Short abstract
Cigarette smoking increases cerebral blood flow. Both nicotine and carbon monoxide contribute to the flow increase. Due to carbon monoxide’s high affinity to hemoglobin and slow clearance from the blood, the effect lasts for hours. Nicotine also stays in the organism for some hours. This immediate effect of smoking may explain a recently observed higher cerebral blood flow in current-smokers as compared to former-smokers.
Keywords: Carbon monoxide, cerebral blood flow regulation, cerebral blood flow, cigarette smoking, nicotine, smoking
In the recent volume of Journal of Cerebral Blood Flow & Metabolism, Elbejjani et al. published an article with the above title.1 Their main findings were that (i) compared to never-smokers, former-smokers had lower cerebral blood flow (CBF) in several parts of the brain; in contrast, current-smokers did not have lower CBF and (ii) among current-smokers, higher pack-years were associated with higher CBF in several parts of the brain as compared to former-smokers who had lower CBF in parts of the brain with increasing pack-years.
This raises the question of whether the higher CBF in current-smokers as compared to former-smokers is related to an influence on the brain “per se” or whether it is a simple consequence of temporary smoking-related changes in the blood composition which modifies the cerebral circulation.
Before speculating, let us look on to the immediate biology of smoking with relevance to CBF. Smoking of one cigarette has been shown to be accompanied by increases of global CBF of 16 and 19%.2,3 Two factors seems responsible for this increase, the accumulation of carboxyhemoglobin and a direct influence of nicotine.
London smokers have a carboxyhemoglobin of 5–8%, heavy smokers even higher as compared to non-smokers with a level of 1–3%.4 Carbon monoxide binds as carboxyhemoglobin 200 times more tightly to hemoglobin than oxygen, and has an half time in blood of 4–6 h. In the study of London smokers, carboxyhemoglobin was rather stable throughout the day, but with a clearance during the night and an increase during the morning.4 CBF is heavily influenced by both the hematocrit and the presence of carboxyhemoglobin.5 Thus, hemodilution of 26% will increase CBF by 19% leaving the oxygen tension in the jugular venous blood unchanged. The influence of carbon monoxide is twofold. It binds part of the hemoglobin which no longer can transport oxygen, and it shifts the oxyhemoglobin dissociation curve to the left. The latter implies that at a given tissue oxygen tension, less oxygen will be released from the blood. The net effect is that binding 20% of the hemoglobin with carbon monoxide will lead to a 26% increase in CBF and a slight reduction in the cerebral venous oxygen tension.5
Intravenous infusion of nicotine (1.5 mg/min) increases CBF by 30%.2 The effect of nicotine smoking has been further evaluated by comparing smoking cigarettes with and without nicotine, 1.0 and 0.08 mg per cigarette, respectively, but otherwise identical including the same amount of tar.6 Smoking nicotine as compared to non-nicotine cigarettes showed an increase in CBF of about 6.5% in large cerebral areas, e.g. the occipital cortex and cerebellum. When taking into consideration that nicotine has a pharmacologic half-life of one or two hours and carboxyhemoglobin an even longer half-life, then information about the time of the last cigarette smoked prior to the flow investigation seems essential.
Studies on long-term cessation of smoking have shown diverging results. In the study of Elbejjani et al., former-smokers had lower CBF compared to never-smokers.1 Other studies have shown significant increase in cerebral perfusion within a year.7 Still other studies have shown a decrease in CBF after six years, but with a following increase after to baseline values after nine years.8
In the study of Elbejjani et al., the authors did not obtain information on the time of the last cigarette smoked before the flow investigation, and did not specifically ask about or control for some factors that have been shown to influence CBF measurements, including blood gasses, carboxyhemoglobin, hematocrit levels, and food and caffeine restrictions.1 For that reason and for the consideration on hematocrit, carbon monoxide and nicotine discussed above, it is hypothesized: The higher CBF observed in current-smokers as compared to former-smokers could be caused by the effect of actual levels of carbon monoxide and nicotine as well as of possible differences in hematocrit, and by an immediate biological effect of smoking on the brain pr se. This also implies that had they given the former-smokers a few cigarettes, then it might have resulted in the same flow patterns as in the current-smokers.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Declaration of conflicting interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
ORCID iD
Olaf B Paulson https://orcid.org/0000-0001-7712-8596
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