Effect of pentoxiphylline on oxygen transport during hypothermia

At least two investigators have demonstrated a reduction in O2 extraction during induced hypothermia (Cain and Bradley, J. Appl. Physiol. 55: 1713-1717, 1983; Schumacker et al., J. Appl. Physiol. 63: 1246-1252, 1987). We hypothesized that administration of pentoxiphylline (PTX), a theobromine that lowers blood viscosity and has vasodilator effects, would increase O2 extraction during hypothermia. To test this hypothesis, we studied O2 transport in anesthetized, paralyzed, mechanically ventilated beagles exposed to hypoxic hypoxia during either 1) normothermia (38 degrees C), 2) hypothermia (30 degrees C), or 3) hypothermia + PTX (30 degrees C and PTX, 20 mg.kg-1.h-1). Measurements included arterial and mixed venous PO2, hemoglobin concentration and saturation, cardiac output, systemic vascular resistance (SVR), blood viscosity, and O2 consumption (VO2). Critical levels of O2 delivery (DO2, the product of arterial O2 content and cardiac output) were determined by a system of linear regression. Hypothermia significantly decreased base line cardiac output (-35%), DO2 (-37%), and VO2 (-45%), while increasing SVR and blood viscosity. Addition of PTX increased cardiac output (35%) and VO2 (14%), and returned SVR and blood viscosity to normothermic levels. Hypothermia alone failed to significantly reduce the critical level of DO2, but addition of PTX did [normothermia, 11.4 +/- 4.2 (SD) ml.kg-1.min-1; hypothermia, 9.3 +/- 3.6; hypothermia + PTX, 6.6 +/- 1.3; P less than 0.05, analysis of variance]. The O2 extraction ratio (VO2/DO2) at the critical level of DO2 was decreased during hypothermia alone (normothermia, 0.60 +/- 0.13; hypothermia, 0.42 +/- 0.16; hypothermia + PTX, 0.62 +/- 0.19; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lymphocyte proliferation responses after exercise in men: fitness, intensity, and duration effects

This study investigated the effects of intensity and duration of exercise on lymphocyte proliferation as a measure of immunologic function in men of defined fitness. Three fitness groups--low [maximal O2 uptake (VO2max) = 44.9 +/- 1.5 ml O2.kg-1.min-1 and sedentary], moderate (VO2max = 55.2 +/- 1.6 ml O2.kg-1.min-1 and recreationally active), and high (VO2max = 63.3 +/- 1.8 ml O2.kg-1.min-1 and endurance trained)--and a mixed control group (VO2max = 52.4 +/- 2.3 ml O2.kg-1.min-1) participated in the study. Subjects completed four randomly ordered cycle ergometer rides: ride 1, 30 min at 65% VO2max; ride 2, 60 min at 30% VO2max; ride 3, 60 min at 75% VO2max; and ride 4, 120 min at 65% VO2max. Blood samples were obtained at various times before and after the exercise sessions. Lymphocyte responses to the T cell mitogen concanavalin A were determined at each sample time through the incorporation of radiolabeled thymidine [( 3H]TdR). Despite differences in resting levels of [3H]TdR uptake, a consistent depression in mitogenesis was present 2 h after an exercise bout in all fitness groups. The magnitude of the reduction in T cell mitogenesis was not affected by an increase in exercise duration. A trend toward greater reduction was present in the highly fit group when exercise intensity was increased. The reduction in lymphocyte proliferation to the concanavalin A mitogen after exercise was a short-term phenomenon with recovery to resting (preexercise) values 24 h after cessation of the work bout. These data suggest that single sessions of submaximal exercise transiently reduce lymphocyte function in men and that this effect occurs irrespective of subject fitness level.     

Intrapulmonary oxygen consumption in experimental pneumococcal pneumonia

To test the hypothesis that lung affected by acute bacterial pneumonia consumes significant amounts of O2, whole-body O2 consumption (VO2) was measured simultaneously by collection of expired gas (VO2exp) and by the Fick principle (VO2Fick) in five dogs with acute experimental pneumococcal pneumonia and in five uninfected controls. This approach is based on the premise that VO2Fick will not detect lung VO2, whereas the expired gas measurement represents the true whole-body VO2, including the lung. In controls VO2 exp averaged 110 +/- 20 ml/min (4.78 +/- 0.78 ml.min-1.kg-1), and VO2Fick was nearly identical at 114 +/- 21 ml/min (4.96 +/- 0.79 ml.min-1.kg-1). The VO2Fick in the pneumonia group was 127 ml/min, similar to both control group values when indexed for body weight (4.91 +/- 1.17 ml.min-1.kg-1). VO2exp, however, was 146 +/- 46 ml/min (5.74 +/- 1.57 ml.min-1.kg-1), exceeding VO2Fick by an average of 20 +/- 9 ml/min (P less than 0.01). This between-method difference of 20 +/- 9 ml/min (or 24 ml/min if the difference in the control group is assumed to apply to the pneumonia group) amounted to 13-15% of whole-body VO2 and can be attributed to VO2 in the lung, presumably by cells involved in the acute inflammatory response. Implications include the potential for significant underestimate of whole-body VO2 by the Fick method when used in the presence of lung inflammation and overestimate of blood flow to shunting or low ventilation-perfusion ratio lung units by the O2 method of measuring venous admixture-like perfusion. This observation may also explain the disproportionate hypoxemia sometimes seen in patients with severe pneumonia.     

Effect of endurance exercise training on ventilatory function in older individuals

To evaluate the effect of endurance training on ventilatory function in older individuals, 1) 14 master athletes (MA) [age 63 +/- 2 yr (mean +/- SD); maximum O2 uptake (VO2max) 52.1 +/- 7.9 ml . kg-1 . min-1] were compared with 14 healthy male sedentary controls (CON) (age 63 +/- 3 yr; VO2max of 27.6 +/- 3.4 ml . kg-1 . min-1), and 2) 11 sedentary healthy men and women, age 63 +/- 2 yr, were reevaluated after 12 mo of endurance training that increased their VO2max 25%. MA had a significantly lower ventilatory response to submaximal exercise at the same O2 uptake (VE/VO2) and greater maximal voluntary ventilation (MVV), maximal exercise ventilation (VEmax), and ratio of VEmax to MVV than CON. Except for MVV, all of these parameters improved significantly in the previously sedentary subjects in response to training. Hypercapnic ventilatory response (HCVR) at rest and the ventilatory equivalent for CO2 (VE/VCO2) during submaximal exercise were similar for MA and CON and unaffected by training. We conclude that the increase in VE/VO2 during submaximal exercise observed with aging can be reversed by endurance training, and that after training, previously sedentary older individuals breathe at the same percentage of MVV during maximal exercise as highly trained athletes of similar age.     

Effect of L-NAME on oxygen uptake kinetics during heavy-intensity exercise in the horse.

There is evidence that oxidative enzyme inertia plays a major role in limiting/setting the O(2) uptake (VO(2)) response at the transition to higher metabolic rates and also that nitric oxide (NO) competitively inhibits VO(2) within the electron transport chain. To investigate whether NO is important in setting the dynamic response of VO(2) at the onset of high-intensity (heavy-domain) running in horses, five geldings were run on a treadmill across speed transitions from 3 m/s to speeds corresponding to 80% of peak VO(2) with and without nitro-L-arginine methyl ester (L-NAME), an NO synthase inhibitor (20 mg/kg; order randomized). L-NAME did not alter (both P > 0.05) baseline (3 m/s, 15.4 +/- 0.3 and 16.2 +/- 0.5 l/min for control and L-NAME, respectively) or end-exercise VO(2) (56.9 +/- 5.1 and 55.2 +/- 5.8 l/min for control and L-NAME, respectively). However, in the L-NAME trial, the primary on-kinetic response was significantly (P < 0.05) faster (i.e., reduced time constant, 27.0 +/- 2.7 and 18.7 +/- 3.0 s for control and L-NAME, respectively), despite no change in the gain of VO(2) (P > 0.05). The faster on-kinetic response was confirmed independent of modeling by reduced time to 50, 63, and 75% of overall VO(2) response (all P < 0.05). In addition, onset of the VO(2) slow component occurred earlier (124.6 +/- 11.2 and 65.0 +/- 6.6 s for control and L-NAME, respectively), and the magnitude of the O(2) deficit was attenuated (both P < 0.05) in the L-NAME compared with the control trial. Acceleration of the VO(2) kinetics by L-NAME suggests that NO inhibition of mitochondrial VO(2) may contribute, in part, to the intrinsic metabolic inertia evidenced at the transition to higher metabolic rates in the horse.     

Oxygen debt in submaximal and supramaximal exercise in children at high and low altitude

The effect of high altitude (HA) on O2 debt and blood lactate concentration [( L]) was examined in 10- to 13-yr-old children who exhibited the same level of physical fitness. Fifty-one children acclimatized to HA (3,700 m) were compared with 40 children living at low altitude (LA, 330 m) during submaximal (20-95% maximal aerobic power, MAP), maximal and supramaximal (115% MAP) bicycle exercise. Results showed that 1) maximal O2 uptake (VO2max) and maximal heart rate were significantly (P less than 0.001) lower at HA than at LA by 15% and 11 beats X min-1, respectively; 2) for a given absolute work load, O2 debt was higher at HA than at LA, and the slopes of the linear relationships between O2 debt and O2 uptake were significantly higher at HA; 3) when related to percent of VO2max, O2 debts in HA and LA were similar; for 115% MAP maximal O2 debt and [L] were not significantly different (maximal O2 debt, 45.7 +/- 2.7 and 45.9 +/- 3.8 ml X kg-1; [L], 6.0 +/- 0.3 and 6.7 +/- 0.5 mM); and 4) linear relationships between maximal O2 debt and [L] were the same at HA and LA. This suggests that HA did not modify the anaerobic capacity in children.     

Flow redistribution during progressive hemorrhage is a determinant of critical O2 delivery

O2 consumption (VO2) of anesthetized whole mammals is independent of O2 delivery (DO2) until DO2 declines to a critical value (DO2c). Below this value, VO2 becomes O2 supply dependent. We assessed the influence of whole body DO2 redistribution among organs with respect to the commencement of O2 supply dependency. We measured DO2, VO2, and DO2c of whole body, liver, intestine, kidney, and remaining carcass in eight mongrel dogs during graded progressive hemorrhage. Whole body DO2 was redistributed such that the organ-to-whole body DO2 ratio declined for liver and kidney and increased for carcass. We then created a mathematical model wherein each organ-to-whole body DO2 ratio remained approximately constant at all values of whole body DO2 and assigned organ VO2 to predicted organ DO2 by interpolation and extrapolation of observed VO2-DO2 plots. The model predicted that O2 supply dependency without redistribution would have commenced at a higher value of whole body DO2 for whole body (8.11 +/- 0.89 vs. 6.98 +/- 1.16 ml.kg-1.min-1, P less than 0.05) and carcass (6.83 +/- 1.16 vs. 5.06 +/- 1.15 ml.kg-1.min-1, P less than 0.01) and at a lower value of whole body DO2 for liver (6.33 +/- 1.86 vs. 7.59 +/- 1.95, ml.kg-1.min-1, P less than 0.02) and kidney (1.25 +/- 0.64 vs. 4.54 +/- 1.29 ml.kg-1.min-1, P less than 0.01). We conclude that redistribution of whole body DO2 among organs facilitates whole body O2 regulation.     

Effect of dopamine on transient ventilatory response to exercise

The effect of exogenous dopamine on the development of exercise hyperpnea was studied. Using a bicycle ergometer, five subjects performed repetitive square-wave work-load testing from unloaded pedaling to 80% of each subject's estimated anaerobic threshold. The breath-by-breath ventilation (VE), CO2 production (VCO2), and O2 consumption (VO2) responses were analyzed by curve fitting a first-order exponential model. Comparisons were made between control experiments and experiments with a 3-micrograms X kg-1 X min-1 intravenous infusion of dopamine. Steady-state VE, VCO2 and VO2 were unchanged by the dopamine infusion, both during unloaded pedaling and at the heavier work load. The time constants for the increase in VE (tau VE) and VCO2 (tau CO2) were significantly (P less than 0.05) slowed (tau VE = 56.5 +/- 16.4 s for control, and tau VE = 76.4 +/- 26.6 s for dopamine; tau CO2 = 51.5 +/- 10.6 s for control, and tau CO2 = 64.8 +/- 17.4 s for dopamine) (mean +/- SD), but the time constant for VO2 (tau O2) was not significantly affected (tau O2 = 27.5 +/- 11.7 s for control, and tau O2 = 31.0 +/- 10.1 s for dopamine). We conclude that ablation of carotid body chemosensitivity with dopamine slows the transient ventilatory response to exercise while leaving the steady-state response unaffected.     

Oxygen consumption by portal vein-drained organs and by whole animal in conscious growing swine

A method was developed to measure simultaneously the O2 consumption (VO) by the whole animal and by the hepatic portal vein-drained organs (PVDO), including the gastrointestinal tract, spleen, and pancreas in conscious 3.5- to 4-month-old swine. The method was used to determine (i) the effect of feeding on hepatic portal vein blood flow rate (Qpv) and VO by PVDO and by the whole animal, and (ii) the significance of PVDO on the oxidative demand in the pig. Chronic cannulas were placed in the hepatic portal vein, carotid artery, and ileal vein. The Qpv was determined by an indicator dilution technique employing continuous constant infusion of 1% p-aminohippuric acid into the ileal vein. The VO2 by PVDO was estimated by multiplying Qpv by arterial-portal vein O2 difference measured with an arterial-venous O2 difference analyzer connected to the carotid artery and portal vein cannulas. Whole animal VO2 was measured with an open circuit indirect calorimeter. In seven pigs (3.5- to 4-month-old, 37.4 +/- 0.8 kg) trained to be fed once daily, feeding (1.2 kg of feed mixed with 1.2 liter of H2O) caused postprandial (6 hr) Qpv to increase more than 34 +/- 15% above the preprandial value of 34.5 +/- 4.2 ml.min-1.kg-1 body wt. The postprandial VO2 by PVDO was elevated more than 46 +/- 12% above the value of 1.52 +/- 0.20 ml.min-1.kg-1 body wt observed during the preprandial period. Whole animal VO2 increased 45 +/- 9 and 33 +/- 7% above the preprandial value of 6.23 +/- 0.57 ml.min-1.kg-1 body wt for the first 6 hr and the 7 to 12 hr after feeding, respectively. Although PVDO represent only 5% of body weight, they used 25% of whole body VO2. The study clearly illustrates the significance of PVDO on the whole animal oxidative demand in conscious growing swine.     

Oxygen delivery rate and sufficiency of oxygenation during ECMO in newborn baboons

Minimum acceptable O2 delivery (DO2) during extracorporeal membrane oxygenation (ECMO) remains to be defined in a newborn primate model. The right atrium, carotid artery, and femoral artery were cannulated, and the ductus arteriosus, aorta, and pulmonary artery ligated in neonatal baboons (Papio cynocephalus) under a combination of ketamine, diazepam, and pancuronium. The internal jugular vein was also cannulated retrograde to the level of the occipital ridge. We measured hemoglobin, pH, arterial and venous PO2 (both from the pump circuit and from the cerebral venous site), serum lactate and bicarbonate concentrations, and pump flow, and we calculated hemoglobin saturations, (DO2), O2 consumption (VO2), systemic O2 extraction, and cerebral O2 extraction. Six baboons were studied during each of two phases of the experiment. In the first, flow rates were varied sequentially from 200 to 50 ml.kg-1.min-1 with saturation maximized. In the second, flow was maintained at 200 ml.kg-1.min-1 and saturation was reduced sequentially from 100 to 38%. VO2 fell significantly below baseline at a flow rate of 50 ml.kg-1.min-1 and a DO2 of 8 +/- 2 (SE) ml.kg-1.min-1 in phase 1 and at DO2 of 12 +/- 5 in phase 2. Both systemic and cerebral O2 extraction rose significantly at a flow of 100 ml.kg-1.min-1 and DO2 of 17 +/- 4 ml.kg-1.min-1 in phase 1, whereas neither rose with decreasing DO2 in phase 2. In fact, cerebral extraction fell significantly DO2 of 16 +/- 6 ml.kg-1.min-1.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dynamic exercise training in foxhounds. I. Oxygen consumption and hemodynamic responses

Ten foxhounds were studied during maximal and submaximal exercise on a motor-driven treadmill before and after 8-12 wk of training. Training consisted of working at 80% of maximal heart rate 1 h/day, 5 days/wk. Maximal O2 consumption (VO2max) increased 28% from 113.7 +/- 5.5 to 146.1 +/- 5.4 ml O2 X min-1 X kg-1, pre- to posttraining. This increase in VO2max was due primarily to a 27% increase in maximal cardiac output, since maximal arteriovenous O2 difference increased only 4% above pretraining values. Mean arterial pressure during maximal exercise did not change from pre- to posttraining, with the result that calculated systemic vascular resistance (SVR) decreased 20%. There were no training-induced changes in O2 consumption, cardiac output, arteriovenous O2 difference, mean arterial pressure, or SVR at any level of submaximal exercise. However, if post- and pretraining values are compared, heart rate was lower and stroke volume was greater at any level of submaximal exercise. Venous lactate concentrations during a given level of submaximal exercise were significantly lower during posttraining compared with pretraining, but venous lactate concentrations during maximal exercise did not change as a result of exercise training. These results indicate that a program of endurance training will produce a significant increase in VO2max in the foxhound. This increase in VO2max is similar to that reported previously for humans and rats but is derived primarily from central (stroke volume) changes rather than a combination of central and peripheral (O2 extraction) changes.     

Rectal and rectal vs. esophageal temperatures in paraplegic men during prolonged exercise

This study investigated the rectal (Tre), esophageal (Tes), and skin (Tsk) temperature changes in a group of trained traumatic paraplegic men pushing their own wheelchairs on a motor-driven treadmill for a prolonged period in a neutral environment. There were two experiments. The first experiment (Tre and Tsk) involved a homogeneous group (T10-T12/L3) of highly trained paraplegic men [maximum O2 uptake (VO2max) 47.5 +/- 1.8 ml.kg-1.min-1] exercising for 80 min at 60-65% VO2max.Tre and Tsk (head, arm, thigh, and calf) and heart rate (HR) were recorded throughout. O2 uptake (VO2), minute ventilation (VE), CO2 production (VCO2), and heart rate (HR) were recorded at four intervals. During experiment 1 significant changes in HR and insignificant changes in VCO2, VE, and VO2 occurred throughout prolonged exercise. Tre increased significantly from 37.1 +/- 0.1 degrees C (rest) to 37.8 +/- 0.1 degrees C after 80 min of exercise. There were only significant changes in arm Tsk. Experiment 2 involved a nonhomogeneous group (T5-T10/T11) of active paraplegics (VO2max 39.9 +/- 4.3 ml.kg-1.min-1) exercising at 60-65% VO2max for up to 45 min on the treadmill while Tre and Tes were simultaneously recorded. Tes rose significantly faster than Tre during exercise (dT/dt 20 min: Tes 0.050 +/- 0.003 degrees C/min and Tre 0.019 +/- 0.005 degrees C/min), and Tes declined significantly faster than Tre at the end of exercise. Tes was significantly higher than Tre at the end of exercise. Our results suggest that during wheelchair propulsion by paraplegics, Tes may be a better estimate of core temperature than Tre.     

Decline in VO2max with aging in master athletes and sedentary men

Fifteen well-trained master endurance athletes [62.0 +/- 2.3 (SE) yr] and 14 sedentary control subjects (61.4 +/- 1.4 yr) were reevaluated after an average follow-up period of approximately 8 yr to obtain information regarding the effects of physical activity on the age-related decline in maximal O2 uptake capacity (VO2max). The master athletes had been training for 10.2 +/- 2.9 yr before initial testing and continued to train during the follow-up period. The sedentary subjects' VO2max declined by an average of 3.3 ml.kg-1.min-1 (33.9 +/- 1.7 vs. 30.6 +/- 1.6, P less than 0.001) over the course of the study, a decline of 12% per decade. In these subjects maximal heart rate declined 8 beats/min (171 vs. 163) and maximal O2 pulse decreased from 0.20 to 0.18 ml.kg-1.beat (P less than 0.05). The master athletes' VO2 max decreased by an average of 2.2 ml.kg-1.min-1 (54.0 +/- 1.7 vs. 51.8 +/- 1.8, P less than 0.05), a 5.5% decline per decade. The master athletes' maximal heart rate was unchanged (171 +/- 3 beats/min) and their maximal O2 pulse decreased from 0.32 to 0.30 ml.kg-1.beat (P less than 0.05). These findings provide evidence that the age-related decrease in VO2max of master athletes who continue to engage in regular vigorous endurance exercise training is approximately one-half the rate of decline seen in age-matched sedentary subjects. Furthermore our results suggest that endurance exercise training may reduce the rate of decline in maximal heart rate that typically occurs as an individual ages.     

Increased dependence on blood glucose after acclimatization to 4,300 m

To evaluate the hypothesis that altitude exposure and acclimatization result in increased dependency on blood glucose as a fuel, seven healthy males (23 +/- 2 yr, 72.2 +/- 1.6 kg, mean +/- SE) on a controlled diet were studied in the postabsorptive condition at sea level (SL), on acute altitude exposure to 4,300 m (AA), and after 3 wk of chronic altitude exposure to 4,300 m (CA). Subjects received a primed continuous infusion of [6,6-2D]glucose and rested for a minimum of 90 min, followed immediately by 45 min of exercise at 101 +/- 3 W, which elicited 51.1 +/- 1% of the SL maximal O2 consumption (VO2 max; 65 +/- 2% of altitude VO2 max). At SL, resting arterial glucose concentration was 82.4 +/- 3.2 mg/dl and rose significantly to 91.2 +/- 3.2 mg/dl during exercise. Resting glucose appearance rate (Ra) was 1.79 +/- 0.02 mg.kg-1.min-1; this increased significantly during exercise at SL to 3.71 +/- 0.08 mg.kg-1.min-1. On AA, resting arterial glucose concentration (85.8 +/- 4.1 mg/dl) was not different from sea level, but Ra (2.11 +/- 0.14 mg.kg-1.min-1) rose significantly. During exercise on AA, glucose concentration rose to levels seen at SL (91.4 +/- 3.0 mg/dl), but Ra increased more than at SL (to 4.85 +/- 0.15 mg.kg-1.min-1; P less than 0.05). Resting arterial glucose was significantly depressed with CA (70.8 +/- 3.8 mg/dl), but resting Ra increased to 3.59 +/- 0.08 mg.kg-1.min-1, significantly exceeding SL and AA values.(ABSTRACT TRUNCATED AT 250 WORDS)     

Atrial natriuretic factor attenuates the pulmonary pressor response to hypoxia

The influence of endogenous and exogenous atrial natriuretic factor (ANF) on pulmonary hemodynamics was investigated in anesthetized pigs during both normoxia and hypoxia. Continuous hypoxic ventilation with 11% O2 was associated with a uniform but transient increase of plasma immunoreactive (ir) ANF that peaked at 15 min. Plasma irANF was inversely related to pulmonary arterial pressure (Ppa; r = -0.66, P less than 0.01) and pulmonary vascular resistance (PVR; r = -0.56, P less than 0.05) at 30 min of hypoxia in 14 animals; no such relationship was found during normoxia. ANF infusion after 60 min of hypoxia in seven pigs reduced the 156 +/- 20% increase in PVR to 124 +/- 18% (P less than 0.01) at 0.01 microgram.kg-1.min-1 and to 101 +/- 15% (P less than 0.001) at 0.05 microgram.kg-1.min-1. Cardiac output (CO) and systemic arterial pressure (Psa) remained unchanged, whereas mean Ppa decreased from 25.5 +/- 1.5 to 20.5 +/- 15 mmHg (P less than 0.001) and plasma irANF increased two- to nine-fold. ANF infused at 0.1 microgram.kg-1.min-1 (resulting in a 50-fold plasma irANF increase) decreased Psa (-14%) and reduced CO (-10%); systemic vascular resistance (SVR) was not changed, nor was a further decrease in PVR induced. No change in PVR or SVR occurred in normoxic animals at any ANF infusion rate. These results suggest that ANF may act as an endogenous pulmonary vasodilator that could modulate the pulmonary pressor response to hypoxia.     

Pulmonary vasodilator responses to atrial natriuretic factor and sodium nitroprusside

The objective of this study was to determine the direct actions of atrial natriuretic factor (ANF) on the pulmonary vascular bed and to compare these actions with those of sodium nitroprusside (SNP). The responses to incremental infusion rates of 1, 5, 10, and 50 ng.kg-1.min-1 synthetic human ANF and to 1-2 micrograms.kg-1.min-1 SNP were examined in the in situ autoperfused lung lobe of open-chest anesthetized pigs under conditions of normal and elevated pulmonary vascular tone. During basal conditions, ANF and SNP caused small but significant reductions in pulmonary artery pressure (Ppa) and pulmonary venous pressure (Ppv) with no change in lobar vascular resistance (LVR). When pulmonary vascular tone was increased by prostaglandin F2 alpha (20 micrograms/min), ANF infusion at doses greater than 1 ng.kg-1.min-1 decreased Ppa and LVR in a dose-related fashion. Infusion of 50 ng.kg-1.min-1 ANF and of 2 micrograms.kg-1.min-1 SNP maximally decreased Ppa, from 33 +/- 3 to 20 +/- 2 mmHg (P less than 0.001) and from 31 +/- 4 to 18 +/- 1 mmHg (P less than 0.001), respectively. At these doses, ANF reduced systemic arterial pressure by only 11.5 +/- 3% compared with 34 +/- 4% decreased with SNP (P less than 0.001). The results indicate that ANF, similarly to SNP, exerts a direct potent vasodilator activity in the porcine pulmonary vascular bed, which is dependent on the existing level of vasoconstrictor tone.     

Exercise training and "ventilation threshold" in elderly

Dynamic exercise training of the elderly increases maximal O2 uptake (VO2max); however, the effects of training on the ventilation threshold (VET) have not been studied. VET was identified as the final point before the ventilatory equivalent for O2 (VE/VO2) increased, without an increase in the ventilatory equivalent for CO2 (VE/VCO2). Inactive elderly males (mean age, 62 yr) were randomly assigned to a control (C, n = 44) or activity (A, n = 45) group. VO2max and VET were determined from an incremental treadmill test. Initial VO2max was not different between the C (2.34 +/- 0.42 l X min-1) and A (2.28 +/- 0.44 l X min-1) groups, nor was there a significant difference in the VO2 at the VET (C = 1.39 +/- 0.26 l X min-1; A = 1.31 +/- 0.23 l X min-1). The activity group trained for 30 min/day, 3 days/wk at an intensity of approximately 65-80% of VO2max. After 1 yr of training the activity group exhibited an 18% increase in VO2max (A = 2.70 +/- 0.54 l X min-1), but the change in VET was not significant (A = 1.39 +/- 0.28 l X min-1). There was no significant change in VO2max (C = 2.45 +/- 0.68 l X min-1) or VET (C = 1.38 +/- 0.31 l X min-1) in the control group. VET/VO2max declined significantly in the activity group (from 58 to 52% of VO2max). Change in VET/VO2max with training was not correlated with the initial VO2max value. We conclude that increases in aerobic capacity are more readily effected than alterations of the VET in elderly subjects.     

Effect of hyperoxia on substrate utilization during intense submaximal exercise

Six trained males [mean maximal O2 uptake (VO2max) = 66 ml X kg-1 X min-1] performed 30 min of cycling (mean = 76.8% VO2max) during normoxia (21.35 +/- 0.16% O2) and hyperoxia (61.34 +/- 1.0% O2). Values for VO2, CO2 output (VCO2), minute ventilation (VE), respiratory exchange ratio (RER), venous lactate, glycerol, free fatty acids, glucose, and alanine were obtained before, during, and after the exercise bout to investigate the possibility that a substrate shift is responsible for the previously observed enhanced performance and decreased RER during exercise with hyperoxia. VO2, free fatty acids, glucose, and alanine values were not significantly different in hyperoxia compared with normoxia. VCO2, RER, VE, and glycerol and lactate levels were all lower during hyperoxia. These results are interpreted to support the possibility of a substrate shift during hyperoxia.     

Effects of training on lactate production and removal during progressive exercise in humans.

To determine whether the reduced blood lactate concentrations [La] during submaximal exercise in humans after endurance training result from a decreased rate of lactate appearance (Ra) or an increased rate of lactate metabolic clearance (MCR), interrelationships among blood [La], lactate Ra, and lactate MCR were investigated in eight untrained men during progressive exercise before and after a 9-wk endurance training program. Radioisotope dilution measurements of L-[U-14C]lactate revealed that the slower rise in blood [La] with increasing O2 uptake (VO2) after training was due to a reduced lactate Ra at the lower work rates [VO2 less than 2.27 l/min, less than 60% maximum VO2 (VO2max); P less than 0.01]. At power outputs closer to maximum, peak lactate Ra values before (215 +/- 28 mumol.min-1.kg-1) and after training (244 +/- 12 mumol.min-1.kg-1) became similar. In contrast, submaximal (less than 75% VO2max) and peak lactate MCR values were higher after than before training (40 +/- 3 vs. 31 +/- 4 ml.min-1.kg-1, P less than 0.05). Thus the lower blood [La] values during exercise after training in this study were caused by a diminished lactate Ra at low absolute and relative work rates and an elevated MCR at higher absolute and all relative work rates during exercise.     

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)