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More damage from smoke

Cigarettes impair the functioning of the heart muscles

MIGUEL BOYAYANThe effects of cigarette smoke are no longer restricted to the better known ones, such as the higher risk of a heart attack and lung, throat and mouth cancer. Recent research studies conducted on lab animals, conducted at the Federal University of São Paulo/Unifesp and Paulista State University/ in Botucatu, showed that this smoke can be even more harmful, overburdening and hardening the cardiac muscle, to the point of deforming the heart and impairing its functioning. Another study, conducted at the University of /USP in Ribeirão Preto, showed that smoke, when acting on the nasal cells, prevents the formation of the nasal hairs that filter the impurities found in the air that enters the nostrils.

Experiments on animals are helping to accurately evaluate hazards to the health of 20 million smokers in Brazil, which is equivalent to 16% of the population over the age of 18, that will probably no longer be allowed to smoke in public facilities in the State of São Paulo, beginning in August, in compliance with a law that is still being debated. “Several studies have shown that people exposed to cigarette smoke have a higher risk of developing chronic sinusitis and, further, that exposure to cigarette smoke worsens the evolution of patients operated for chronic sinusitis”, says Edwin Tamashiro, who detailed the alterations caused by smoke on the development of cilia in an article published in the American Journal of Rhinology and Allergy in April. Other studies are a warning, such as the one conducted at Unifesp, showing that physical exercise can intensify the damage provoked by exposure to cigarette smoke instead of mitigating such damage, as had been expected.

“In human beings, the effect of smoking on the coronary arteries is more drastic and quicker than the effect on the coronary muscle”, says cardiologist Paulo Tucci, a professor at Unifesp. This is how he explains why the other effects are less known and less studied, but no less worrying. Every year, approximately 5 million people around the world – half of them in developing countries – die because of the more than 50 diseases associated with the smoking habit, which is viewed nowadays as a form of chemical and psychological addiction. The whitish smoke that helped comprise the style of Humphrey Bogart in Casablanca, of Rita Hayworth in Gilda and of so many other leading characters in film is the result of a combination of approximately 4 thousand toxic substances, of which 250 are harmful to the human body and 50 specifically cause cancer. To become better acquainted with the effects of cigarette smoke and foresee what could go on in the human body, researchers expose rats to cigarette smoke for hours in sealed chambers. “In the normal rat, the diameter of the left ventricle cavity increased and the heart’s capacity to contract diminished”, says Sérgio Paiva, a researcher at Unesp in Botucatu, on the basis of findings obtained in 2003. “These alterations get worse in animals submitted to acute myocardial infarction.” The animals that had had heart attacks were obliged to inhale heavy cigarette smoke. As a result, their left atrium and left ventricle – that pump oxygenated blood to the entire body – became dilated. In principle, this would be nothing serious because the left side of the heart in people who exercise regularly is also bigger than that of people who don’t. The problem is that the damages were much more extensive and deeper in the case of the rats, especially in rats that exercised and were exposed to heavy cigarette smoke.

More refined studies on four groups of rats (the control group, the trained group which had to swim two hours a day, the smokers’ group that had been exposed to cigarette smoke for two hours in a sealed chamber and the trained smokers) showed that the heart was heavier and the myocardium contracted and relaxed more slowly in the group of trained smokers in comparison with the control group. The trained smokers also showed a 50% reduction in the strength of the papillary muscles that control the mitral valve, which prevents the flow of blood from the ventricle to the left atrium. In addition, the volume of the cell nuclei practically doubled, indicating the increase in DNA synthesis. It is still not clear why physical exercise increased, instead of preventing – as had been expected – the effects of cigarette smoke; one of the possibilities is that the heart’s hypertrophy could be a combined response to the stimuli generated by physical exercise and by cigarette smoke. However, progress has been made in relation to the hypotheses on the action mechanisms of cigarette smoke. “The biggest villain for the heart”, says Tucci, “seems to be carbon monoxide”. A residue of cigarette smoke – and also from the smoke from cars and industries – carbon monoxide (CO) acts in two ways on hemoglobin, the molecule that distributes oxygen to all of the cells in the body. CO binds more easily than oxygen to the hemoglobin, thus taking up the space for oxygen (each hemoglobin molecule is able to carry four oxygen atoms at a time). In addition, the affinity of oxygen for hemoglobin increases; as a result, the hemoglobin does not release oxygen easily as it goes through the cells.

Proteins undergo changes inside of the myocardial cells, as more cigarette smoke goes through the airways and influences the bonding of oxygen and hemoglobin. These proteins mediate the action of calcium ions, which regulate the contraction of the cardiac muscles. “The contraction of the myocardium is weaker as less calcium enters the cell”, says Tucci, who in 2006 demonstrated the direct association between the quantity of calcium ions and heartbeats (see The channels of the heart, Pesquisa FAPESP nº 122). As a result of these changes, – the heart loses its capacity to pump blood to the body”. In infarcted rats, therefore, due to cardiac insufficiency, the venous blood, high in carbon dioxide, that returns to the lungs, congests the blood capillaries next to the lungs and sometimes even spills over into the lung alveoli that should contain only air, instead of exchanging the carbon gas for oxygen and circulating. “In smokers’ organisms”, says the researcher from Unifesp, “the volume of gas retained in the lungs and in the heart, which is normally equivalent to 5% of the total volume circulating in the body, can come to 25%”. As a result of this congestion, the oxygen that returns to the lungs with the air will take longer to enter the blood circulation and all the cells in the body that need  oxygen to produce the energy that keeps them alive.

MIGUEL BOYAYANEffects on pregnancy
Débora Damaceno and her team from Unesp at Botucatu used glass-walled sealed chambers to observe how cigarette smoke also jeopardizes fetuses, born at lower than normal weight when pregnant rats continuously breathe cigarette smoke-filled air. In a study published this year in Reproductive BioMedicine Online, Maricelma Souza, under the guidance of Débora, observed that the placenta was bigger and the fetuses smaller as a probable separate and cumulative effect of two problems, namely, diabetes and prolonged exposure to cigarette smoke. “The biggest worry was that, although the female rats from the lineage used in these experiments are very resistant, in 20 days they were already damaged”, says Débora. “It’s frightening. Perhaps women are more seriously affected, but we cannot state this for sure.”

The experiments have led to new hypotheses to verify effects on women’s bodies that have not been extensively explored. One of these effects, being investigated by Débora’s team, is that the compounds in cigarette smoke – especially benzo-alpha-pinene, the harm it does to the body is being intensely investigated – might act on the hormones produced by the ovaries and thus be one of the causes of natural miscarriages in women as well. According to a study conducted by the US’s National Cancer Institute, published in October 2008, Brazil has one of the highest rates of women who smoke during pregnancy (6.1%), after Uruguay (18.3%) and Argentina (10.3%).

Edwin Tamashiro also obtained clear results at USP in Ribeirão Preto when he investigated the effects of cigarette smoke on the cilia of the cells that line the nasal and lung airways. “The cilia of the epithelium cells are very important primary defense of the organism”, he says. “We are able to filter the impurities and microorganisms that we inhale every day because of the movements of the cilia”. He demonstrated in vitro that exposure to cigarette smoke hampers the formation of cilia in maturing cells, which suggests that the organism might become more susceptible to infections caused by viruses and bacteria in the air. Apparently paradoxical results on the effects of smoking, however, are common. Débora’s team verified that both diabetes and smoking, separately, caused damage to the DNA of young rats whose mothers had been exposed to cigarette smoke. In another experiment, where she investigated the DNA of young rats whose mothers were smokers and had diabetes, she had expected that the damage would double; however, this was not the case – there was less damage. In this case, it is difficult to imagine what to propose to pregnant women smokers because other experiments with animals showed that quitting smoking in the middle of pregnancy can lead to withdrawal syndromes. Débora acknowledges that the recommendation of international medical associations that women should avoid the damage caused by smoking – whether through quitting or avoiding breathing smoke five years before getting pregnant – is quite unfeasible.

At Unesp, Paiva had noticed in 2005 what he referred to as the paradoxical effect of cigarette smoke: rats that had taken in great quantities of smoke and had then undergone an induced heart attack survived longer than the rats of the control group, who had only undergone a heart attack. “Perhaps smoking creates a pre-condition against the lack of oxygen, thus protecting the heart from the bigger evil, which is a heart attack waiting to happen”, Paiva supposes.

An unexpected result came from another experiment: beta carotene, a substance that should protect the organism from chronic diseases, eliminated the protective effect of cigarettes. A substance that eliminates residues called free radicals, beta carotene is found in carrots, papaya and mango; beta carotene protected the hearts of normal rats, according to a study published in 2006 in Toxicological Sciences. In another study, published in the Arquivos Brasileiros de Cardiologia journal in 2007, beta carotene increased the damage from smoking on the heart of rats that had undergone induced acute myocardial infarction and afterwards had been exposed to cigarette smoke.

Experiments with lab animals are useful because they help formulate hypotheses on what can happen to people; however, they have to be viewed moderately because, among other reasons, “lab experiments are conducted under super stimuli and for a short time”, says Tucci. “We have to consider experimental results from a non-terrorist point of view”.

The Projects
Effects of exposure to cigarette smoke and to dietary supplements with beta carotene on the intracellular communication in rat cardiomyocites; Modality: Regular Funding of Research Project; Coordinator: Sergio Alberto Rupp de Paiva – Unesp; Investment: R$ 110.885,88
2. Adjustment mechanism in calcium kinetics in the myocardium following sudden ventricular dilatation (nº 05/55980-3); Modality: Regular Funding of Research Project; Coordinator: Paulo José Ferreira Tucci – Unifesp; Investment: R$ 91.736,88
3. Evaluation of genotoxicity in the pregnancy of rats with moderate diabetes (nº 06/06056-4); Modality: Regular Funding of Research Project; Coordinator: Débora Cristina Damasceno – Unesp; Investment: R$ 119.103,28

Scientific Articles
Portes, L.A. et al. Swimming training attenuates remodeling, contractile dysfunction and congestive heart failure in rats with moderate and large myocardial infarctions. Clinical and Experimental Pharmacology & Physiology. v. 36, p. 394-399. 2009.
Lima, P.H.O. et al. Levels of DNA damage in blood leukocyte samples from non-diabetic and diabetic female rats and their fetuses exposed to air or cigarette smoke. Mutation Research. v. 31, p. 44-49. 2008.
Castardeli, et al. Exposure time and ventricular remodeling induced by tobacco smoke exposure in rats. Medical Science Monitor. v. 14, p. 62-66. 2008.