Maximal heart rates and plasma lactate concentrations observed in middle-aged men and women during a maximal cycle ergometer test

Summary The purpose of this study was to investigate criteria for maximal effort in middle-aged men and women undertaking a maximal exercise test until they were exhausted if no measurements of oxygen uptake are made. A large group of 2164 men and 975 women, all active in sports and aged between 40 and 65 years, volunteered for a medical examination including a progressive exercise test to exhaustion on a cycle ergometer. In the 3rd min of recovery a venous blood sample was taken to determine the plasma lactate concentration ([la^–]_{p, 3min}). Lactate concentration and maximal heart rate (f _{c, max}) were lower in the women than in the men (P<0.001). Multiple regression analyses were performed to assess the contribution of sex to [la^–]_{p, 3 min}, independent of age and f _c max, It was found that [la^–]_{p,3 min} was about 2.5 mmol·l^–1 lower in women than in men of the same age and f _{c, max}. In our population 88% of the men and 85% of the women met a combination of the following f _{c, max} and [la^–]_{p, 3min} criteria: f _{c, max} equal to or greater than 220 minus age beats·min^–1 and/or [la^–]_{p, 3min} equal to or greater than 8 mmol·l^–1 in the men and f _{c, max} equal to or greater than 220 minus age beats·min^–1 and/or [la^–]_{p, 3min} equal to or greater than 5.5 mmol·1^–1 in the women.     

Endurance training slows down the kinetics of heart rate increase in the transition from moderate to heavier submaximal exercise intensities

Summary To find out whether endurance training influences the kinetics of the increases in heart rate (f _c) during exercise driven by the sympathetic nervous system, the changes in the rate off _c adjustment to step increments in exercise intensities from 100 to 150 W were followed in seven healthy, previously sedentary men, subjected to 10-week training. The training programme consisted of 30-min cycle exercise at 50%–70% of maximal oxygen uptake ( O_2max) three times a week. Every week during the first 5 weeks of training, and then after the 10th week the subjects underwent the submaximal three-stage exercise test (50, 100 and 150 W) with continuousf _c recording. At the completion of the training programme, the subjects' O_2max had increased significantly(39.2 ml·min^–1·kg^–1, SD 4.7 vs 46 ml·min^–1·kg^–1, SD 5.6) and the steady-statef _c at rest and at all submaximal intensities were significantly reduced. The greatest decrease in steady-statef _c was found at 150 W (146 beats·min^–1, SD 10 vs 169 beats·min^–1, SD 9) but the difference between the steady-statef _c at 150 W and that at 100 W (f _c) did not decrease significantly (26 beats·min^–1, SD 7 vs 32 beats·min^–1, SD 6). The time constant () of thef _c increase from the steady-state at 100 W to steady-state at 150 W increased during training from 99.4 s, SD 6.6 to 123.7 s, SD 22.7 (P<0.01) and the acceleration index (A=0.63·f _c·^–1) decreased from 0.20 beats·min^–1·s^–1, SD 0.05 to 0.14 beats·min^–1·s^–1, SD 0.04 (P<0.02). The major part of the changes in and A occurred during the first 4 weeks of training. It was concluded that heart acceleration following incremental exercise intensities slowed down in the early phase of endurance training, most probably due to diminished sympathetic activation.     

Pathways of phosphate transport in chick jejunum

The effect of vitamin D₃ on intestinal phosphate (P_i) absorption was studied in everted sacs prepared from jejunum of either vitamin D-deficient (–D) or vitamin D-replete (+D) chicks. Vitamin D₃ stimulates the maximal velocity (V _max) of a mucosal active P_i transport mechanism from 125 to 314 nmol·min^–1·g^–1 tissue.K _m of this process remains virtually unchanged (–D: 0.15 mmol·l^–1; + D: 0.18 mmol·l^–1).Active P_i entry into the epithelium depends on extracellular Na⁺. Reduction of buffer Na⁺ reducesV _max in the + D group to 182 nmol·min^–1·g^–1 tissue but has no significant effect in the –D animals (V _max=105 nmol·min^–1·g^–1 tissue). In this group, the predominant effect of Na⁺ substitution is a shift ofK _m to 1.13 mmol·l^–1, whileK _m in the +D group is changed only to 0.53 mmol·l^–1.Transeptithelial P_i transport in the + D group involves the mucosal phosphate pump and hence an intracellular pathway, proceeding at a rate of 48 nmol·min^–1·g^–1 tissue. This is in contrast to –D P_i transfer (8 nmol·l^–1·g^–1 tissue) which is by a diffusional, Na⁺-insensitive, and presumably paracellular pathway.Transepithelial calcium transport (–D: 3.3 nmol·min^–1·g^–1; + D: 7.6 nmol·min^–1·g^–1 tissue) does not require the presence of extracellular Na⁺ and apparently involves pathways different from those of the P_i absorptive system.Presented in part at the Annual Meeting of the Austrian Biochemical Society, Salzburg, September 1978     

Stroke volume response to progressive exercise in athletes engaged in different types of training

Summary Using the impedance cardiography method, heart rate ( _c) matched changes on indexed stroke volume (SI) and cardiac output (CI) were compared in subjects engaged in different types of training. The subjects consisted of untrained controls (C), volleyball players (VB) who spent about half of their training time (360 min · week^–1) doing anaerobic conditioning exercises and who had a maximal oxygen uptake ( ) 41% higher than the controls, and distance runners (D) who spent all their training time (366 min·week^–1) doing aerobic conditioning exercises and who had a 26% higher than VB. The subjects performed progressive submaximal cycle ergometer exercise (10 W·min^–1) up to _c of 150 beats·min^–1. In group C, SI had increased significantly (P<0.05) at _c of 90 beats·min^–1 ( + 32%) and maintained this difference up to 110 beats·min^–1, only to return to resting values on reaching 130 beats·min^–1 with no further changes. In group VB, SI peaked (+ 54%) at _c of 110 beats·min^–1, reaching a value significantly higher than that of group C, but decreased progressively to 22010 of the resting value on reaching 150 beats·min^–1. In group D, SI peaked at _c of 130 beats·min^–1 (+ 54%), reaching a value significantly higher than that of group VB, and showed no significant reduction with respect to this peak value on reaching 150 beats·min^–1. As a consequence, the mean CI increase per _c unit was progressively higher in VB than in C (+46%) and in D than in VB (+ 105%). It was concluded that thef _c value at which SI ceased to increase during incremental exercise was closely related to the endurance component in the training programme.     

Heart rate overshoot at the beginning of muscle exercise

Summary A characteristic notch in the heart rate (f _c) on-response at the beginning of square-wave exercise is described in 7 very fit marathon runners and 12 sedentary young men, during cycle tests at 30% and 60% of maximal oxygen consumption (VO_2max). The (f _c) notch revealed af _c overshoot with respect to the (f _c) values predicted from exponential beat-by-beat fitted models. While at 30% of (VO_2max). all subjects showed af _c over-shoot, at 60% of (VO_2max). it occurred in the marathon runners but not in the sedentary subjects. The mean time of occurrence of thef _c overshoot from the onset of the exercise was 16.7 (SD 4.7) s and 12.2 (SD 3.2) s at 30% of (VO_2max). in the runners and the sedentary subjects respectively, and 23.8 (SD 8.8) s at 60% of (VO_2max). in the runners. The amplitude of the overshoot, with respect to rest, was 41 (SD 12) beats·min^–1and 31 (SD 4) beats·min^–1 at 30% of (VO_2max). in the runners and the sedentary subjects respectively, and 46 (SD 19) beats·min^–1 at 60% of (VO_2max). in the runners. The existence and the amplitude of thef _c overshoot may have been related to central command and muscle heart reflex mechanisms and thus may have been indicators of changes in the balance between sympathetic and parasympathetic activity occurring in fit and unfit subjects.     

Perceived exertion and blood lactate concentration during graded treadmill running

The purpose of this study was to investigate the influences of treadmill gradients on the rating of perceived exertion (RPE) at two fixed blood lactate concentrations ( [La^–]_b). Ten subjects performed three different incremental treadmill protocols by running either uphill (concentrically-biased), downhill (eccentrically-biased), or on the flat (non-biased). Individual data of each protocol were interpolated to reflect [La^–]_b corresponding to 2.0 and 4.0 mmol·l^–1. At 2.0 mmol·l^–1 [La^– _b, RPE and treadmill speed during downhill running were greater than during level running which was greater than during uphill running (p < 0.05) . Also, the downhill heart rate (HR) was greater than the uphill HR, and downhill minute ventilation ( ) was greater than the level . Treadmill speed was the only measure at 4.0 mmol·l^–1 [La^–]_b to differ between gradients. There was a moderate correlation of RPE with HR at both [La^–]_b (r = 0.73 at 2.0 mmol·l^–1;r = 0.48 at 4.0 mmol·l^–1) while treadmill speed was moderately correlated with RPE only at 2.0 mmol·l^–1 [La^–]_b (r = 0.70). The results of this study demonstrated that the degree of eccentric-bias during running exercise is an influence of perceived exertion at a moderate but not at a high exercise intensity.     

Effect of very low calorie diet on body composition and exercise response in sedentary women

Summary The effect of very low calorie diet (VLCD) on fat-free mass (FFM) and physiological response to exercise is a topic of current interest. Ten moderately obese women (aged 23–57 years) received VLCD (1695 kJ·day^–1) for 6 weeks. FFM, estimated by four conventional techniques, and heart rate (f _c), blood lactate (la_b), mean arterial pressure (MAP), respiratory exchange ratio (R) and rating of perceived exertion (RPE) were measured during a submaximal cycle ergometry test 1 week bevore, in the 2nd and 6th week, and 1 week after VLCD treatment. Strength and muscular endurance of the quadriceps and hamstrings were tested by isokinetic dynamometry. The 11.5-kg reduction in body mass was approximately 63% fat and 37% FFM. The latter was attributed largely to the loss of water associated with glycogen. Whilst exercise f _c increased by 9–14 beats·min^–1 (P<0.01), there were substantial decreases (P<0.01) in submaximal MAP (1.07–1.73 kPa), lab (0.75–1.00 mmol·1^–1 and R (0.07–0.09) during VLCD. R and f _c returned to normal levels after VLCD. Gross strength decreased (P<0.01) by 9 and 13% at 1.05 rad·s^–1 and 3.14 rad·s^s–1, respectively. Strength expressed relative to body mass (Nm·kg^–1) increased (P<0.01) at the lower contraction velocity, but there was no change at the faster velocity. Muscular endurance also decreased (P<0.01) by 62 and 82% for the hamstrings and quadriceps, respectively: We concluded that the strength decrease was a natural adaptation to the reduction in body mass as the ratio of strength to FFM was maintained. Despite the physiological alterations, subjects could tolerate short-term, steady-state exercise during VLCD, with only slight increases in RPE. However, greater fatigue is associated with long duration strength training exercises during VLCD.     

Cardiovascular response to static handgrip in trained and untrained men

Summary The influence of aerobic capacity on the cardiovascular response to handgrip exercise, in relation to the muscle mass involved in the effort, was tested in 8 trained men (T) and 17 untrained men (U). The subjects performed handgrip exercises with the right-hand (RH), left-hand (LH) and both hands simultaneously (RLH) at an intensity of 25% of maximal voluntary contraction force. Maximal aerobic capacity was 4.3 l·min^–1 in T and 3.21·min^–1 in U (P<0.01). The endurance time for handgrip was longer in T than in U by 29% (P<0.05) for RH, 38% (P<0.001) for LH and 24% (P<0.001) for RLH. Heart rate (f _c) was significantly lower in T than in U before handgrip exercise, and showed smaller increases (P<0.01) at the point of exhaustion: 89 vs 106 beats·min^–1 for RH, 93 vs 100 beats·min^–1 for LH and 92 vs 108 beats·min^–1 for RLH. Stroke volume (SV) at rest was greater in T than in U and decreased significantly (P<0.05) during handgrip exercise in both groups of subjects. At the point of exhaustion SV was still greater in T than in U: 75 vs 57 ml for RH, 76 vs 54 ml for LH and 76 vs 56 ml for RLH. During the last seconds of handgrip exercise, the left ventricular ejection time was longer in T than in U. Increases in cardiac output (Q _c) and systolic blood pressure did not differ substantially between T and U, nor between the handgrip exercise tests. It was concluded that handgrip exercise caused similar increases inQ _c in both T and U but in T the increased level ofQ _c was an effect of greater SV and lowerf _c than in U. Doubling the muscle mass did not alter the cardiovascular response to handgrip exercise in either T or U.     

Effect of pyridostigmine on the exercise-heat response of man

Summary The effect of pyridostigmine on thermoregulatory responses was evaluated during exercise and heat stress. Eight heat acclimated, young adult male subjects received four doses of pyridostigmine (30 mg) or identical placebo tablets every 8 h, in a double blind, randomized, cross-over trial. A 30.3%, SD 4.6% inhibition of the circulating cholinesterase (ChE) activity was induced in the pyridostigmine-treated group. The subjects were exposed to 170-min exercise and heat-stress (dry bulb temperature, 33° C; relative humidity 60%) consisting of 60 min in a sitting position and two bouts of 50-min walking (1.39 m · s^–1, 5% gradient) which were separated by 10-min rest periods. No differences were found between treatments in the physiological responses and heat balance parameters at the end of exposure: heart rate (f _c) was 141 beats · min^–1, SD 16 and 150 beats · min^–1, SD 12, rectal temperature (T _re) was 38.5°C, SD 0.4° and 38.6°C, SD 0.3°, heat storage was 60 W · m^–2, SD 16 and 59 W · m^–2, SD 15 and sweat rate was 678 g · h^–1, SD 184 and 661 g · h^–1, SD 133, in the pyridostigmine and placebo treatments, respectively. The changes in T _re and f _c over the heat-exercise period were parallel in both study and control groups. Pyridostigmine caused a slight slowing of f _c (5 beats·min^–1) which was consistent throughout the entire exposure (P<0.001) but was of no clinical significance. The overall change in f_c was similar for both groups. We have concluded that pyridostigmine administration, in a dose sufficient to induce a moderate degree of ChE inhibition, does not significantly affect performance of exercise in the heat.     

Cardiac output during exercise in paraplegic subjects

Summary The purpose of this study was to measure the cardiac output using the CO₂ rebreathing method during submaximal and maximal arm cranking exercise in six male paraplegic subjects with a high level of spinal cord injury (HP). They were compared with eight able bodied subjects (AB) who were not trained in arm exercise. Maximal O₂ consumption ( O_2max) was lower in HP (1.1 1·min^–1, SD 0.1; 17.5 ml·min^–·kg, SD 4) than in AB (2.5 1·min^–1, SD 0.6; 36.7 ml·min^–1·kg, SD 10.7). Maximal cardiac output was similar in the groups (HP, 141·min^–1 SD 2.6; AB, 16.81·min^–1 SD 4). The same result was obtained for maximal heart rate (f _c,max (HP, 175 beats·min^–1, SD 18; AB, 187 beats·min^–, SD 16) and the maximal stroke volume (HP, 82 ml, SD 13; AB, 91 ml, SD 27). The slopes of the relationshipf _c/ O₂ were higher in HP than AB (P<0.025) but when expressed as a % O_2max there were no differences. The results suggests a major alteration of oxygen transport capacity to active muscle mass in paraplegics due to changes in vasomotor regulation below the level of the lesion.     

Respiratory and cardiac responses to exercise — simulating peripheral perfusion in endurance trained and untrained rats

Summary Ventilatory and circulatory drives elicited by exercise-simulating perfusion of the circulatory isolated hindleg were examined in 10 trained (TR) and untrained (UTR) rats. TR were submitted to endurance training on a motordriven treadmill (30·min^–1 at a grade of 10%, 5 days a week for 30 min). Exercise was simulated by perfusion with modified tyrode solutions:I.) hypoxic, enriched with lactic acid (15 mmol·l^–1), II.) normoxic, enriched with lactic acid. III.) hypoxic without lactic acid. Perfusion was performed in anaesthetized animals through cannulae in the femoral artery and vein; the hindled was connected to the rest of the body only by nerve and bone. 10 min of control perfusion (normoxic tyrode solution) was followed by a 20 min test period and another 10 min control perfusion. Apart from heart rate (HR), respiratory rate (RR) and several outflow parameters were measured ([K⁺], [Na⁺], [lactate], pH, PO₂, PCO₂). During control periods HR was slightly higher in UTR than in TR (375.5±3.9 (SE) vs. 364.1±5.5 beats/min^–1,p<0.6 n.s.), and RR in UTR was significantly higher than those in TR (61.5±0.4 bpm vs. 55.5±3.9 breaths·min^–1,p<0.001). During the test periods both HR and RR in UTR increased significantly while in TR they did not (e.g. in series I mean HR and RR in UTR increased by 8.9±1.2 beats·min^–1 and 1.4±0.1 breaths·min^–1 respectively, whereas in TR the changes were-2.9±1.5 beats·min^–1 and -0.8±0.2 breaths·min^–1. A significant difference between UTR and TR can only partly be due to diminished venous [H⁺] caused by better H⁺ buffering in TR. Particularly in the tests with lactic acid, lactate was far above threshold level. It can be concluded that the metabolic stimulus and the afferent branch of the cardiorespiratory reflex have been attenuated by endurance training.Dedicated to J. Stegemann on the occasion of his 60^th anniversary     

Electrophysiological effects of acetylcholine in sheep cardiac Purkinje fibers

The addition of acetylcholine (ACh) in concentrations of 10^–7 to 10^–5 mol·l^–1 to normal Tyrode solution results in the following changes of the electrical activity in sheep cardiac Purkinje fibers: prolongation of the action potential and shift of the plateau to more positive values, hyperpolarization of the maximum diastolic potential (E _max), and increase of the rate of diastolic depolarization.Prolongation of the action potential and shift of the plateau in the positive direction were more pronounced in distal Purkinje fibers, at low frequencies of stimulation, and in the presence of a reduced Ca (<3.6 mmol·l^–1) or K extracellular concentration (<5.4 mmol·l^–1); the effects persisted in Cl free media or after addition of Mn (2–10 mmol·l^–1) or verapamil (1–5 mg·l^–1).The effect of Ach on the maximum diastolic potential (stimulation frequency 60/min) was dependent on K₀. At 5.4 mmol·l^–1,E _max increased by 2 mV; at higher K₀ concentrations the change was less pronounced or absent; at low K₀ concentrations (membrane potential arrested at the plateau level) the addition of Ach invariably caused a depolarization. In unstimulated preparations the effect of Ach was unpredictable.The increase in rate of diastolic depolarization by Ach in 3.4 or 2.7 mmol·l^–1 K was large enough to result in spontaneous activity. When the membrane was depolarized to the plateau level (K₀<1.35 mmol·l^–1) Ach frequently reduced the frequency of oscillations.The effect of Ach was dose-dependent; desensitization was absent. Similar results were obtained with carbachol (10^–6 mol·l^–1) or choline (5·10^–3 mol·l^–1). The effect of Ach could selectively be abolished by atropine (10^–8 to 10^–6 mol·l^–1); it was not modified by succinylcholine (8·10^–5 mol·l^–1), phentolamine (10^–6 mol·l^–1) or propranolol (10^–6 mol·l^–1). The results indicate that the electrophysiological changes are due to stimulation of muscarinic receptors.Except for the hyperpolarization ofE _max the results in sheep Purkinje fibers are different and even opposite to those observed in the sino-atrial node and atrial muscle. Possible mechanisms and functional significance of the results are discussed.Supported by F.G.W.O. Belgium 3.0087.74     

Changes in acid-base status of marathon runners during an incremental field test

Summary Four top-class runners who regularly performed marathon and long-distance races participated in this study. They performed a graded field test on an artificial running track within a few weeks of a competitive marathon. The test consisted of five separate bouts of running. Each period lasted 6 min with an intervening 2-min rest bout during which arterialized capillary blood samples were taken. Blood was analysed for pH, partial pressure of oxygen and carbon dioxide (P0₂ and PCO₂) and lactate concentration ([la^–]_b). The values of base excess (BE) and bicarbonate concentration ([HCO₃ ^–]) were calculated. The exercise intensity during the test was regulated by the runners themselves. The subjects were asked to perform the first bout of running at a constant heart rate f _c which was 50 beats · min^–1 below their own maximal f _c. Every subsequent bout, each of which lasted 6 min, was performed with an increment of 10 beats · min^–1 as the target f _c. Thus the last, the fifth run, was planned to be performed with fc amounting to 10 beats · min^–1 less than their maximal f _c. The results from these runners showed that the blood pH changed very little in the bouts performed at a running speed below 100% of mean marathon velocity ( _m). However, once _mwas exceeded, there were marked changes in acid-base status. In the bouts performed at a velocity above the _mthere was a marked increase in [la^–]_b and a significant decrease in pH, [HCO₃ ^–], BE and PCO₂. The average marathon velocity ( _m) was 18.46 (SD 0.32) km·h^–1. The [la^–]_b at a mean running velocity of 97.1 (SD 0.8) % of _mwas 2.33 (SD 1.33) mmol ·l^–1 which, compared with a value at rest of 1.50 (SD 0.60) mmol·l^–1, was not significantly higher. However, when running velocity exceeded the vm by only 3.6 (SD 1.9) %, the [la^–]b increased to 6.94 (SD 2.48) mmol·l-1 (P<0.05 vs rest). We concluded from our study that the highest running velocity at which the blood pH still remained constant in relation to the value at rest and the speed of the run at which [la^–]_b began to increase significantly above the value at rest is a sensitive indicator of capacity for marathon running.     

Cardiac responses to maximal anisotonic isometric contractions during handgrip and leg extension

A group of 14-healthy men performed anisotonic isometric contractions (AIC), for 60 s, at an intensity of 100% maximal voluntary contraction force (MVC) during handgrip (HG) and leg extension (LE). Heart rate (f _c), stroke volume index (SVI) and cardiac output index (Q_cI) were measured during the last 10 s of both AIC by an impedance reography method. Force (F) exerted by the subjects was recorded continuously and reported as a relative force (F _r) (% MVC). The F generated during MVC was greater for LE than for HG (502.I N compared to 374.6 N, P < 0.001). The rate of decrease in F _r was significantly slower for LE than HG for the first 25 s of the exercise (phase 1 of AIC). The F _r developed by the subjects at the end of AIC was 40% MVC for both LE and HG. The increase in f _c was greater for LE (63 beats · min^–1) than for HG (52 beats · min^–1), P < 0.01. The SVI decreased significantly from the resting level by 17.0 ml · m^–2 and by 18.2 ml · m^–2 for LE and HG, respectively. The Q_cI increased insignificantly for HG by 0.091 · min^–1 · m^–2 andsignificantly forLE by 0.561 · min^–1 · m^–2 (P < 0.001). It was concluded that although both AIC caused a significant decrease in SVI, greater increases in f _c and Q_c were observed for LE than for HG. The greater f _c and Q_c reported during LE was probably related to the greater relative force exerted by LE during phase 1 of AIC. It seems, therefore that central command might have dominated for phase 1 of AIC but that the muscle reflex also contributed significantly to the control of the cardiac response to the high intensity AIC.     

Ca2+ influx induced by store release and cytosolic Ca2+ chelation in HT29 colonic carcinoma cells

Cl^– secretion in HT₂₉ cells is regulated by agonists such as carbachol, neurotensin and adenosine 5-triphosphate (ATP). These agonists induce Ca²⁺ store release as well as Ca²⁺ influx from the extracellular space. The increase in cytosolic Ca²⁺ enhances the Cl^– and K⁺ conductances of these cells. Removal of extracellular Ca²⁺ strongly attenuates the secretory response to the above-mentioned agonists. The present study utilises patch-clamp methods to characterise the Ca²⁺ influx pathway. Inhibitors which have been shown previously to inhibit non-selective cation channels, such as flufenamate (0.1 mmol·l^–1, n=6) and Gd³⁺ (10 mol·l^–1, n=6) inhibited ATP (0.1 mmol·l^–1) induced increases in whole-cell conductance (G _m). When Cl^– and K⁺ currents were inhibited by the presence of Cs₂SO₄ in the patch pipette and gluconate in the bath, ATP (0.1 mmol·l^–1) still induced a significant increase in G _m from 1.2±0.3 nS to 4.7±1 nS (n=24). This suggests that ATP induces a cation influx with a conductance of approximately 3–4 nS. This cation influx was inhibited by flufenamate (0.1 mmol·l^–1, n=6) and Gd³⁺ (10 mol·l^–1, n=9). When Ba²⁺ (5 mmol·l^–1) and 4,4-diisothiocyanatostilbene-2-2-disulphonic acid (DIDS, 0.1 mmol·l^–1) were added to the KCl/K-gluconate pipette solution to inhibit K⁺ and Cl^– currents and the cells were clamped to depolarised voltages, ATP (0.1 mmol·l^–1) reduced the membrane current (I _m) significantly from 86±14 pA to 54±11 pA (n=13), unmasking a cation inward current. In another series, the cation inward current was activated by dialysing the cell with a KCl/K-gluconate solution containing 5–10 mmol·l^–1 1,2-bis-(2-aminoethoxy)ethane-N,N,N,N-tetraacetic acid (EGTA) or 1,2-bis-(2-aminophenoxy) ethane-N,N,N,N-tetraacetic acid (BAPTA). The zero-current membrane voltage (V _m) and I _m (at a clamp voltage of +10 mV) were monitored as a function of time. A new steady-state was reached 30–120 s after membrane rupture. V _m depolarised significantly from –33±2 mV to –12±1 mV, and I _m fell significantly from 17±2 pA to 8.9±1.0 pA (n=71). This negative current, representing a cation inward current, was activated when Ca²⁺ stores were emptied and was reduced significantly (I _m) when Ca²⁺ and/or Na⁺ were removed from the bathing solution: removal of Ca²⁺ in the absence of Na⁺ caused a I _m of 5.0±1.2 pA (n=12); removal of Na⁺ in the absence of Ca²⁺ caused a I _m of 12.8±3.5 pA (n=4). The cation inward current was also reduced significantly by La³⁺, Gd³⁺, and flufenamate. We conclude that store depletion induces a Ca²⁺/Na⁺ influx current in these cells. With 145 mmol·l^–1 Na⁺ and 1 mmol·l^–1 Ca²⁺, both ions contribute to this cation inward current. This current is an important component in the agonist-regulated secretory response.     

Intravenous instrumentation alters the autonomic state in humans

Intravascular instrumentation may induce syncope or presyncope. It is not known whether asymptomatic subjects also have autonomic reactions, albeit concealed. We addressed this issue by studying 44 healthy young male subjects of various levels of fitness, ranging from inactivity to athletic [mean maximal oxygen uptake was 49.1 (SD 10.7) ml·kg^–1·min^–1, range 28.7–71.9 ml·kg^–1·min^–1]. The autonomic response to venous cannulation was quantified by measuring heart rate before cannulation (HR1), after cannulation (HR₂), and after complete pharmacological autonomic blockade (HR₀ = the intrinsic heart rate). The sympathovagal balance before and after cannulation was computed as HR₁/HR₀ and HR₂/HR₀, respectively. The group means of heart rate and sympathovagal balance decreased significantly (paired Student's t-test P <0.01) from 62.5 to 59.9 beats·min^–, and from 0.71 to 0.68, respectively. The maximal decrease in heart rate was 8.8 beats·min^–1, and in the sympathovagal balance was 0.11. Our study demonstrated that the asymptomatic subjects responded to intravenous instrumentation with a concealed autonomic reaction. Thus, from our findings it would seem that intravenous instrumentation interferes with measurements relating to autonomic nervous system activity.     

Transport ofl-cystine in isolated perfused proximal straight tubules

Unidirectional fluxes ofl-³⁵S-cystine and intracellular³⁵S activity were measured in isolated perfused segments of rabbit proximal straight tubule. The absorptive (lumen-to-both) flux ofl-³⁵S-cysteine showed a tendency toward saturation within the concentration limits imposed by the low solubility of cystine (0.3 mmol·l^–1). In contrast, for the bath-to-lumen fluxes, there was a linear relation between the bathing solution concentration ofl-³⁵S-cystine and the rate of³⁵S appearance in the lumen. Nonlinear fitting of both sets of unidirectional flux data gave a maximal cystine transport rate (J _max) of 1.45±0.27 (SEM) pmol min^–1 mm^–1, a Michaelis constant (K _m) of 0.20±0.07 mmol·l^–1, and an apparent permeability coefficient of 0.27±0.11 pmol min^–1 mm^–1 (mmol·l^–1)^–1 (approximately 0.06 m/s). The³⁵S concentration in the cell exceeded that in the lumen by almost 60-fold during the lumen-to-bath flux, and exceeded the bathing solution concentration by 4.7-fold during the bath-to-lumen flux. Thus cystine was accumulated by the cells across either membrane, but over 77% of the intracellular activity was in the form of cysteine. Although the presence of luminall-lysine or cycloleucine inhibited the absorptive flux of cystine, neither amino acid affected the bath-to-lumen flux.Some of the work described here was presented as an abstract at the 8th International Congress of Nephrology, Athens, Greece, 1981     

Neuromuscular characteristics and fatigue in endurance and sprint athletes during a new anaerobic power test

The purpose of this study was to investigate neuromuscular and energy performance characteristics of anaerobic power and capacity and the development of fatigue. Ten endurance and ten sprint athletes performed a new maximal anaerobic running power test (MARP), which consisted ofn x 20-s runs on a treadmill with 100-s recovery between the runs. Blood lactate concentration [la^–]_b was measured after each run to determine submaximal and maximal indices of anaerobic power (P _3mmol·1 ^–1,P_5mmol·1 ^–1,P_10mmol·1 ^–1andP _max) which was expressed as the oxygen demand of the runs according to the American College of Sports Medicine equation: the oxygen uptake (ml·kg^–1·min^–1)=0.2·velocity (m·min^–1) +0.9·slope of treadmill (frac)·velocity (m·min^–1)+3.5. The height of rise of the centre of gravity of the counter movement jumps before (CMJ_rest) and during (CMJ) the MARP test, as well as the time of force production (t _F) and electromyographic (EMG) activity of the leg muscles of CMJ performed after each run were used to describe the neuromuscular performance characteristics. The maximal oxygen uptake ( _max), anaerobic and aerobic thresholds were determined in the _max test, which consisted ofn x 3-min runs on the treadmill. In the MARP-testP _max did not differ significantly between the endurance [116 (SD 6) ml·kg^–1·min^–1] and sprint [120 (SD 4) ml·kg^–1·min^–1] groups, even though CMJ_rest and peak [la^–]_b were significantly higher and _max was significantly lower in the sprint group than in the endurance group and CMJ_rest height correlated withP _max (r=0.50,P<0.05). The endurance athletes had significantly higher mean values ofP _3mmol·1 ^–1andP _5mmol·1 ^–1[89 (SD 7) vs 76 (SD 8) ml·kg^–1·min^–,P<0.001 and 101 (SD 5) vs 90 (SD 8) ml·kg^–1·min^–1,P<0.01. Significant positive correlations were observed between theP _3mmol·l ^–1and _max, anaerobic and aerobic thresholds. In the sprint group CMJ and the averaged integrated iEMG decreased andt _F increased significantly during the MARP test, while no significant changes occurred in the endurance group. The present findings would suggest thatP _max reflected in the main the lactacid power and capacity and to a smaller extent alactacid power and capacity. The duration of the MARP test and the large number of CMJ may have induced considerable energy and neuromuscular fatigue in the sprint athletes preventing them from producing their highest alactacidP _max at the end of the MARP test. Due to lower submaximal [la^–]_b (anaerobic sprinting economy) the endurance athletes were able to reach almost the sameP _max as the sprint athletes.     

Coupling of metabolic CO2 production to ion transport in isolated rat thick ascending limbs and collecting tubules

Metabolic CO₂ production from appropriate [U-¹⁴C]-labelled substrates (eitherl-lactate ord-glucose) was measured in single pieces of tubule as previously described (Le Bouffant et al. 1984). Changing the incubate osmotic pressure by mannitol addition resulted in an increase in oxidative metabolism which was more marked in outermedullary segments (MAL and MCT) than in cortical segments (CAL and CCT). Availability of metabolic substrate was not rate limiting under these conditions because FCCP addition (1 mol·l^–1) produced a marked rise in CO₂ production in these structures.Ouabain (1 mmol·l^–1) decreased by more than 50% the CO₂ production by CAL, MAL, CCT and MCT samples, indicating that the larger part of oxidative metabolism was coupled to active Na transport. Furosemide addition (10^–5 mol·l^–1) to CAL and MAL samples, or amiloride addition (10^–4 mol·l^–1) to CCT and MCT samples reduced the rate of CO₂ production to an extent almost similar to that obtained with ouabain, an observation suggesting that apical entry of Na⁺ was present in these non-perfused tubules.Finally, the effects of changing the concentration of either K⁺ or Cl^– was tested in CAL samples. K⁺ suppression greatly depressed the rate of CO₂ production. Replacement of chloride with sulfate also decreased this rate to an extent similar to that observed with furosemide. The CO₂ production increased in a sigmoid way (apparentK _a=41 mmol·l^–1, Hill coefficient=2.12) as a function of [Cl^–] in the incubate, suggesting that oxidative metabolism was coupled to bath chloride via the Cl^–-requiring Na entry along the 1 Na⁺–1K⁺–2Cl^– luminal contrasport system.     

The effects of extracellular potassium,ouabain, and prostaglandins on intracellular potassium activity in sheep cardiac Purkinje fibers

(1) Intracellular K activity (a _K ⁱ ) of sheep heart Purkinje fibers was measured using K-selective microelectrodes (liquid ion exchanger).a _K ⁱ in the resting state with an extracellular K of 4 mmol·l^–1 was 112.9±6.1 mmol·l^–1 (n=47) for a membrane potential (V _M) of –73.3±0.9 mV.V _M deviated from the calculated potassium equilibrium potential (E _K=–93 mV). (2) When extracellular K was decreased to 2 mmol·l^–1 or increased to 6 and 10 mmol·l^–1 E _K changed from –114 to –84 and –73 mV, with little change ina _K ⁱ . (3)a _K ⁱ andV _M significantly decreased after administration of 10^–6 mol·l^–1 ouabain. (4) Prostaglandins (PGI₂ 10–100 g·l^–1 and PGE₂ 0.01–1 g·l^–1) decreaseda _K ⁱ without greatly changingV _M. The differences betweenV _M andE _K became smaller. These effects indicate an increase in K permeability and may explain the antiarrhythmic action of prostaglandins.This study was supported by the Deutsche Forschungsgemeinschaft (grant Wi 328). In preliminary form part of the data has been presented (Pflügers Arch. 384: R 13, 1980, and Proc. XXVIII. Int Congr Physiol Sci, Vol XIV: 279, 1980)