Decreased leg glucose uptake during exercise contributes to the hyperglycaemic effect of octreotide

Aim: During prolonged infusion of somatostatin, there is an increase in arterial glucose concentration, and this increase persists even during prolonged exercise. The aim of the study was to measure glucose uptake in the leg muscles during infusion of the somatostatin analogue octreotide before and during leg exercise. Material and methods: Eight healthy male subjects were investigated twice in the fasting state: during 3 h infusion of octreotide [30 ng (kg min)^?1] or sodium chloride with exercise at 50% of maximal VO₂ in the last hour. Glucose uptake and oxygen uptake in the leg were measured using Fick’s principle by blood sampling from an artery and a femoral vein. Blood flow in the leg was measured using the indicator (indocyanine green) dilution technique. Results: After an initial decrease during rest, octreotide infusion resulted in a significant increase in arterial glucose concentrations compared to control conditions during exercise (mean ± SEM: 7·6 ± 0·6 versus 5·6 ± 0·1 mmol l^?1, P<0·01). During rest, octreotide did not change the leg glucose uptake (59 ± 10 versus 55 ± 11 μmol min^?1). In contrast, leg glucose uptake was significantly lower during exercise compared to control conditions (208 ± 79 versus 423 ± 87 μmol min^?1, P<0·05). During exercise, leg oxygen uptake was not different in the two experiments (20·4 ± 1·3 versus 19·5 ± 1·1 μmol min^?1). Conclusion: In conclusion, infusion of octreotide reduced leg glucose uptake during exercise, despite the same leg oxygen consumption and blood flow compared to control conditions. The hyperglycaemic effect of octreotide can partly be explained by the reduction in leg glucose uptake. Furthermore, the results suggest that a certain level of circulating insulin is necessary to obtain sufficient stimulation of glucose uptake in the exercising muscles.     

Effects of physical exercise on insulin absorption in insulin-dependent diabetics. A comparison between human and porcine insulin

Summary. Nine insulin-dependent diabetics with undetectable plasma C-peptide (<0·05 nmol 1^-1) and without insulin antibodies (insulin binding to IgG<0·05 Ul^-1) received subcutaneous injections of 10 U ¹²⁵I-labelled soluble human or porcine insulin in the thigh on 2 consecutive days. Disappearance rates of ¹²⁵I were monitored continuously by external counting and plasma insulin levels were determined during rest for 30 min, bicycle exercise of moderate intensity for 40 min, and 60 min recovery. Subcutaneous blood flow was measured concomitantly in the contralateral thigh by the ¹³³Xenon clearance technique. During the initial period of rest human insulin was absorbed approximately 40% faster than its porcine analogue (first order rate constants 0·37±0·06 vs 0·27±0·06% min^-1, P<0·05) and the increment of the area under the plasma insulin curve was greater after hum-ii than after porcine insulin (184±46 vs 112±42 mUl^-1 min, P<0·05). Exercise enhanced the absorption rates for both ¹²⁵I-insulins to 0·50±0·06 and 0·48±0·10% min^-1 for human and porcine insulin, respectively (P<0·05). This increase was less pronounced for human compared to porcine insulin (49±19 vs 105±40%, P=0·06). During exercise plasma insulin rose to 37±5 mUl^-1 after human and 30±5 mUl^-1 after porcine insulin and the areas under the plasma insulin curves were similar. During the recovery phase the absorption rates decreased slightly compared to the exercise value for both insulins. The blood glucose lowering effect was similar for the two insulins. Subcutaneous blood flow was not significantly altered by exercise in either group. It is concluded that during rest human soluble insulin is more rapidly absorbed than porcine insulin. Physical exercise tends to increase porcine insulin absorption more and eliminates the basal difference in the absorption kinetics between human and porcine insulin. The increased insulin absorption during exercise is not coupled to corresponding changes in the subcutaneous blood flow.     

Leg uptake of calcitonin gene‐related peptide during exercise in spinal cord injured humans

Exercise‐induced increases in cardiac output (CO) and oxygen uptake (VO₂) are tightly coupled, as also in absence of central motor activity and neural feedback from skeletal muscle. Neuromodulators of vascular tone and cardiac function – such as calcitonin gene related peptide (CGRP) – may be of importance. Spinal cord injured individuals (six tetraplegic and four paraplegic) performed electrically induced cycling (FES) with their paralyzed lower limbs for 29 ± 2 min to fatigue. Voluntary cycling performed both at VO₂ similar to FES and at maximal exercise in six healthy subjects served as control. In healthy subjects, CGRP in plasma increased only during maximal exercise (33·8 ± 3·1 pmol l^?1 (rest) to 39·5 ± 4·3 (14%, P<0·05)) with a mean extraction over the working leg of 10% (P<0·05). Spinal cord injured individuals had more pronounced increase in plasma CGRP (33·2 ± 3·8 to 46·9 ± 3·6 pmol l^?1, P<0·05), and paraplegic and tetraplegic individuals increased in average by 23% and 52%, respectively, with a 10% leg extraction in both groups (P<0·05). The exercise induced increase in leg blood flow was 10–12 fold in both spinal cord injured and controls at similar VO₂ (P<0·05), whereas CO increased more in the controls than in spinal man. Heart rate (HR) increased more in paraplegic subjects (67 ± 7 to 132 ± 15 bpm) compared with controls and tetraplegics (P<0·05). Mean arterial pressure (MAP) was unchanged during submaximal exercise and increased during maximal exercise in healthy subjects, but decreased during the last 15 min of exercise in the tetraplegics. It is concluded that plasma CGRP increases during exercise, and that it is taken up by contracting skeletal muscle. The study did not allow for a demonstration of the origin of the CGRP, but its release does not require activation of motor centres. Finally, the more marked increase in plasma CGRP and the decrease in blood pressure during exercise in tetraplegic humans may indicate a role of CGRP in regulation of vascular tone during exercise.     

Standardized intermittent static exercise increases peritendinous blood flow in human leg

Alteration in tendinous and peritendinous blood flow during and after exercise is suggested to contribute to the development of Achilles tendon injury and inflammation. In the present study a method for evaluating the influence of standardized workload on peritendinous flow is presented. The radioactive isotope xenon-133 was injected just ventrally to the Achilles tendon 5 cm proximal to the tendon's insertion on the calcaneus. The disappearance of ¹³³Xe was used to determine blood flow during intermittent static exercise of the calf muscle (1·5 s exercise/1·5 s rest) for 30 min at a workload equivalent to individual body weight (1 BW) in six healthy volunteers around both Achilles tendons (n = 12). During intermittent static exercise, blood flow was increased from 1·8 ± 0·3 ml 100 g tissue^?1 min^?1 (mean value and SEM) (rest) to 6·1 ± 1·3 ml 100 g tissue^?1 min^?1 (exercise) (P<0·05). The exercise induced an average increase in blood flow (3·4-fold) equivalent to results previously obtained during regular dynamic heel raises (P>0·05). It is concluded that the method is well suited to study the influence of standardized workload on the physiology and pathophysiology of the tissue around the Achilles tendon in humans.     

Abnormal vascular reactivity at rest and exercise in obese boys

Background Obese children exhibit vascular disorders at rest depending on their pubertal status, degree of obesity, and level of insulin resistance. However, data regarding their vascular function during exercise remain scarce. The aims of the present study were to evaluate vascular morphology and function at rest, and lower limb blood flow during exercise, in prepubertal boys with mild‐to‐moderate obesity and in lean controls. Materials and methods Twelve moderately obese prepubertal boys [Body Mass Index (BMI: 23·9 ± 2·6 kg m^?2)] and thirteen controls (BMI:17·4 ± 1·8 kg m^?2), matched for age (mean age: 11·6 ± 0·6 years) were recruited. We measured carotid intima‐media thickness (IMT) and wall compliance and incremental elastic modulus, resting brachial flow‐mediated dilation (FMD) and nitrate‐dependent dilation (NDD), lower limb blood flow during local knee‐extensor incremental and maximal exercise, body fat content (DEXA), blood pressure, blood lipids, insulin and glucose. Results Compared to lean controls, obese boys had greater IMT (0·47 ± 0·06 vs. 0·42 ± 0·03 mm, P < 0·05) but lower FMD (4·6 ± 2·8 vs. 8·8 ± 3·2%, P < 0·01) in spite of similar maximal shear rate, without NDD differences. Lower limb blood flow (mL min^?1·100 g^?1) increased significantly from rest to maximal exercise in both groups, although obese children reached lower values than lean counterparts whatever the exercise intensity. Conclusions Mild‐to‐moderate obesity in prepubertal boys without insulin resistance is associated with impaired endothelial function and blunted muscle perfusion response to local dynamic exercise without alteration of vascular smooth muscle reactivity.     

Muscle ammonia and amino acid metabolism during dynamic exercise in man

Summary. The effect of dynamic exercise on muscle and blood ammonia (NH₃) and amino acid contents has been investigated. Eight healthy men cycled at 50% and 97% of maximal oxygen uptake for 10 min and 5·2 min (to fatigue), respectively. Biopsies (quadriceps femoris muscle), arterial and femoral venous blood samples were obtained at rest and during exercise. Muscle NH₃ at rest and after submaximal exercise was (x?±SE) 0·5±0·1 mmol/kg dry muscle (d.m.) and increased to 4·1 ±0·5 mmol/kg d.m. at fatigue (P<0·001). The total adenine nucleotide (TAN) pool (TAN=ATP+ADP+AMP) did not change after submaximal exercise but decreased significantly at fatigue (P<0·01). The decrease in TAN was similar to the increase in NH₃. Muscle lactate was 3±1 mmol/kg d.m. at rest and increased to 104±5 mmol/kg d.m. at fatigue. Whole blood and plasma NH₃ did not change significantly during submaximal but both increased significantly during maximal exercise (P<0·001). During maximal exercise the leg released 7,120 μmol/min of lactate, whereas only 89 μmol/min of NH₃ were released. NH₃ accumulation in muscle could buffer only 3% of the hydrogen ions released from lactate, and NH₃ release could account for only 1% of the net hydrogen ion transport out of the cell. Muscle glutamine was constant throughout the study, whereas glutamate decreased and alanine increased during exercise (P<0·001). No significant changes in either arterial whole blood glutamine or glutamate were observed. Arterial plasma glutamine and glutamate concentrations, however, increased and decreased (P<0·001), respectively, during exercise. It is concluded that (1) muscle and blood NH₃ levels increase only during strenuous exercise and (2) NH₃ accumulation is of minor importance for regulating acid-base balance in body fluids during exercise.     

Kinetics of 13CO2 elimination after ingestion of 13C bicarbonate: the effects of exercise and acid base balance

Abstract. In order to investigate the effects of muscular work and preceding exercise on the retention of exogenous labelled bicarbonate, we studied the effects of oral administration of [¹³C]bicarbonate (0·1 mg kg^-1) in five subjects at rest before exercise and during and after 1 h of treadmill walking at 73% VO_2max on three separate occasions. Elimination of CO₂ from labelled bicarbonate was 62·6±8·1% at rest, 103·6±11·3% during exercise (P<0·01) and 43·0±4·7% during recovery from exercise (P= 0·01). During exercise mean residence time (MRT) was shorter than at rest (35±7 min vs. 54±9min, P < 0·02) and CO₂ pool size was larger (998±160 ml CO₂kg^-1, vs. 194±28ml CO₂kg^-1, P < 0·001). Compared to values obtained at rest, during recovery from exercise, MRT and CO₂ pool size were reduced (34±5min, P < 0·05; 116±19 ml CO₂kg^-1, P < 0·02, respectively). In an additional five subjects acidosis and alkalosis were induced prior to administration of oral [¹³C]bicarbonate at rest. Elimination of bicarbonate was lower during acidosis (46·1±5·6%, P < 0·01) but was unaltered (50·9±5·6%, NS) during alkalosis, compared to the values obtained at resting pH. During acidosis MRT and CO₂ pool size decreased (37±3min, P<0·01 and 123±10ml CO₂kg^-1, P < 0·01, respectively) whereas in alkalosis MRT was unchanged (65±8 min NS) but CO₂ pool size was increased (230±23ml CO₂kg^-1, P < 0·05). The kinetics of elimination of ¹³CO₂ from administered bicarbonate after exercise are different to those at rest and resemble acidosis. The appropriate correction factor for sequestered ¹³C should be used in metabolic studies of the post-exercise state when using ¹³C tracers.     

Measurement of cardiac output with non-invasive Aesculon impedance versus thermodilution

Background: This study compared the non‐invasive thoracic electrical bioimpedance Aesculon^® technique (TEB_Aesculon) with thermodilution (TD) to evaluate whether TEB_Aesculon may offer a reliable means for estimating cardiac output (CO) in humans. Material and method: Cardiac output was measured with TD and TEB_Aesculon in 33 patients, with a mean age ± SEM of 59 ± 2·7 years, that underwent right heart catheterization for clinical investigation of pulmonary hypertension or severe heart failure. Four to five CO measurements were performed with each technique simultaneously in 33 patients at rest, 11 during exercise and seven during NO inhalation. Result: Cardiac output correlated poorly between TEB_Aesculon and TD at rest (r = 0·46, P<0·001), during exercise (r = 0·35, P<0·013) and NO inhalation (r = 0·41, P<0·017). CO was higher for TEB_Aesculon than TD with 0·86 ± 0·14 l min^?1 at rest (P<0·001) and 2·95 ± 0·69 l min^?1 during exercise (P<0·003), but similar during NO inhalation, with a tendency (P<0·079) to be 0·44 ± 0·19 l min^?1 higher for TEB_Aesculon than TD. CO increased from rest to exercise for TEB_Aesculon and TD with 6·11 ± 0·6 l min^?1 (P<0·001) and 3·91 ± 0·36 l min^?1 (P<0·001), respectively; an increase that was higher (P<0·002) for TEB_Aesculon than TD. During NO inhalation, compared to rest, CO decreased for TEB_Aesculon with 0·62 ± 0·11 l min^?1 (P<0·002), but not significantly for TD with 0·21 ± 0·12 l min^?1 (P<0·11). Bland–Altman analysis showed a poor agreement between TEB_Aesculon and TD. Conclusion: TEB_Aesculon overestimated CO compared to TD with ～17% at rest and ～34% during exercise, but the techniques showed similar results during NO inhalation. CO, furthermore, correlated poorly between TEB_Aesculon and TD. TEB_Aesculon may at present not replace TD for reliable CO measurements in humans.     

Biotelemetric detection of the disappearance of subcutaneously injected 125I-NPH insulin

Summary. A biotelemetric method with Geiger-Müller (GM) detectors fixed to the skin surface was used for continuous registration of the disappearance rate of subcutaneously injected ¹²⁶I-NPH insulin. Methodological problems concerning counting geometry were investigated by comparing the disappearance of radioactivity, measured with GM- and NaI-detectors, respectively, and by scanning of the radioactive source. The size and position of the subcutaneous depot was unchanged throughout the study. Movement artifacts could be avoided. The coefficient of variation for distribution of ratios between count rates for GM- and NaI-detectors was 3·0%±1·1 (SD) (range 0·9-4·0%) over periods of 24 h. It is concluded that the biotelemetry technique proved to be a clinically useful procedure for insulin absorption studies.     

Carbohydrate utilization by exercising muscle following pre-exercise glucose ingestion

Summary. The effect on exercising muscle metabolism of prior ingestion of 200 g glucose was examined in six healthy subjects during 40 min leg exercise at 30% of maximal oxygen uptake. Leg glucose uptake during exercise was on average two- to three-fold higher after glucose (E+G) compared to exercise without glucose (E) and could account for 44–48% of the oxidative leg metabolism (control value: 19%, P<0·05-0·01). In contrast to E, which was associated with a significant release of leg lactate, pyruvate and alanine, E+G gave no leg production of lactate or alanine and an uptake of pyruvate. The respiratory exchange ratios (R) were higher during G + E and corresponded to a carbohydrate oxidation of 54–69% as against 46–49% (P0<·05-0·01) during E. Estimated from R-values and leg oxygen and glucose uptakes, carbohydrate oxidation during G<E was almost completely accounted for by blood glucose. During E, on the other hand, carbohydrate oxidation exceeded leg glucose uptake, indicating a small but significant muscle glycogen breakdown (P<0·01). The rate of glycogen utilization during E or G + E was too small to be detected by direct measurements of muscle glycogen content. The results demonstrate that glucose ingestion prior to light exercise is followed by increased uptake and more efficient oxidation of glucose, as well as by insignificant muscle glycogen degradation by exercising muscle. Although the present findings suggest a glycogen-conserving effect of glucose ingestion under these conditions, the main fuel shift is from fat to glucose oxidation.     

Influence of glucose and fructose ingestion on the capacity for long-term exercise in well-trained men

Summary. The aim of the present study was to examine the influence of glucose and fructose ingestion on the capacity to perform prolonged heavy exercise. Eight well-trained healthy volunteers exercised on a bicycle ergometer at 68±3% of their VO₂ max until exhaustion, on three occasions, with 8-day intervals. During the exercise they ingested either glucose (250 ml, 7%), fructose (250 ml, 7%) or water (250 ml) every 20 min in a double-blind randomized study design. Arterial blood samples were collected at rest and during exercise for the determination of substrates and hormones. Muscle glycogen content (m. quadriceps femoris) was measured before and after exercise. The duration of exercise lengthened with repeated exercise (3rd test: 136±13 min v. 1st test: 110±12 min, P<0·01). Corrected for the sequence effect, total work time until exhaustion was significantly longer with glucose (137±13 min) than with either fructose (114±12 min) or water (116±13 min) (both P<0·01). When glucose or fructose was ingested, the arterial plasma glucose concentration was maintained at the normoglycaemic level; with water ingestion, plasma glucose values fell during exercise in seven subjects and remained at the resting level in the eighth subject. The muscle glycogen concentration was 467±29 mmol kg d.w.^-1 at rest and fell to approximately half the initial value at exhaustion. In the subgroup of seven subjects in whom glucose values decreased with water intake, the mean rate of glycogen degradation was significantly lower (P<0·05) with the ingestion of glucose (1·3±0·4 mmol kg d.w.^-1 min^-1) as compared to fructose (2·1±0·5 mmol kg d.w.^-1 min^-1) or water (2·3±0·5 mmol kg d.w.^-1 min^-1). Intermittent glucose ingestion (3×17·5 g h^-1) during prolonged, heavy bicycle exercise postpones exhaustion and exerts a glycogen-conserving effect in the working muscles. In contrast, fructose ingestion during exercise maintains the glucose concentration at the basal level but fails to influence either muscle glycogen degradation or endurance performance.     

Maintained cerebral metabolic ratio during exercise in patients with β‐adrenergic blockade

Background: Decreased cerebral metabolic ratio (CMR) [molar uptake of O₂ versus molar uptake of (glucose + ½ lactate)] during exercise is attenuated by intravenous administration of the non‐selective β‐adrenergic receptor antagonist propranolol. We evaluated to what extent cirrhotic patients in oral treatment with propranolol are able to mobilize brain non‐oxidative carbohydrate metabolism. Methods: Incremental cycle ergometry to exhaustion (86 ± 4·2 W; mean ± SD) was performed in eight cirrhotic patients instrumented with a catheter in the brachial artery and one retrograde in the right internal jugular vein. Healthy subjects form the control group. Results: In β‐blocked cirrhotic patients arterial lactate increased from 1·5 ± 0·3 to 5·1 ± 0·8 mM (P<0·05) and the arterial–jugular venous difference (a–v diff) from ?0·01 ± 0·03 to 0·30 ± 0·05 mM (P<0·05) at rest and during exercise, respectively. During exercise the glucose a–v diff of 0·46 ± 0·06 mM remained at a level similar to rest (0·54 ± 0·03 mM) and at exhaustion the CMR was not significantly changed (5·8 ± 1·1 versus 6·0 ± 0·6). In controls, CMR decreased from 5·6 ± 0·9 at rest to 3·4 ± 0·7 (P<0·05) during maximal exercise and at a lactate level comparable to that achieved by the patients it was 3·8 ± 0·4. Conclusion: During exhaustive exercise in cirrhotic patients the CMR is maintained and a significant cerebral uptake of lactate is demonstrated. The data suggest that oral treatment with a non‐selective β‐adrenergic receptor antagonist attenuates cerebral non‐oxidative metabolism.     

Influence of exercise training on heart rate variability in post-menopausal women with elevated arterial blood pressure

Low heart rate variability (HRV) has been reported to be an independent risk factor for the development of coronary heart disease in women and has recently been identified as a risk factor for cardiac sudden death and all-cause mortality. We have recently demonstrated that endurance-trained post-menopausal women demonstrate higher levels of HRV than sedentary control subjects. The purpose of the present study was to test the hypothesis that 12 weeks of regular aerobic exercise would increase HRV in sedentary post-menopausal women with elevated arterial blood pressure (BP) (i.e. either high normal BP or stage I hypertension). A secondary aim was to test the hypothesis that the increase in HRV with exercise training, if observed, would be associated with an increase in spontaneous cardiac baroreflex sensitivity (SBRS), an important physiological determinant of HRV. To accomplish these aims, we studied eight sedentary post-menopausal women (age=54·5±1·3 years) before and after 12 weeks of aerobic exercise training (3·3±0·3 days per week at 70%±2% of maximal heart rate for 43±3 min per day). Maximal oxygen uptake and body weight did not change (P>0·05) with training, but percentage fat (35·5±2·6% vs. 34·5±2·3%, P<0·05) decreased and treadmill time to exhaustion increased (9·8±0·5 vs. 11·3±0·5 min, P<0·05). Supine resting levels of heart rate, RR interval and the standard deviation of the RR interval (time domain measure of HRV) were unchanged (all P>0·05) from baseline levels after 12 weeks of aerobic training. Similarly, the high-frequency, low-frequency and total power of HRV (frequency domain measures) were also unchanged from baseline (all P>0·05). SBRS was also not different before and after aerobic exercise training (1062 vs. 1363 ms mmHg^?1 respectively, P>0·05). In contrast, systolic and diastolic BP were reduced approximately 8 and approximately 5 mmHg with training (both P<0·05) respectively. These results indicate that 12 weeks of moderate-intensity aerobic exercise training does not increase HRV or SBRS, despite producing a clinically significant reduction in BP at rest in post-menopausal women with elevated BP. Considered together with our previous findings in female master endurance athletes, these findings suggest that more intense and prolonged exercise training may be required to produce increases in HRV and SBRS in sedentary post-menopausal women.     

Exercise increases insulin clearance in healthy man and insulin-dependent diabetes mellitus patients

Exercise is known to decrease insulin secretion, but the effect on insulin clearance is unclear. We examined the effect of exercise on insulin clearance with euglycaemic insulin clamp in 28 healthy men either 12 h after a marathon run (n=14) or 44 h after a 2-h treadmill exercise (n=14), and in seven insulin-dependent diabetes mellitus (IDDM) patients 12 h after a marathon run, and after a resting, control day. During the post-exercise insulin infusion, steady-state plasma insulin concentration was reduced by 9% in healthy men after both types of exercise, and by 16% in the diabetic subjects compared with the control study (P<0·05 in all). In healthy men, C-peptide concentrations were more than one-third lower during insulin infusion, both after the marathon run (P<0·001) or treadmill exercise (P<0·02) compared with the control study. Insulin clearance was significantly increased by exercise both in healthy men (9%, P<0·05) and in IDDM subjects (15%, P<0·05). After exercise, endogenous insulin secretion in healthy men is reduced and insulin clearance is enhanced both in healthy men and in IDDM patients. Decreased insulin availability may allow enhanced muscle lipid utilization and spare glucose after long-term exercise.     

Effects of intense exercise training on endothelium-dependent exercise-induced vasodilatation

To determine whether intense exercise training affects exercise-induced vasodilatation, six subjects underwent 4 weeks of handgrip training at 70% of maximal voluntary contraction. Exercise forearm vascular conductance (FVC) responses to an endothelium-dependent vasodilator (acetylcholine, ACH; 15, 30, 60 μg min^?1) and an endothelium-independent vasodilator (sodium nitroprusside, SNP; 1·6, 3·2, 6·4 μg min^?1) and FVC after 10 min of forearm ischaemia were determined before and after training. Training elicited significant (P<0·001) increases in grip strength (43·4 ± 2·3 vs. 64·1 ± 3·5 kg, before vs. after, mean ± SEM), forearm circumference (26·7 ± 0·4 vs. 27·9 ± 0·4 cm) and maximal FVC (0·4630 ± 0·0387 vs. 0.6258 ± 0·0389 units, P<0·05). Resting FVC did not change significantly with training (0·0723 ± 0·0162 vs. 0.0985 ± 0·0171 units, P>0·4), but exercise FVC increased (0·1330 ± 0·0190 vs. 0.2534 ± 0·0387 units, P<0·05). Before and after the training, ACH increased exercise FVC above the control (no drug) exercise FVC, whereas SNP did not. Training increased (P<0·05) the exercise FVC responses to ACH (0·3344 ± 0·1208 vs. 0.4303 ± 0·0858 units, before vs. after training, 60 μg min^?1) and SNP (0·2066 ± 0·0849 vs. 0.3172 ± 0·0628 units, 6·4 μg min^?1). However, these increases were due to the increase in control (no drug) exercise FVC, as the drug-associated increase in exercise FVC above control did not differ between trials (P>0·6). These results suggest that exercise FVC is increased by both exercise training and stimulating the release of endothelium-dependent vasodilators. However, training does not affect the vascular response to these vasodilators.     

A fractal approach for evaluation of pulmonary circulation in man at rest and during exercise

Changes in pulmonary circulation caused by muscular exercise and body position are usual in daily life. By using first-pass radiocardiography and fractal analysis, pulmonary circulation in man was evaluated at rest and during muscular exercise. At rest, pulmonary circulation was heterogeneous as described by the relative dispersion (which is the coefficient of variation, i.e. the standard deviation of the pulmonary transit times divided by the mean transit time; RD = 0·51 ± 0·06) and fractal in nature. During exercise, pulmonary circulation became more homogeneous (RD = 0·35 ± 0·04; P<0·001). The calculated fractal dimension decreases from 1·09 at rest to 1·06 during exercise. The model identifies a cubic-law response for circulation heterogeneity and a quarter-power law for resistance during muscular exercise.     

Left ventricular response to graded isometric exercise in patients with coronary heart disease

Summary. The effects of graded isometric exercise on left ventricular performance were characterized in 11 male patients (53 ± 2 years) with coronary artery disease (CAD) and in 12 normal subjects (11 male and one female, 36 ± 5 years). The echocardiographic indices of left ventricular function at rest were similar in both groups. Heart rate and blood pressure increased significantly in both groups in response to 40 and 60% of handgrip maximal voluntary contraction (MVC). Left ventricular end-diastolic dimension increased significantly (from 50 ± 1 to 56 ± 1 mm; P < 0·01) with 60% of MVC in CAD group but not in the healthy subjects. The patients with CAD also exhibited significant (P < 0·01) increases in end-systolic dimension (from 34 ± 1 to 40 ± 2 with 40% and to 44 ± 1 mm with 60% MVC). End-diastolic and end-systolic dimensions did not change during isometric exercise in the healthy subjects. Mean velocity of circumferential shortening (mV_CF) increased with 60% MVC in normal subjects. In the CAD group mV_CF decreased significantly (from 1.08 ± 0·06 to 0·86 ± 0·06 with 40% and to 0·74 ± 0·04 d·s^-1 with 60% MVC; P < 0·01). At comparable mean blood pressures, mV_CF was significantly lower in the CAD group than in normal subjects. These results demonstrate that progressive deterioration of left ventricular function during increasing levels of isometric exercise in patients with CAD can be detected with echocardiography.     

Pulmonary vasodilatation and augmentation of right ventricular function following terbutaline infusion in severe chronic pulmonary disease

Summary. Twenty patients with a median age of 61 years and a median forced expired volume in 1 s (FEV₁) after bronchodilatating therapy of 0·55 1 were studied in order to measure the effect of intravenous terbutaline on bronchial tone, cardiac function, pulmonary haemodynamics, gas exchange, and oxygen transport capacity during rest and in 10 patients during exercise. Terbutaline infusion during rest resulted in an increase in heart rate from 84 to 103 beats min^-1 (P < 0·01), a decrease in mean systemic arterial pressure from 95 to 80 mmHg (P < 0·02), an unchanged mean pulmonary arterial pressure (18 mmHg), an increase in cardiac index from 2·89 to 3·86 1 min^-1 m^-2 (P < 0·01), an increase in right ventricular ejection fraction from 45 to 53% (P < 0·01), an increase in left ventricular ejection fraction from 63 to 67% (NS), an unchanged arterial oxygen tension, and an increase in calculated oxygen delivery from 533 to 638 ml O₂ min^-1 m^-2 (P < 0·01). During exercise terbutaline infusion resulted in an increase in heart rate from 108 to 120 beats min^-1 (P < 0·05), a decrease in mean systemic arterial pressure from 117 to 106 mmHg (P < 0·01), a decrease in mean pulmonary arterial pressure from 29 to 22 mmHg (P < 0·01), an increase in cardiac index from 4·53 to 4·64 min^-1 m^-2 (NS), an unchanged arterial oxygen tension, and an increase in the calculated oxygen delivery from 834 to 856 ml O₂ min^-1 m^-2 (NS). It was concluded that terbutaline augments right ventricular function: increases right ventricular ejection fraction and decreases right ventricular end-diastolic volume, and further decreases pulmonary vascular resistance without decreasing arterial oxygen tension, and increases oxygen delivery in patients with chronic pulmonary disease during rest and exercise.     

Tissue oxygenation,strength and lactate response to different blood flow restrictive pressures

This study aimed to determine whether changes in initial restrictive pressures (IRP, tightness of the cuff before inflation with air) affect tissue oxygenation, lactate production and leg strength before, during and after knee extension exercises. The cuff was positioned on the right thigh, and the IRP of either 40–45 or 60–65 mmHg were applied randomly prior to inflating the cuff to the final restrictive pressure (the pressure reached after inflating the cuff with air). Subjects performed four sets (30, 15, 15 and 15 reps) of isotonic knee extensions with 1‐min rest between sets. Tissue oxygenation and blood lactate levels were assessed prior to, during and after exercise, and leg strength was assessed pre‐ and postexercise. There were significant condition by time interactions (P<0·01) and main effects for both condition (P<0·01) and time (P<0·01) for tissue oxygenation, deoxyhaemoglobin, total haemoglobin. Significant main effects were detected for both condition (P<0·01) and time (P<0·01) for leg strength values. There was only a significant time main effect for lactate concentrations. This study is the first to show that a higher IRP had a significant impact on percent tissue oxygenation, leg strength and deoxygenated haemoglobin accumulation during exercise.     

Cholinergic blockade and the mesenteric artery response to head-up tilt-induced central hypovolaemia

The influence of muscarinic blockade on the superior mesenteric artery (SMA) response to head-up tilt (HUT) was assessed by Doppler ultrasound in eight healthy adults pretreated with i.v. glycopyrron. During supine rest, cholinergic blockade increased heart rate from 58 ± 3 to 106 ± 6 beats min^?1 (mean ± SE) and mean arterial pressure from 81 ± 3 to 97 ± 4 mmHg (P<0·01) and it reduced the cardiac stroke volume from 89 ± 6 to 59 ± 7 ml (P<0·01) with no significant effect on the SMA diameter and blood flow velocities. HUT provoked a further increase in heart rate to 134 ± 5 beats min^?1(P<0·01) and a reduction in stroke volume to 45 ± 4 ml (P<0·01). The early diastolic velocity increased from ?51 ± 4 to 6 ± 8 cm s^?1 during the normotensive stage of HUT and further to 21 ± 9 cm s^?1 during the hypotensive stage with a reduction in mean arterial pressure from 97 ± 4 to 73 ± 7 mmHg (P<0·01) but, in contrast to control HUT (without cholinergic blockade), the end-diastolic velocity did not change significantly. Maintenance of blood velocity and diameter in spite of an increase in arterial pressure at rest indicates increased SMA impedance. Likewise, during hypovolaemia, a glycopyrron-induced inhibition in diastolic velocity supports an increase in SMA impedance. The results indicate cholinergic vasorelaxing influence on the superior mesenteric artery both at rest and during normotensive central hypovolaemia.