuous infusion technique to quantify regional myocardial lactate release. D-[U-13C]glucose or D-[6-14C]glucose was simultaneously infused to determine the contribution of exogenous glucose to lactate release. Graded coronary ischemia (two to three levels) was created in the left anterior descending coronary arterial distribution by mechanically constricting the artery in five animals or by decreasing flow through a cannulated left anterior descending artery in four animals. In all nine animals, subendocardial blood flow was 0.99 +/- 0.21 (ml/min)/g during control and 0.34 +/- 0.14 (ml/min)/g during the most severe grade of underperfusion (p less than 0.001) in the left anterior descending coronary arterial distribution. Regional myocardial lactate release was 0.15 +/- 0.09 and 1.19 +/- 0.75 mumols/ml, respectively (p less than 0.003). A highly significant inverse correlation was observed between subendocardial blood flow and myocardial lactate release during the graded reductions in blood flow (r = -0.71, p less than 0.001). Results from sonomicrometry showed a significant reduction in contractile ventricular function in the anterior wall during the graded reductions in blood flow. The regional arterial-venous glucose difference increased significantly with underperfusion in the left anterior descending coronary arterial distribution, from 0.14 +/- 0.15 to 0.56 +/- 0.37 mumols/ml (p less than 0.003). The contribution of exogenous glucose to lactate release also increased significantly; 0.04 +/- 0.03 mumols/ml of the lactate came from exogenous glucose during control compared with 0.64 +/- 0.59 mumols/ml during the most severe underperfusion (p less than 0.02). A significant positive correlation exists between lactate release and lactate from exogenous glucose during graded underperfusion (r = 0.96, p less than 0.001). In summary, these data demonstrate a close inverse relation between regional myocardial lactate release and regional subendocardial blood flow during graded ischemia.

Animals↗

PubMed1990

Effects of acute hyperglycemia on myocardial glycolytic activity in humans.

The effects of hyperglycemia on myocardial glucose metabolism were investigated in seven healthy male subjects (age 24 +/- 4 yr). [6-14C]Glucose and [U-13C]lactate were infused as tracers. Circulating glucose was elevated to two hyperglycemic levels using a clamp technique for 1 h at each level. The mean arterial glucose concentration was 4.95 +/- 0.29 (control), 8.33 +/- 0.31 and 10.84 +/- 0.60 mumols/ml, respectively. Glucose extraction increased significantly from control (0.15 +/- 0.13 mumols/ml) during each level of the glucose clamp (0.28 +/- 0.12, P less than 0.02, and 0.54 +/- 0.14 mumols/ml, P less than 0.005, respectively). Myocardial production of 14CO2 showed that during control 9 +/- 10% of exogenous glucose was oxidized immediately upon extraction. Despite a significant increase in the amount of exogenous glucose oxidized with level II hyperglycemia, it represented only 32 +/- 10% of the glucose extracted. [13C]Lactate analysis showed that the myocardium was releasing lactate; during control 40 +/- 30% of this lactate was derived from exogenous glucose and during hyperglycemia this value increased to 97 +/- 37% (P less than 0.005). Thus, these data show that during short-term hyperglycemia, myocardial glucose extraction is enhanced. However, despite increases in exogenous glucose oxidation and the contribution of exogenous glucose to lactate release, the majority of the extracted glucose (i.e., 57%) is probably stored as glycogen.

Acetates↗

PubMed1989

Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium.

Ischemically injured reperfused myocardium is characterized by increased 18F-fluorodeoxyglucose uptake as demonstrated by positron emission tomography. To elucidate the metabolic fate of exogenous glucose entering reperfused myocardium, D-[6-14C] glucose and L-[U-13C] lactate were used to determine glucose uptake, glucose oxidation and the contribution of exogenous glucose to lactate production. The pathologic model under investigation consisted of a 3 h balloon occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion in canine myocardium. The extent and severity of myocardial injury after the ischemia and reperfusion were assessed by histochemical evaluation (triphenyltetrazolium chloride and periodic acid-Schiff stains). Thirteen intervention and four control dogs were studied. The glucose uptake in the occluded/reperfused area was significantly enhanced compared with that in control dogs (0.40 +/- 0.14 versus 0.15 +/- 0.10 mumol/ml, respectively). In addition, a significantly greater portion of the glucose extracted immediately entered glycolysis in the intervention group (75%) than in the control dogs (33%). The activity of the nonoxidative glycolytic pathway was markedly increased in the ischemically injured reperfused area, as evidenced by the four times greater lactate release in this area compared with the control value. The dual carbon-labeled isotopes showed that 57% of the exogenous glucose entering glycolysis was being converted to lactate. Exogenous glucose contributed to greater than 90% of the observed lactate production. This finding was confirmed by the histochemical finding of sustained glycogen depletion in the occlusion/reperfusion area. The average area of glycogen depletion (37%) significantly exceeded the average area of necrosis (17%). These data demonstrate enhanced and sustained activity of the nonoxidative glycolytic pathway after a prolonged occlusion with reperfusion in canine myocardium. Because glycogen stores remain depleted, exogenous glucose becomes an important myocardial substrate under these pathologic conditions.

Animals↗

PubMed1988

Glucose and lactate interrelations during moderate-intensity exercise in humans.

To evaluate circulating lactate and glucose kinetics during moderate-intensity exercise, we studied ten healthy endurance-trained men (aged 25 +/- 6 years) during 30 to 50 minutes of supine cycle ergometer exercise at 43% +/- 5% of maximal oxygen consumption (VO2 max) using isotopic tracer techniques. Seven subjects received [U-13C]-lactate and [6-14C]-glucose, and three received [1-14C]-lactate and [U-13C]-glucose. Arterial glucose and lactate concentrations were 94.0 +/- 4.1 and 5.66 +/- 0.87 mg/dL at rest, and 95.7 +/- 3.4 and 8.38 +/- 3.87 mg/dL, respectively, after 25 minutes of exercise. The rate of glucose disappearance (RdG) increased from 2.41 +/- 0.40 at rest to 3.38 +/- 0.77 mg x kg-1 x min-1 during exercise, compared with the much larger rise in the rate of lactate appearance (RaL), which increased from 1.25 +/- 0.20 to 3.47 +/- 0.79 mg x kg-1 x min-1. During exercise RaL was 103% of RdG, compared with only 52% at rest. The rate at which the blood was cleared of lactate increased from 22.7 +/- 2.2 at rest to 44.2 +/- 11.2 ml x kg-1 x min-1 after 25 minutes of exercise. From secondary labeling of lactate with glucose carbons, the rate of glucose conversion to lactate was estimated to be 0.65 +/- 0.16 mg x kg-1 x min-1 during exercise. Twenty percent of the glucose utilization went to lactate formation during exercise, and 20% of the blood lactate appearance came from blood glucose, with the balance presumably coming from muscle glycogen.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1988

Myocardial substrate utilization during exercise in humans. Dual carbon-labeled carbohydrate isotope experiments.

The purpose of this study was to investigate myocardial substrate utilization during moderate intensity exercise in humans. Coronary sinus and arterial catheters were inserted in nine healthy trained male subjects (mean age, 25 +/- 6 (SD) years). Dual carbon-labeled isotopes were infused, and substrate oxidation was quantitated by measuring myocardial production of 14CO2. Supine cycle ergometer exercise was performed at 40% of the subject's maximal O2 uptake. With exercise there was a significant increase in the arterial lactate level (P less than 0.05). A highly significant positive correlation was observed between the lactate level and the isotopic lactate extraction (r = 0.93; P less than 0.001). The myocardial isotopic lactate uptake increased from 34.9 +/- 6.5 mumol/min at rest to 120.4 +/- 36.5 mumol/min at 5 min of exercise (P less than 0.005). The 14CO2 data demonstrated that 100.4 +/- 3.5% of the lactate extracted as determined by isotopic analysis underwent oxidative decarboxylation. Myocardial glucose uptake also increased significantly with exercise (P less than 0.04). The [14C]glucose data showed that only 26.0 +/- 8.5% of the glucose extracted underwent immediate oxidation at rest, and during exercise the percentage being oxidized increased to 52.6 +/- 7.3% (P less than 0.01). This study demonstrates for the first time in humans an increase in myocardial oxidation of exogenous glucose and lactate during moderate intensity exercise.

Adult↗

PubMed1987

Myocardial metabolism of free fatty acids. Studies with 14C-labeled substrates in humans.

Free fatty acids are considered to be the major energy source for the myocardium. To investigate the metabolic fate of this substrate in humans, 24 subjects underwent coronary sinus and arterial catheterization. 13 subjects were healthy volunteers and 11 subjects had symptoms of ischemic heart disease. [1-14C]oleate or [1-14C]palmitate bound to albumin was infused at a constant rate of 25 microCi/h. Oxidation was determined by measuring the 14CO2 production. The data demonstrated that a high percentage (84 +/- 17%) of the palmitate and oleate extracted by the myocardium underwent rapid oxidation. A highly significant correlation was present between the arterial level and the amount oxidized (r = 0.82, P less than 0.001 for palmitate; r = 0.77, P less than 0.001 for oleate). The isotope extraction ratio was greater than the chemical extraction ratio. This difference of 6 +/- 2 nmol/ml of blood in the young normal subjects was significantly less than the 12 +/- 4 nmol/ml observed in the ischemic heart disease patients (P less than 0.001).

Adolescent↗

PubMed1986

Lactate extraction during net lactate release in legs of humans during exercise.

Lactate metabolism was studied in six normal males using a primed continuous infusion of lactate tracer during continuous graded supine cycle ergometer exercise. Subjects exercised at 49, 98, 147, and 196 W for 6 min at each work load. Blood was sampled from the brachial artery, the iliac vein, and the brachial vein. Arteriovenous differences were determined for chemical lactate concentration and L-[1-14C]-lactate. Tracer-measured lactate extraction was determined from the decrease in lactate radioactivity per volume of blood perfusing the tissue bed. Net lactate release was determined from the change in lactate concentration across the tissue bed. Total lactate release was taken as the sum of tracer-measured lactate extraction and net (chemical) release. At rest the arms and legs showed tracer-measured lactate extraction, as determined from the isotope extraction, despite net chemical release. Exercise elicited an increase in both net lactate release and tracer-measured lactate extraction by the legs. For the legs the total lactate release (net lactate release + tracer-measured lactate extraction) was roughly equal to twice the net lactate release under all conditions. The tracer-measured lactate extraction by the exercising legs was positively correlated to arterial lactate concentration (r = 0.81, P less than 0.001) at the lower two power outputs. The arms showed net lactate extraction during exercise, which was correlated to the arterial concentration (r = 0.86). The results demonstrate that exercising skeletal muscle extracts a significant amount of lactate during net lactate release and that the working skeletal muscle appears to be a major site of blood lactate removal during exercise.

Adult↗

PubMed1985

Absence of myocardial biochemical toxicity with a nonionic contrast agent (iopamidol).

To evaluate the myocardial metabolic effects of a new nonionic contrast agent, iopamidol, a randomized, double-blind study was performed comparing iopamidol with sodium meglumine diatrizoate (Renografin-76) in 23 patients with ischemic heart disease. Coronary sinus and arterial metabolic samples were obtained prior to and during the 20-minute period following the contrast left ventriculogram. Ten patients received iopamidol and 13 received Renografin-76. The chemical lactate extraction in the iopamidol group was 13 +/- 9% prior to left ventriculography and 17 +/- 12% following the contrast injection (p less than 0.005). In the Renografin-76 group, the lactate extraction was 23 +/- 13% and decreased significantly to 12 +/- 24% following the ventriculogram (p less than 0.01). In a subset of these patients (n = 10), [1-(14)C] lactate was infused as a tracer to quantitate the amount of lactate released by the myocardium. [1-(14)C] lactate analysis demonstrated that the fall in lactate extraction ratio following Renografin-76 was due to an increase in myocardial lactate release. In the Renografin-76 group there was a 53 +/- 37% increase in lactate release at 10 minutes after contrast agent injection (p less than 0.005), while in the iopamidol patients there was no significant change in lactate release following contrast ventriculography. The increase in lactate release in the Renografin-76 group suggests that myocardial ischemia is induced with this ionic contrast agent. In comparison, the nonionic contrast agent is less toxic to the myocardium and is not associated with the biochemical changes of cellular ischemia.

Aged↗

PubMed1985

Dual carbon-labeled isotope experiments using D-[6-14C] glucose and L-[1,2,3-13C3] lactate: a new approach for investigating human myocardial metabolism during ischemia.

Simultaneous lactate production and extraction have been previously demonstrated in the myocardium in patients with coronary artery disease. To quantitate this lactate production and determine its source, dual carbon-labeled isotope experiments were performed. L-[1,2,3-13C3] lactate and D-[6-14C] glucose were infused in 10 patients with significant coronary artery disease. Metabolic samples were obtained at rest and during atrial pacing. Despite net chemical myocardial lactate extraction in the 10 patients at rest and no evidence of clinical ischemia, the L-[1,2,3-13C3] lactate analysis demonstrated that lactate was being released by the myocardium. During atrial pacing, seven patients did not develop clinical symptoms of ischemia, and the chemical lactate analysis showed net lactate extraction. However, tracer analysis demonstrated that there was a significant increase in the lactate released during atrial pacing (from 6.9 +/- 2.3 to 16.2 +/- 10.1 mumol/min) (p less than 0.05). In these seven patients, circulating glucose was the source of 23 +/- 15% of the lactate released at rest, and there was no significant change during pacing. The remaining three patients had mild chest pain and net chemical lactate production during pacing. Lactate release detected by the tracer increased from 5.7 +/- 3.0 mumol/min at rest to 50.9 +/- 16.8 mumol/min during pacing (p less than 0.01). In these patients, the contribution of glucose to lactate production increased significantly during pacing-induced clinical ischemia from 25 +/- 22 to 67 +/- 14% (p less than 0.005). Thus, dual carbon-labeled isotopic experiments are powerful tools for investigating myocardial metabolic pathways.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1985

Systemic lactate kinetics during graded exercise in man.

To investigate the relationships between oxygen consumption (VO2) and the rates of systemic lactate appearance (Ra) and disappearance (Rd), six healthy males were studied at rest and during continuous graded exercise using a primed continuous infusion of lactate tracer. Subjects exercised for 6 min at 300, 600, 900, and 1,200 kg . m . min-1. L-(+)-[1-14C]lactate was infused intravenously, and arterial samples were drawn at rest and every 2 min throughout the exercise period. Ra and Rd were calculated using nonsteady-state equations. At rest Ra and Rd were 14.4 +/- 1.8 and 15.1 +/- 2.2 mumol . kg-1 . min-1, respectively. Near steady-state values were observed toward the end of the first two work loads. Ra and Rd values were 32.8 +/- 2.3 and 37.4 +/- 1.3 mumol . kg-1 . min-1 during min 5 and 6 at 300 kg . m . min-1 and were 59.1 +/- 2.6 and 55.4 +/- 2.3 mumol . kg-1 . min-1 during min 5 and 6 at 600 kg . m . min-1. Ra was significantly greater than Rd at both 900 and 1,200 kg . m . min-1. Ra and Rd averaged 145.4 +/- 10.5 and 110.2 +/- 5.6 mumol . kg-1 . min-1, respectively, during the last 2 min at 900 kg . m . min-1, and 309.4 +/- 20.8 and 169.7 +/- 10.6 mumol . kg-1 . min-1, respectively, at 1,200 kg . m . min-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗