the Departments of Internal Medicine and Veterinary Anatomy,
Physiology, and Cell Biology, University of California, Davis.
Correspondence to John C. Rutledge, MD, Division of Cardiovascular
Medicine, T.B. 172, Bioletti Way, University of California, Davis, CA 95616.
Background Previous research has shown that exposure to environmentaltobacco smoke (ETS) increases the risk of atherosclerosis.
Totest the hypothesis that exposure to ETS increases LDL accumulationin the artery wall, we developed
a model to measure the rateof LDL accumulation in individually perfused rat carotid arteriesafter
the artery had been perfused with plasma taken from ratsexposed to ETS (ETS-plasma).
Methods and Results Rats were exposed to ETS in a chamber inwhich
steady-state sidestream smoke was continuously circulating.After exposure, blood from the animals was collected.
Carotidarteries from unexposed rats were perfused first with normalplasma containing fluorescently
labeled LDL. Then, the samearteries (10 arteries from five rats) were perfused with ETS-plasmaplus
fluorescently labeled LDL. Photometric measurements weremade during perfusion of the arteries with fluorescently
labeledLDL, and rate of LDL accumulation (mV/min) and lumen volume(mV) (volume of fluorescently labeled
LDL solution) were determined.Perfusion with ETS-plasma increased the rate of LDL accumulation(mean±SEM,
6.9±1.8 mV/min) compared with control(1.6±0.40 mV/min, P.02). LDL
accumulation was primarilydependent on LDL interaction with ETS-plasma rather than theinteraction
of ETS-plasma with the artery wall. Also, ETS-plasmasignificantly increased lumen volume (43.3±5.1 mV) comparedwith control (35.1±4.4 mV, P.005).
Conclusions Exposure to ETS acutely increased LDL accumulationin
perfused arteries. Repeated exposure to ETS may representimportant early events in atherogenesis.
Endothelial Dysfunction, Impaired Endogenous Fibrinolysis,
and Cigarette Smoking
A Mechanism for Arterial Thrombosis and Myocardial Infarction
David E. Newby, BA, BSc, BM, MRCP
; Robert A. Wright, MB, ChB, MRCP; Catherine Labinjoh, BSc, MB, ChB,
MRCP; Christopher A. Ludlam, PhD, FRCP, FRCPath; Keith A. A. Fox, BSc, MB, ChB, FRCP, FESC;
Nicholas A. Boon, MD, FRCP; David J. Webb, MD, FRCP, FRCPE, FFPM
From the Clinical Pharmacology Unit and Research Centre, University
of Edinburgh, Western General Hospital (D.E.N., C.L., D.J.W.), and the Departments of Cardiology (D.E.N., R.A.W., C.L., K.A.A.F.,
N.A.B.) and Haematology (C.A.L.), University of Edinburgh, Royal Infirmary, Edinburgh, Scotland, UK. Dr Wright is now at the
Department of Cardiology, The Ayr Hospital, Ayr, Scotland, UK.
Correspondence to Dr D.E. Newby, Clinical Pharmacology Unit
and Research Centre, University of Edinburgh, Western General Hospital, Crewe Rd, Edinburgh EH4 2XU, Scotland, UK. E-mail
endogenous fibrinolysis requires rapid releaseof tissue plasminogen activator (tPA) from the vascular endothelium.Smoking is a known risk factor for arterial thrombosis and myocardialinfarction, and it causes endothelial
dysfunction. We therefore examinedthe effects of cigarette smoking on substance P–inducedtPA
release in vivo in humans.
Methods and Results—Blood
flow and plasma fibrinolyticfactors were measured in both forearms of 12 smokers and 12age- and sex-matched
nonsmokers who received unilateral brachialartery infusions of substance P ( pmol/min). In both smokersand nonsmokers, substance P caused dose-dependent
increasesin blood flow and local release of plasma tPA antigen and activity (P<0.001for
all) but had no effect on the local release of plasminogenactivator inhibitor type 1. Compared with nonsmokers,
increasesin forearm blood flow (P=0.03) and release of tPA antigen (P=0.04)and activity
(P<0.001) caused by substance P were reducedin smokers. The area under the curve for release of tPA
antigenand activity decreased by 51% and 53%, respectively.
smoking causes marked inhibitionof substance P–induced tPA release in vivo in humans. Thisprovides
an important mechanism whereby endothelial dysfunctionmay increase the risk of atherothrombosis through a reductionin the acute fibrinolytic capacity.
in identical twins discordant for cigarette smoking
Plaque found to bed 3.2 times greater in smoking twins--jk
A Haapanen, M Koskenvuo, J Kaprio, YA Kesaniemi and K Heikkila Department of Public Health, University of Turku, Finland.
From a nationwide twin panel, identical twin pairs with highest discordancein cigarette smoking were selected for a study
of arteriosclerosis (49pairs with a mean
age of 52 years). Smoking history was obtained in
1975,1981, and 1986. The mean life-long smoking
dose of the smoking cotwins was20 package-years.
The smoking and nonsmoking cotwins had similar systolicand diastolic blood pressures, total
plasma cholesterol level, body massindex, and some psychosocial factors; the only difference was found in useof alcohol, which was greater among smoking
cotwins. Duplex sonography ofcarotid arteries was performed. Carotid artery stenoses (narrowing of areaof
the lumen with 15-60%) were found in nine pairs: in nine smoking
twinsand in two of their nonsmoking cotwins
(p = 0.036). The
total area ofcarotid plaques was 3.2 times larger in smoking
cotwins (p less than0.001). The thickness of the
inner layer of carotid arteries was moremarked in smoking
cotwins (p less than 0.001). The size of plaques and thedegree of inner layer thickening correlated with the dose
of smoking (NS).The association of smoking with carotid arteriosclerosis was highlysignificant even after the adjustment for age, total plasma
cholesterollevel, diastolic blood pressure, and body mass index in multiple logisticregression analyses.
Enter supporting content here
SMOKING SHORTENS LIFE AN AVERAGE OF 7 MINUTES PER CIGARETTE
FOR AN ARTICLE EXPLAINING WITH EXCEPTIONAL CLARITY CANCER; FOR ARTICLE ON LUNG CANCER, AND 2 DOZEN RELATED ARTICLES
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