Metabolic studies on the human heart in vivo

100

The effects of hyperglycemia on myocardial glucose metabolism were investigated in seven healthy male subjects (age 24±4 yr). I6-C4qGlucose and IU-'3Cilactate 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 jumol/ml, respectively. Glucose extraction increased significantly from control (0.15±0.13 gsmol/ ml) during each level of the glucose clamp (0.28±0.12, P < 0.02, and 0.54±0.14 ;tmol/ml, P < 0.005, respectively). Myocardial production of '4CO2 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.[I3C]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 < 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. (J. Clin. Invest. 1990Invest. . 85:1648Invest. -1656.) myocardial metabolism * glucose oxidation * lactate release * glycogen * free fatty acids

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Effects of acute hyperglycemia on myocardial glycolytic activity in humans.

Wisneski¹,

Stanley²,

Neese³

et al. 1990

100

“…The heart preferentially uses substrates that yield energy by mitochondrial metabolism such as free fatty acids (FFA) and lactate, while glycolysis normally produces only -30% of energy for the heart (3)(4)(5)(6)(7). However, the contribution of different fuels vary depending on the substrate availability, myocardial blood flow, oxygen supply, and energy needs of the heart.…”

Section: Introductionmentioning

confidence: 99%

Different alterations in the insulin-stimulated glucose uptake in the athlete's heart and skeletal muscle.

Nuutila¹,

Knuuti²,

Heinonen³

et al. 1994

Physical training increases skeletal muscle insulin sensitivity. Since training also causes functional and structural changes in the myocardium, we compared glucose uptake rates in the heart and skeletal muscles of trained and untrained individuals. Seven male endurance athletes (VO2max 72±2 ml/kg/min) and seven sedentary subjects matched for characteristics other than VO2max (43±2 ml/kg/min) were studied. Whole body glucose uptake was determined with a 2-h euglycemic hyperinsulinemic clamp, and regional glucose uptake in femoral and arm muscles, and myocardium using "F-fluoro-2-deoxy-D-glucose and positron emission tomography. Glucose uptake in the athletes was increased by 68% in whole body (P < 0.0001), by 99% in the femoral muscles (P < 0.01), and by 62% in arm muscles (P = 0.06), but it was decreased by 33% in the heart muscle (P < 0.05) as compared with the sedentary subjects. The total glucose uptake rate in the heart was similar in the athletes and control subjects. Left ventricular mass in the athletes was 79% greater (P < 0.001) and the meridional wall stress smaller (P < 0.001 ) as estimated by echocardiography. VO2max correlated directly with left ventricular mass (r = 0.87, P < 0.001) and inversely with left ventricular wall stress (r = -0.86, P < 0.001). Myocardial glucose uptake correlated directly with the rate-pressure product (r = 0.75, P < 0.02) and inversely with left ventricular mass (r = -0.60, P < 0.05) or with the whole body glucose disposal (r = -0.68, P < 0.01). Thus, in athletes, (a) insulin-stimulated glucose uptake is enhanced in the whole body and skeletal muscles, (b) whereas myocardial glucose uptake per muscle mass is reduced possibly due to decreased wall stress and energy requirements or the use of alternative fuels, or both. (J. Clin. Invest. 1994Invest. . 2267Invest. -2274

“…Animal and human studies have shown that the myocardial extractions of the various substrates used for energy are correlated with the circulating levels of these substrates (5)(6)(7)(8). During moderate intensity exercise, elevations of circulating lactate have been well documented (9)(10)(11)(12)(13).…”

Section: Introductionmentioning

confidence: 99%

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

Gertz¹,

Wisneski²,

Stanley³

et al. 1988

320

289

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 "CO2. Supine cycle ergometer exercise was performed at 40% of the subject's maximal 02 uptake.With exercise there was a significant increase in the arterial lactate level (P < 0.05). A highly significant positive correlation was observed between the lactate level and the isotopic lactate extraction (r = 0.93; P < 0.001). The myocardial isotopic lactate uptake increased from 34.9±6.5 gmol/min at rest to 120.4±36.5 Mmol/min at 5 min of exercise (P < 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 < 0.04). The [l4Cjglucose 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 < 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.