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!p_"o A1"RES. EVANS. AND BUEHLER 1 10 12 1A 16 GrEvyreeor/rEin Salurtliu~ S - F1G 2. Cumulative frequency dislnbution of carbo.yber:wglobin in smokers. group is 1.58%; t_he difference due to smoking within each group may be as great as 5%. Considerable information relative to smoking habits and carboxyhemoglobin saturation emerges from the-studies performed on individuals sampled at random in Union Square. Table 2 shows that hipher carbon monoxide levels were ob- served in cigarette smokers compared jtjkother smokers, long standing smokers compared t6'Irecent smokers. factory workers compared lo:,clerica] and profes- sional individuals, and men compared to~women. The brand of cigarette and the presence of a filter tip made no difference in the levels of carbox,yhemoglobin. The data also show the importance of time of smoking to measurement of blood carbon monoxide concentrations. Figure 3 demonstrates that carboxyhemoglobin saturation was directly related to the number of cigarettes smoked prior to sam- pling and to the time of the last cigarette. The half-time for carbon monoxide excretion calculated from this data is 204 min or about 3-5 hr. TABLE 2 Dnnusers t. CAReoxsHewoeweis Swrrz.no. uio.e G¢ocvs oF S•~o.eas Group characteristics - COHb (S'a) I P Cigarettes only 4.00 c L9u - <0AI Pipe and/or cigan only 2.80 ='.00 - Cgarette smokers > 10 years 4.3t m 1.95 <0.05 Cigarette smoken < 10 yean /1Y Y 3.78 c 2-09 - Male smokers 11 4.01-c 2.16 <005 Femalc smok<rs 3.41 c'L71 Faciory s.orkers 4.60 - ±.37 <0D5 Cterical and professional 3.42c L85 e Mean m SD. LI

WORr:5110P: CARBON SIO\O7CIpi nttD CVD TABLE 1 "VV- C..nntsru,in,.r nnis Co.,.cr a.nuss r. 1.,. 1'onr a. Conctnlralion Iil Group Nnnsmolcn - - smokcrs Policemen (highC - 1,14 = 0..4• 8.11 c-'_.S1 Policemen (Io.) 9_ 0.57 6?9 - 2.66 Tunnel workers A r~ 2.93 c 1.36 3.01 -"5 Bridge aorkers lnYWO '.1?c 1.08 . 3.90 ~_'.13 Union Square' 1.93 = 0_35 - 3.89 -?.06 Hospitalized t_s6 0 0.35 ' High and low refer to highly and less highly concested precincts in New York City- • Mean - SD. - _ ' Union Square studies are on New Yorkers picked at random_ _ . the-higher mean values for both smokers and nonsmokers working in highly con- gested areas (midtown Manhattan and East River lunnels) compared with those working in less highly congested areas. Lower concentrations were observed in the group studied in Union Square; the lowest valuPs were found in patients resting in a filtered-air facility five floors above ground level. Significantly higher concentrations were observed in those studied in Union Square who had been riding in a bus or car immediately prior to testing (2.28 :t 0.80%) compared i% ith those sho had been traveling in subway or train (l.74 - 0.47i). The studies of the policemen were performed immediately after a tour of duty in a squad car. Two men were stationed in each car: the issue of passive smoking was not evaluated. Smoking, the data reveals, is the most important determinant of blood car- boxyhemoglobin saturation `7he difference in mean carboxyhemoglobin satura- tion in nonsmokers from the lowest to the highest automotive pollution exposure 3 [ CartaytervfYin SYUn:kxt s Fio. I. Cumulalive frequency distribution of carMv)hcmog!obin in nommokcrs.

%A'ORi;SHOP: CARBON MONOXIDE AND C%'D f l . T Lrv • ~ -r- ~ . • • 0 DOGS 5sC(+ ~ • 141vAN5 5iCo i . A R',N'A!S .UCO Lal C9FC0 L30 CEF~, ry L2C L IL LW • °CO s~ to ts m a w is ao cuRe, S sxujvtia, Fie. 4. Changes in coronary blood now rollowing acuwe increase in carboxyhemoglobin. Larger inaeases are obsen'ed following the higher concentration of carbon monoxide. I by the effect of venous blood of lower oxygen tension perfusing existing venouX Yrterial communications. The reduction in mixed venous oxygen tension is a direct result of the leftward shift of the oxyhemoglobin dissociation curve with unchanged arterial-venous oxygen extraction. The resultant decrease in mean systemic capillan• oxygen tension explains the increased oxygen debt following exercise and the difficulty in performing maximum exercise observed by several investigators (6, II). ~ Our observations indicate that acute elevation of carboxyhemoglobin decreases the extraction of oxygen by the myocardium from arterial blood. This is opposite from the effect on peripheral oxygen extraction and derives from the flow-limited nature of the coronary vascular bed. Close to 75% of the arterial oxygen content is extracted by the myocardium while only 25r/o is extracted by the body in general. This near maximal extraction limits the response of the coronary vascular bed to increased metabolic requirements. Further increase in extraction would decrease- myocardial oxygen tension to unacceptably low levels; increase in blood flow : remains the onlv available adjustment. - ~ A sudden increase in carboxyhemoglobin concentration could lead to a substan- j tial decrease in myocardial oxygen tension because of the leftward shift of the . oxyhemoglobin curve and the decrease in p;4 of the circulating hemoglobin. This . potentially dangerous reduction in oxygen tension is minimized by decreasing the i amount of oxygen extracted and increasing the rate of coronary blood flow in an i attempt to maintain oxygen consumption without decreasing myocardial oxygen tension. Figure 5 demonstrates the effects of carboxyhemoclobinemia on myocardial I oxygen extraction. The closed circles show arterial and coronary sinus oxygen content and tension values with normal hemoglobin; open circles indicate the ~ same points in the presence of 8% carboxyhemoglobin. The vertical lines show the I i

WORKSHOP: CARBON A7ONOxIDI AND C% 'D ' HcAeff d Cperes 2 4 6 B O R ~ rre, t+rvb 20 Q 60 BO 00 IYJ FiG. 3. Dependence of earboxchemoelobin in smokers on number of cigareues smoked and rime since last ci¢zret[ec - - Functional Responses to Acare Elevation of Carbo.cvhernoglvhin Carboxyhemoglobin was raised to levels similar to those observed in cigarette smokers by breathing 5% carbon monoxide for 30 to 120 sec or 0.1% carbon monoxide for 8 to 15 min. The systemic circulatory response to 5ry carbon monoxide is shown in Table 3. Arterial and mixed venous oxygen tensions decreased 6 and'_19c from control levels. respectively. The arterial-venous oxygen difference increased but the change was not statistically significant. Cardiac output and mimute ventilation both increased. Similar decreases in arterial and mixed venous oxygen tension were observed following the inhalation of 0.15'r carbon monoxide but cardiac output either decreased sliehUy or was unchanged. The responses of the coronary vascular bed, show'n in Table 3 and Fig. 4, were quite different from those-of the systemic circulation. Arterial-coronary sinus oxygen difference decreased by 12% and the macnitude of chanee could be corre- lated stith the increase in carboxyhemoglobin. Coronary blood flow increased by 25`h. More modest chanees were observed following breathing of 0.1`/c carbon monoxide: arterial-coronar,v sinus oxygen difference decreased 7.55'r and coro- nary blood flow increased by W-'c. Coronary sinus oxygen tension, a reflection of myocardial oxygen tension. decreased by 10 and 15~/c, respectively, in the two series of experiments. Fifteen of the patients had coronary artery disease.Those studied following 5% carbon monoxide had a mean oxygen extraction ratio of 0.75 compared ~0.68 for the group receiving the lower concentration suggesting that they had more exten- sive impairment of coronary circulation. All patients receiving the higher concen- tration either decreased lactate extraction or switched to lactate production. Only 4 of ll patients breathing 0.1% carbon monoxide developed abnormal lactate me taboli s m. ' , Smoking. Heruoglobin Concerrlrafion. and Coroean- Arrcrv Disease Smokers with arteriographically proven coronary anery disease had hemoglo- s averaging 14.88 g1100 ml compared w'ith 13.92 g1100 ml in : bin concentration ~ _ ., ~ -- - ---- '~ ~--- - C_

w'ORASHOP: ('ARnON AfONOXIpF,/AND CvD YN ' vi. , di~miCpq 5 In 15 2n - `rmarn't t. ./naa .+s ro ts 20 rfo. .erq B 20 ss 24 26 29 30 Fso. 6. Effect of changes in myocardial oxygen consumption (Mt'O;), oxygen sapacity of hemoglo- bin, and posilion of oxyhemopJobin dissociation curve (p,.) on coronary' blood flok- - points B illustrate the theoretical effects of increasing carbozyhemoglobin from 0 to 20So. Thus carbon monoxide increases coronary blood flow by two mech- - anisms: part of the hemoglobin is not available for trar,sport-reducing capac- ity and the unloading function of the available hemoglobin is altered as reflected in a decreased p.. Cigarette smoking adds a third dimension by adding nicotine and increasing myocardial oxygen consumption. Cryer et al- (7) showed the impor- - - tance of this factor by demonstrating substantial increases in heart rate, systolic - t and diastolic pressures, and plasma catecholamine concentrations within 10 min of smoking two cigarettes. Myocardial oxygen consumption, as estimated by the pressure-heart rate product, increased 39`7r: reference to Fig~ndicates this would have led to an increase in coronary blood flow of greater than 50%. Modest polycythemia has long been sugeested as a risk factor for coronary - artery disease. More recent studies reviewed by Smith and Landaw (13) have - reported higher hematocrits in smokers compared with nonsmokers. The possibil- ; ity that polycythemia may be an adaptive mechanism secondary to tissue hypoxia - was suggested by DeBias et al. (8) who observed that chronic elevation of car- ' boxyhemoglobin in cynomolgus monkeys to an average of 12.4% increased he- ~ matocrit from 35 to 50`'/a We were unable to find a significant relationship between i carboxyhemoglobin and h_ematocrit in a group of patients admitted for arteriog- ~ raphy but many may have decreased smoking because of chest pain or medical ~ advice so that any relationship was obscured. A significant relationship betwee +n the presence of arteriographically proven disease and inereased hemoglobin con- centrations was observed, suggesting a complex relationship among smoking, . carboxyhemoglobin saturation, polycythernia, and coronary artery disease. These experimental studies suggest that both carbon monoxide and nicotine play an important part in the response of the myocardium to cigarette smoking. While they provide no information as to the etiologic role of smoking in the I I l I

'faTio _- , AYRES, EVANS. AND BUEHLER i TABLE ) Mu. Ht'vs. Rt.anuu:rr Rrsrn,sr_c to Csnao.' Mo..oxinr. Measurement Control Following CO F• P - Systemic (5:u CO, n = 26) COHb (9 saturation) - 0.98 8.96 - - Arterial qOr (mm H81 81 76 2_'.I <0 01 Venous p0r (mm Hg) 39 31 94.5 <0.001 Arterial pCO, (mm Hg) 40 38 4.2 <0 05 Vcntilalian (li¢rs/min) 6.86 8.64 4.1 <0-05 Cardiac output (lilers'mir•.) 5.01 " 5.56 4.4 <0.05 Ancrial-venous 0, difference (mV100 ml) 4.30 4.56 27 <020 - Alveolar-ancrial 0, di1lerencc (mm Hg) 20 29 7.0 <0.05 si s 0 ri l A hly'ocardial (0.lir CO, n = 15) nu ne a -coronary , difTerence (mL'100 mll 11.59 10.71 13.9 <00l Coronary blood Bow• (ml/miN100 g) 91 104 22.3 <0.001 Myocardial ox)gen consumption (ml/midlrA g) - 10.39 _ 11.14 3.5 NS. Coronary sinus pO. (mm Hg) 22 20 29.1 <0.001 - Myocardial (5Sc CO, n = 11) . r i l- o i A 0 - er a c ronary s nus r , . difterence (mB100 mb 1216 - 8.86 83.2 <0.001 Coronary blood floy~ (mVmiN100 g) 102 127 9.2 <0.02 Myocardial oxygen cnnsumption . (ml/miro'100 g) 1' 95 11.41 2.4 NS Coronary sinus pO: (mm Hg) - 20 17 4.5 NS • F,.Variance ratio calculated ror paired data with interaction as denominalor. smokers without coronary artery disease (P < 0.05). Hemoglobin concentration was also higher in the nonsmoker with coronary disease (14.39 g/l00 rnl) than in the nonsmoker without disease (13.92 g/100 ml) but the difference did not reach the usual levels of statistical significance (0.05 <P < 0.1). There was no difference in hemoglobin concentration between smokers and nonsmokers. DISCUSSION The hemodynamic and metabolic data presented indicate that concentrations of carboxyhemoglobin commonly found in smokers may produce significant changes in myocardial metabolic function. The epidemiologic data further suggest that only those individuals exposed to extremely high levels of automotive pollution would have carboxyhemoglobin concentrations approaching that of the smoker. The mean concentration oftarboxyhemoglobin found in nonsmoking policemen working in highly congested Manhattan precincts was still lower than that of smokers studied in less highly polluted areas of New York City. The reduction in arterial oxygen tension was unexpected but may be explained r-- ' l` I I

AYRES, EvAl.'S, AND BUEHLER B+CC+fl 20 40 60 BJ - IDO _ 120 I>u= - Flo. 5. Oxyhemoglobin dissociation curves demonstrating oxygen conient in;lead ofoxyhcmoglobin turation for normal hemop.lobin and in the presence of 8 r aarboxyhemoglobin t mount of arterial-coronary-sinus oxygen extraction. A decrease in extraction till results in a somewhat lower coronary sinus oxygen tension; were the same :vel of extraction maintained, as-in the example without carbon monoxide, oxy- en tension would decrease to less than 10 mm Hg. These considerations explain recently published observations that carbon ionoxide inhalation leads to-decreased exercise performance in patients with oronary artery disease. Thrce separate studies, two by Aronow el al. (2, 3) and ne by Anderson er al. (I), demonstrate that raising carhoxyhemoglobin concen- ations from about I to somewhat less than 3% saturation led to a 15% reduction t the exercise duration tolerated prior to the onset of angina pectoris. While oronary blood flow is readily increased in most normal individuals, coronary arrowing limits regional blood.flow in patients with coronary artery disease. In hese patients, small concentrations of carboxyhemogiobin lead to tissue-hypoxia t areas of myocardium supplied by vessels that cannot dilate in response to ecreased oxygen availability. As a result, angina pectoris, decreased exercise bility, ventricular arrhythmias, or sudden death may occur. The observation that changes in coronary blood flow constitute a sensitive idicator of myocardial'nypoxia enable the conceptualization of the net effects of igarette smoking on the myocardium. Figure 6 shows a model drawn from ex- erimental and theoretical material published by Duvelleroy er al. (10). Each urve represents the relationship between coronary blood flow and one of three tctors that influence it. Increasing myocardial oxygen consumption or decreasing ither hemoglobin oxygen capacity orp,,, produces an increase in coronary blood ow. Should coronary blood flow not increase adequately because of vascular arrowing, myocardial ischemia would result. Points A represent coronary blood flow at normal p,o and hemoglobin capacity: cPJri9nr `7

_Irbi= - Al"RES, EVANS, AND BUEHLER 7-The present study presents data demonstrating that extremely high concentra- tions of carboxyhemoglobin may be observed in many cigarette smokers and that . the level is-related to both-the intensity and frequency of cigaiette smoking. Additional data show.that acute administration of carbon monoxide decreases _ oxygen extraction by the myocardium and increases coronary blood flow prevent- ing major decreases in coronary sinus oxygen tension. - EL METHODS 1 Several different groups of individuals were studied. The extent of car- bozyhemoglobinemia was evaluated by obtaining alveolar air samples of over 1,000 individuals engaged in various activities in New York City- The bridge and tunnel workers (BTOs) worked primarily in the toll-collecting areas of the bridges and tunnels operated by the Triborough Bridge and Tunnel Authority; the-two major tunnels studied, the Queens Ntidtown Tunnel and the Brooklyn Batterc~ Tunnel, connect Manhattan with Queens and Brooklyn, respectively. The details' f thi t d h b i l 4 d Th N Y k Ci - I? t ave u y een prev o s s ous y reporte ). ew ( e or ty pa}- f ~ ci~- were studied a ter a tour of duty in a patrol car: the midtown Manhattan(pre were considered "high pollution" while precincts located in other parts o were considered "low pollution". New Yorkers were studied at random A a sidewalk station located at Union Square. A detailed questionnaire was also ob- tained. A group of hospitalized patients, all nonsmokers, were studied in a filtered-air environment located on the fifth floor of Saint Vincent's Hospital.- - I The studies on hemoglobin concentration were performed on 196 patients ad- mitted to Saint Vincent's Hospital for coronary arteriography- The blood samples ' were obtained at the time of arteriography- Blood carboxyhemoglobin was measured from alveolar samples for the epide- miology study. Almost all samples were analyzed by gas chromatography using a Beckman GC-5 chromatograph and a molecular sieve column" The samples from the policemen were analyzed by a CO detector that catalytically converts carbon ~ monoxide-to carbon d(Ade and measures the hydrogen ion so generated (Ecotyzer). We and others (15) have shown the accuracy of this instrument rela- tive to other techniques such as gas chromatography and infrared analysis" ': Blood carboxyhemoglobin was directly measured on venous or arterial samples for the hemodynamic studies and the studies made during coronary arteriography. f~Hemodynamic studies were performed on 41 patients during diagnostic cath- eterization and on 40 dogs- Myocardial metabolic studies were performed on "2fi of the patients and in 25 of the canine studies. The precise details of these studies have been previously published (5)-. ~ Y RESULTS Determinants of Carboxvhentoglobin Concentrnrion .~ Group means for carboxyhemoglobin saturations ranged from 8.11ri'o in the smoking policemen working in congested traf6c to 1.56% in the nonsmokers studied in a filtered-air facility on the fifth floor of a metropolitan hospital. Group means and standard deviations are shown in Table I; complete data are plotted as /\ 6equency-distribution curves in Figs. I and 2. - ;` The_in_ fluence of automotive sources of carbon monoxide is demonstrated by

t~ - Th(s set of prc, f3,t /aEvENTI IEDICI\E 8. 0Bf)-B0B (1979) ' ~ . : .. : 'P .~~ 1 ~~R ur queries. kut~,ar ;;f _ ;,"; / _ -+ t Indiqte all correclions o ihis set, FFFT///he Pr valence ofOLCa oxyh moglobinemiwa in New ~ , f Yorkers and Its Effects on the Coronary and Systemic Circulation' STEPHEN I\t. AYRES,r ROBERT G. EVANS, AND META E. BUEHL$R Depanmrnt of fnternnl tlediciua Sr. L.via Unfrrcai{v Srhoul nf.7lcdirinr. - S/. Lwrit. Ariarorni 6JfOf Carbox}hemoglobin saturations ranging from 8.11 to 1.56:r were found in a sample of more Ihan I 0(1n individuals engagcd in various ar-tiv(ties in New York City. The difference from tov.tst to highest carboxvhemoglobin in nonsmokers was 1.58r: in smoL.crs il was as greal as 5.Br;r. Experimenlal elevation of carbophemoglobin to levels similar to that seen in cigarette smokers produced a decrease in arterial and venous oxygen tensions and an in- crease in cardiac output and coronary blood flow. in contrast to the effect on the syst<mic vascular hed- carbon monoxide inhalation produced a decrease in myocardial oxygen ex- traction. These obsen'ations suggest that changes in coronary blood Bov' are a useful indi- eator ofahe effects of carbon monoxide when hemodpnamically signi6canl coronary artery disease prevents the expected increase in mocardial blood Oow. I A large collection of epidemiologic observations has shown that mortality from coronary anerv disease is several times more common in smoking men compared with nonsmoking men under the age of 60 (14). Similar data has been presented for women and it has been shown that the)Fontraceptivepitl~ acts as a powerful cofactor with ciearetle smoking (12). Since it can be maintained that the genetic predisposition to smoke and to develop coronary disease are linked, studies showing the effect of smoking cessa- tion become extremely important. Almost half of all British physicians stopped smoking during the past 20 years and the incidence of deaths from ischemic heart disease in-exsmokers provides important evidence that smoking directly contritr utes to death from coronary artery disease (9). The death rate for physicians from ischemic heart disease under the age of 55 who continued to smoke was 3.5 times that of the lifelong nonsmokers- It fell to 1.9 in those who had stopped smoking for less than 5 years and to 1.3 in those who had stopped for between 5 and 9 years. Both nicotine and carbon monoxide could be responsible for the increased mortality associated with cigarette smoking. Nicotine produces sympathetic stimulation increasing cardiac work and oxygen requirements: a-adrenergic stimu- lation may produce constriction of the larger coronary arteries (7). Carbon monoxide decreases oxygen availability by binding with hemoglobin and interfer- ing with the release of oxygen in the coronary microcirculation (5). ' Presented at a!~Drkshop on Carbon bfonoxide and Cardiovascular Disease. Sponsored by Ihe American Health FSundation and the Federal Health OfGce, Federal Republic of Germany. Berlin. October 10-1'_. 1978 - s To whom requests for reprims should be addressed: Department ot Internal hledicine, St. Louis University Hospital. 1325 S. Grand Blvd., Sl- Louis- Mo. 63103. I .. I. I (Z -- - - -- 0091-7a35/79:03000t100S02.00.0 - ~ cN0^rbl ~~ 14/Y b ecaJemm Po.. Im. i ~ AII n1MS r{ rtp•W~I•~'^ ° rq fmn rrnrd. u r :.,;_~ N . ~ ( 31C~

AYRES, EVANS, AND BUEHLER . development of coronary atherosclerosis, they sugcest an important mechanism for the development of ischemic episodes in patients with existing coronary artery disease and provide an explanation for the increased death rate from coronary disease in young smokers. - REFERENCES 1. Anderson, E. W., Andelman. R. J.. Strauch. J. h1.. Fortuin, N. J., and Knclson. 1- H. Effect of lo+..lc.cl carbon monoxide exposure on onsct and duration of angina pecloris: A study of len patients with ischemic heart disease. Ann. Lrrrrn. dlcd- 79, 46-50 (1973) 2. Aronow, W. S.. Harris. C. N.. :sbell, h1. W.. Rokasc. S. N.. and Imparato, B. Effect of freeway travel on angina pcctoris. Ann. Intern. 1_Ird. 77, 669-676 (1972). 3. Aronov+, W. S.. and IsbclL M. W. Carbon monoxide eRcct on cxcrciscinduccd angina pcctoris. Ann. Inrrsn. Ilyd. 79, 39?-395 (1973). 4. Ayres, S. M.. Evans. R., Licht. D.. Griesbach. J.. Reimold, F., Ferrand. E.. and Cris~i!ello. A. Health eRects of exposure to high concentration of awomotive emissions. Arch. EnLiron. Healrh 27, 168- 178 (1978). 5. Ayres. S hl., GianetG, S.. Jr., and Mueller, H. hlyocardial and systemic responses to car- boxyhemo¢Jobin_ Ann. N-Y. Arad. Sri. 174. 268-'-93 (1970). j 6.' Chevalier. R. B.. Krumhotz, R. A.. and Ross. J. C. Reaction of nonsmokers to carbon monoxide inhalatioa, mrdiopulmonary responses at rest and during exercise. JA31A 198, 1061-I066 (1966). 7. Cryer. P. E.. Haymond, 11.1- W-, Santia€o.1. V.-and Shah. S. D. Norepinephrine and epinephrine rcleax and adrenergic mediation of smoking-associated hemodynamic and metabolic even(s. h^Engl. J. Afrd. 295, 573-577 (1976). - 8. DeBias. D. A.. Banerjce. C. M.. BirJread, N. C., Harrer. W- V., and Karal. L. A. Carbon monoxide iMalation effects (ollow'mg m7 ocardial infarction in monkeys.Arch. &rciron- Hralrh- 27, 161 -167 91973). - 9. DoH. R., and Peto. R. Mortality in relation to smokin(r 20 years' obscrvalions on male British doetors. Bdr. Afed. J. 2. 15'5-1536 (1976). 10. ITtvdleruy. M. A.. hfahmel. H.. and (aver% h1. B. Hemoglobin-oxygen equi{ibrium and coronary blood flov.- An analog model_ J- Appl. P/resiol. 35, a80-484 (1973). 11. -Raven, P. H.. Drinkv.ater, B. L-.. Ruhling. R. 0.. 8olduan. N. W.. Taguchi. S.. Gliner. J. A.. and Honath, S. M. Effect of carbon monoxide and perax)acetyl nitrate on man's-mazimal aerobic capacity. J. Appl. Ph, riol. 36. 388-393 (1974). 12. Slone-D-. Shapiro, S-. Rosenberg. L- Kaufman. D. W.- Hartz. S. C.. Rossi. A: C.. Stollcy. P. D.. and hlkttinen.0. S. Relation of cigarette smoking to mcocardial infarction in .cung women. A^ r gl.rgl. J. Slyd. 298, C73-1276 ( 19781. Fi 1). Smith, J. R., and Landavr, S. A. Smokers" pol)c)shemia. A^En,e7. J. Alyd. 298, 6-10 (1938). 14. U.S. Department of Health Education and Wclfare.'•Smokingand Health: Repen ofthe Advisory - Cornmittee to the Surgeon General of the PubLic Health Ser,icc" Public Health Scrvice Publi- mtion No. 1103. 196L 13. Wrig2t, G. R., Jeuczyk. S..Onrot. J., Tomilson. P.-and Sh<phard, R. J. Carbon monoxide in the vrban atroosphere: Hazards to the pedeslrian and the street-worker. Arch. Enriron. Hralrh 30. '123-129(1975). r- A ri9~ hf - tj ew , t~ ir ~{le c~