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Biomedical subjects

E R Nadel

Publications and source records attributed to E R Nadel.

At least 73 records · Page 4Linked to original sources

Isotopic determination of amino acid-urea interactions in exercise in humans.

We recently reported that in light exercise (30% VO2max) the oxidation of [1-13C]leucine was significantly increased but the rate of urea production was unchanged (J. Appl. Physiol: Respirat. Environ. Exercise Physiol. 52: 458-466, 1982). We have therefore tested three possible explanations for this apparent incongruity. 1) We infused NaH13CO3 throughout rest and exercise and found that, although altered bicarbonate kinetics in exercise resulted in greater recovery of 13CO2, the difference between rest and recovery was small compared with the increase in the rate of 13CO2 excretion during exercise when [1-13C]leucine was infused. 2) We infused [15N]leucine and isolated plasma urea N to determine directly the rate of incorporation of the 15N. During exercise there was no increase in the rate of 15N incorporation. Simultaneously, we infused [2,3-13C]alanine and quantified the rate of incorporation of 15N in alanine. We found that [15N]alanine production from [15N] leucine more than doubled in exercise, and by deduction, alanine production from other amino acids also doubled. 3) We tested our previous assumption that [1-13C]leucine metabolism in exercise was representative of the metabolism of other essential amino acids by infusing [1-13C] and [alpha-15N]lysine throughout rest and exercise. We found that the rate of breakdown of lysine during exercise was not increased in a manner comparable to that of leucine. Thus, these data confirm our original findings that leucine decarboxylation is enhanced in light exercise but urea production is unchanged.(ABSTRACT TRUNCATED AT 250 WORDS)

Alanine↗

Effect of substrate intake and physiological state on background 13CO2 enrichment.

The natural enrichment of 13C in energy substrates varies, and this variation must be taken into account when stable isotopic tracers are used in metabolic studies. This is conventionally accomplished by measuring background samples taken before the tracer infusion begins and subtracting these values from postinfusion values. Whereas this approach is satisfactory if no perturbation occurs between the collection of the background samples and the collection of postinfusion sample, the data presented in this paper show that any change in the metabolic state can significantly alter the background enrichment of expired CO2. This study not only confirmed that the introduction of natural energy sources may alter the background enrichment of CO2, but we also found that changes in substrate oxidation induced by different physiological states, such as exercise, can cause significant changes in expired CO2 enrichments. Conclusions from studies in which oxidation of substrates were measured by means of a 13C tracer but potential changes in background enrichments were not accounted for must, therefore, be reassessed.

Animals↗

Effect of temperature and baroreceptor stimulation on reflex venomotor responses.

To investigate the interaction of thermal reflexes and baroreflexes in the control of the peripheral veins, we studied in supine humans the effects of lower body negative pressure (LBNP) and neck suction (NS) on forearm veins at ambient temperatures (Ta) of 18, 28, and 37 degrees C. Forearm venous volume (FVV)-venous pressure (FVP) relations (forearm venous capacitance) on six subjects showed an increase from 18 through 28 to 37 degrees C (P less than 0.001). Heart rate increased (P less than 0.001) and forearm venous capacitance decreased (P less than 0.001) in proportion to the level of LBNP applied from 20 to 50 Torr at all Ta. At 50 Torr LBNP, FVV at 30 cmH2O, FVP decreased from control values of 2.5, 3.8, and 4.4 to 1.6, 2.7, and 3.4 ml/100 ml at 18, 28, and 37 degrees C, respectively. We also studied venomotor responses using the occluded limb technique. Although LBNP caused venoconstriction, NS applied either alone or during LBNP produced no change in venomotor tone. Therefore we concluded that carotid baroreceptors play little role in reflex venomotor adjustments. Since changes in mean arterial and pulse pressures during LBNP did not account for the observed venomotor responses, we concluded that low-pressure baroreceptors initiate significant venoconstrictor reflexes over a wide range of Ta.

Adult↗

Effect of hyperosmolality on control of blood flow and sweating.

To study the effect of hyperosmolality on thermoregulatory responses, five men [average maximal O2 consumption (VO2 max) = 48 ml X kg-1 X min-1] cycled at 65-75% VO2max for up to 30 min in a 30 degrees C, 40% relative humidity environment under three conditions. First, control tests (C) were performed where preexercise plasma volume (PV) and osmolality (Osm) averaged 3,800 ml and 282 mosmol X kg-1, respectively. Second, exercise tests (D) were performed following dehydration induced by fluid restriction and mild exercise (30% VO2max) in hot (40 degrees C) ambient conditions. Each subject then rested in cool surroundings 1 h before performing the exercise test. Preexercise PV and Osm averaged 3,606 ml and 293 mosmol X kg-1, respectively. Third, exercise tests (I) were performed following dehydration, but during the 1-h rest interval, 3% saline was infused so that PV was restored to 3,826 ml and Osm averaged 294 mosmol X kg-1 prior to exercise. During D, esophageal temperatures (Tes) were significantly higher than C, an avg 0.56 degrees C after 20 min exercise due to a 0.22 degrees C increase in Tes threshold for vasodilation, a 39% reduction in slope of the forearm blood flow (BF)-Tes relationship, a 32% average reduction in maximal exercise BF, and a 0.22 degrees C increase in Tes sweating threshold. During I, responses were similar to D, except the BF-Tes slope and the maximum BF were not significantly different from C. Thus hyperosmolality modifies thermoregulation by elevating thresholds for both vasodilation and sweating even without decreases in PV.

Adult↗

Energy exchanges in water.

The thermal physical properties of water make water a medium of high heat transfer relative to air. This paper describes the body temperature pattern during immersion in still and moving water, the avenues for energy exchange, the energy transfer characteristics of humans, and the physiological means by which the body attempts to compensate for the excess heat loss in water. Fat is the major defense against cooling in water when exercising or shivering. Skeletal muscle is a significant additional factor during quiet rest.

Body Temperature↗

Temperature regulation and hyperthermia during exercise.

This article first describes the physical aspects of heat transfer from skeletal muscles to the environment during exercise, emphasizing environmental factors that affect these transfers. Next, the characteristics of the human thermoregulatory mechanism are described, illustrating the ability to modify rates of heat transfer over a wide range in response to changes in the body temperatures. Finally, problems that develop during exercise in the heat are described, and practical information for minimizing such problems is given.

Body Temperature↗

Effect of blood volume on forearm venous and cardiac stroke volume during exercise.

Five healthy men exercised at 65-70% of maximum O2 uptake (VO2 max) for 30 min in an ambient temperature of 30 degrees C. Duplicate experiments were conducted at three levels of plasma volume:control, hypovolemia, in which blood volume (BV) was reduced an average of 490 ml (9.7%) with diuretics, and hypervolemia, in which BV was increased an average of 440 ml (7.8%) by infusing an isotonic solution containing 5% human serum albumin. Marked venoconstriction occurred during exercise in all conditions and persisted despite large increases in deep body temperature. The degree of venoconstriction was similar during control and hypervolemic conditions, but was potentiated during hypovolemia. The observed venoconstriction appeared to consist of two components: an early one related to autonomic adjustments at the onset of exercise, and a later one possibly related to progressive decreases in cardiac filling. Heart rate, cardiac stroke volume (SV), and cardiac output during exercise were significantly affected by changes in BV. During hypovolemia the average differences from control values were 10 beats X min-1, -14 ml, and -2.2 l X min-1, respectively; during hypervolemia the differences from control were -7 X min-1, 10 ml, and 1.0 l X min-1, respectively. The pattern of SV over the course of exercise indicates that pooling of blood in veins may be quantitatively more important than plasma water loss in reducing cardiac filling pressure in the heat.

Adult↗

Effects of training with eccentric muscle contractions on exercise performance, energy expenditure, and body temperature.

To study the effects of exercise training with eccentric muscle contractions on body temperatures, energy cost, and performance capacity, six human subjects were tested before and after a 5-week training program of eccentric exercise. Exercise was performed as leg cycling on a motor-driven ergometer at power levels ranging 252-316 W. Training consisted of three sessions/week for 1 h/session. As a result of the training, VO2, fH, and mean skin temperature were lowered for each subject at the same absolute exercise intensities. Ability to continue exercise as indicated by endurance time improved with training. Before training, four subjects terminated exercise after 30 min because of localized leg exhaustion and one subject could not continue longer than 45 min. After training, all six subjects completed 45 min of the exercise test without difficulty. Esophageal and muscle temperatures evidenced no changes as a result of training. It was concluded that the inability of subjects to perform eccentric exercise in the untrained state was not related to muscle temperature.

Adult↗

Isotopic analysis of leucine and urea metabolism in exercising humans.

We have used the primed constant infusion of di-[15N]urea and [1-13C]leucine to determine the effects of mild exercise (approx 30% Vo2max for 105 min) on urea production and leucine metabolism in human subjects. The oxidation of plasma leucine was distinguished from the oxidation of leucine that never entered the plasma pool ("intracellular" leucine) by means of determining the enrichment of alpha-ketoisocaproic acid (alpha-KICA). Total leucine oxidation increased from 0.38 +/0 0.05 to 1.41 +/- 0.14 micromol . kg-1 . min-1 during exercise due to increases in the oxidation of plasma leucine (150%) and intracellular leucine (600%). Plasma leucine flux decreased slightly, but not significantly (0.1 greater than P greater than 0.05), and the percent of alpha-KICA derived from plasma leucine dropped significantly (P less than 0.05) from 79.5 +/- 4.3 at rest to 62.0 +/- 5.3% over the last 30 min of exercise. Despite the increase in leucine oxidation during exercise, urea concentration and production did not change. Thus in exercise urea production does not accurately reflect all aspects of amino acid metabolism.

Adult↗

Leucine and urea metabolism in acute human cold exposure.

Four healthy males voluntarily underwent acute cold exposure at 10 degrees C. Metabolic rate doubled for the 100-min exposure. [1-13C]leucine and [15N2]urea were used as tracers of protein metabolism via a primed constant infusion. Total and plasma transported leucine oxidation approximately doubled, but the oxidation of leucine derived from protein in the tissue where oxidation occurred ("intracellular oxidation") did not change as it did when the same subjects underwent mild exercise. Rate of appearance of urea and leucine in plasma were not significantly different between control and cold. Although the rate of protein synthesis calculated from the leucine data did not change, the rate of catabolism increased. Net protein catabolism based on the urea data agreed well with the leucine data at rest but did not exhibit a significant increase during exposure. However, net protein catabolism based on the leucine data did increase significantly during acute cold exposure. Further, there appears to be a qualitative difference in the protein catabolism associated with the voluntary muscular activity of exercise and muscular shivering aimed at thermogenesis.

Blood Proteins↗

Effect of acute alterations of blood volume on circulatory performance in humans.

Six subjects exercised (60% VO2 max) in a 35 degree C environment on the day prior to (C1) and 1 h after withdrawal (PW) of 10% of each subject's blood volume, and 2 wk later on the day prior to (C2) and 1 h after infusion (PI) of the stored blood. Esophageal and mean skin temperatures (Tes and Tsk), forearm blood flow (FBF), cardiac output (Q), heart rate (HR), and blood samples were taken at intervals. Blood withdrawal had no major effect on either Q or stroke volume (SV), as plasma volume was largely restored prior to exercise. Following blood infusion Q and SV during exercise were significantly increased 1.4 1.min-1 and 15 ml.beat-1 above C2 levels and HR was significantly reduced at any Tes. Blood withdrawal decreased the slope of the FBF:Tes relationship. The resulting decrease in cutaneous perfusion caused a significantly greater body heat storage during PW. In contrast during PI, the slope of the FBF:Tes relation was somewhat increased. We conclude that cardiac stroke volume and cutaneous blood flow vary in proportion to changes in absolute blood volume. The rise in body temperature during exercise was significantly greater in hypovolemia but was not significantly reduced following volume expansion.

Adult↗

Effect of blood volume on sweating rate and body fluids in exercising humans.

Five relatively fit men performed cycle ergometer exercise (65-70% VO2max) for up to 30 min at 30 degrees C, 40% rh. The data from control (normo-volemic), hypovolemic [8.7% reduction in blood volume (BV) induced by diuretics], and hypervolemic [7.9% expansion of BV induced by infusion if isotonic serum albumin] tests revealed significant effects of BV on body fluid and sweating responses. During control exercise, BV decreased an average (+/- SE) 370 +/- 64 ml at 20 min. A significantly smaller loss occurred after 20 min of hypovolemic exercise (270 +/- 29 ml). The decrease in BV during 30 min of hypervolemic exercise (541 +/- 43 ml) was significantly greater than during control (421 +/- 50 ml). Blood volume reduction also significantly altered the control of sweating rate independent of changes in plasma osmolality. The slope of the sweating rate-to-esophageal temperature relationship (SR/Tes) was significantly reduced from the mean value of 1.07 +/- 0.16 and 1.09 +/- 0.18 mg X min-1 X cm-2 X degrees C-1 during control tests, measured from the chest and arm, respectively, to 0.64 +/- 0.11 and 0.63 +/- 0.11 mg X min-1 X cm-2 X degrees C-1 during hypovolemia. The SR/Tes slope was unchanged in hypovolemia over active tissues (calf). Hypervolemia had no effect on the control of sweating at any site. Both the body fluid and sweating responses during hypovolemia act to conserve circulating blood volume during exercise.

Adult↗

Effect of hydration state of circulatory and thermal regulations.

To determine the influence of hydration state upon circulatory controls, we studied four relatively fit subjects during duplicate 30-min cycle ergometer exercise bouts (55% VO2max) in euhydrated, hypohydrated, and hyperhydrated conditions. Ambient temperature was 35 degrees C. Hypohydration was achieved by 4 days of diuretic administration and resulted in a whole-body weight loss of 2.2 kg and a plasma volume decrease of approximately 700 ml. Hyperhydration was achieved by ADH administration plus ingestion of 2 liters water but caused only a minor increase volume. Hypohydration resulted in a significantly reduced cardiac output during exercise; this the result of a reduction in stroke volume of 17 ml.beat-1 without adequate elevation in heart rate. the internal temperature (Tes) threshold for cutaneous vasodilation was elevated by 0.42 degree C in hypohydrated conditions; but once vasodilation occurred, the slope of the arm blood flow:Tes relation was unchanged from control. Maximal arm blood flow was reduced by nearly 50% in hypohydration. These restrictions in cutaneous blood flow served to maintain an already compromised venous return, but due to the limitation of core-to-skin heat transfer, forced Tes to nearly 39 degrees C, significantly higher than in euhydrated conditions.

Adult↗

Circulatory and thermal regulations during exercise.

During physical activity there is a demand for increased blood flow to the contracting muscles to meet oxygen delivery requirements and to the skin to meet the heat transfer requirements of the temperature regulatory system. This paper evaluates the control mechanisms that provide for the meeting of these simultaneous demands when possible and the compromises that are made when the meeting of simultaneous demands is not possible, such as in conditions of heavy exercise in the heat. Also, an initial attempt is made to invoke these same control mechanisms in the events that accompany the circulatory and thermal changes observed in conditions of dehydration.

Blood Volume↗

Circulatory regulation during exercise in different ambient temperatures.

Three relatively fit subjects performed duplicate 20- to 25-min cycle ergometer exercise bouts at moderate and heavy intensities (40% and 70% Vo2 max) in ambient temperatures of 20, 26, and 36 degrees C. They approached a steady state in internal body temperature (Tes) in all but the heavy exercise in the heat, where Tes rose consistently, averaging 38.84 degrees C at the termination of exercise. Cardiac output (Q), estimated by a rebreathing technique, was proportional to Vo2 and independent of the body temperatures, except during the lower exercise intensity in the heart, where Q averaged 1.31 . min -1 higher throughout. In any environment, forearm blood flow was linearly related to Tes above the Tes threshold for vasodilation, but during heavy exercise in the heat this relationship was severely attenuated above a Tes around 38.0 degrees C, when forearm blood flow exceeded 15 ml.min -1 .100 ml -1. Plasma volume decreases during exercise were primarily a function of the intensity of exercise. During heavy exercise in the heat the relative vasconstriction contributes to the maintenance of an adequate stroke volume preventing a fall in Q. In this case, circulatory regulation has precedence over temperature regulation.

Adult↗

Thermogenic control during exercise in a cold environment.

To determine whether the voluntary contractions of exercise interfere with involuntary shivering contractions, four male subjects were each exposed to a 10 degrees C environment for 60 min of rest followed by either another rest period or 30 min of cycleergometer exercise. On different days exercise was performed at zero load, light load, and moderate load. Each experiment was performed twice, resulting in a minimum of eight experiments for each subject. Esophageal temperature (Tes), eight skin temperatures (Tsk), oxygen uptake (VO2), and the integrated electrical activity from a neck muscle (EMG) were continuously monitored. Pedaling flushed cold blood into the body core, causing Tes to fall. The rate and absolute magnitude of the decrease in Tes was proportional to the intensity of exercise. Thermoregulatory VO2 (attributable to shivering) and EMG were inversely related both to Tsk during rest, prior to any changes in Tes, and to Tes during exercise, when Tsk was constant, once shivering thresholds were surpassed. The slope of the thermoregulatory VO2-to-Tes relation was significantly suppressed by increasing exercise intensity. The slope of the EMG-to-Tes relation was similarly suppressed; since the neck muscles are not involved in the additional acitivity of exercise, we concluded that the graded inhibition of shivering during exercise was of central origin rather than from the rhythmic contractions required to sustain exercise.

Adult↗

Control of sweating rate while exercising in the heat.

All of the heat produced during exercise in a hot environment is either stored in the body or dissipated to the environment by evaporation of sweat. In order to minimize the storage of heat, thereby resisting circulatory strain, the body must be able to effectively increase sweating rate in these conditions. This paper characterizes the physiological control of sweating as a proportional control system, with increases in internal temperature having the greatest effect upon increasing the sweating rate. Factors which modify the threshold and gain of the sweating response, such as occur with dehydration or physical training, affect the storage of heat and therefore the steady state internal temperature during exercise in the heat.

Acclimatization↗