Systemic iron deficiency was found in 63 (56%) of 113 joggers and competition runners (33 women and 80 men). Thirteen women and ten men had latent anemia. A majority of the women were fertile with iron loss from menstruation; the men were runners training long distances. The average transferrin iron-binding capacity was 80 mu mol/l serum in the women and 77 (iron-binding groups) in the men. The haptoglobin and iron concentrations in serum were remarkably low (most often below 10 and 20 mu mol/l, respectively). Three of the long-distance runners ran 25 km daily. They returned with so much free hemoglobin in their plasma that an accompanying iron loss (integrated over months), if not balanced by diet, would lead to iron deficiency and anemia. Oral iron therapy (200 mg ferrous sulphate per day) normalized the hemoglobin concentration and improved the transferrin saturation fraction in 61 persons. The competition runners reported personal records.

Benzodiazepines, a class of drugs widely used as anxiolytics, can induce a depression of respiration. This study was designed to determine if endogenous benzodiazepine ligands could act in a similar fashion and exert a tonic inhibitory influence on respiration. Administration of a benzodiazepine antagonist should then facilitate respiration. This might be especially visible in hypoxia, the condition characterized by both central respiratory depression and potentially enhanced benzodiazepine expression. We addressed this issue by comparing the effects on the phrenic neurogram of the specific benzodiazepine antagonist flumazenil (200 μg i.v. boluses) in the contrasting conditions of hypoxia and hyperoxia in anesthetized, both spontaneously breathing and paralyzed ventilated cats. Contrary to our hypothesis, flumazenil showed a modest but definite inhibitory effect on respiration. Flumazenil also lengthened the duration of the Hering-Breuer inspiratory inhibition. The respiratory depression was neither related to chemical drive nor to the GABA receptor complex, for it was sustained after antagonism of GABA with picrotoxin and bicuculline. We conclude that the endogenous benzodiazepine system is unlikely to play an inhibitory role in the regulation of respiration. The physiologic role of this system remains to be established.

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.

The purpose of this study was to evaluate the ventilatory and cardiovascular responses to static handgrip exercise at different levels of arterial chemoreceptor activation. The study was done on 10 healthy subjects. They performed handgrip of 50% of maximal voluntary contraction on a background of either hypoxia (PE'O2 approximately 47 mm Hg) or hyperoxia (PE'O2 approximately 216 mm Hg), i.e., enhanced or suppressed chemoreceptor activity. The subjects were able to sustain the handgrip for 50-60 sec, during which time no steady-state responses were attainable. Minute ventilation (VI), cardiac output (Q), heart rate (HR), and a number of other variables were recorded. Handgrip exercise resulted in a rapid initial VI rise followed by a subsequent slow increase. Hyperoxia diminished the VI response over the exercise range. The ventilatory response was associated with an HR acceleration, increased arterial pressure and peripheral vascular resistance. No appreciable changes in Q were noted, nor was there any particular relationship between ventilatory and circulatory changes. These results provide no support for the Q mediated ventilatory stimulus during static handgrip exercise in man. It is concluded that the ventilatory and cardiovascular responses are of independent nature.

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.

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.

The purpose of this study was to evaluate the effect of interruption of the descending supraspinal sympathetic outflow on heart rate control during exposures to chemical stimuli. We investigated the heart rate responses to progressive isocapnic hypoxia and hyperoxic hypercapnia using the rebreathing technique and quantified the relationship between heart rate (HR), oxygen saturation (SaO2), alveolar PCO2 (PACO2), and minute ventilation (VE) in 16 chronic tetraplegic subjects with low cervical spinal cord transection. The HR responses were determined from the linear slopes of HR on SaO2 and HR on PACO2. We found that mean resting heart rate was within normal range; 66 +/- 3 (SEM) beats min-1. HR increased as oxygenation fell or CO2 tension rose. The mean tetraplegic delta HR/delta SaO2 was 0.83 +/- 0.14 beats min-1 per 1% fall in SaO2 and that of delta HR/delta PACO2 was 0.30 +/- 0.13 beats min-1 per mmHG rise in PACO2. The HR and VE responses to either hypoxia or hypercapnia were related in the tetraplegic subjects. We conclude that the stimulatory HR responses to chemical stimuli are not suppressed by cervical spinal cord transection. Thus, the descending sympathetic activity does not underlie the HR acceleration by chemical stimuli.

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.

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There is ample evidence that the ventrolateral medulla (VLM) is involved in regulation of respiration. The VLM is considered to be the site of location of the central respiratory chemoreceptors. Neither neuroanatomical nor neurophysiological coordinates of the chemoreceptor have ever been indisputably identified or verified, despite decades of research. This commentary addresses new hypotheses concerning the process of central chemoreception and recent findings calling into question the exclusivity of VLM for the chemoreceptor location and function. These findings rekindle the possibility of medullary respiratory neurons being chemosensors. Crucial issues concerning the central chemoreception remain unsettled and are open to further research.

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.

The cardiovascular responses to breath-holding (BH) during short-lasting supramaximal exercise (415 W) on a cycle ergometer were investigated in 15 healthy male subjects. The arterial oxygen saturation, heart rate (HR), endtidal PO2 and PCO2 were continuously monitored. Firstly, 15 subjects performed exercise during BH, preceded by air breathing (air-BH test), and secondly, exercise without BH. Then 9 of the subjects performed the same procedure as in the air-BH test, except that all subjects breathed 100% O2 for 1 min before apnoea (O2-BH test). In 2 of these subjects, the systemic arterial blood pressure was continuously measured via a catheter in the radial artery and plasma catecholamine concentration [CA] was also measured both during the air-BH and the O2-BH tests. In the later period of the air-BH test, the high HR level became progressively depressed. This response, however, was absent in the O2-BH test. There was a late increase in the arterial blood pressure in both tests, and both tests produced hypercapnia. Only the air-BH test resulted in hypoxia, substantial hypertension and HR-depression. The increase in plasma CA was similar in both tests. The marked HR-depression demonstrated here is ascribed mainly to activation of the peripheral arterial chemoreceptors by asphyxia, and partially to baroreceptor activity due to elevated blood pressure.

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.

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.