Contribution of exercising legs to the slow component of oxygen uptake kinetics in humans.

Rates of performing work that engender a sustained lactic acidosis evidence a slow component of pulmonary O2 uptake (VO2) kinetics. This slow component delays or obviates the attainment of a stable VO2 and elevates VO2 above that predicted from considerations of work rate. The mechanistic basis for this slow component is obscure. Competing hypotheses depend on its origin within either the exercising limbs or the rest of the body. To resolve this question, six healthy males performed light nonfatiguing [approximately 50% maximal O2 uptake (VO2max)] and severe fatiguing cycle ergometry, and simultaneous measurements were made of pulmonary VO2 and leg blood flow by thermodilution. Blood was sampled 1) from the femoral vein for O2 and CO2 pressures and O2 content, lactate, pH, epinephrine, norepinephrine, and potassium concentrations, and temperature and 2) from the radial artery for O2 and CO2 pressures, O2 content, lactate concentration, and pH. Two-leg VO2 was thus calculated as the product of 2 X blood flow and arteriovenous O2 difference. Blood pressure was measured in the radial artery and femoral vein. During light exercise, both pulmonary and leg VO2 remained stable from minute 3 to the end of exercise (26 min). In contrast, during severe exercise [295 +/- 10 (SE) W], pulmonary VO2 increased 19.8 +/- 2.4% (P less than 0.05) from minute 3 to fatigue (occurring on average at 20.8 min). Over the same period, leg VO2 increased by 24.2 +/- 5.2% (P less than 0.05). Increases of leg and pulmonary VO2 were highly correlated (r = 0.911), and augmented leg VO2 could account for 86% of the rise in pulmonary VO2.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evidence for tissue diffusion limitation of VO2max in normal humans

We recently found [at approximately 90% maximal O2 consumption (VO2max)] that as inspiratory PO2 (PIO2) was reduced, VO2 and mixed venous PO2 (PVO2) fell together along a straight line through the origin, suggesting tissue diffusion limitation of VO2max. To extend these observations to VO2max and directly examine effluent venous blood from muscle, six normal men cycled at VO2max while breathing air, 15% O2 and 12% O2 in random order on a single day. From femoral venous, mixed venous, and radial arterial samples, we measured PO2, PCO2, pH, and lactate and computed mean muscle capillary PO2 by Bohr integration between arterial (PaO2) and femoral venous PO2 (PfvO2). VO2 and CO2 production (VCO2) were measured by expired gas analysis, VO2max averaged 61.5 +/- 6.2 (air), 48.6 +/- 4.8 (15% O2), and 38.1 +/- 4.1 (12% O2) ml.kg-1.min-1. Corresponding values were 16.8 +/- 5.6, 14.4 +/- 5.0, and 12.0 +/- 5.0 Torr for PfVO2; 23.6 +/- 3.2, 19.1 +/- 4.2, and 16.2 +/- 3.5 Torr for PVO2; and 38.5 +/- 5.4, 30.3 +/- 4.1, and 24.5 +/- 3.6 Torr for muscle capillary PO2 (PmCO2). Each of the PO2 variables was linearly related to VO2max (r = 0.99 each), with an intercept not different from the origin. Similar results were obtained when the subjects were pushed to a work load 30 W higher to ensure that VO2max had been achieved. By extending our prior observations 1) to maximum VO2 and 2) by direct sampling of femoral venous blood, we conclude that tissue diffusion limitation of VO2max may be present in normal humans. In addition, since PVO2, PfVO2, and PmCO2 all linearly relate to VO2max, we suggest that whichever of these is most readily obtained is acceptable for further evaluation of the hypothesis.     

Maximal O2 uptake of in situ dog muscle during acute hypoxemia with constant perfusion

We investigated the relationships among maximal O2 uptake (VO2max), effluent venous PO2 (PvO2), and calculated mean capillary PO2 (PCO2) in isolated dog gastrocnemius in situ as arterial PO2 (PaO2) was progressively reduced with muscle blood flow held constant. The hypothesis that VO2max is determined in part by peripheral tissue O2 diffusion predicts proportional declines in VO2max and PCO2 if the diffusing capacity of the muscle remains constant. The inspired O2 fraction was altered in each of six dogs to produce four different levels of PaO2 [22 +/- 2, 29 +/- 1, 38 +/- 1, and 79 +/- 4 (SE) Torr]. Muscle blood flow, with the circulation isolated, was held constant at 122 +/- 15 ml.100 g-1.min-1 while the muscle worked maximally (isometric twitches at 5-7 Hz) at each of the four different values of PaO2. Arterial and venous samples were taken to measure lactate, pH, PO2, PCO2, and muscle VO2. PCO2 was calculated using Fick's law of diffusion and a Bohr integration procedure. VO2max fell progressively (P less than 0.01) with decreasing PaO2. The decline in VO2max was proportional (R = 0.99) to the fall in both muscle PvO2 and calculated PCO2 while the calculated muscle diffusing capacity was not different among the four conditions. Fatigue developed more rapidly with lower PaO2, although lactate output from the muscle was not different among conditions. These results are consistent with the hypothesis that resistance to O2 diffusion in the peripheral tissue may be a principal determinant of VO2max.     

Effect of respiratory alkalosis on skeletal muscle metabolism in the dog

These experiments were conducted to determine whether changes in skeletal muscle metabolism contribute to the previously reported increase in whole-body O2 uptake (VO2) during respiratory alkalosis. The hind-limb and gastrocnemius-plantaris preparations in anesthetized and paralyzed dogs were used. VO2 of the hindlimb and gastrocnemius muscle was calculated from measurements of venous blood flow and arterial and venous O2 concentrations (Van Slyke analysis). Whole-body VO2 was measured by the open-circuit method. Minute ventilation (hence blood gases and pH) was controlled by a mechanical respirator. Whole-body, hind-limb, and gastrocnemius muscle VO2 increased 14, 19, and 20%, respectively, during alkalosis (P less than 0.05). In all experiments, arterial lactate concentration increased significantly (P less than 0.05) during alkalosis. A positive venoarterial lactate difference across muscle during alkalosis indicated that skeletal muscle is a source of the elevated blood lactate. We concluded that VO2 of resting skeletal muscle is increased during states of respiratory alkalosis and that this increase can account for much of the increase in whole-body VO2.     

Disposal of blood [1-13C]lactate in humans during rest and exercise

Lactate irreversible disposal (RiLa) and oxidation (RoxLa) rates were studied in six male subjects during rest (Re), easy exercise [EE, 140 min of cycling at 50% of maximum O2 consumption (VO2max)] and hard exercise (HE, 65 min at 75% VO2max). Twenty minutes into each condition, subjects received a Na+-L(+)-[1-13C]lactate intravenous bolus injection. Blood was sampled intermittently from the contralateral arm for metabolite levels, acid-base status, and enrichment of 13C in lactate. Expired air was monitored continuously for determination of respiratory parameters, and aliquots were collected for determination of 13C enrichment in CO2. Steady-rate values for O2 consumption (VO2) were 0.33 +/- 0.01, 2.11 +/- 0.03, and 3.10 +/- 0.03 l/min for Re, EE, and HE, respectively. Corresponding values of blood lactate levels were 0.84 +/- 0.01, 1.33 +/- 0.05, and 4.75 +/- 0.28 mM in the three conditions. Blood lactate disposal rates were significantly correlated to VO2 (r = 0.78), averaging 123.4 +/- 20.7, 245.5 +/- 40.3, and 316.2 +/- 53.7 mg X kg-1 X h-1 during Re, EE, and HE, respectively. Lactate oxidation rate was also linearly related to VO2 (r = 0.81), and the percentage of RiLa oxidized increased from 49.3% at rest to 87.0% during exercise. A curvilinear relationship was found between RiLa and blood lactate concentration. It was concluded that, in humans, 1) lactate disposal (turnover) rate is directly related to the metabolic rate, 2) oxidation is the major fate of lactate removal during exercise, and 3) blood lactate concentration is not an accurate indicator of lactate disposal and oxidation.     

Dissociation of maximal O2 uptake from O2 delivery in canine gastrocnemius in situ

To test the hypothesis that maximal O2 uptake (VO2max) can be limited by O2 diffusion in the peripheral tissue, we kept O2 delivery [blood flow X arterial O2 content (CaO2)] to maximally contracting muscle equal between 1) low flow-high CaO2 and 2) high flow-low CaO2 conditions. The hypothesis predicts, because of differences in the capillary PO2 profile, that the former condition will result in both a higher VO2max and muscle effluent venous PO2 (PVO2). We studied the relations among VO2max, PVO2, and O2 delivery during maximal isometric contractions in isolated, in situ dog gastrocnemius muscle (n = 6) during these two conditions. O2 delivery was matched by varying arterial O2 partial pressure and adjusting flow to the muscle accordingly. A total of 18 matched O2 delivery pairs were obtained. As planned, O2 delivery was not significantly different between the two treatments. In contrast, VO2max was significantly higher [10.4 +/- 0.5 (SE) ml.100 g-1.min-1; P = 0.01], as was PVO2 (25 +/- 1 Torr; P less than 0.01) in the low flow-high CaO2 treatment compared with the high flow-low CaO2 treatment (9.1 +/- 0.4 ml.100 g-1.min-1 and 20 +/- 1 Torr, respectively). The rate of fatigue was greater in the high flow-low CaO2 condition, as was lactate output from the muscle and muscle lactate concentration. The results of this study show that VO2max is not uniquely dependent on O2 delivery and support the hypothesis that VO2max can be limited by peripheral tissue O2 diffusion.     

Effect of pH on metabolic and cardiorespiratory responses during progressive exercise

Six healthy male subjects performed three exercise tests in which the power output was increased by 100 kpm/min each minute until exhaustion. The studies were carried out after oral administration of CaCO3 (control), NH4Cl (metabolic acidosis), and NaHCO3 (metabolic alkalosis). Ventilation (VE), O2 intake (VO2), and CO2 output (VCO2) were monitored continuously. Arterialized-venous blood samples were drawn at specific times and analyzed for pH, PCO2, and lactate concentration. Resting pH (mean +/- SE) was lowest in acidosis (7.29 +/- 0.01) and highest in alkalosis (7.46 +/- 0.02). A lower peak power output (kpm/min) was achieved in acidosis (1,717 +/- 95) compared with control (1,867 +/- 120) alkalosis (1,867 +/- 125). Submaximal VO2 and VCO2 were similar, but peak VO2 and VCO2 were lower in acidosis. Plasma lactate concentration was lower at rest and during exercise in acidosis. Although lactate accumulation was reduced in acidosis, increases in hydrogen ion concentration were similar in the three conditions. We conclude that acid-base changes influence the maximum power output that may be sustained in incremental dynamic exercise and modify plasma lactate appearance, but have little effect on hydrogen ion appearance in plasma.     

Effect of respiratory acidosis on metabolism in exercise

Five healthy males took part in two separate studies. In one study subjects breathed air (control, C) and in the other 5% CO2 in 21% O2 (respiratory acidosis, RA). Measurements were made at rest, during exercise at 30 and 60% maximal O2 uptake (VO2 max), (20 min each) and in recovery. RA was associated with higher arterial CO2 partial pressure (PCO2) and bicarbonate and lower pH than C. The increase with exercise in plasma lactate (mmol . l-1) was less in RA than C from 1.0 +/- 0.15 (SE) (C = 1.1 +/- 0.17) at rest to 5.3 +/- 1.25 (C = 6.8 +/- 0.98) at 60% VO2 max (P less than 0.10). Plasma pyruvate, alanine, and glycerol concentrations increased with exercise; free fatty acids did not change. There were no significant differences between RA and C in any of these metabolites. Norepinephrine concentrations were similar at rest but increased to a greater extent during exercise in RA than C (P less than 0.02). Epinephrine levels were also higher in RA than C at 60% VO2 max (NS); the two subjects in whom lactate was not lower with RA showed the greatest increase in epinephrine. Exercise in RA was associated with higher heart rates (P less than 0.05), blood pressures (NS), and ventilation (P less than 0.01). In hypercapnia the metabolic effects of acidosis are modified by increased levels of circulating catecholamines.     

Limitation of maximal O2 uptake and performance by acute hypoxia in dog muscle in situ

The factors that determine maximal O2 uptake (VO2max) and muscle performance during severe, acute hypoxemia were studied in isolated, in situ dog gastrocnemius muscle. Our hypothesis that VO2max is limited by O2 diffusion in muscle predicts that decreases in VO2max, caused by hypoxemia, will be accompanied by proportional decreases in muscle effluent venous PO2 (PvO2). By altering the fraction of inspired O2, four levels of arterial PO2 (PaO2) [21 +/- 2, 28 +/- 1, 44 +/- 1, and 80 +/- 2 (SE) Torr] were induced in each of eight dogs. Muscle arterial and venous circulation was isolated and arterial pressure held constant by pump perfusion. Each muscle worked maximally (3 min at 5-6 Hz, isometric twitches) at each PaO2. Arterial and venous samples were taken to measure lactate, [H+], PO2, PCO2, and muscle VO2. Muscle biopsies were taken to measure [H+] (homogenate method) and lactate. VO2max decreased with PaO2 and was linearly (R = 0.99) related to both PVO2 and O2 delivery. As PaO2 fell, fatigue increased while muscle lactate and [H+] increased. Lactate release from the muscle did not change with PaO2. This suggests a barrier to lactate efflux from muscle and a possible cause of the greater fatigue seen in hypoxemia. The gas exchange data are consistent with the hypothesis that VO2max is limited by peripheral tissue diffusion of O2.     

Progressive hypoxia until brain electrical silence: a useful model for studying protective interventions

Anesthetized spontaneously breathing rats, fitted with epicortical electrodes and catheters for sampling arterial, venous, and cerebral venous blood, were exposed to standardized progressive hypoxia. Three minutes of hypoxia sequentially caused hyperpnea, hypopnea, apnea, and cessation of electrocorticogram "spiking," of synchronization, and of background in electroencephalogram (EEG). Blood data and cerebral blood flow and metabolism were measured throughout and at "insults," i.e., at apnea and cessation events, to clarify their interdependence. Arterial and brain venous PO2 fell linearly with inspired oxygen (final value of 2% at 280 s). Hyperpnea induced arterial alkalosis; subsequent hypopnea led to near-normal PCO2 and pH when EEG ceased. Hypercapnia was more pronounced in cerebral than in systemic venous blood; time courses of pH changes were similar. Sagittal sinus blood pressure and outflow were linearly related and resembled the time course of local cerebral blood flow. Blood flow increased by 25% at apnea and only 60% at EEG silence. Cerebral metabolic rate of O2 rose during the hyperpnea phase and fell exponentially thereafter. Cerebral glucose uptake and lactate release increased within the first 3 min but fell abruptly when cortico-electric spiking ceased. Time courses of cerebral O2 consumption and spike rate were linearly related; both showed inverse linear relations to cerebral perfusion. The hypoxic insults were well defined by blood data; critical PO2 values were lower than previously assumed. This model is proving to be a useful, controlled method by which mechanisms of cerebral hypoxia tolerance may be studied in vivo.     

Supramaximal exercise after training-induced hypervolemia. I. Gas exchange and acid-base balance

The effect of an exercise-induced reduction in blood O2-carrying capacity on ventilatory gas exchange and acid-base balance during supramaximal exercise was studied in six males [peak O2 consumption (VO2peak), 3.98 +/- 0.49 l/min]. Three consecutive days of supramaximal exercise resulted in a preexercise reduction of hemoglobin concentration from 15.8 to 14.0 g/dl (P less than 0.05). During exercise (120% VO2peak) performed intermittently (1 min work to 4 min rest); a small but significant (P less than 0.05) increase was found for both O2 consumption (VO2) (l X min) and heart rate (beats/min) on day 2 of the training. On day 3, VO2 (l/min) was reduced 3.2% (P less than 0.05) over day 1 values. No changes were found in CO2 output and minute ventilation during exercise between training days. Similarly, short-term training failed to significantly alter the changes in arterialized blood PCO2, pH, and [HCO-3] observed during exercise. It is concluded that hypervolemia-induced reductions in O2-carrying capacity in the order of 10-11% cause minimal impairment to gas exchange and acid-base balance during supramaximal non-steady-state exercise.     

Breath holding during intense exercise: arterial blood gases, pH, and lactate

Seven healthy endurance-trained [maximal O2 uptake (VO2max) = 57.1 +/- 4.1 ml.kg-1.min-1)] female volunteers (mean age 24.4 +/- 3.6 yr) served as subjects in an experiment measuring arterial blood gases, acid-base status, and lactate changes while breath holding (BH) during intense intermittent exercise. By the use of a counterbalance design, each subject repeated five intervals of a 15-s on:30-s off treadmill run at 125% VO2max while BH and while breathing freely (NBH). Arterial blood for pH, PO2, PCO2, O2 saturation (SO2) HCO3, and lactate was sampled from a radial arterial catheter at the end of each work and rest interval and throughout recovery, and the results were analyzed using repeated-measures analysis of variance. Significant reductions in pHa (delta mean = 0.07, P less than 0.01), arterial PO2 (delta mean = 24.2 Torr, P less than 0.01), and O2 saturation (delta mean = 4.6%, P less than 0.01) and elevations in arterial PCO2 (delta mean = 8.2 Torr, P less than 0.01) and arterial HCO3 (delta mean = 1.3 meq/l, P = 0.05) were found at the end of each exercise interval in the BH condition. All of the observed changes in arterial blood gases and acid-base status induced by BH were reversed during the rest intervals. During recovery, significantly (P less than 0.025) greater levels of arterial lactate were found in the BH condition.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increases in coronary vein CO2 during cardiac resuscitation

We investigated the aortic, mixed venous, and great cardiac vein acid-base changes in eight domestic pigs during cardiac arrest produced by ventricular fibrillation and during cardiopulmonary resuscitation (CPR). The great cardiac vein PCO2 increased from a control value of 52 +/- 2 to 132 +/- 28 (SD) Torr during CPR, whereas the arterial PCO2 was unchanged (39 +/- 4 vs. 38 +/- 4). The coronary venoarterial PCO2 gradient, therefore, increased remarkably from 13 +/- 2 to 94 +/- 29 Torr. The simultaneously measured great cardiac vein lactate concentrations increased from 0.24 +/- 0.06 to 7.3 +/- 2.34 mmol/l. Much more moderate increases in the lactate content of aortic blood from 0.64 +/- 0.25 to 2.56 +/- 0.27 mmol/l were observed. Increases in great cardiac vein PCO2 and lactate were highly correlated during CPR (r = 0.91). After successful CPR, the coronary venoarterial PCO2 gradient returned to normal levels within 2 min after restoration of spontaneous circulation. Lactate content was rapidly reduced and lactate extraction was reestablished within 30 min after CPR. These studies demonstrate marked but reversible acidosis predominantly as the result of myocardial CO2 production during CPR.     

Metabolic component of intestinal PCO(2) during dysoxia.

The adequacy of intestinal perfusion during shock and resuscitation might be estimated from intestinal tissue acid-base balance. We examined this idea from the perspective of conventional blood acid-base physicochemistry. As the O(2) supply diminishes with failing blood flow, tissue acid-base changes are first "respiratory, " with CO(2) coming from combustion of fuel and stagnating in the decreasing blood flow. When the O(2) supply decreases to critical, the changes become "metabolic" due to lactic acid. In blood, the respiratory vs. metabolic distinction is conventionally made using the buffer base principle, in which buffer base is the sum of HCO(3)(-) and noncarbonate buffer anion (A(-)). During purely respiratory acidosis, buffer base stays constant because HCO(3)(-) cannot buffer its own progenitor, carbonic acid, so that the rise of HCO(3)(-) equals the fall of A(-). During anaerobic "metabolism," however, lactate's H(+) is buffered by both A(-) and HCO(3)(-), causing buffer base to decrease. We quantified the partitioning of lactate's H(+) between HCO(3)(-) and A(-) buffer in anoxic intestine by compressing intestinal segments of anesthetized swine into a steel pipe and measuring PCO(2) and lactate at 5- to 10-min intervals. Their rises followed first-order kinetics, yielding k = 0. 031 min(-1) and half time = approximately 22 min. PCO(2) vs. lactate relations were linear. Over 3 h, lactate increased by 31 +/- 3 mmol/l tissue fluid (mM) and PCO(2) by approximately 17 mM, meaning that one-half of lactate's H(+) was buffered by tissue HCO(3)(-) and one-half by A(-). The data were consistent with a lumped pK(a) value near 6.1 and total A(-) concentration of approximately 30 mmol/kg. We conclude that the respiratory vs. metabolic distinction could be made in tissue by estimating tissue buffer base from measured pH and PCO(2).     

Effects of acute hypoxia on the estimation of lactate threshold from ventilatory gas exchange indices during an incremental exercise test

The purpose of this study was to investigate the validity of non-invasive lactate threshold estimation using ventilatory and pulmonary gas exchange indices under condition of acute hypoxia. Seven untrained males (21.4+/-1.2 years) performed two incremental exercise tests using an electromagnetically braked cycle ergometer: one breathing room air and other breathing 12 % O2. The lactate threshold was estimated using the following parameters: increase of ventilatory equivalent for O2 (VE/VO2) without increase of ventilatory equivalent for CO2 (VE/VCO2). It was also determined from the increase in blood lactate and decrease in standard bicarbonate. The VE/VO2 and lactate increase methods yielded the respective values for lactate threshold: 1.91+/-0.10 l/min (for the VE/VO2) vs. 1.89+/-0.1 l/min (for the lactate). However, in hypoxic condition, VE/VO2 started to increase prior to the actual threshold as determined from blood lactate response: 1.67+/-0.1 l/min (for the lactate) vs. 1.37+/-0.09 l/min (for the VE/VO2) (P=0.0001), i.e. resulted in pseudo-threshold behavior. In conclusion, the ventilatory and gas exchange indices provide an accurate lactate threshold. Although the potential for pseudo-threshold behavior of the standard ventilatory and gas exchange indices of the lactate threshold must be concerned if an incremental test is performed under hypoxic conditions in which carotid body chemosensitivity is increased.     

Relation between the change of slope of heart rate and second lactic and ventilatory thresholds in muscular exercise with large load]

The time-course of heart rate, blood lactate, and ventilatory gas exchange was studied during an incremental exercise test on cycloergometer in order to ascertain whether heart rate deflection occurred at the same load as the second lactate S[La]2) and ventilatory (SV2) thresholds. Twelve moderately trained subjects, 22 to 30 years old, participated in the study. The initial power setting was 30 W for 3 min with successive increases of 30 W every min except at the end of the test where the increase was reduced to 20 and 10 W.min-1. Ventilatory flow (VE), oxygen uptake (VO2), carbon dioxide production (VCO2, ventilatory equivalents of O2 (EO2 = VE/VO2) and CO2 (ECO2 = VE/VCO2), and heart rate (HR) were determined during the last 20 s of every min. Venous blood samples were drawn at the end of each stage of effort and analyzed enzymatically for lactate concentration ([La]). The HR deflection, S[La]2, and SV2 were represented graphically by two investigators using a double blind procedure. Following the method proposed by Conconi et al. 1982, the deflection in HR was considered to begin at the point beyond which the increase in work intensity exceeded the increase in HR and the linearity of the work rate/HR relationship was lost. S[La]2 corresponded to the second breaking point of the lactate time-course curve (onset of blood lactate accumulation) and SV2 was identified at the second breaking point in the increase in VE and ventilatory equivalent for O2 uptake accompanied by a concomitant increase in ventilatory equivalent for CO2 output. We observed that the deflection point in HR was present only in 7 subjects. The work load, VO2, HR, and [La] levels at which heart rate departed from linearity did not differ significantly from those determined with S[La]2 ans SV2. The VO2 and HR values at HR deflection point were significantly correlated with those measured at S[La]2 and SV2. It is concluded that deflection in heart rate does not always occur, and when it does, it coincides with the second lactate and ventilatory gas exchange thresholds. It can thus be used for the determination of optimal intensity for individualized aerobic training.     

The influence of a respiratory acidosis on the exercise blood lactate response

The purpose of the present study was to examine the influence of a respiratory acidosis on the blood lactate (La) threshold and specific blood La concentrations measured during a progressive incremental exercise test. Seven males performed three step-incremental exercise tests (20 W.min-1) breathing the following gas mixtures; 21% O2 balance-nitrogen, and 21% O2, 4% CO2 balance-nitrogen or balance-helium. The log-log transformation of La oxygen consumption (VO2) relationship and a 1 mmol.l-1 increase above resting values were used to determine a La threshold. Also, the VO2 corresponding to a La value of 2 (La2) and 4 (La4) mmol.l-1 was determined. Breathing the hypercapnic gas mixtures significantly increased the resting partial pressure of carbon dioxide (PCO2) from 5.6 kPa (42 mm Hg) to 6.1 kPa (46 mm Hg) and decreased pH from 7.395 to 7.366. During the incremental exercise test, PCO2 increased significantly to 7.2 kPa (54 mm Hg) and 6.8 kPa (51 mm Hg) for the hypercapnic gas mixtures with nitrogen and helium, respectively, and pH decreased to 7.194 and 7.208. In contrast, blood PCO2 decreased to 4.9 kPa (37 mm Hg) at the end of the normocapnic exercise test and pH decreased to 7.291. A blood La threshold determined from a log-log transformation [1.20 (0.28) l.min-1] or as an increase of 1 mmol.l-1 [1.84 (0.46) l.min-1] was unaffected by the acid-base alterations. Similarly, the VO2 corresponding to La2 and La4 was not affected by breathing the hypercapnic gas mixtures [2.12 (0.46) l.min-1 and 2.81 (0.52) l.min-1, respectively].(ABSTRACT TRUNCATED AT 250 WORDS)     

Immediate effects of cigarette smoking on cardiorespiratory responses to exercise

To determine the acute action of cigarette smoking on cardiorespiratory function under stress, the immediate effects of cigarette smoking on the ventilatory, gas exchange, and cardiovascular responses to exercise were studied in nine healthy male subjects. Each subject performed an incremental exercise test to exhaustion on two separate days, one without smoking (control) and one after smoking 3 cigarettes/h for 5 h. The order of the two tests was randomized. Arterial blood gases and pH were measured during rest and all levels of exercise; CO blood levels confirmed the absorption of cigarette smoke. In addition, minute ventilation (VE), end-tidal PCO2 and PO2, O2 uptake (VO2), CO2 production, directly measured blood pressure, electrocardiogram, and heart rate (HR) were recorded every 30 s. The dead space-to-tidal volume ratio (VD/VT), maximal aerobic capacity (VO2max), and anaerobic threshold (AT) were determined from the gas exchange data. Cigarette smoking resulted in a significantly lower VO2max, AT, and VO2/HR (O2 pulse) and a significantly higher HR, pulse-pressure product, and pulse pressure (P less than 0.05) compared with the control. Additionally, a trend toward a higher VD/VT and arterial-end-tidal PCO2 difference was found during exercise after smoking. We conclude that cigarette smoking causes immediate detrimental effects on cardiovascular function during exercise, including tachycardia, increased pulse-pressure product, and impaired O2 delivery. The acute effects on respiratory function were less striking and primarily limited to abnormalities reflecting ventilation-perfusion mismatching.(ABSTRACT TRUNCATED AT 250 WORDS)     

Blood oxygen transport in common map turtles during simulated hibernation

We assessed the effects of cold and submergence on blood oxygen transport in common map turtles (Graptemys geographica). Winter animals were acclimated for 6-7 wk to one of three conditions at 3 degrees C: air breathing (AB-3 degrees C), normoxic submergence (NS-3 degrees C), and hypoxic (PO2=49 Torr) submergence (HS-3 degrees C). NS-3 degrees C turtles exhibited a respiratory alkalosis (pH 8.07; PCO2=7.9 Torr; [lactate]=2.2 mM) relative to AB-3 degrees C animals (pH 7.89; PCO2=13.4 Torr; [lactate]=1.1 mM). HS-3 degrees C animals experienced a profound metabolic acidosis (pH 7.30; PCO2=7.9 Torr; [lactate]=81 mM). NS-3 degrees C turtles exhibited an increased blood O2 capacity; however, isoelectric focusing revealed no seasonal changes in the isohemoglobin (isoHb) profile. Blood O2 affinity was significantly increased by cold acclimation; half-saturation pressures (P50's) for air-breathing turtles at 3 degrees and 22 degrees C were 6.5 and 18.8 Torr, respectively. P50's for winter animals submerged in normoxic and hypoxic water were 5.2 and 6.5 Torr, respectively. CO2 Bohr slopes (Delta logP50/Delta pH) were -0.15, -0.16, and -0.07 for AB-3 degrees C, NS-3 degrees C, and HS-3 degrees C turtles, respectively; the corresponding value for AB-22 degrees C was -0.37. The O2 equilibrium curve (O2EC) shape was similar for AB-3 degrees C and NS-3 degrees C turtles; Hill plot n coefficients ranged from 1.8 to 2.0. The O2EC shape for HS-3 degrees C turtles was anomalous, exhibiting high O2 affinity below P50 and a right-shifted segment above half-saturation. We suggest that increases in Hb-O2 affinity and O2 capacity enhance extrapulmonary O2 uptake by turtles overwintering in normoxic water. The anomalous O2EC shape and reduced CO2 Bohr effect of HS-3 degrees C turtles may also promote some aerobic metabolism in hypoxic water.     

Distribution of blood flow in muscles of miniature swine during exercise

The purpose of this study was to determine how the distribution of blood flow within and among the skeletal muscles of miniature swine (22 +/- 1 kg body wt) varies as a function of treadmill speed. Radiolabeled microspheres were used to measure cardiac output (Q) and tissue blood flows in preexercise and at 3-5 min of treadmill exercise at 4.8, 8.0, 11.3, 14.5, and 17.7 km/h. All pigs (n = 8) attained maximal O2 consumption (VO2max) (60 +/- 4 ml X min-1 X kg-1) by the time they ran at 17.7 km/h. At VO2max, 87% of Q (9.9 +/- 0.5 l/min) was to skeletal muscle, which constituted 36 +/- 1% of body mass. Average total muscle blood flow at VO2max was 127 +/- 14 ml X min-1 X 100 g-1; average limb muscle flow was 135 +/- 17 ml X min-1 X 100 g-1. Within the limb muscles, blood flow was distributed so that the deep red parts of extensor muscles had flows about two times higher than the more superficial white portions of the same muscles; the highest muscle blood flows occurred in the elbow flexors (brachialis: 290 +/- 44 ml X min-1 X 100 g-1). Peak exercise blood flows in the limb muscles were proportional (P less than 0.05) to the succinate dehydrogenase activities (r = 0.84), capillary densities (r = 0.78), and populations of oxidative (slow-twitch oxidative + fast-twitch oxidative-glycolytic) fiber types (r = 0.93) in the muscles. Total muscle blood flow plotted as a function of exercise intensity did not peak until the pigs attained VO2max, although flows in some individual muscles showed a plateau in this relationship at submaximal exercise intensities. The data demonstrate that blood flow in skeletal muscles of miniature swine is distributed heterogeneously and varies in relation to fiber type composition and exercise intensity.