Linkage analysis using multiple DNA polymorphic markers in normal families and in families with fragile X syndrome

Summary Linkage data, using the polymorphic markers 52A (DXS51), F9, 4D-8(DXS98), and St14(DXS52), are presented from 14 fragile X pedigrees and from 7 normal pedigrees derived from the collection of the Centre d'Étude du Polymorphisme Humaine. A multipoint linkage analysis indicates that the most probable order of these four loci in normal families is DXS51-F9-DXS98-DXS52. Recombination frequencies ( ) corresponding to maximum LOD scores ( ) were obtained by two-point linkage analysis for a nuber of linkage groups, including: DXS51-F9 ( =5.94, =0.03), F9-DXS98 ( =0.51, =0.26), F9-DXS52 ( =0.84, =0.27), and DXS98-DXS52 ( =0.32, =0.20). A multipoint linkage analysis of these loci, including the fragile X locus, was also performed for the fragile X population and the data support the relative order (DSX51, F9, DXS98)-FRAXA-DXS52. Recombination frequencies and maximum LOD scores, which again were derived from two-point linkage analyses, were obtained for the linkage groups DXS51-F9 ( =9.96, =0) and F9-DXS52 ( =0.07, =0.45), as well as for the groups DXS51-FRAXA ( =2.42, =0.15), F9-FRAXA ( =1.30, =0.18), DXS98-FRAXA ( =0.05 =0.36), and DXS52-FRAXA ( =2.42 =0.15). The linkage data was further tested for the presence of genetic heterogeneity both within and between the fragile X and normal families for the intervals DXS51-F9, F9-DXS52, F9-FRAXA, and DXS52-FRAXA using a modification of the A test. Except for the interval F9-FRAXA (P<0.10) there was no evidence of genetic heterogeneity for each of the various linkage groups examined. The heterogeneity detected for the interval F9-FRAXA, however, was most likely due to one family (Fx-28) that displayed very tight linkage between these two loci.     

Evidence for linkage of the gene causing familial Mediterranean fever to chromosome 17q in non-Ashkenazi Jewish families: second locus or type I error?

Familial Mediterranean fever (FMF) is an autosomal recessive disorder of unknown pathogenesis, characterized by recurrent, selflimited attacks of fever with synovitis, peritonitis, or pleurisy. Using DNAs from affected Israeli families, we have recently mapped the gene causing FMF (designated MEF) to the short arm of chromosome 16, with two-point lod scores in excess of 20. In this report we consider the possibility of a second FMF susceptibility locus. Before discovering linkage to markers on chromosome 16, we had found suggestive evidence for linkage to chromosome 17q, with the following maximal two-point lod scores: D17S74 (pCMM86), = 2.47, ( = 0.20); D17S40 (pLEW101), = 2.15( = 0.15); D17S35 (CRI-pP3-1), = 1.78 ( = 0.15); D17S46 (pLEW108), = 1.69 ( = 0.18), D17S254, = 2.30 ( = 0.20). Moreover, multipoint linkage analysis using D17S74 and D17S40 as fixed loci gave = 3.27 approximately 10 centimorgans (cM) telomeric to D17S40. Data with the chromosome 17 markers alone in our families suggested locus heterogeneity. Nevertheless, our families were not separable into complementary subsets showing linkage either to chromosome 16 or to chromosome 17. We also examined the possibility that the positive lod scores for chromosome 17 might reflect a secondary, modifying locus. By several measures of disease severity, families with positive lod scores for chromosome 17 loci had no worse disease than those with negative lod scores for these loci. We conclude that chromosome 17 does not encode a major FMF susceptibility gene for some of the families, nor does it encode a disease-modifying gene. Rather, it would appear that linkage to chromosome 17 is a false positive (type I) error. These results reemphasize the fact that a lod score of 3.0 corresponds to a posterior probability of linkage of 95%, with an attendant 1 in 20 chance of observing a false positive.     

Likely linkage: Inv with Jk

Summary In a data base consisting of 1665 pairs of loci linkage between Inv and Jk is significant . Recombination is nearly the same in the two sexes . The reason why this linkage was not noticed earlier is discussed.     

Breathing pattern and growth: comparative aspects

Summary The resting oxygen consumption and breathing pattern of nine newborn and adult species (ranging in body size from mouse to human) have been compared on the basis of data collected from the literature. Minute ventilation is similarly linked to at both ages, the percent of extracted as O₂ about 2.2. Tidal volume/kg is an interspecies constant in newborns and adults, approximately 8 ml/kg. Breathing frequency decreases with the increase in size in a different way at the two ages: large species have newborns breathing at rates 2–3 times above the corresponding adults' values, while in the small species newborns and adults breathe at almost the same rate. Therefore the newborns of the smallest species have both and below the expected values, implying a greater inability to cope with the external demands than newborns of larger species. Several considerations indicate that in the smallest newborns the mechanical properties of the respiratory system could be a constraint to resting ventilations larger than observed. It is therefore possible that their low is the cause, and not the effect, of the relatively small .     

Estimating the Recombination frequency for the PTC-Kell linkage

Summary Two data sets are analyzed for linkage between the PTC and Kell blood group loci. The original report of close linkage for these loci was that of Conneally et al. (1976), where the maximum likelihood estimate of was 0.05. These two new data sets give a combined maximum likelihood estimate of _m=f =0.28. Estimating the recombination frequency for the sexes separately gave _m =0.29, _f =0.23. The combined maximum likelihood estimate over all published data sets including this report is _m=f =0.14, _max=8.94. There is statistically significant evidence of heterogeneity among the published studies.     

Dynamics of cardiorespiratory function in Standardbred horses during different intensities of constant-load exercise

Summary Six Standardbred horses were used to evaluate the time course of pulmonary gas exchange, ventilation, heart rate (HR) and acid base balance during different intensities of constant-load treadmill exercise. Horses were exercised at approximately 50%, 75% and 100% maximum oxygen uptake ( max) for 5 min and measurements taken every 30 s throughout exercise. At all work rates, the minute ventilation, respiratory frequency and tidal volume reached steady state values by 60 s of exercise. At 100% max, the oxygen consumption ( ) increased to mean values of approximately 130 ml/kg·min, which represents a 40-fold increase above resting . At the low and moderate work rates, showed no significant change from 30 s to 300 s of exercise. At the high work rate, the mean at 30 s was 80% of the value at 300 s. The HR showed no significant change over time at the moderate work rate but differing responses at the low and high work rates. At the low work rate, the mean HR decreased from 188 beats/min at 30 s to 172 beats/min at 300 s exercise, whereas at the high work rate the mean HR increased from 204 beats/min at 30 s to 221 beats/min at 300 s exercise. No changes in acid base status occurred during exercise at the low work rate. At the moderate work rate, a mild metabolic acidosis occurred which was nonprogressive with time, whereas the high work rate resulted in a progressive metabolic acidosis with a base deficit of 16 mmol/l by 300 s exercise. It is concluded that the kinetics of gas exchange during exercise are more rapid in the horse than in man, despite the relatively greater change in in the horse when going from rest to high intensity exercise.Symbols and abbreviations E minute ventilation - V _T tidal volume - oxygen uptake - carbon dioxide output - oxygen pulse - ventilatory equivalent for oxygen - ventilatory equivalent for carbon dioxide - R respiratory exchange ratio - HR heart rate - SBC standard bicarbonate - STPD standard temperature and pressure dry - BTPS body temperature and pressure saturated - arterial oxygen content - arteriovenous oxygen content difference - Rf respiratory frequency     

Influence of lifting technique on perceptual and cardiovascular responses to submaximal repetitive lifting

Oxygen consumption ( O₂), heart rate, ventilation and central rating of perceived exertion (RPE) in repetitive lifting while executing squat and stoop techniques were investigated in ten male forestry workers. In all five mass/frequency combinations studied, O₂ was significantly higher for the squat than for the stoop technique. No differences were found in RPE between the techniques. The O₂ and RPE recordings were also related to those obtained during maximal repetitive lifting (same lifting technique) and maximal treadmill running. The O₂ expressed as a percentage of that obtained during maximal repetitive lifting with the same lifting technique was defined as relative aerobic intensity (% O_{2max, lifting}). The % O_{2max, lifting} was not significantly different between the techniques except for the lowest mass lifted (1 kg). This study therefore would support the hypothesis that RPE is more closely related to % O_{2max, lifting} than to absolute aerobic intensity. Related to maximal treadmill running, it was demonstrated for both lifting techniques that relative RPE (percentage of the RPE during maximal running) was more accurate than relative O₂ (percentage of maximal O₂ during maximal running) for determining the % O_{2max, lifting} in repetitive lifting. The study showed that the higher O₂ during squat. lifting compared to stoop lifting was caused by the O₂ expended in lifting and lowering the body rather than the O₂ expended lifting and lowering the external mass. It was concluded that the stoop technique was not superior to the squat technique in terms of central RPE. Based on % O_{2max, lifting}, there may be a rationale for choosing the stoop technique during repetitive lifting with light masses, but not with heavy masses.     

Aerobic and anaerobic contribution to Wingate test performance in sprint and middle-distance runners

We investigated the aerobic and anaerobic contributions to performance during the Wingate test in sprint and middle-distance runners and whether they were related to the peak aerobic and anaerobic performances determined by two commonly used tests: the force-velocity test and an incremental aerobic exercise test. A group of 14 male competitive runners participated: 7 sprinters, aged 20.7 (SEM 1.3) years, competing in 50, 100 and 200-m events and 7 middle-distance runners, aged 20.0 (SEM 1.0) years, competing in 800, 1,000 and 1,500 m-events. The oxygen uptake ( ) was recorded breath-by-breath during the test (30 s) and during the first 20 s of recovery. Blood samples for venous plasma lactate concentrations were drawn at rest before the start of the test and during the 20-min recovery period. During the Wingate test mean power ( ) was determined and three values of mechanical efficiency, one individual and two arbitrary, 16% and 25%, were used to calculate the contributions of work by aerobic ( _{aer,ind,16%,25%}) and anaerobic ( _{an,ind,16%,25%}) processes. Peak anaerobic power ( _an,peak) was estimated by the force-velocity test and maximal aerobic energy expenditure ( _aer,peak) was determined during an incremental aerobic exercise test. During the Wingate test, the middle-distance runners had a significantly greater than the sprinters (P < 0.001), who had significantly greater venous plasma lactate concentrations (P < 0.001). Moreover, _{aer,ind,16%,25%} were also significantly higher (P < 0.05) in the middle-distance runners [ _aer,ind 45 (SEM 4) % vs 28 (SEM 2) %; _aer,16% 30 (SEM 3) % vs 19 (SEM 2) %; _aer,25% 46 (SEM 3) % vs 29 (SEM 2)%]; _{an,ind,16%,25%} in the sprint runners (P < 0.05) [ _an,ind 72 (SEM 3) % vs 55 (SEM 4) %; _an,16% 81 (SEM 2) % vs 70 (SEM 3) %; _an,25% 71 (SEM 2) % vs 54 (SEM 3) %]. The _aer,ind/ _aer,peak and × _an,ind/ _an,peak ratios, however, were not significantly different between the two groups of athletes. These results would indicate that the sprinters and middle-distance runners used preferentially a metabolic system according to their speciality. Nevertheless, under the conditions of its experiment, they seemed to rely on the same percentage of both peak anaerobic and peak aerobic performance for a given exercise task.     

Respiratory responses of elite oarsmen, former oarsmen, and highly trained non-rowers during rowing, cycling and running

The position of the body and use of the respiratory muscles in the act of rowing may limit ventilation and thereby reduce maximal aerobic power relative to that achieved in cycling or running, in spite of the greater muscle mass involved in rowing. This hypothesis was investigated for three groups of male subjects: nine elite senior oarsmen, eight former senior oarsmen and eight highly trained athletes unskilled in rowing. The subjects performed graded exercise to maximal effort on a rowing ergometer, cycle ergometer and treadmill while respiratory minute volume and oxygen consumption were monitored continuously. The VE at a given during intense submaximal exercise (greater than 75% of maximal ) was not significantly lower in rowing compared with that in cycling and treadmill running for any group, which would suggest that submaximal rowing does not restrict ventilation. At maximal effort, and for rowing were less than those for the other types of exercise in all the groups, although the differences were not statistically significant in the elite oarsmen. These data are consistent with a ventilatory limitation to maximal performance in rowing that may have been partly overcome by training in the elite oarsmen. Alternatively, a lower maximal VE in rowing might have been an effect rather than a cause of a lower maximal if maximal was limited by the lower rate of muscle activation in rowing.     

Activity and oxygen consumption during hypoxic exposure in high altitude and lowland sceloporine lizards

Summary Resting rates of O₂ consumption against , exercise endurance times and during recovery from vigorous exercise were measured inSceloporus occidentalis captured near sea level and inS. graciosus captured above 2850 m. Oxygen consumption against was also measured inS. occidentalis captured above 2850 m. When was recorded continuously, as ambient was slowly reduced from 155 Torr, it became directly dependent upon ambient between 110 and 120 Torr. The critical for the high altitude lizards was lower than that for the lowland lizards, which enabled the former to maintain relatively higher 's when ambient was reduced below 120 Torr. The high altitude lizards also had significantly greater endurance when stimulated to exercise at 1600 m ( 130 Torr). Both the higher under hypoxia and the greater endurance roughly parallel a significantly greater maximum in the high altitude lizards. At a simulated altitude of 3600 m ( 100 Torr), maximum and rate of recovery of the O₂ debt calculated from post active were significantly reduced in the lowland but not the high altitude lizards. The effects of simulated altitude conditions on the lowland but not the mountaine animals indicate adaptations to altitude in these sceloporine lizards. We did not find any consistent relationship between organ/body weight ratios or hematocrit and our measures of endurance or the altitude at which the lizards were captured.     

Estimation of surface charges in some biological membranes

Summary The resting membrane potential data existing in the literature for the giant axon of the squid, frog muscle and barnacle muscle have been analyzed from the standpoint of the theory of membrane potential due to Kobatake and co-workers. The average values derived for the effective charge density (where is a constant, , and represents the fraction of counterions that are free, and is the stoichiometric charge density in the membrane) present on the different biomembranes existing in their normal ionic environment are 0.3, 0.325 and 0.17 M for the squid axon, frog and barnacle muscles, respectively. On the assumption that the values of are 0.4 and 0.2 for nerve and muscle membranes, respectively, values of 0.75, 1.62 and 0.85 M have been derived for the stoichiometric charge density present in the respective biological membranes. These correspond to 1 negative charge per 222, 103 and 195 Å of the membrane area of the squid axon, frog and barnacle muscles, respectively.     

Energetics of vocalization by an anuran amphibian (Hyla versicolor)

Summary The metabolic demands of vocalization byHyla versicolor were determined by measuring oxygen consumption and whole body lactate content of calling animals. A stepwise multiple regression analysis identified both calling rate (calls/h) and call duration (s/call) as significant determinants of oxygen consumption during calling. These two variables accounted for 84% of the total variation in oxygen consumption observed in calling frogs. Aerobic metabolism increased linearly with calling rate and call duration, reaching a peak value of 1.7 ml O₂/(g·h) at the highest vocalization effort. For comparison, metabolic rates of the same individuals were also measured during short bouts of vigorous locomotor exercise induced by mechanical stimulation. The mean value of was only 62% of the peak , and 5 of 13 frogs had rates of oxygen consumption during calling that exceeded their . Whole body lactate levels were measured in two samples of calling frogs, one collected early in the evening (2100–2115 h) and the other 1.5 h later (2230–2245 h). The frogs in the second sample had significantly lower lactate levels (0.10 mg/g) than the frogs collected early in the evening (0.22 mg/g). Hence, vocalization does not entail the use of anaerobic metabolism, although lactate levels may be slightly elevated at the onset of an evening of calling. Calling rates of unrestrained frogs in a large chorus were measured at regular intervals during an evening. During the first half hour of calling, rates increased gradually from an initial mean value of 600 calls/h at 2030 h to nearly 1400 calls/h at 2100 h. These data indicate that acoustic advertisement byHyla versicolor is among the most energetically expensive activities regularly undertaken by any anuran, and indeed, is the most demanding yet measured in an ectothermic vertebrate.Abbreviations resting rate of oxygen consumption - maximum rate of oxygen consumption - rate of oxygen consumption during forced exercise - rate of oxygen consumption during calling     

Effects of root temperature on uptake of nitrate and ammonium ions by barley grown in flowing-solution culture

Summary Barley plants (Hordeum vulgare L.) grown from seed for 28 days in flowing solution culture were subjected to different root temperatures (3, 5, 7, 9, 11, 13, 17, 25°C) for 14 days with a common air temperature of 25/15°C (day/night). Uptake of NH₄ and NO₃ ions was monitored separately and continuously from solutions maintained at 10 M NH₄NO₃ and pH 6.0. Effects of root temperature on unit absorption rate , flux and inflow were compared. After 5 days , and increased with temperature over the range 3–11°C for NH₄ ions and over the range 3–13°C for NO₃ ions, with little change for either ion above these temperatures. Q₁₀ temperature coefficients for NH₄ ions (3–13°C) were 1.9, 1.7 and 1.6 for , and respectively, the corresponding values for NO₃ ions being 5.0, 4.5 and 4.6. For both ions, , and changed with time as did their temperature dependence over the range 3–25°C, suggesting that rates of ontogenetic development and the extent of adaptation to temperature may have varied among treatments.     

Times to exhaustion at 100% of velocity at [(V)\dot]\textO\text2 \dot V{\text{O}}_{\text{2}} max and modelling of the time-limit / velocity relationship in elite long-distance runners

The aim of this study was to measure running times to exhaustion (Tlim) on a treadmill at 100% of the minimum velocity which elicits _{max max} in 38 elite male long - distance runners _max = 71.4 ± 5.5 ml.kg^–1.min^–1 and _max = 21.8 ± 1.2 km.h^–1). The lactate threshold (LT) was defined as a starting point of accelerated lactate accumulation around 4 mM and was expressed in _max. Tlim value was negatively correlated with _max (r = -0.362, p< 0.05) and _max (r = –0.347, p< 0.05) but positively with LT (%v _max) (r = 0.378, p < 0.05). These data demonstrate that running time to exhaustion at _max in a homogeneous group of elite male long-distance runners was inversely related to _max and experimentally illustrates the model of Monod and Scherrer regarding the time limit-velocity relationship adapted from local exercise for running by Hughson et al. (1984) .     

Prediction of individual oxygen uptake on-step transients from frequency responses

Power-oxygen uptake ( ) frequency responses can be used to predict responses to arbitrary exercise intensity patterns. It is still an open question for which range of exercise intensities such computed response patterns yield valid predictions. In the present study, we determined the power- frequency response of nine sports students by means of pseudo-randomised switching between 20 W and 80 W during upright and supine cycle exercise. Starting from a baseline of 20 W each subject also performed sustained step increases to 40 W, 80 W, 120 W, and 160 W in both positions. The individual step responses were then compared with the expected time-courses predicted on the basis of the individual frequency responses. The comparison showed a close agreement for the 20 W–40 W and 20 W–80 W steps in both positions. With larger step amplitudes the kinetics became increasingly slower than the predicted time course in both positions. During additional ramp tests (10 W · 30 s^–1) whole blood lactic acid concentration [1a^–]_b tended to be higher in the supine position at exercise intensities higher than 160 W. The mean power at 4 mmol · 1^–1 [la^–]_b amounted to 234 (SD 32) W and 253 (SD 44) W (P<5%) in the supine and the upright position, respectively. The maximal oxygen uptake relative to body mass was not found to be significantly different [upright, mean 57 (SD 10) ml · (min · kg)^–1;supine, mean 54 (SD 10) ml · (min · kg)]. These findings would suggest that for a range of mild exercise intensities kinetics are not appreciably influenced by the step amplitude or by cardiovascular changes associated with the upright and the supine position.     

The estimation of Wright's fixation index from genotypic frequencies

For populations in which the genotypic frequencies are estimated, it is customary to test the deviation of the estimates from those predicted by the Hardy-Weinberg Law using the x² goodness-of-fit statistic. Maximum likelihood estimation ofWright's F statistic and its variance furnishes a similar test. Following the derivation of the variance of , this note reviews the relation between the two tests. The F statistic possesses the advantages of full sufficiency and an easier formulation of the power function. Its bias is negligible when sample size exceeds 20.     

Temperature induced peripheral blood flow changes in lizards

Summary The influence of local temperature changes within the posterior portion of the body on dorsal aorta blood flow ( ), femoral arterial pressure (P _a ), peripheral resistance (R), skin blood flow ( ) and skeletal muscle blood flow ( ) was examined in unanesthetized lizards (Iguana iguana andTubinambis nigropunctatus). In response to local heating of the hind legs and tail and increased,P _a was generally unchanged,R decreased and decreased or was unchanged (Fig. 2). It is suggested that the acquisition of heat may be favored by diverting the increase in away from the muscle to the warmer skin. In response to cooling and decreased,P _a was generally unchanged, R increased and increased or was unchanged. Hence, during cooling the retention of heat may be favored by diverting blood away from the skin to the deeper muscle. The muscle-skin shunt is under sympathetic control since following blockade with phenoxybenzamine HCL (Dibenzyline) muscle blood flow changes in response to temperature were qualitatively similar to those of skin (Fig. 4). These changes in peripheral circulatory patterns are independent of changes in heart rate or deep body temperature.Baker and Weathers were predoctoral and postdoctoral trainees, respectively, under USPHS Grant HE-05696. This study was also supported by NSF Grant GB-8523 and Los Angeles County Heart Association Grant 437IG.     

Shifts of thermogenesis in the prairie vole (Microtus ochrogaster)

Summary The weight-specific oxygen consumption ( ) of prairie voles caught in winter is 24% higher at 27.5° C and 29% higher at 7.5° C than that of summer animals, thus affording a higher weight-specific thermogenesis in winter than in summer which may allow tolerance to lower thermal exposures. Coincident with the increase in weight-specific rates of oxygen consumption is a decrease in body weight. When total energetic cost to maintain an animal per unit time is calculated, the cost at 27.5° C is the same for both summer and winter animals. Further, the cost to maintain an animal at 7.5° C is less in winter than in summer. Arguments are presented suggesting that prairie voles compensate for increased weight-specific thermogenesis in winter by lowering body weight. The responses to thermal acclimation are quite different in summer and winter animals, thus implying different sorts of metabolic organization. Acclimation to 5° C effects a 26% increase in at 27.5° C of winter voles, and acclimation to 30° C does not change . In contrast, at 27.5° C of summer animals is unaffected by 5° C acclimation, and depressed 20% by 30° C acclimation. Thus, the animals are capable of considerable physiological adjustment to varying thermal conditions in different seasons.     

Are oxygen uptake kinetics at the onset of exercise speeded up by local metabolic status in active muscles?

To assess the rate-limiting factor of oxygen uptake ( ) kinetics at the onset of exercise, six healthy male sedentary subjects performed repeated one-legged constant-load cycle exercise. The one-legged constant-load exercise test consisted of two 5-min periods of pedalling at an exercise intensity of 50 W, with a 5-min rest between periods (these exercise periods, i.e. first and second exercises, were performed by the same leg). The exercise was then repeated using the other leg. In addition, two-legged incremental exercise was investigated to establish whether kinetics were affected by slower heart rate kinetics. The incremental exercise test consisted of two-legged pedalling first with the cycle unloaded as a warm-up for 5 min followed by 50-W exercise for 5 min. The exercise intensity was then increased to 100 W for 5 min. During exercise, gas exchange parameters were determined by the breath-by-breath method and cardiac output ( ) was determined continuously by an impedance technique with a computer-based automated system. To determine the kinetics of heart rate (HR), and , a best fit procedure was employed using least-squares criteria with a time delay, except during the initial increase. During the one-legged constant-load exercise test, kinetics were significantly accelerated by repeated exercise using the same leg. On the other hand, when the exercise was changed to the other leg, kinetics were significantly slower, although kinetics continued to be faster. During the incremental exercise test, although the HR response was slower at the transition from 50-W to 100-W exercise than at the transition from warm-up to 50-W exercise, there were no significant changes in kinetics. These findings suggest that kinetics may be affected by metabolic conditions in the muscle, but not by blood flow ( and/or HR) kinetics.     

Relationship between cardiac output and oxygen uptake at the onset of exercise

The purpose of the present study was to assess the relationship between the rapidity of increased gas exchange (i.e. oxygen uptake ) and increased cardiac output ( ) during the transient phase following the onset of exercise. Five healthy male subjects performed multiple rest-exercise or light exercise (25 W)-exercise transitions on an electrically braked ergometer at exercise intensities of 50, 75, or 100 W for 6 min, respectively. Each transition was performed at least eight times for each load in random order. The was obtained by a breath-by-breath method, and was measured by an impedance method during normal breathing, using an ensemble average. On transitions from rest to exercise, rapidly increased during phase I with time constants of 6.8–7.3 s. The also showed a similar rapid increment with time constants of 6.0–6.8 s with an apparent increase in stroke volume (SV). In this phase I, increased to about 29.7%–34.1% of the steady-state value and increased to about 58.3%–87.0%. Thereafter, some 20 s after the onset of exercise a mono-exponential increase to steady-state occurred both in and with time constants of 26.7–32.3 and 23.7–34.4 s, respectively. The insignificant difference between and time constants in phase I and the abrupt increase in both and SV at the onset of exercise from rest provided further evidence for a cardiodynamic contribution to following the onset of exercise from rest.