Altitude adaptation through hematocrit changes.

Adaptation takes place not only when going to high altitude, as generally accepted, but also when going down to sea level. Immediately upon ascent to high altitude, the carotid body senses the lowering of the arterial oxygen partial pressure due to a diminished barometric pressure. High altitude adaptation is defined as having three stages: 1) acute, first 72 hours, where acute mountain sickness (CMS or polyerythrocythemia) can occur; 2) subacute, from 72 hours until the slope of the hematocrit increase with time is zero; here high altitude subacute heart disease can occur; and 3) chronic, where the hematocrit level is constant and the healthy high altitude residents achieve their optimal hematocrit. In the chronic stage, patients with CMS increase their hematocrit values to levels above that of normal individuals at the same altitude. CMS is due to a spectrum of medical disorders focused on cardiopulmonary deficiencies, often overlooked at sea level. In this study we measured hematocrit changes in one high altitude resident traveling several times between La Paz (3510 m) and Copenhagen (35 m above sea level) for the past 3 years. We have also studied the fall in hematocrit values in 2 low-landers traveling once from La Paz to Copenhagen. High altitude adaptation is altitude and time dependent, following the simplified equation: Adaptation=Time/Altitude where High altitude adaptation factor=Time at altitude (days)/Altitude in kilometers (km). A complete and optimal hematocrit adaptation is only achieved at around 40 days for a subject going from sea level to 3510 m in La Paz. The time in days required to achieve full adaptation to any altitude, ascending from sea level, can be calculated by multiplying the adaptation factor of 11.4 times the altitude in km. Descending from high altitude in La Paz to sea level in Copenhagen, the hematocrit response is a linear fall over 18 to 23 days.

beta-Blockade used in precision sports: effect on pistol shooting performance.

In a double-blind cross-over study of 33 marksmen (standard pistol, 25 m) the adrenergic beta 1-receptor blocker, metoprolol, was compared to placebo. Metoprolol obviously improved the pistol shooting performance compared with placebo. Shooting improved by 13.4% of possible improvement (i.e., 600 points minus actual points obtained) as an average (SE = 4%, 2P less than 0.002). The most skilled athletes demonstrated the clearest metoprolol improvement. We found no correlation between the shooting improvement and changes in the cardiovascular variables (i.e., changes of heart rate and systolic blood pressure) and no correlation to the estimated maximum O2 uptake. The shooting improvement is an effect of metoprolol on hand tremor. Emotional increase of heart rate and systolic blood pressure seem to be a beta 1-receptor phenomenon.

Dermal excretion of iron in intensely training athletes.

The iron concentration in sweat and serum and related variables (transferrin saturation percentage, hemoglobin concentration) was measured in two groups of distance runners, each consisting of ten persons. In the first group unclear sweat was collected from the back of the athletes during cycling (without previous washing). The iron concentration (means +/- SEM) was 5.2 +/- 1.0 mumol/l of sweat. In the second group the sweat collection was performed similarly, but following elimination of the very first sweat from the site of collection (back) before three consecutive samples were taken. The iron concentration of the three samples was 3.6 +/- 1.1, 2.3 +/- 0.2 and 2.4 +/- 0.3 mumol/1. There was no statistically significant difference between the consecutive samples on the p less than 0.001 level. These results are in accordance with the lowest values found in the literature. There was no correlation between the iron concentration in sweat and in serum of the 20 persons. Seven of the runners had transferrin saturation percentages below 20, suggesting a possible iron deficiency. A daily loss in sweat of more than 18 mumol (1 mg) is possible in these runners training 125-350 km/week all the year round. The dominating iron loss of male endurance athletes is probably through the sweat.

Inter-laboratory comparison of acid-base variable in human blood and in quality control materials.

Routine results, pH, partial pressure of carbon dioxide (pCO2) and of oxygen (pO2), and standard hydrogen carbonate ion concentration (SBC) in identical specimens of arterial blood from patients deviate substantially. The results from seven laboratories (each laboratory examining the same 12 patients and the same five types of quality control materials) and evaluation in terms of accuracy and precision suggest the variations between days (delta 2) and single measurements (sigma 2) to be the main factors for these deviations. A reduction of these variations must have the highest priority in quality control programmes, since the variations mask possible true level deviations between laboratories. The five control materials (Qualicheck, Quantra whole blood level I-II-III and hemolyzed donor blood) are not fully optimal as substitutes for patient blood in such quality control programmes.

Ductus arteriosus in pilot whales.

The ductus arteriosus (DA), connecting the aorta with the pulmonary artery in the fetus, which normally closes up just after birth in terrestrial mammals, has been claimed not to close, but to remain open in normal, adult cetaceans, just as in the adult lungfish. We have examined the hearts from two Pilot Whales. In those we found no persisting DA, but an almost totally obliterated lumen. Blood flow through the ductus of these two whales could be excluded. Instead of an anatomical shunt mammals may use a functional pulmonary shunt. To the extent diving mammals can empty their alveoli for air at depth through reinforced bronchioli, and their very compliant thorax, they block alveolar gas exchange, and thus avoid decompression sickness, nitrogen narcosis and pulmonary squeeze.

Cardiorespiratory reactions to static, isometric exercise in man.

Cardiac output (Q), stroke volume (SV), heart rate (HR), and respiratory variables were measured in ten healthy men performing static, isometric muscular contraction (handgrip) during air breathing. We found an instantaneous rise in ventilation (VI) and in HR, accompanied by a minimal rise in cardiac output. The rise in VI was due to a rise in tidal volume (VT) and a reduction in expiratory duration (TE). These effects of isometric exercise are explainable as due to a muscle reflex instantly inhibiting the cardiac, vagal motoneurons and, at the same time, stimulating neurons in the respiratory area of the medulla. These medullary neurons seem capable of independent operation. The rise in mean arterial pressure (MAP) during isometric exercise is 27% just as the rise in total peripheral vascular resistance (TPVR). The MAP rise is too high to be caused by vascular occlusion due to the high tension of contracted muscles in only one upper extremity. Thus, redistribution of Q in the system of many parallel vascular resistances is a likely possibility--with possible cutaneous vasodilation and dominating vasoconstriction of other vascular regions.

Brady- and tachycardia in light of the Valsalva and the Mueller maneuver (apnea).

With a computerized impedance cardiograph we measured stroke volume (sv), cardiac output and heart rate (HR) in four men, during apnea with positive or negative intrapulmonic pressure (i.e., Valsalva and Mueller maneuver) in air. During Valsalva maneuvers the sv was reduced, and the compensatory rise in HR failed to keep the cardiac output at the control level before apnea. During both types of apnea, the diastolic pressure was increased as was the total peripheral resistance (TPR). The vasoconstriction and tachycardia during Valsalva maneuvers can be explained as a sino-aortic baroreceptor phenomenon in man. The smaller changes occurring during Mueller maneuvers result in no change in the transmural arterial pressure in the thorax, compared to the control level. Thus, without a stimulus there is no change in heart rate. The alveolar oxygen uptake and carbon dioxide elimination during apnea at total lung capacity was much larger than in the control phase before both types of apnea. The arteriolar vasoconstriction with increased TPR during the Valsalva apnea, was accompanied by a reduction in the stroke work of the left ventricle to approximately 50% of the work in the control phase.

Circulatory and respiratory responses to lower body negative pressure in man.

Circulatory and ventilatory responses to lower body negative pressure (LBNP) were simultaneously investigated in 8 healthy men before, during, and after the application of -20, -40, and -60 mmHg pressure. Minute ventilation (VE) decreased during LBNP due to a fall in respiratory frequency with sustained tidal volume. The cardiac output (Q) was reduced in proportion to the applied LBNP exposure, while VE decreased to almost the same level at all LBNP applications. In spite of decreased VE, end-tidal PO2 and PCO2 were increased and decreased, respectively, indicating a relative alveolar hyperventilation. The ventilation equivalent for O2 (VE/VO2) increased, while the cardiac output equivalent for O2 (Q/VO2) decreased. The relation between VE/VO2 and Q/VO2 showed a significant negative correlation (r = -0.93, p less than 0.01). The veno-arterial CO2 concentration difference (CvCO2--CaCO2) increased with LBNP, due to a fall in CaCO2 with constant CvCO2. The constant CvCO2 indicated a constant tissue acid-base balance. These observations suggest the existence of a ventilatory mechanism improving the efficiency of respiration in order to compensate for the sustained LBNP depression of Q at a given gas exchange.

Cardiac output and heart rate in man during simulated swimming while breath-holding.

We measured stroke volume (SV), heart rate (HR), cardiac output (Q), arterial pressure and intrapulmonic (mouth) pressure in four healthy, male subjects during simulated swimming (i.e., performing crawl movements with the legs continuously at a constant rhythm) with and without apnea (water temperature: 31 degrees C). We wanted to see whether the exercise tachycardia response persisted, or whether the HR decreased during apnea, just as in the "diving response" of diving animals. The SV and the Q fell to half its value in the control phase (i.e., swimming with normal breathing), when the 15-s apnea was performed at a high mouth-pressure; at low mouth-pressure, SV and Q hardly changed. These results are replicates of our previous findings in man during rest in air. Due to the light work, HR increased slightly from rest, but the exercise HR did not change much during apnea with or without high mouth-pressure. The results show that man tends to preserve his exercise HR response, and does not react as an oxygen-conserving animal, whether he is in air or in water under these conditions. However, man, as well as diving animals, may well have a "diving response" as an emergency reaction, which may not be restricted to only the water environment.

A constant flux of carbon dioxide injected into the airways mimics metabolic carbon dioxide in exercise.

This paper reports the expired minute-ventilation (VE) responses of 5 subjects to three step levels in a) work rate on a bicycle ergometer (30, 50, and 70 W), b) inhaled constant fraction (CF) of CO2 (3, 5, and 7%), and c) inhaled constant flux (CFlux) of CO2 (0.3, 0.4, and 0.5 l/min (STPD) injected in the inspired air-stream). Both exercise (isocapnic with regulated PETCO2) and CFlux provoke larger and similar steady-state responses in VE, than CF. Both the CF and CFlux responses are hypercapnic, but the CFlux responses show evidence of "hypercapnic regulation." VE and total CO2 input into the alveoli (i.e., VCO2 plus inhaled CO2) are excellently correlated in both the CF and the CFlux cases. However, the CFlux delivery provokes a far greater VE for a given total input of CO2 than CF, and the CFlux response resembles the VE/VCO2 plot of exercise. We conclude that CFlux inhalation of CO2 simulates the metabolic CO2 production rate of exercise, and thus the humoral aspects of exercise hyperpnea in the steady state.

Modeling of alveolar carbon dioxide oscillations with or without exercise.

In five persons the transient ventilatory response was measured to three step levels of exercise, inhaled constant fraction of CO2, and inhaled constant flux of CO2. With constant CO2 fraction inhalation (3, 5, and 7%), the transient response of the minute-ventilation (VE) is associated with on- and off-time delays (Td). Our Td periods include equipment delay, and our bolus inhalations by constant flux provoke on- and off-Td's of 6-8 s, which approximate to the transport delay of blood passing from the alveoli to the peripheral chemosensitive areas. With exercise (30, 50, and 70 W) we found a fast rise in VE (i.e., mainly in respiratory frequency) within the first breath, but no detectable on- and off-Td. The ventilatory responses to exercise are equal to those of constant CO2 flux inhalation. We modeled PACO2 oscillations, which occur through a respiratory cycle, and show that the oscillations provoked by constant CO2 flux have modified timing, amplitude, and slope compared with those of constant CO2 fraction. The increase in ventilation is the same when the CO2 is achieved by constant flux inhalation at rest or by exercise.

Estimation of peripheral chemoreceptor contribution to exercise hyperpnea in man.

Nine normal male subjects were studied at three levels of exercise (0, 40, and 80 W). Single vital capacity breath test was applied at rest and during exercise (phases 2 and 3). Minimum minute ventilation found within 4 breaths following the test was compared to the control value. Significant depression in minute ventilation was invariably observed. The minute ventilation was depressed more and more with increasing intensity of exercise. A significant difference was found between exercise and rest. However, the relative contribution of chemoreceptor activity remained the same 10-20% at all exercise levels. The magnitude of ventilatory depression (delta V resp) in phase 2 was larger than that in phase 3, when work rate increased to 80 W, both relative and absolute. A significant part of the exercise hyperpnea is due to peripheral chemoreceptor activity. The peripheral chemoreceptor activity is greater in phase 2 than in phase 3 at work rates of light to moderate intensity.

Opioid involvement in the perception of pain due to endurance exercise in trained man.

The purpose of this study was to evaluate the role of endogenous opiates in modulating physical performance during dynamic exercise in conscious man. The plasma concentration of beta-endorphin (BEP) and of adrenocorticotropic hormone (ACTH) along with muscle pain (McGuill Pain Questionnaire) were assessed in 17 trained, male runners before and after running the longest possible distance within 12 min (i.e., the Cooper test). Each runner participated twice in the test (double-blind cross-over design), with a 1-week interval--with or without an injection of the opiate antagonist naloxone (0.8 mg i.v.). The average (SEM) distance reached was 3,198 (45) m in the naloxone test and 3,240 (38) m in the placebo test. The BEP increased significantly during the tests by a factor of 4.1 on naloxone and by 2.8 on placebo (from the normal resting averages of 1.7 and 2.1 pmol/l, respectively). The ACTH also increased significantly by a factor of 2.0 on naloxone and 2.5 on placebo (from the normal resting averages of 19.3 and 16.8 pmol/l, respectively). There were no significant differences between the naloxone and the placebo test with respect to the increments of BEP or ACTH by exercise. However, the perception of muscle pain was enhanced with naloxone. The increased perception of pain did not decrease the athletes ability to perform in terms of the distance run. We conclude that endogenous opiates are involved in the perception of pain associated with exhaustive exercise and may subserve psychological rather than physiological functions during exercise.

Respiratory and cardiac responses to dynamic exercise in man.

Ventilation (VE), cardiac output (Q), oxygen consumption (VO2), carbon dioxide production (VCO2), and end tidal gas tensions (PETO2 and PETCO2) were measured in four healthy men during stepwise, steady state increases in work rate on a bicycle ergometer (25, 50, 75, 100, 125, and 150 W). Both the ventilation equivalent (VE/VCO2) and the cardiac equivalent (Q/VCO2) for carbon dioxide, fell during a steady state exercise at 150 W to 2/3 and to 1/3 of the initial levels, respectively. This stepwise reduction in the carbon dioxide production with increasing work rate was compatible with a non-chemical stimulus increasing in proportion to work rate, and governing both ventilation and circulation. These observations do not support the cardio-dynamic hypothesis.

Facial cold receptors and the survival reflex "diving bradycardia" in man.

We measured heart rate (HR), stroke volume (SV), systemic arterial blood pressure (BP), and mean arterial pressure (MAP) in 7 healthy volunteers in response to face immersion in water with concomitant breath-holding at different lung volumes. The subjects were at rest in the prone position. During breath-holding at total lung capacity (TLC), baseline HR (70 to 75 beats/min) fell by 10% within fractions of a second, both in the control preimmersion state when the head was surrounded by room air, and when it was immersed in water of 33 degrees C. This response was associated with rises in MAP and in SV. Immersion of the face in 10 degrees C water while breath-holding, was associated with a strong, negative chronotropic effect (22% fall in HR), which developed within 10 s. Breath-holding at functional residual capacity (FRC) reduced HR substantially only in 10 degrees C water, and in contrast to that at TLC, the response was slowly developing with a latency of 10-15 s. All these reductions in HR were significant and accompanied by increases in BP and MAP. The strong, negative chronotropic effect of cold water was typically linked to a rise in SV. The study identified two temporal components of HR reduction to face immersion: a fast parasympathetic response dependent on the input from the high pressure baroreceptors, and a late response mediated, in all likelihood, by sympathetic efferent activity. Facial receptors sensitive to cold seem to be vital in the largest responses observed. The fast response to breath-holding with the face in water of neutral temperature was equal to that in air. Thus "diving bradycardia" is in fact a basic survival response independent of water.