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Legs of lead

Competition for oxygen causes the fatigue common in cardiac and pulmonary insufficiency

EDUARDO CESARIn the laboratory the cyclist looks like a puppet given the quantity of wires attached to his chest, back, hand and leg. He is suffering from chronic obstructive pulmonary disease (DPOC), a sickness caused by smoking that combines irreversible damage to the alveoli with symptoms of chronic bronchitis, such as narrowing of the airways and a cough. So far study of the disease has concentrated on the lungs, despite complaints from patients that along with the lack of air it was frequently the tiredness in the legs that prevented them from going up stairs without stopping. When they do stress tests on ergometric bicycles some patients now have the chance of doing more than explaining their symptoms: they are helping neurologist José Alberto Neder, from the Federal University of São Paulo (Unifesp) understand the relationship between lungs and legs.

The equipment, which seems to entrap the patient and is the only one of its kind in the country, provides Neder with a complete picture, placing him in a privileged position when it comes to understanding how pulmonary deficiency functions. Electrodes on the chest and back monitor heart beat and record the volume of blood the patient’s heart pumps with every contraction; a clip on the forefinger measures the concentration of oxygen in the blood; the mask, in addition to helping with breathing when regulated for this purpose, also measures how much oxygen the cyclist exhales and allows the researcher to calculate how much the organism has absorbed;  and a detector on the leg throws a beam of light (spectroscopy by almost infrared rays) that measures how much oxygen reaches the thigh muscles. All this is done without the need for sticking any needles at all into the patient. Up until now no study has combined all these parameters. With this integrated overview, Neder has shown that patients with DPOC have something in common with elite athletes: the lungs steal the blood from the legs, which are unable to keep up their physical effort without oxygen from the circulating red corpuscles.

The study is innovative because it deals with circulation and breathing as interlinked systems, although normally they are studied by different specialists. It is when it is passing through the lungs that blood fills with oxygen which it then takes to all the cells in the body. When a person is undergoing intense physical activity, such as running or going uphill on a bicycle, most of the blood needs to be sent to the muscles that are in action and which to keep moving need large quantities of oxygen. The body then faces the challenge of maintaining a delicate balance: supplying the legs and at the same time sending a sufficient amount of blood to the muscles that move the lungs where it is oxygenated.

Using the full laboratory apparatus the group from Unifesp submitted ten men with DPOC to stress tests and evaluated their circulatory and respiratory parameters. The results, which are being published in the Journal of Applied Physiology, show that the disease reduces the volume of blood pumped with each heart beat and leads to a rapid loss of oxygen in the leg muscles – as oxygenation is deficient all the oxygen arriving at the muscles is quickly consumed, making the legs feel heavy, as if they were filled with lead. More surprisingly the work reveals what these patients and elite athletes have in common.

Sports people, like professional sprinters, develop their own technique and musculature – including the respiratory and cardiac muscles – in order to reach the maximum yield needed in competitions. But at times they exaggerate and the effort exceeds the velocity with which the blood can take oxygen to the tissues. Some ten years ago the team of North American neurologist, Jerome Dempsey, from the University of Wisconsin, described what happens when these athletes exceed their capacity for doing exercise. At this point the interconnecting system that shares out the blood flow between the lungs and legs works almost like the points on a railroad, when the mechanism suddenly alters the course of the train. The lung muscles produce substances that, when they reach a certain concentration, send a message to the brain. The central organ of the nervous system acts instantly by reducing the diameter of the blood vessels in the legs. The blood flow is then mainly diverted to the lungs. With less blood (and less oxygen) the legs become heavy. “When a competition arises between the leg and respiratory muscles that move the lungs, the latter win”, explains Neder. “There’s no use in maintaining blood flowing to the muscles that are exercising if there’s no blood for the muscles that move the lungs, precisely the organs that supply the oxygen that is so vital for the muscle system.” Organs that are fundamental for maintaining the organism functioning, like the brain, heart and lungs, take preference in the body’s hierarchy.

EDUARDO CESARFrustrated athletes
Neder showed that this same mechanism limits the capacity of patients with DPOC to take exercise; they only need to take a few steps upstairs or walk to the corner bakery for their respiratory muscles to clamor for more blood. Understanding this opens up the way to looking for means of providing a more active life for people who suffer from respiratory and cardiac deficiencies.

In the pneumology sector of Unifesp, Neder has been testing alternatives so that these patients have it easier in their daily activities, such as working or shopping. In the meantime they have obtained good results in the laboratory. Helping the patient with a mask, through which ordinary air or heliox (less dense air because it is rich in helium, which is a lighter gas) enters under pressure, reverses the process and gives them a degree of vitality on the ergometric bicycle. In measurable terms the time they can bear to do intense exercise triples or is four times longer, with less of a feeling of being out of breath and of tiredness in the legs. The treatment does not increase the level of oxygen taken in; it simply forces air into the respiratory tracts in a way that reduces the effort demanded of the pulmonary muscles. The effect of heliox is more intense because the less dense air spreads more easily through the respiratory tracts. “The air enters like an arrow”, says Neder. But it has a side effect that restricts laboratory treatment even more: helium has a temporary effect on the vocal chords that leaves the voice sounding like Donald Duck of cartoon fame. Because of this the pneumologist recommends that the patient does not speak during treatment. The article that is being published in Thorax makes it clear that it is enough just to facilitate the access of air to the lungs to increase the amount of oxygenated blood circulating in the muscles.

The same goes for those who suffer from chronic cardiac insufficiency (ICC). Unlike what was believed previously, the physical capacity of these patients is limited, not by the heart, but by oxygenation of the muscles. Neder tested the same treatment on these patients and shows in an article that has been available since March on the website of the American Journal of Physiology – Heart and Circulatory Physiology, that assisted breathing increases the amount of oxygen reaching the legs and makes exercise possible. This improvement, however, does not reflect an increase in the general level of oxygen in the blood; this is still the same as measured by a clip on the forefinger. The authors claim that helping breathing eliminates the signs of tiredness in the respiratory muscles, which because of this stop inducing closure of the blood vessels feeding the legs. The most efficient circulation carries the most oxygen.

Treatment with a respirator is limited to sessions of exercise in the laboratory or sessions of physiotherapy and rehabilitation in the future. But its effects are long-lasting and are also making themselves felt in the normal daily activities of the patients who are treated. “The muscles of these people atrophy for lack of use, which leads to an increasing deterioration in their physical condition”, explains the pneumologist. Making the muscles more efficient allows them to use oxygen in a more efficient way, which accelerates improvement.

Neder does not intend to stop there and is now trying to develop a treatment that is more accessible to people. “We’ve already started testing a way of training the respiratory muscles”, says the pneumologist. Patients are instructed to do several daily sessions in which they breathe using the apparatus, which demands a greater effort, like breathing through a slightly blocked straw; this is something like a breathing workout which, according to the preliminary tests, may be an effective solution for improving the oxygenation of those who suffer from pulmonary deficiency. Another therapy that Neder is going to start testing shortly is sildenafil, the active ingredient of Viagra. “It’s a drug that dilates blood vessels and improves circulation, so we hope that it will help to spread oxygen more efficiently through the body’s muscles”, he explains.

The Project
Peripheral muscular oxygenation during dynamic exercise in patients with DPOC: the effects of a reduction in ventilator work induced by positive pressure non-invasive ventilation (nº 05/00722-0); Modality: Regular Research Awards; Coordinator: Alberto Neder Serafini (EPM/Unifesp); Investiment: R$ 277.572,52