Longitudinal associations between anaerobic threshold and distance running performance

Longitudinal alterations in anaerobic threshold (AT) and distance running performance were assessed three times within a 4-month period of intensive training, using 20 male, trained middle-distance runners (19-23 yr). A major effect of the high intensity regular intensive training together with 60- to 90-min AT level running training (2 d X wk-1) was a significant increase in the amount of O2 uptake corresponding to AT (VO2 AT; ml O2 X min-1 X kg-1) and in maximal oxygen uptake (VO2max; ml O2 X min-1 X kg-1). Both VO2 AT and VO2max showed significant correlations (r = -0.69 to -0.92 and r = -0.60 to -0.85, respectively) with the 10,000 m run time in every test. However, further analyses of the data indicate that increasing VO2 AT (r = -0.63, P less than 0.05) rather than VO2max (r = -0.15) could result in improving the 10,000 m race performance to a larger extent, and that the absolute amount of change (delta) in the 10,000 m run time is best accounted for by a combination of delta VO2 AT and delta 5,000 m run time. Our data suggest that, among runners not previously trained over long distances, training-induced alterations in AT in response to regular intensive training together with AT level running training may contribute significantly to the enhancement of AT and endurance running performance, probably together with an increase in muscle respiratory capacity.     

Critical determinants of endurance performance in middle-aged and elderly endurance runners with heterogeneous training habits

The current investigation was designed to determine which factor or what combination of factors would best account for distance running performance in middle-aged and elderly runners (mean age 57.5 years SD +/- 9.7) with heterogeneous training habits. Among 35 independent variables which were arbitrarily selected as possible prerequisites in the distance running performance of these runners, oxygen uptake (VO2) at lactate threshold (LT) (r = 0.781-0.889), maximal oxygen uptake (VO2 max) (r = 0.751 approximately 0.886), and chronological age (r = -0.736-(-)0.886) were found to be the 3 predictor variables showing the highest correlations with the mean running velocity at 5 km (V5km), 10 km (V10km), and marathon (VM). When all independent variables were used in a multiple regression analysis, any 3 or 4 variables selected from among VO2 at LT, chronological age, systolic blood pressure (SBP), atherogenic index (AI), and Katsura index (KI) were found to give the best explanation of V5km, V10km, or VM in a combined linear model. Linear multiple regression equations constructed for predicting the running performances were: V5km = 0.046X1-0.026X2-0.0056X3+5.17, V10km = 0.028X1-0.028X2-0.190X4-1.34X5+6.45, and VM = -0.0400X2-0.324X4-1.16X5+7.36, where X1 = VO2 at LT (ml.min-1.kg-1), X2 = chronological age, X3 = SBP, X4 = AI, and X5 = KI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Calculation of record-time in the 800-meter run: predictive value of Margaria's equation

Margaria's equation (1976)--describing the relationship between the minimum time necessary to cover a distance equal or longer than 1,000 m (record-time TR) and the maximal oxygen consumption (VO2 max)--has been modified in order to be applied to the calculation of TR in the 800 m foot race. Fifteen subjects participated in this study (VO2 max = 63 +/- 3.5 ml O2 X kg-1 X min-1, measured TR = 131 +/- 10 seconds). It has been found the TR calculated from Margaria's equation (TRc) are underestimated (TRc = 104 +/- 10 seconds). By taking into account the actual energy cost of running (0.19 ml O2 X kg-1 X m-1) and the kinetics of VO2 at the onset of exercise, TRc averaged 133 +/- 8.5 seconds. Moreover, the relationship between TRc and measured TR (TRm) is highly significant (TRc = 50.4 + 0.65 TRm; r = 0.75; P less than 0.01). These results validate Margaria's equation modifications.     

Prerequisites in distance running performance of female runners

We investigated which attribute or what combination of attributes would best account for distance running performance of female runners. The subjects were 30 well-trained female distance runners, aged 19 to 23 years. Anthropometric and body composition characteristics, pulmonary function characteristics, blood properties, and cardiorespiratory function characteristics were measured at rest or during submaximal and maximal exercise. Analyses of the data showed that the relationship of oxygen uptake corresponding to lactate threshold (VO2T, ml.kg-1.min-1) with each distance running performance was substantially higher as compared with the relationship of other independent variables including maximal oxygen uptake (VO2max). Furthermore, multiple regression analysis indicated that running performances in 3,000m, 5,000m, and 10,000m are best accounted for by a combination of VO2/LT (X1), fat-free weight (X2), and/or mean corpuscular volume (X3). A multiple regression equation for predicting the 5,000m (Y, s) running performance was formulated as Y = -14.75X1-3. 03X2-5.79X3 + 2282.1. We suggest that VO2max would not stand alone as a decisive factor of distance running success in female runners, and that the distance running performance could be better accounted for by a combination of several attributes relating to lactate threshold, body composition, and/or hematological status. The linear regression of the predicted running performance on the actually measured running performance can be accepted in the range of 986-1197s.     

Decline in peripheral chemoreceptor excitatory stimulation during acute hypoxia in the lamb

Chemoreceptor function was studied in eight 2- to 3-day-old unanesthetized lambs to sequentially assess hypoxic chemoreflex strength during an 18-min exposure to hypoxia [inspired O2 fraction (FIO2) = 0.08]. The immediate ventilatory (VE) drop in response to five breaths of pure O2 was measured at 3, 7, and 15 min during hypoxia. Each lamb was studied again at 10-11 days of age. At 2-3 days of age VE increased, with the onset of hypoxia, from 658 +/- 133 (SD) ml.min-1 X kg-1 to a peak of 1,124 +/- 177 ml.min-1 X kg-1. A dampening of the VE response then occurred, with a mean decline in VE of 319 ml.min-1 X kg-1 over the 18-min hypoxia period. Each pure O2 test (Dejours test) resulted in an abrupt fall in VE (delta VEDejours). This VE drop was 937 +/- 163, 868 +/- 244, and 707 +/- 120 ml.min-1 X kg-1 at 3, 7, and 15 min of hypoxia, respectively. Comparing the three O2 tests, delta VEDejours was significantly decreased by 15 min, indicating a loss of about one-fourth of the O2 chemoreflex drive during hypoxia. Testing at 10-11 days of age revealed a smaller VE decline during hypoxia. O2 tests at the beginning and end of the hypoxic period were not significantly different, indicating a smaller loss of hypoxic chemoreflex drive in the more mature animals.(ABSTRACT TRUNCATED AT 250 WORDS)     

Is running performance enhanced with creatine serum ingestion?

Runners Advantage (RA) creatine (Cr) serum has been marketed to increase running performance. To test this claim, cross-country runners completed baseline testing (BASE), an outdoor 5,000-m run followed by treadmill Vo(2)max testing on the same day. Subjects repeated testing after ingesting 5 ml of RA (n = 13) containing 2.5 g of Cr or placebo (n = 11). Heart rate (HR), rating of perceived exertion (RPE), and run time were recorded. With RA (56.48 +/- 8.93 ml.kg(-1.)min(-1)), Vo(2)max was higher (p = 0.01) vs. BASE (54.07 +/- 9.36 ml.kg(-1.)min(-1)), yet the magnitude of the increase was within the coefficient of variation of Vo(2)max. No effect of RA on maximal HR was exhibited, yet Vco(2)max and duration of incremental exercise were significantly higher (p < 0.025) vs. BASE. Vo(2)max was similar in PL (58.85 +/- 6.67 ml.kg(-1).min(-1)) and BASE (57.28 +/- 7.22 ml.kg(-1.)min(-1)). With RA, the 5,000-m time was unchanged, and RPE was lower (p < 0.025) vs. BASE. These data do not support the ergogenic claims of RA in its current form and dose.     

Predictors of sweat loss in man during prolonged exercise

Nineteen healthy male subjects, differing in training status and Vo2max (52 +/- 1 ml.min-1.kg-1, mean +/- SEM; 43-64 ml.min-1.kg-1, range), exercised for 1 h at an absolute workload of 192 +/- 8 W (140-265 W); this was equivalent to 70 +/- 1% Vo2max (66-74%). Each exercise test was performed on an electrically braked cycle ergometer at a constant ambient temperature (22.5 +/- 0.0 degrees C) and relative humidity (85 +/- 0%). Nude body weight was recorded prior to and after each exercise test. Absolute sweat loss (body weight loss corrected for respiratory weight loss) during each test was 910 +/- 82 g (426-1665 g); this was equivalent to 1.3 +/- 0.1% (0.7-2.2%) of pre-exercise body weight (relative sweat loss). Weighted mean skin temperature and rectal temperature increased after 5 min of exercise from 30.5 +/- 0.3 degrees C and 37.2 +/- 0.1 degrees C respectively to 32.5 +/- 0.2 degrees C and 38.8 +/- 0.1 degrees C respectively, recorded immediately prior to the end of exercise. Bivariate linear regression and Pearson's correlation demonstrated absolute sweat loss was related to Vo2max (r = 0.72, p less than 0.001), absolute exercise workload (r = 0.66, p less than 0.01), body surface area (r = 0.62, p less than 0.01), weight (r = 0.60, p less than 0.01) and height (r = 0.53, p less than 0.05). Relative sweat loss was related to VO2max (r = 0.77, P less than 0.001) and absolute exercise workload (R = 0.59, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

The role of anaerobic ability in middle distance running performance

The purpose of this study was to assess the relationship between anaerobic ability and middle distance running performance. Ten runners of similar performance capacities (5 km times: 16.72, SE 0.2 min) were examined during 4 weeks of controlled training. The runners performed a battery of tests each week [maximum oxygen consumption (VO2max), vertical jump, and Margaria power run] and raced 5 km three times (weeks 1, 2, 4) on an indoor 200-m track (all subjects competing). Regression analysis revealed that the combination of time to exhaustion (TTE) during the VO2max test (r2 = 0.63) and measures from the Margaria power test (W.kg-1, r2 = 0.18; W, r2 = 0.05) accounted for 86% of the total variance in race times (P less than 0.05). Regression analysis demonstrated that TTE was influenced by both anaerobic ability [vertical jump, power (W.kg-1) and aerobic capacity (VO2max, ml.kg-1.min-1)]. These results indicate that the anaerobic systems influence middle distance performance in runners of similar abilities.     

Physiological differences between black and white runners during a treadmill marathon

To determine why black distance runners currently out-perform white distance runners in South Africa, we measured maximum oxygen consumption (VO2max), maximum workload during a VO2max test (Lmax), ventilation threshold (VThr), running economy, inspiratory ventilation (VI), tidal volume (VT), breathing frequency (f) and respiratory exchange ratio (RER) in sub-elite black and white runners matched for best standard 42.2 km marathon times. During maximal treadmill testing, the black runners achieved a significantly lower (P less than 0.05) Lmax (17 km h-1, 2% grade, vs 17 km h-1, 4% grade) and VI max (6.21 vs 6.82 l kg-2/3 min-1), which was the result of a lower VT (101 vs 119 ml kg-2/3 breath-1) as fmax was the same in both groups. The lower VT in the black runners was probably due to their smaller body size. The VThr occurred at a higher percentage VO2max in black than in white runners (82.7%, SD 7.7% vs 75.6%, SD 6.2% respectively) but there were no differences in the VO2max. However, during a 42.2-km marathon run on a treadmill, the black athletes ran at the higher percentage VO2max (76%, SD 7.9% vs 68%, SD 5.3%), RER (0.96, SD 0.07 vs 0.91, SD 0.04) and f (56 breaths min-1, SD 11 vs 47 breaths min-1, SD 10), and at lower VT (78 ml kg-2/3 breath-1, SD 15 vs 85 ml kg-2/3 breath-1, SD 19). The combination of higher f and lower VT resulted in an identical VI.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effectiveness of cycle cross-training between competitive seasons in female distance runners

The purpose of this study was to examine whether substituting 50% of run training volume with cycling ("cross-training") would maintain 3,000-m race time and estimated Vo(2)max in competitive female distance runners during a 5-week recuperative phase. Eleven collegiate runners were randomly assigned to either the run training-only (R) group (n = 6) or the cycle training (R/C) group (n = 5), which cross-trained on alternate days. The groups trained daily at a reduced intensity (75-80% of maximum heart rate). Training volume was similar to the competitive season (40-50 mi x wk(-1)) except that cycling represented 50% of volume for the R/C group. On follow-up, 3,000-m time was 1.4% (9 seconds) slower in the R group and 3.4% (22 seconds) slower in the R/C group. No important change in estimated Vo(2)max was found for either group. It was concluded that cycle cross-training adequately maintained aerobic performance during the recuperative phase between the cross-country and track seasons, comparable to the primary sport of running.     

Improved running economy in elite runners after 20 days of simulated moderate-altitude exposure.

To investigate the effect of altitude exposure on running economy (RE), 22 elite distance runners [maximal O(2) consumption (Vo(2)) 72.8 +/- 4.4 ml x kg(-1) x min(-1); training volume 128 +/- 27 km/wk], who were homogenous for maximal Vo(2) and training, were assigned to one of three groups: live high (simulated altitude of 2,000-3,100 m)-train low (LHTL; natural altitude of 600 m), live moderate-train moderate (LMTM; natural altitude of 1,500-2,000 m), or live low-train low (LLTL; natural altitude of 600 m) for a period of 20 days. RE was assessed during three submaximal treadmill runs at 14, 16, and 18 km/h before and at the completion of each intervention. Vo(2), minute ventilation (Ve), respiratory exchange ratio, heart rate, and blood lactate concentration were determined during the final 60 s of each run, whereas hemoglobin mass (Hb(mass)) was measured on a separate occasion. All testing was performed under normoxic conditions at approximately 600 m. Vo(2) (l/min) averaged across the three submaximal running speeds was 3.3% lower (P = 0.005) after LHTL compared with either LMTM or LLTL. Ve, respiratory exchange ratio, heart rate, and Hb(mass) were not significantly different after the three interventions. There was no evidence of an increase in lactate concentration after the LHTL intervention, suggesting that the lower aerobic cost of running was not attributable to an increased anaerobic energy contribution. Furthermore, the improved RE could not be explained by a decrease in Ve or by preferential use of carbohydrate as a metabolic substrate, nor was it related to any change in Hb(mass). We conclude that 20 days of LHTL at simulated altitude improved the RE of elite distance runners.     

The influence of cardiorespiratory fitness on the decrement in maximal aerobic power at high altitude

There are conflicting reports in the literature which imply that the decrement in maximal aerobic power experienced by a sea-level (SL) resident sojourning at high altitude (HA) is either smaller or larger for the more aerobically "fit" person. In the present study, data collected during several investigations conducted at an altitude of 4300 m were analyzed to determine if the level of aerobic fitness influenced the decrement in maximal oxygen uptake (VO2max) at HA. The VO2max of 51 male SL residents was measured at an altitude of 50 m and again at 4300 m. The subjects' ages, heights, and weights (mean +/- SE) were 22 +/- 1 yr, 177 +/- 7 cm and 78 +/- 2 kg, respectively. The subjects' VO2max ranged from 36 to 60 ml X kg -1 X min -1 (mean +/- SE = 48 +/- 1) and the individual values were normally distributed within this range. Likewise, the decrement in VO2max at HA was normally distributed from 3 ml X kg-1 X min-1 (9% VO2max at SL) to 29 ml X kg-1 X min-1 (54% VO2max at SL), and averaged 13 +/- 1 ml X kg-1 X min-1 (27 +/- 1% VO2max at SL). The linear correlation coefficient between aerobic fitness and the magnitude of the decrement in VO2max at HA expressed in absolute terms was r = 0.56, or expressed as % VO2max at SL was r = 0.30; both were statistically significant (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological analysis of running performance: revision of the hyperbolic model

1 This paper presents a physiological model for the analysis of the "running curve" (i.e. the relationship between running time and power output) (Table I and Fig. 1). This model is derived from the basic hyperbolic model (Eq. 2: Fig. 2 a) modified in order to take into account the slow adjustment of oxygen utilization and of glycolysis at the onset of exercise (Eq. 7) and the progressive reduction of average aerobic power sustained with increasing running time for races lasting longer than 7 min (Eq. 10; Fig. 2 b, 2 d). 2 This model provides a satisfactory smoothing of the running curve from 200 m to marathon. Average errors (in absolute value) between actual and estimated power output are 0.9 +/- 0.2% (+/- SE) and 1.3 +/- 0.4% for male and female world records respectively (Table II). The basic hyperbolic model (Ptc = A/tc + B) provides a satisfactory smoothing of the running curve on comparatively narrow ranges of events (Table III). 3 Estimations of anaerobic energy stores and of VO2 max made for male and female from world records (1,219 J.kg-1 and 76.4 ml.kg-1.min-1; 1,118 J.kg-1 and 67.8 ml.kg-1.min-1 respectively) are in reasonable agreement with expected values in elite runners (Table IV). 4 The model allows the computation of an objective measure of endurance, i.e. the so-called "ability to sustain a high percentage of VO2 max for a long period of time".(ABSTRACT TRUNCATED AT 250 WORDS)     

Oxygen delivery and utilization in hypothermic dogs

Hypothermia produces a decrease in metabolic rate that may be beneficial under conditions of reduced O2 delivery (Do2). Another effect of hypothermia is to increase the affinity of hemoglobin for O2, which can adversely affect the release of O2 to the tissues. To determine the overall effect of hypothermia on the ability of the peripheral tissues to extract O2 from blood, we compared the response to hypoxemia of hypothermic dogs (n = 8) and of normothermic controls (n = 8). The animals were anesthetized, mechanically ventilated, and paralyzed to prevent shivering. The inspired concentration of O2 was progressively reduced until the dogs died. The core temperatures of the control and hypothermic dogs were 37.7 +/- 0.3 and 30.5 +/- 0.1 degree C, respectively (P less than 0.01). The O2 consumption (VO2) of the control dogs was significantly greater than that of the hypothermic dogs (P less than 0.05), being 4.7 +/- 0.4 and 3.2 +/- 0.3 ml X min-1 X kg-1, respectively. Hypothermia produced a left shift of the oxyhemoglobin dissociation curve (ODC) to a PO2 at which hemoglobin is half-saturated with O2 of 19.8 +/- 0.7 Torr (control = 32.4 +/- 0.7 Torr, P less than 0.01). The O2 delivery at which the VO2 becomes supply dependent (DO2crit) was 8.5 ml X min-1 X kg-1 for control and 6.2 ml X min-1 X kg-1 for hypothermia. The hypothermic dogs maintained their base-line VO2's at lower arterial PO2's than control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Physiological factors associated with the lower maximal oxygen consumption of master runners

We examined the hemodynamic factors associated with the lower maximal O2 consumption (VO2max) in older formerly elite distance runners. Heart rate and VO2 were measured during submaximal and maximal treadmill exercise in 11 master [66 +/- 8 (SD) yr] and 11 young (32 +/- 5 yr) male runners. Cardiac output was determined using acetylene rebreathing at 30, 50, 70, and 85% VO2max. Maximal cardiac output was estimated using submaximal stroke volume and maximal heart rate. VO2max was 36% lower in master runners (45.0 +/- 6.9 vs. 70.4 +/- 8.0 ml.kg-1.min-1, P less than or equal to 0.05), because of both a lower maximal cardiac output (18.2 +/- 3.5 vs. 25.4 +/- 1.7 l.min-1) and arteriovenous O2 difference (16.6 +/- 1.6 vs. 18.7 +/- 1.4 ml O2.100 ml blood-1, P less than or equal to 0.05). Reduced maximal heart rate (154.4 +/- 17.4 vs. 185 +/- 5.8 beats.min-1) and stroke volume (117.1 +/- 16.1 vs. 137.2 +/- 8.7 ml.beat-1) contributed to the lower cardiac output in the older athletes (P less than or equal 0.05). These data indicate that VO2max is lower in master runners because of a diminished capacity to deliver and extract O2 during exercise.     

Oxygen uptake during running as related to body mass in circumpubertal boys: a longitudinal study

To investigate the effect of endurance training on physiological characteristics during circumpubertal growth, eight young runners (mean starting age 12 years) were studied every 6 months for 8 years. Four other boys served as untrained controls. Oxygen uptake (VO2) and blood lactate concentrations were measured during submaximal and maximal treadmill running. The data were aligned with each individual's age of peak height velocity. The maximal oxygen uptake (VO2max; ml.kg-1.min-1) decreased with growth in the untrained group but remained almost constant in the training group. The oxygen cost of running at 15 km.h-1 (VO2 15, ml.kg-1.min-1) was persistently lower in the trained group but decreased similarly with age in both groups. The development of VO2max and VO2 15 (l.min-1) was related to each individual's increase in body mass so that power functions were obtained. The mean body mass scaling factor was 0.78 (SEM 0.07) and 1.01 (SEM 0.04) for VO2max and 0.75 (SEM 0.09) and 0.75 (SEM 0.02) for VO2 15 in the untrained and trained groups, respectively. Therefore, expressed as ml.kg-0.75.min-1, VO2 15 was unchanged in both groups and VO2max increased only in the trained group. The running velocity corresponding to 4 mmol.l-1 of blood lactate (nu la4) increased only in the trained group. Blood lactate concentration at exhaustion remained constant in both groups over the years studied. In conclusion, recent and the present findings would suggest that changes in the oxygen cost of running and VO2max (ml.kg-1.min-1) during growth may mainly be due to an overestimation of the body mass dependency of VO2 during running.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary fibrin microembolism with Echis carinatus venom in dogs: effects of a synthetic thrombin inhibitor

We produced pulmonary fibrin microembolism using an infusion of a prothrombin activator (Echis carinatus venom, 30 min, 0.5 NIH thrombin equivalent units/kg) in open-chest mongrel dogs. To determine the nonclotting effects of this venom on edemagenesis we infused an irreversible thrombin inhibitor, D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone (PPACK, 57 nmol X kg-1 X min-1 for 120 min), alone (n = 5) or with venom (Echis + PPACK, n = 5). The control group (n = 5) was given 1 ml of 0.9% NaCl. A decline in left atrial pressure (means +/- SE, 5.3 +/- 0.4 to 4.0 +/- 0.5 mmHg, P less than 0.05) and cardiac index (149 +/- 10 to 82 +/- 13 ml X min-1 X kg-1, P less than 0.01) in association with a marked increase in pulmonary arterial pressure (14.5 +/- 0.6 to 26.6 +/- 2.5 mmHg, P less than 0.001) and pulmonary vascular resistance (64 +/- 5 to 304 +/- 42 mmHg X ml-1 X min-1 X kg-1, P less than 0.001) was observed after 20 min of venom infusion. During this interval, pulmonary artery wedge pressure increased (4 +/- 1 to 12 +/- 4 mmHg, P less than 0.01) in four of eight animals. Fibrinogen declined below measurable levels and fibrin microemboli were seen in many pulmonary arterioles. These changes were not observed in the Echis + PPACK, PPACK, or control groups. Leukopenia and thrombocytopenia were observed in the Echis and Echis + PPACK groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Abnormal oxidative metabolism and O2 transport in muscle phosphofructokinase deficiency

Humans who lack availability of carbohydrate fuels may provide important models for the study of physiological control mechanisms. We compared seven patients who had unavailability of muscle glycogen and blood glucose as oxidative fuels due to muscle phosphofructokinase deficiency (PFKD) with five patients who had a selective defect in long-chain fatty acid oxidation due to carnitine palmitoyltransferase deficiency (CPTD) and with six healthy subjects. Peak cycle exercise work rate, peak O2 uptake (Vo2), and arteriovenous O2 difference were markedly lower (P less than 0.001) for PFKD patients (23 +/- 6 W, 14 +/- 2 ml.min-1.kg-1, and 7.1 +/- 0.5 ml/dl, respectively) than for CPTD patients (142 +/- 33 W, 31 +/- 4 ml.min-1.kg-1, and 15.0 +/- 0.8 ml/dl, respectively) or healthy subjects (171 +/- 17 W, 36 +/- 1 ml.min-1.kg-1, and 16.4 +/- 0.7 ml/dl, respectively). Peak cardiac output (Q) was similar (P less than 0.05) in all three groups, but the slope of increase in Q (l/min) on Vo2 (l/min) from rest to exercise (delta Q/ delta Vo2) was more than twofold greater (P less than 0.001) for PFKD patients (11.2 +/- 1.2) than for CPTD patients (4.6 +/- 0.6) and healthy subjects (4.6 +/- 0.2). Increasing availability of blood-borne oxidative substrates capable of metabolically bypassing the defect at phosphofructokinase (by fasting plus prolonged moderate exercise to increase plasma free fatty acids or by iv lactate infusion) increased peak work rate, Vo2, and arteriovenous O2 difference, lacked consistent effect on peak Q, and normalized delta Q/ delta Vo2 in PFKD patients. The results extend our previous observations in patients with a block in muscle glycogen but not blood glucose oxidation due to phosphorylase deficiency and imply that specific unavailability of muscle glycogen as an oxidizable fuel is primarily responsible for abnormal muscle oxidative metabolism and associated exercise intolerance and exaggerated delta Q/ delta Vo2 in muscle PFKD. The findings also endorse the concept that factors closely linked with muscle oxidative phosphorylation participate in regulating delta Q/ delta Vo2, likely via activation of metabolically sensitive muscle afferents.