Substrate availability limits human skeletal muscle oxidative ATP regeneration at the onset of ischemic exercise.

We have demonstrated previously that dichloroacetate can attenuate skeletal muscle fatigue by up to 35% in a canine model of peripheral ischemia (Timmons, J.A., S.M. Poucher, D. Constantin-Teodosiu, V. Worrall, I.A. Macdonald, and P.L. Greenhaff. 1996. J. Clin. Invest. 97:879-883). This was thought to be a consequence of dichloroacetate increasing acetyl group availability early during contraction. In this study we characterized the metabolic effects of dichloroacetate in a human model of peripheral muscle ischemia. On two separate occasions (control-saline or dichloroacetate infusion), nine subjects performed 8 min of single-leg knee extension exercise at an intensity aimed at achieving volitional exhaustion in approximately 8 min. During exercise each subject's lower limbs were exposed to 50 mmHg of positive pressure, which reduces blood flow by approximately 20%. Dichloroacetate increased resting muscle pyruvate dehydrogenase complex activation status by threefold and elevated acetylcarnitine concentration by fivefold. After 3 min of exercise, phosphocreatine degradation and lactate accumulation were both reduced by approximately 50% after dichloroacetate pretreatment, when compared with control conditions. However, after 8 min of exercise no differences existed between treatments. Therefore, it would appear that dichloroacetate can delay the accumulation of metabolites which lead to the development of skeletal muscle fatigue during ischemia but does not alter the metabolic profile when a maximal effort is approached.

Maximal oxygen uptake is not limited by a central nervous system governor.

We tested the hypothesis that the work of the heart was not a limiting factor in the attainment of maximal oxygen uptake (VO2 max). We measured cardiac output (Q) and blood pressures (BP) during exercise at two different rates of maximal work to estimate the work of the heart through calculation of the rate-pressure product, as a part of the ongoing discussion regarding factors limiting VO2 max. Eight well-trained men (age 24.4 +/- 2.8 yr, weight 81.3 +/- 7.8 kg, and VO2 max 59.1 +/- 2.0 ml x min(-1) x kg(-1)) performed two maximal combined arm and leg exercises, differing 10% in watts, with average duration of time to exhaustion of 4 min 50 s and 3 min 40 s, respectively. There were no differences between work rates in measured VO2 max, maximal Q, and peak heart rate between work rates (0.02 l/min, 0.3 l/min, and 0.8 beats/min, respectively), but the systolic, diastolic, and calculated mean BP were significantly higher (19, 5, and 10 mmHg, respectively) in the higher than in the lower maximal work rate. The products of heart rate times systolic or mean BP and Q times systolic or mean BP were significantly higher (3,715, 1,780, 569, and 1,780, respectively) during the higher than the lower work rate. Differences in these four products indicate a higher mechanical work of the heart on higher than lower maximal work rate. Therefore, this study does not support the theory, which states that the work of the heart, and consequently VO2 max, during maximal exercise is hindered by a command from the central nervous system aiming at protecting the heart from being ischemic.

Theophylline decreases pain in the ischaemic forearm test.

To study the hypothesis that endogenous adenosine is a mediator of the ischaemic pain sensation, the effect of the adenosine receptor blocker theophylline (5.5 mg of the ethylendiamine salt.kg-1 intravenously) was tested in a placebo controlled double blind cross over study (placebo/theophylline/placebo or placebo/placebo/theophylline) in five healthy volunteers. Ischaemic work was performed with a spring loaded hand ergometer (1 Hz). The pain sensation was continuously reported using the Borg scale. Blood flow was measured by occlusion plethysmography. Pain was reported 18 (SEM 2.4) s after starting the ischaemic work and increased continuously to a maximum after 129(18) s (placebo). Theophylline at a plasma concentration of 75(7) mumol.litre-1 decreased the pain sensation in relation to working time. With theophylline, 12(3)% more work (p less than 0.01) was performed for the same reported pain estimate. Blood flow increased from a basal level of 52(9) to 495(55) ml.min-1.100 ml-1 30 s after work and returned to normal within 30-40 min. Theophylline did not affect blood flow. In conclusion, theophylline has a small but significant inhibitory effect on the ischaemic pain sensation compatible with a hyperalgesic effect of adenosine.

Myocardial enzyme activities in patients with mitral regurgitation or mitral stenosis.

To determine the adaption of myocardial metabolism in mitral regurgitation and mitral stenosis, human papillary muscles obtained during open heart surgery were analysed to measure selective enzyme activities in energy metabolism. All enzyme activities were expressed per unit dry weight muscle, per unit alkali soluble protein, and per unit total creatine and the different results compared. The activities of enzymes concerned with mitochondrial energy production and energy transfer (namely, citrate synthase and mitochondrial creatine kinase) tended to be higher in papillary muscles from hearts with mitral regurgitation than in those with mitral stenosis. The activities of enzymes concerned with cytoplasmic energy production (creatine kinase MM, lactate dehydrogenase, and phosphofructokinase) did not show statistically significant differences between mitral regurgitation and mitral stenosis. The ratio of creatine kinase MB activity to total creatine content showed the greatest difference when papillary muscles from patients with mitral regurgitation and mitral stenosis were compared (31% higher in mitral regurgitation; p less than 0.001). The specific function of creatine kinase MB, which is located in cytoplasm, is not well defined. Creatine kinase MB activity increases with extreme endurance training of human skeletal muscle. Thus the higher creatine kinase MB activity in papillary muscle of mitral regurgitation may represent an adaptation to increased physical demand.

Adenosine injection into the brachial artery produces ischaemia like pain or discomfort in the forearm.

To determine whether pain or discomfort could be provoked by adenosine in skeletal muscle and, if so, whether it was dependent on the vasodilatation produced by adenosine, eight male volunteers were given intra-arterial bolus injections of adenosine and glyceryl trinitrate into the forearm. Local pain was assessed on a scale rate, forearm blood flow was measured by venous occlusion plethysmography, and blood was sampled simultaneously from the deep vein of the same arm. Five different doses of adenosine, ranging between the maximum tolerable and the lowest producing pain or discomfort, were given intra-arterially in random order and repeated in reverse order. Glyceryl trinitrate was given intra-arterially in increasing doses from 1 to 20 micrograms. Pain or discomfort began 12(1)(SEM) s after administration reached its maximum after 17(1) s, and disappeared after 40(2) s. Pain or discomfort appeared 8(1) s (p less than 0.001) after the first recorded increase in forearm blood flow, whereas maximum pain or discomfort preceded maximal forearm blood flow by 5(1) s (p less than 0.001). The flow remained increased after the disappearance of pain or discomfort. The effects of adenosine on pain or discomfort and vasodilatation were dose dependent. Glyceryl trinitrate provoked a similar increase in flow to that with adenosine without producing pain or discomfort. Arterial occlusion for 5 min at rest or forearm exercise with arterial occlusion increased forearm blood flow to the same extent as the maximum dose of adenosine. In addition, ischaemic work slightly increased the plasma concentration of adenosine. The pain or discomfort after ischaemic work was not considered different from the adenosine provoked pain or discomfort by four of the subjects. It is concluded that the symptoms did not appear to be dependent on vasodilatation and therefore adenosine may contribute to ischaemic pain or discomfort.

Adenine nucleotide degradation in the human myocardium during cardioplegia.

The tissue content of adenine nucleotides and their metabolites, inosine monophosphate, adenosine, hypoxanthine, and uric acid, were determined in biopsy specimens from the left ventricle of six patients during cardioplegia for open heart surgery. Biopsy specimens were collected immediately after the induction and at the end of cardioplegia (51-82 min) and were analysed by high performance liquid chromatography. After the induction of cardioplegia (cold potassium enriched solution) the left coronary artery was continuously perfused with cold (10 degrees C), potassium enriched, diluted blood. The adenosine triphosphate concentration decreased from 13 to 8 mmol.kg-1 dry muscle (p less than 0.01) during cardioplegia. Adenosine diphosphate and adenosine monophosphate concentrations were 6 and 3 mmol.kg-1 dry muscle respectively and remained unaffected. The adenosine concentration (0.3 mmol.kg-1 dry muscle) was three times higher than that of inosine monophosphate. Inosine concentrations increased from 0.8 to 2.7 mmol.kg-1 dry muscle (p less than 0.01) in parallel with the increase in hypoxanthine from 0.1 to 0.4 mmol.kg-1 dry muscle (p less than 0.01). The total adenine nucleotide pool decreased by 5 mmol.kg-1 dry muscle (p less than 0.01), whereas the corresponding increase in nucleotides and bases only was 2 mmol.kg-1 dry muscle. In conclusion, the adenosine triphosphate content and the adenine nucleotide pool were appreciably reduced during continuous cold blood cardioplegia as used in the present study. The tissue content of adenosine and further metabolites was considerably increased.(ABSTRACT TRUNCATED AT 250 WORDS)

Lactate dehydrogenase and its isoenzyme activities in different parts of the normal human heart.

Activity and distribution of lactate dehydrogenase (LD) and its isoenzymes (LD1-5) were determined and both the heart (H) and muscle (M) subunit activities were calculated in myocardial samples from six brain dead human organ donors with normal hearts. Ten parts of each heart were analysed. LD1-3 were found to be the main LD isoenzymes. The LD1 activity predominated in all parts analysed. The activities of total LD, H subunit and LD1 increased from atria and auricular appendages via the right ventricle to the left ventricle. The H subunit activity varied more than twofold and the M subunit activity by only 20% between different locations of the heart. The left ventricular papillary muscle was found to have higher activities than other locations of both H and M subunits. It is concluded that the isoenzyme profile could be a metabolic adaptation to divergent work demand on the different heart chambers.

Peak skeletal muscle perfusion is maintained in patients with chronic heart failure when only a small muscle mass is exercised.

OBJECTIVES: The issue to be resolved was whether peripheral leg blood flow in patients with chronic heart failure (CHF) is reduced by low local flow capacity or as a function of the amount of muscle mass activated during exercise. METHODS AND RESULTS: In ten CHF patients (ejection fraction 26 (9)%), and 12 healthy controls central and peripheral circulatory responses were assessed during dynamic one- and two-legged knee extensor work. The patients reached a peak perfusion of 234 (16) ml 100 g-1 min-1 in the one-legged mode, which was similar to the controls (244 (11) ml 100 g-1 min-1). At peak two-legged work muscle perfusion was reduced in the patients by 24% (P < 0.05). In contrast the controls maintained their peak muscle perfusion. The mass of the quadriceps femoris muscle and peak leg blood flow correlated closely for both groups at peak one-legged work (r = 0.85, P < 0.001). Peak oxygen uptake in the active limb during one-legged exercise was similar for patients and controls (0.52 (0.06) vs. 0.63 (0.06) l min-1), but it was 38% lower (P < 0.05) in patients than controls during exhaustive two-legged exercise. Arterial systemic oxygen delivery (cardiac output x arterial oxygen content), at peak exercise was highly correlated with peak one- and two-legged workload for both groups, explaining 70% of the difference in peak workload attained (P < 0.001). At peak two-legged exercise non-exercising tissues of the body in the male CHF patients with the largest limb muscle mass, received a blood flow of only 1.2 (0.7) 1 min-1. Mean arterial blood pressure at peak work in both test conditions was significantly lower for the patients than the controls. A higher sympathetic nerve activity in the patients, as evaluated by arterial noradrenaline concentration (NA) and leg NA spillover, contributed to maintain the perfusion pressure. CONCLUSIONS: Patients with moderate CHF can reach a peak skeletal muscle perfusion and a leg oxygen uptake comparable to that of healthy individuals when a sufficiently small muscle mass is activated. Exercise involving a larger muscle mass, for the patients in this study about 4 kg, markedly reduces peak leg blood flow, perfusion and oxygen uptake as well as blood flow to non-exercising organs and tissues.

Adenosine induced chest pain--a comparison between intracoronary bolus injection and steady state infusion.

OBJECTIVE: Adenosine may induce chest pain in at least two ways, either by direct stimulation of sensory afferents before actual ischaemia occurs or secondary to ischaemia. The aim was to study if the mechanism of pain induction may depend on the method of adenosine administration. METHODS: Increasing doses of adenosine were given to seven male patients with ischaemic heart disease referred for coronary angiography: first as a bolus intracoronary injection (2.5-50 mumol), second as a 1 ml.min-1 steady state infusion (0.01-20 mumol.min-1) and third as an intravenous steady state infusion (0.076-0.76 mumol.kg-1 x min-1). Pain, rate-pressure product, coronary sinus blood flow, and ECG were monitored. Lactate was analysed in coronary sinus and arterial blood. RESULTS: After intracoronary bolus injection there were no signs of myocardial ischaemia, whereas during intracoronary steady state infusion, and in spite of a lower, but definite, degree of pain, 5/7 patients showed myocardial lactate production and three patients showed ST depression. During the intravenous steady state infusion 6/6 patients showed ST depression. CONCLUSIONS: These findings suggest that when using adenosine for studies on the mechanisms of chest pain in patients with ischaemic heart disease it is preferable to use an intracoronary bolus injection technique rather than a steady state infusion, as the risk of inducing ischaemia with the latter model cannot be ignored.

Creatine supplementation in chronic heart failure increases skeletal muscle creatine phosphate and muscle performance.

BACKGROUND: Cardiac creatine levels are depressed in chronic heart failure. Oral supplementation of creatine to healthy volunteers has been shown to increase physical performance. AIM: To evaluate the effects of creatine supplementation on ejection fraction, symptom-limited physical endurance and skeletal muscle strength in patients with chronic heart failure. METHODS: With a double-blind, placebo-controlled design 17 patients (age 43-70 years, ejection fraction < 40) were supplemented with creatine 20 g daily for 10 days. Before and on the last day of supplementation ejection fraction was determined by radionuclide angiography as was symptom-limited 1-legged knee extensor and 2-legged exercise performance on the cycle ergometer. Muscle strength as unilateral concentric knee extensor performance (peak torque, Nm at 180 degrees/s) was also evaluated. Skeletal muscle biopsies were taken for the determination of energy-rich phosphagens. RESULTS: Ejection fraction at rest and at work did not change. Performance before creatine supplementation did not differ between placebo and creatine groups. While no change was seen in the placebo group compared to baseline, creatine supplementation increased skeletal muscle total creatine and creatine phosphate by 17 +/- 4% (P < 0.05) and 12 +/- 4% (P < 0.05), respectively. Increments were seen only in patients with < 140 mmol total creatine/kg d.w. (P < 0.05). One-legged performance (21%, P < 0.05), 2-legged performance (10%, P < 0.05), and peak torque, Nm (5%, P < 0.05) increased. Both peak torque and 1-legged performance increased linearly with increased skeletal muscle phosphocreatine (P < 0.05). The increments in 1-legged, 2-legged and peak torque were significant compared to the placebo group, (P < 0.05). CONCLUSIONS: One week of creatine supplementation to patients with chronic heart failure did not increase ejection fraction but increased skeletal muscle energy-rich phosphagens and performance as regards both strength and endurance. This new therapeutic approach merits further attention.

Increased expression of the lactate dehydrogenase M subunit in myocardial regions with decreased thallium uptake.

OBJECTIVE: In ischaemic heart disease, the heart muscle is subjected to repeated episodes of regional ischaemia or to a constant underperfusion. The purpose of the present investigation was to study the myocardial metabolic adaptation to this stress. METHODS: Eighteen male patients with ischaemic heart disease were studied by biopsies taken from the left ventricular septum during bypass surgery. Citrate synthase, total lactate dehydrogenase and its H and M subunits, coenzyme Q10, and myoglobin were determined in all biopsies. Concentrations of ATP, ADP, and AMP were determined and energy charge calculated in the biopsies from the patients with ischaemic heart disease. Biopsies from the septal region of hearts obtained from brain dead kidney and liver donors were used as reference and preoperative myocardial thallium scintigraphy was performed in the patients with ischaemic heart disease to relate the myocardial biochemical markers to thallium uptake at the biopsy site. RESULTS: Myocardial activities of citrate synthase as well as contents of coenzyme Q10 and myoglobin in patients with ischaemic heart disease were not different from those of the reference group, and no linear relation was found between these three markers on the one hand and thallium uptake on the other. The energy charge was directly related and the M subunit of lactate dehydrogenase inversely related to the thallium uptake. CONCLUSION: The results suggest an absence of adaptation to ischaemia in terms of increased myocardial oxidative capacity and O2 transport and storage capacity. Furthermore, it is indicated that a stressed energy metabolism with increasing severity of ischaemic heart disease enhances anaerobic metabolism and induces a shift in myocardial lactate dehydrogenase subunit fractions.

Heparin-induced release of lipase activity in the human forearm: an immunological study.

Low doses of heparin were injected into the brachial artery of three volunteers. The lipase activities in the deep vein of the same forearm, draining mainly muscle tissue, and in the artery were monitored over a 10-min period. Lipase activity, rapidly released by heparin in the deep vein, was immunologically similar to lipoprotein lipase (E.C. 3.1.1.3), i.e. (1) it did not react with antiserum against human post-heparin plasma hepatic lipase and (2) it was inhibited by an antiserum against bovine milk lipoprotein lipase, which cross reacts with human post-heparin plasma lipoprotein lipase. The evidence that human muscle contains lipoprotein lipase is discussed.

Effect of beta 1-selective and nonselective beta blockade on blood pressure relative to physical performance in men with systemic hypertension.

Eleven physically active men with systemic hypertension were studied after 5 weeks of treatment with placebo, atenolol or propranolol. A double-blind, crossover randomized design was used. Blood pressure (BP), heart rate (HR), physical performance capacity, rate of perceived exertion and blood lactate concentrations were measured during rest, exercise to exhaustion and postexercise, at 8 and 24 hours after intake of the last dose. Blood pressure at rest and during exercise was similarly decreased with both drugs (8 and 24 hours), and there was no difference between 8 and 24 hours with any of the treatments. Heart rate (8 hours) was decreased similarly by both drugs, but after 24 hours, HR at increased workloads (above 120 watts) was higher with atenolol compared with propranolol. Maximal HR was lower with propranolol than atenolol at both 8 and 24 hours. Maximal exercise loads (8 and 24 hours) were 231 and 232 watts with placebo, 211 and 212 with propranolol and 228 and 227 with atenolol. That is, maximal workload was decreased with propranolol compared with placebo and atenolol at both 8 and 24 hours. No difference was found between placebo and atenolol at either 8 or 24 hours. The rate of perceived exertion values were higher with propranolol than atenolol. Blood lactate concentrations did not differ according to treatments. The results indicate that atenolol, when given in a dose that decreases resting and exercise BP to the same extent as propranolol, limits physical performance less than propranolol.

Impaired exercise performance but normal skeletal muscle characteristics in female syndrome X patients.

Pathophysiologic mechanisms in syndrome X (anginal chest pain, positive exercise stress test, and angiographically normal coronary arteries) have been extensively studied. Recent reports suggest an ischemic origin of the pain to be less probable. Other contributing mechanisms that have been hypothesized are enhanced sympathetic drive or sensitivity or an abnormal muscle metabolism. Our aim in this study was to characterize exercise performance, skeletal muscle characteristics, and sympathetic control of blood flow in patients with syndrome X. Seven female patients aged 50 to 65 years and 5 matched controls were tested. Exercise test was performed according to clinical routine. Plasma catecholamine and blood lactate levels were measured before, during, and after exercise. Autonomic blood flow control was measured plethysmographically in the resting contralateral forearm during isometric handgrip. Muscle biopsy specimens were obtained at rest from the lateral part of Musculus vastus at midthigh. The biopsy samples were investigated for the relative number of different fiber types, phosphagen content, and energy charge, calculated as (adenosine triphosphate +/- 1/2 adenosine diphosphate)/[adenosine triphosphate +/- adenosine diphosphate +/- adenosine monophosphate]). Exercise capacity was markedly decreased in syndrome X compared with controls (85 +/- 14 vs 156 +/- 11 W, p <0.0005) and all patients discontinued exercise because of chest pain (Borg CR-10, 5 +/- 3). Peak heart rate was lower in syndrome X (150 +/- 18 vs 176 +/- 7 beats/min, p <0.01), whereas systolic blood pressure and double product did not differ. Peak norepinephrine plasma levels were lower than in controls (11 +/- 6 vs 24 +/- 13 nmol/L, p <0.04), whereas peak blood lactate levels did not differ. Blood flow increase in the resting forearm during isometric handgrip was similar to that in controls. The proportion of different fiber types, phosphagen content, and energy charge were normal. Thus, patients with syndrome X have a reduced physical exercise capacity but no skeletal muscle abnormalities. Catecholamine hypersensitivity may contribute to their condition.

Development of femoral atherosclerosis in hypercholesterolemic patients during treatment with cholestyramine and probucol/placebo: Probucol Quantitative Regression Swedish Trial (PQRST): a status report.

The Probucol Quantitative Regression Swedish Trial is being performed to investigate the effects of probucol on atherosclerosis in the femoral artery. Probucol is combined with cholestyramine and dietary management in hypercholesterolemic patients, and the effects of atheroma developing in the femoral artery will be followed by a quantitative angiographic technique. A randomly selected control group is also being managed by dietary therapy and cholestyramine, but receives placebo instead of probucol. The treatment time in this double-blind trial is 3 years, and femoral angiography is performed yearly. Detailed lipoprotein and apolipoprotein analysis are performed at monthly intervals. The basic study design is described here, and some results from the open prerandomization phase of the study are presented.

The effect of probucol on femoral atherosclerosis: the Probucol Quantitative Regression Swedish Trial (PQRST).

The Probucol Quantitative Regression Swedish Trial tested whether treatment of hypercholesterolemic persons with probucol for 3 years affected femoral atherosclerosis. The primary end point was the change in atheroma volume estimated as change in lumen volume of the femoral artery assessed by quantitative arteriography. Three hundred three patients with visible atherosclerosis were randomized to probucol 0.5 g, twice daily, or to placebo. All patients were given diet and cholestyramine, 8 to 16 g/day. Twenty-nine patients were excluded because of inadequate primary end point measurements. The mean age of the remaining 274 subjects (158 were men) was 55 years. Seventeen percent had intermittent claudication and 24% had angina pectoris. After 3 years, the probucol-treated patients had 17% lower serum cholesterol, 12% lower low-density lipoprotein cholesterol, 24% lower total high-density lipoprotein cholesterol, and 34% lower high-density lipoprotein2 cholesterol levels than control subjects. All lipoprotein differences between the treatment groups remained highly significant during the trial. There was no statistically significant change in lumen volume between the probucol and the control group. Furthermore, there was no difference between the treatment groups with regard to change in arterial edge roughness or amount of aorto-femoral atherosclerosis; neither were there any differences between the treatment groups with regard to change in ST-segment depressions on exercise tests or ankle/arm blood pressure (secondary end points). In the control group, lumen volume increased (p < 0.001) and roughness of the femoral artery decreased (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Autonomic regulation of cardiopulmonary functions in sleep apnea syndrome and narcolepsy.

Thirteen patients with sleep apnea syndrome, nine with narcolepsy, and age-matched controls were studied to evaluate possible impairment of autonomic nervous control of cardiovascular and pulmonary function. The sleep apnea group had subnormal increases in heart rate and blood flow in the resting arm upon muscle contraction, although they were higher than seen in the narcolepsy group. Some sleep apnea patients had marked bradycardia in response to a dive reflex test. Other cardiovascular results did not differ from controls. Some sleep apnea patients had low ventilatory response to CO2. One had abnormal spirometry, two had enlarged tonsils, and five were snorers. The narcolepsy group had subnormal heart rate, blood pressure, and forearm blood flow responses to muscle contraction, subnormal respiratory sinus arrhythmia, and subnormal heart rate response to the Valsalva maneuver. Ventilatory function was normal. Thus, narcolepsy is associated with attenuation of some cardiovascular reflexes. The impairment is probably of central origin. The causative factor for the sleep apnea syndrome is probably also in the central nervous system rather than in the pulmonary or upper airway region. Great interindividual variations in the sleep apnea group point to a more multifactorial etiology. Thus, the two conditions of increased sleepiness are associated with autonomic dysfunction, but the differences in autonomic abnormalities reinforce that sleep apnea and narcolepsy, also in this respect, represent different clinical entities.

Myocardial energy depletion during profound hypothermic cardioplegia for cardiac operations.

Myocardial biopsy specimens were taken from 10 patients undergoing aortic valve replacement using extracorporeal circulation and continuous perfusion blood cardioplegia at extremely low myocardial temperature (10 degrees C). They were analyzed for adenosine triphosphate, creatine phosphate, creatine, and lactate before, after 10 minutes, and after 60 minutes of cardioplegia. Patient inclusion criteria were heart volume less than 700 ml/m2 body surface area and no significant coronary atherosclerosis as judged from preoperative angiograms. The profound hypothermic cardioplegia resulted in a smaller intramyocardial lactate accumulation but a greater decrease in adenosine triphosphate and creatine phosphate than a moderate reduction of myocardial temperature (15 degrees C) as previously reported in a similar patient group. This suggests that at the lower temperature energy-generating processes are thwarted more than energy consumption. In addition, the profound hypothermic cardioplegia led to a reduction of the myocardial pool of total creatine, which may delay restitution of myocardial high-energy phosphate and function after cardioplegia.

Increased removal rate of exogenous triglycerides after prolonged exercise in man: time course and effect of exercise duration.

Ten healthy young men exercised for 1.5 and 3 hours, respectively, 4 to 6 weeks apart at the same work intensity, corresponding to 77% of the individual maximal heart rate. In the fasting state 1 mL of 10% Intralipid/kg body weight was injected IV, the fractional removal rate was calculated (k2-value), and fasting lipid and apolipoprotein C-I, C-II, and CIII concentrations were determined one day before, immediately before, immediately after, and one day after the exercise: measurements were also made two and three days after the three-hour session. An increase of the k2-value was found only the day after the three-hour exercise (+66%, P less than .01), while after the 1.5-hour exercise the k2-value was not changed. One and two days after the three-hour exercise the fasting serum triglyceride concentration was significantly decreased by 33% and 16%, respectively. Serum triglyceride concentration was decreased also the day after the shorter session (-17%, P less than .05). Decreases in serum cholesterol concentrations were significant after both exercise bouts, but the significance disappeared if corrections for the changes in calculated plasma volume were made. Serum level of C apolipoproteins was decreased one day after the three-hour exercise, while it was not changed after the shorter exercise. This study shows that prolonged exercise produces an increase in the removal rate of Intralipid triglycerides from the bloodstream, that this change is related to the duration of exercise, and that some time is required following the exercise, before it is manifest.

Substrate utilization and enzymes in skeletal muscle of extremely endurance-trained men.

Substrate utilization during exercise at 65% of maximal O2 uptake (VO2 max) and biochemical characteristics of vastus lateralis were compared between five endurance-trained (T) and five untrained subjects (U). The oxidative enzyme activities were 100% greater in T than in U, and VO2 max was 50% higher. A greater proportion of ATP regeneration occurred through oxidative processes in T than in U (smaller leg lactate release and smaller muscle lactate accumulation). The respiratory exchange ratio together with the local leg respiratory quotient indicated a greater contribution of fat to oxidative metabolism in T than U (53 vs. 33%). No difference, however, in the ratio of plasma free fatty acid extraction to O2 extraction by the working legs was found between T and U. Thus it could be calculated that a greater fraction of fat oxidation would have been covered by intramuscular triglycerides in T than in U (34 vs. 15%, P less than 0.05). T in comparison to U were further characterized by a smaller glycogen breakdown and a smaller glucose uptake, which may have been one contributing factor that prevented the blood glucose level from falling in T. The greater leg muscle citrate concentration in T could have been one factor mediating a lower carbohydrate utilization as a response to an increase in the relative proportion of fat oxidation.