Tobacco Documents Online

«ILBERT 5. ARONOW CO artd Subclinica! Ncarr Dici•ase Fortuin and associates obserrved that 7 of 7 older "normal subjects" with prob- able subclinical coronary heart disease and electrocardiographic abnormalities (ST-segment abnormalities or.arrhythmias) scho breathed 100 ppm of carbon monoxide intermittently for 4 hr to raise their venous carboxyhemoglobin level to 5.7 to 7.1% developed exaggeration of their electrocardiographic abnormalities (32). We found in a double-blind, randomized study that healthy middle-aged persons who breathed 100 ppm-of carbon monoxide for I hr to raise their mean venous carboxyhemoglobin level from 1.67 to 3.9.i % had a reduction in mean exercise time until exhaustion compared with the control periods or after breath- ing compressed• purified air (6). One of our 10 as}mptomatic subjects (107r) manifested ischemic ST-segment depression >1.0 mm aft.er exercise following carbon monoxide exposure but not in the control periods or after breathing-com- pressed, purified air. The increased carboxyhemoglobin level may have precipi- tated myocardial ischemia in this person ssith suspected latent coronary heart disease. - - CO, Meoeardia( Injnrcrion. and Sudden Derrrh Cohen and associates shosced an association benceen atmospheric carbon monoxide pollution in Los Angeles and case fatality rates for patients with acute myocardial infarction admitted to 35 Los Angeles hospitals (28). Carbon monoxide exposure may also precipitate myocardial infarction in patients with - coronary heart disease (45). Decreases in mortality from cardiovascular disease were also observed in San Francisco-county and in Alameda county during the fuel crisis of 1974 (26). DeBias and associates shcnced that in monkeys Hith experimental myocardial infarction, elect rocardiographic evidence of a greater degree of myocardialisch- emia occurred in the monkecs exposed to 100 ppm of carbonn monoxide than in- those breathing room air (31). DeBias and associates also demonstrated that inha- lation of carbon monoxide 100 ppm for 6 hr to raise the mean anerial car- boxyhemogiobin level to 10' <<cas a significant factor in enhancing ventricular fibrillation in monkeys with acute myocardial infarction (30). In addition, we demonstrated in a blind- randomized study that breathine carbon monoxide 100 ppm for 2 hr to raise the mean arterial carbox}hemoglobin level to 634`,'c caused a reduction in ventricular fibrillation threshold in dogs with acute myocardial injury (15). - In my opinion• both nicotine and carbon monoxide contribute to the increase in nonfatal and fatal myocardial infarction and in sudden death from coronary heart disease in cigarette smokers. Carbon monoxide contributes by: (a) carboxyhemo- globin interfering with myocardial oxygen deliver}• at the time nicotine has caused an increase in myocardial ox%gen demand (2, 5, 7-9, 12, 13, 16), aggravating an episode of myocardial ischemia-(31), (b) the negative inotropic effect of car-- :)oxyhemoglobin (7) aggravating an attack of myocardial ischemia, (c) car- 3oxyhemoolobin reducing the threshold for ventricular fibrillation during an :pisode of myocardial ischemia 30), and (d) carboxyhemoglobin increasing DIatelet stickiness (24), thereby, m reastng a thrombotic tendency. 1

k'ORASHOP: CARBON AfONOXIDI AND cV0 CO and Pa1llnccnPsis nj A711t•r,c~clrr,,si.s Coronanhcart disease is a mullifactorial disorder. The presence of other risk factors in addition to smoking fincluding hypercholesterolemia. hypertension, hypertriglyceridemia, diabetes melliius, marked obesiry, and sedentary- living) increases the risk of developing coronary heart disease. The greater the tobacco consumption, the greater the number of coronary risk factors, and the greater the degree of abnormality of these risk factors, the higher the risk of developing coronary heart disease. ` - - Wald and associates have demonstrated that carboxyhemoglobin levels in to- bacco smokers correlatebetter than the smoking history sith the deselopment of mcocardial infarction, angina pectoris. and intermittent claudication (50). These investigators found that the relative risk of developing coronary heart discase or intermittent claudfcation'was ? 1.2 times greater in persons with carboxyhemoglo- bin levels of 57c or greater than in persons with-carboxyhemoglobin levels below 3%. However, it should be pointed out that the higher levels of carboxyhemoglo- bin may also reflect the absorption of other constituents of tobacco smoke in addition to carbon monoxide. Nonsmoking foundry oorkers exposed to carbon monoxide have a high preva- lence of coronanheart disease (35). The prevalence of angina pectoris in foundry workers showed a clear dose-response relationship with regard to carbon monoxide exposure from either occupation, smoking, or both (35). Exposure to carbon monoxide has aiso been associated with acute electrocardiographic changes in apparently-healthy fire Lghters at work (39). In addition, ischemic heart disease has been demonstrated in fire fighters with normal coronary arteries (23). In animal experiments, nicotine does not cause coronary atherosclerosis uhen administered in amounts much hi_eher than the nicotine uptake by a smoker (46). Hoscever- experimental data have implicated carbon monoxide in the concen- trations found in heavy tobacco smokers in the pathogenesis of coronary atherosclerosis. Astrup and associates demonstrated that carbon monoxide or decreased oxygen tension enhances coronary atherosclerosis in cholesterol-fed rabbits (i7-, 18), and that h% peroxia reverses rabbit atherosclerosis (36). Microscopic findings observed in the arterial wall suggested that increased arterial accumulation of lipids was caused byan increased endothelial permeability, leading to subendothelial edema (17. 18). Astrup and co-workers also hypothesized that high carboxyhemoglobir- levels resulting from tobacco smoking were-associated with development of oc- elusive arterial vascular disease (19). Birnstingl and co-sorkers confirmed that carbon monoxide enhances coronary atherosclerosis in cholesterol-fed rabbits (25). In addition, Webster and associates demonstrated that carbon monoxide enhanced coronary atherosclerosis in cholesterol-fed squirrel monkeys (51). Kjeldsen and associates demonstrated that rabbits on a normal diet exposed to carbon monoxide-180 ppm for 2 weeks to lead to a carboxyhemoglobin of 16 to 18% developed aortic lesions indistinguishable from early atherosclerosis (37). In addition, severe ultrastructural changes vrere found in the myocardium of rabbits exposed to carbon monoxide (18, 37)- Thomsen found that monkeys on a normal I C~p/. 3; t

,P KORKSHOP: CARRON MONOXIDE AND (Vp freeway traffic (10) compared with the control periods (3. 4. 10. 13) or after breathing compressed. purified air (l0). Since the patients ~k ith angina pectoris could not adequately increase their coronary blood flow while exercising. and since their elesated carboxyhemoclobin level made less oxygen available for de- livery to the myocardium, their myocardial oxygen demand exceeded their myocardial ax)-gen supply, inducing angina pectoris earlier, and after less myocardial "ork. Two douEle-blind, randomized studies also have confirmed that exposure to carbon monoxide in concentrations found during heavy atmospheric carbon monoxide pollution aggravates exercise-induced angina pectoris. Anderson and associates (1) documented in a double-blind, randomized study that patients with angina pectoris %sho breathed carbon monoxide 50 ppm intermittently for 4 hr to raise their mean cenous carboxvhemoclobin level from 1.3 to ?.9 7r had a decrease in exercise time until theonset of angina pectoris compared %%'ith thyt observed after breathing compressed. purified air. Exposure to carbon monoxide caused deeper ST-segment depression during and after exercise in 5 of their 10 patients. µith earlier onset and loneer duration of ST-segment depression. - We demonstrated in a double-blind, randomized studyihat patients with aneina pecloris due to documented coronary artery disease who breathed 50 ppm of carbon monoxide for 2 hr to raise their mean venous carboxyhemoglobin level from 1_03 to 2.68% had a reduction in exercise time until the onset of angina pectoris and a decrease in the product of systolic blood pressure times heart rate at the onset of angina pectoris (1I). Ischemic ST-segment depression >1.0 mm after exercise>induced angina pectoris occurred earlier, after less exertion, and at a louer product of systolic blood pressure times heart rate at the onset of angina pectoris after exposure to carbon monoxide compared with the control periods or with the periods after breathing compressed, purified air (1 I). Kurt and associates have demonstrated that the ambient level of carbon monoxide in Demer has a lo+s-level association with the frequency of acwe car- diorespiratorc complaints in an emergency room (38). Their data lead one to conclude that carbon monoxide from the macroenvironment must be considered a risk factor for cardiopulmonan disease. CO and /n7erntitfen! Clarrdicarron r We also demonstratedin a double-blind, randomized study that patients with intermittent claudication of the calf or thigh due to angiographically documented iliofemoral occlusive arterial disease who breathed 50 ppm of carbon monoxide for 2 hr to raise their mean venous carboxyhemoglobin level from 1.08 to 2.77% had a reduction in exercise time until the onset of intermittent claudication com- pared xdth the control periods or after breathing compressed, purified air (14). Since the patients with documented iliofemoral occlusive arterial disease could not adequately increase the blood flow to their thigh and calf muscles w'hile exercising, and since the elevated carboxyhemoglobin level made less oxygen available for delivery to their calf and thigh muscles, the oxygen demand exceeded the oxygen supply to these muscles, inducing intermittent claudication sooner, - followine less exercise. F__ _ _ t

ri'IL?ERT S. ARONOW diet exposed to carbon monoxide 250 ppm for 2 sceeks developed ssidening of the ~subendothelial space of the coronary arteries and accumulation of lipid-laden cells there (48). - , _ ' Tillmanns and associates measured lipid synlhesis and cholesterol uptake in rirro in pcrfused human coronary arteries obtained at aulopsy. They found that nicotine failed to influence cholesterol uptake or lipid synthesis, and that carbon monoxide did not influence lipid synthesis in the arterial wall (49). However, these investigators demonstrated that carbon monoxide leads to a marked increase in cholesterol uptake in perfused human coronary arteries, regardless of the concen- tration of carbon monoxide in the perfused (luid. Increased uptake of cholesteror by arteries pcrfused %.ith carbon monoxide is probably the result of tissue hypoxia (44). CONCLUSIONS in conclusion, carbon monoxide exposure from heavy smoking or heavy at- mospheric carbon monoxide pollution depresses myocardial function in patients with coronary heart disease, aeeravates angina pectoris, aggravates intermittent claudication of the calf or thigh, increases myocardial ischemia in patients with clinical and subclinical coronary heart disease, and contributes to an increased incidence of nonfatal and fatal mcocardial infarction and sudden death from coro- nary heart disease- Furthermore, experimental data indicate that exposure to carbon monoxide in concentrations found in heavy tobacco-smokers or in persons with heavy occupational exposure to carbon monoxide-plays- a role in the pathogenesis of cardiovascular disease. _ REFERENCES ~ ~ 1. Anderson. E. W., Andelman. R. 1., Strauch. 1. M.. Fonuin, N. 1.. and Knelson. J. H. Elfect of ~ lou-le+el carbon monoxide exposure on onset and duration of angina pcctoris. A study in ten ~ patients uith ischemic heart disease. Ann. Intern. SJrd. 79. 46-50 (1973). I 2. Aronow. W- S- The effect of smoking cigardles on the apexcardiogram in coronary heart disease , Chur 59, 365-368 (1971) - - ' 3. Arono,.. H'-S. Effect of passice smoking on angina pectoris. Nnr Engf. J. .41ed. 299, 21-24 (19'g) 4. Aronov. W. S._ and Cassidy. 1. Effect of manhuana and placebomarihuana smoking on angina ~ pectnris. AY•' Engf. J. dled. 291, 65-67 (]974). . , S. Aronow. W. S.. and Cassidy. 1. Effect of smokicg matihuana versus a high-nicotine cigarette on . angina peaoris. Clin. Plmrmarol. Ther. 17, 549-554 (1975). - - 6. Aronou. W. S.. and Cassid,v. 3. Effect of earbon monoxide on maximat treadmlf exercise. A , ' study in norm.al persons. Ann. Intern. .lfrd. 83, 496--f99 (19751. • 7, Aronou. W. S.. Cassid) , J., Vangr°w, J. S.. March. H-. Kern, 1. C, Goldsmith. J. R.. Khcmka, ~ i Af.. PaFano. 1., and Na.aar. hf. Effect of cigarette smoking and breathing carbon monoxide on ~ eardiosascvtar hemod; namics in anginal patients. Cirrufnlion 50. 340-347 (1974). ~ 8. Aronou, W. S., Dendinger. J.. and Rokau, S N. Hean rate and carbon monoxide Ievct aficr ' smoking hi5h-, los.-. and nonnicotine eigarettes. A study in male patients with angina pectoris. I Ar,n. Jmern. .ifed. 74, 697-702 (1971). I 9. Arcno.., W. S.. Goldsmith, J. R.. Kern. 1. C. Cassidy, J., Nelson, W. H.. lohnson, L. L_, and ', Adams, W. Effect of smoking cigarettes on cardiovascular hemodynamics. Arch. Enrirun. ' --Hrc!rh 28. 330-332 (1974). -- - -- . i I 10. Arono. . W. S.. Harris, C. N., Isbell. 61. W-, Rokav,. S. N., and Imparatn, B. ERect of freeway trasel on angina pecloris. Amr. lntrrn_ ,ifed. 77, 669-676 (1972). ~ 11. Arono., W-S., and Isbdl. h1. W. Carbon monoxide effect on exercise-induccd angina peaoris. j _Ann. lntrrn_ .Ved. 79, 392-395 (19731. I °Pd` i ( I 7 le 1

NIL9FRT 5. AAO]'O\Y As Ihe affinity of hemoglobin for carbon monoxide is approximately 245 times ~reater than its afGnity for oxycen: carbon monoxide displaces oxygen from hcmoglobin. reducing the amount ofoxsgen available to the myocardium. Ayres Snd associates demonstrated that acute elevation of the ceoous carboxyhemoglo- iin Ies'eI from 0.98 to 8.96Se in patients uith coronary heart disease and noncoro- nary heart disease caused a'_0 r avcrace reduction in mixed venous oxygen ten- sion (21, 22). The greater reduction in mixcd venous otygen tension relative to the rise in venous carboxyhemoglobin level resulted from a leftward shift of the oxyhemoglobin dissociation curce, u$h tighter binding of oxygen to hemoglobin in the presence ofcarboxyhemoglobin, funherreducing the arailability of oxygen tothe myocardiurn.Theincreased carbozyhemoglobinIesclcaused aninereasein coronary blood flow in their pavientS uith noncoronzry heart disease but not in their patients uith coronary heart disease. Myocardial oxygen extraction and extraction ratios decreased in their patients-with eoronaq' heart disease and non- coronary hcart disease, but the mwcardial lactate e*traction ratio changed to lactate production only in their patients uith coronan hean disease (21, 22). Carbon monoxide also combines 'aith m)oglohin and can impair the facilitated diffusion of oxygen to the mimchondria (53). Funhermorc. crtbon monoxide combines directly with eqtochromo oxidasc (i slowing oxidation of reduced nicotinamid,~adenineAdinudeotide (9) In cigar<tne smokers with angina pectoris due to documented coronary artery disease, ue imestigated the effect ofsmoking three hiFh-nicrotine cigarettes within 50 min on cardiovascular hemodynamits (7). Ooe ueek later, we investigated in these patients the effect on cardio.ascular hemodynamics of breathing /5p ppm of carbon monoxide until their rise in coronary sinus carbon monoxide level was similar to that produced after smokinc their third cicarette /7). We found that an increase in mean coronary sinus carbon monoxide level from 2.04103.86^r caused no change in systolic or diastolic blocd pressureand a decrease in left ventricular dpldr. stroke index. and cardiac index. The negative inotropic effect caused by carbaxyhemoglobin was responsible for the decrease in stroke index and for the rise in left ventricutxr end-diavolic pressure ohsen'ed after smoking. The increase in hean nte. blood pressure. and positice inotrupic effect induced by nicotine ehould hace increased the left xentricular dn!dr after vnoking However, these factors were offset by the negative inolropic effect caused by carboxyhemoglobin, resulting in no change in left ventricular dp'dr after smoking. - CO ar:d Angina Pecroris . Increased carboayhemoglobin lescls after smoking nonnicotine cigarettes (13) or placebo marihuana cigarettes (4). ~after exposure to passive smoking (3) or to heavylreeuay traffic (10) caused pa!ients with angina pectoris due to documented coronary artery disease to have a reduction in exercise time until the onset of angina pectoris, associated with a druease in the product of systolic blood pressure times heart rate at the onset of angina pcctoris. Ischemic ST-segment depres- sion a 1.0 mm after exercise-indeccd angina pectoris occurred earlier, after less ucrcisa. and at a losser product of systolic blood pressure times heart rate at the onset of angina pectoris after exposure to carbon monoaide from nonnicotine cigarettes (13),_placebo ma_rihuana cigarettes (4), passive smoking (3), or heavy ~ j I+- p .z ~~2n M s ) 1 (tiwa C~ Ji.rT rle e M S) u rtAer7 rQteJ G YI S e/ Is vels'CrrGUIRh beN fE;r pY~SS~Ye d-~r4sro(r~ J .. V ' "0 F l (Z N N N N Cr^

_ rT5P~. \VIL6CRI 3. AROCU\V ~36: K;rcldan, K., Avrvp. P.. and tiamtrvp.l. Rnn.+l nf raM1M1ll a:Ennmamsis bY h!f<rmla. J. ~' .'Ayrrmdtr.Fcr.l0.liJ-1)F119591. - 37. Kjadse n. K., A.I mp, P., and N]nsl L Cltraarunur.d inllmal cAanFes ic rAe rzbbn aona aL<r, - odtnrm rarMn m caide nposv ^. ArAr.nrdc.nur 16. 6J-EJ 119]]). 31~ Kun, mod tnr mT. L., EfnFidn:cl.i^R P.. and CFand:n. 1. E Assoc(mlon of rhe 6eeuen</ of acw< car • dimtfDinlepcomP:alnn •irh.rnFienr Ind, of <arhon monoJEe. CSrn'1l 10-It 119261. J9. Kun,T. L..and Pntn.1. M. EPl:emi.'.: t1 ef<ardiat nrl.,n Gre Gg1am.Jrn Holler duoo:vfaqnm, and <arbon manmid< <arr.pLaF. Ciardm....r 52. 11-2N /19>O IAhtraul. _ a0.bshv, P. L. and Cem. . B T. C.ia'<Ire ennl.in6 and <apo•ur t•rt ro orbnn monu.lEcc Ann_ , . N.Y. Acud. Sri. 174, 131- 1O 119]O/. . 41, LYnn D. A..T.DOp E.On.u'„ and Smirh. R qrrnr.d by bRe. L. S. Somcec d.zran<mrin, ~ aed fae of armns; Eeric <afbor- menorlde. Ann. A' 1'. Amd. Sr r. 11<,'6 66 tJ9J01 41 Ranuq. i. M. Con tionsof ezrt•m rrm-oaide at Iraf6c in e ne coo.ns in Dzsmn.OAlo. Arr6. ~ Ln4on. Htuhh 13r, a U-J5115(bJ- 10. AmseB. H. A. H_ CNe. P. \'.- and Bro, n. E. At.o:prion Fg n mNcn of c.rMn n.ona.ide Ba 0 I:r d b I . A. fr 1 5 6 9119 }I. IL1 Lrma ] S. M. T'lln 5. H. II d. S G A C Ih E a d BF R.1. Lipid . mt boti pcrf db anF n- A l.C dinI35. 79 .NJ11919. 15. Scbarf, 5 M. T! A1. D. d 5.F R. K. T ral -dlal f - fru e.pr. ~ ' h- uv I aAO na d _- di. A bfl.l. Al J 91 6- 6611411 Ih5yr1' LOHa~Enr~)) R H R- d 1 - 1' H S F A t G . _ ~ . _, -, t6 Shc Ib H. I nd F 9 " l:- d Arios I s%z AJa/f~ -s I90146119701 ~ l9% A eAperwrnfn'a.!Yrrbptr[n 7.0 f1tP 1n{Ivr~GC ~ I(l.SrcbM.DbaroeB.drwr.nti~d<fKsEleno.'!t lybe-mr€ .r=v.hc mP<rsor<rlra/. nlcotne o»fatYHeiatle72tr+,' .~: .aFen n<tn.ot.rr.z.Gt,nr,teeri:6:eio-e60.so-c9a'+.;I ~a.Tnor, n. H~K.Carbtn ride.indu:etamern.atr,ieinPd„ Anri<are n.m _ .er4o.vr. I J v dI, Ih nruy f aca - L r A I r nle 30 3s <0113%U. ' 49. TJL'r H$ rma 1. S/... S I r R d B,F- R I. L p C Mb . p rf <d Irum.n ~ I cur ,yl and fi "A Y. cl - IG ScA<'I and A. titad. . I EdI val.3 PC 186 125 . SD nFa S rlaA 9es. 1orAE rln. 1974 50' R.M, N.. He.vd. S., Smlrh. P. G.. and Ejeld.en. K. Assoc:arlon baae<o aMCroederml< dls- W n and carboqtrennFlobin lestl• in mba<co 1molas. B.ic AGd l. 1. "/61-765119Dr H'ebrler. 9l. S.. Clartson. T. 9.. and Lof,znd. H. B. CarLon n o<Ide-aFFraszl<d I therosduails in tbe sGuinel monlr.. E•v !lol. Pmlyd. 13, 36-50119tAI ' i I7A RTOUt, A. F. Ia a.heroultrosis a drsorder af rnvamlmchronddd resPrrmion' Anr. lnrtm. !Iltd. ~ ? 13.125-IV nTOI. , 7). wuenbeq. J B. Tn<mnlecwar mechanism of hemoFlotnn.facli2m oa!yrn ddrueion.l B,nl. ; Cl:em, ]u, IOa-u. u966Y . *-- k ftwi

\\'ORKSHOP: CARBON MONOXIDE AND CVD 12. Arnnow, W. S.. Kaplan. AI. A.. and Jacnb. D. Tobacco: A precipilwting faclnr in:mgina pencris. A,vr. 6rtrrn. Slyd. 69, 529-536 (I968). 13. Aronow, W. S-, and Rokaw. S. N.-Carbocyhemngbhin causcd by smoking nonnicminc ciga- _ retles. ERects in angina peUoris. Cirrr.lnri.ur 44, 78'_-788 (19711. 14. Arono.. W. S.. Stemmer. E. A.. and Isbeli, >1. W. Effect of carbon monoside ecposure on intermittent elaudication. Cirrnlnrinn 49, 415-417 (1974). - - 15. Aronoa'. W- S.. Sremrncr. E A-. Wood. B.. Zwcig. S.. Tsao. K., and Rzgeio L. Carbon monoxide and ventricular fibrillation lhreshold in dogs with acute myocardial injury..4nrrr. Hrarr J. 95. 7V-756(1978). 16. Aronow. W. S.. and Swanson. A. J. The effect oflo,nicotine cigarettes on angina pectoris. Aun. Lwrrn. lled. 71. 599-601 (1969) . . 17. Aslrup, P. Effects of h)poxia and of carbon monoxide on experimental atherosclernais .4iur. Luern. ,sfrd. 71, 4'_6-427Y(1969). 18- Astrup. P. Carbon monoxide, sm,oking, and cardiovascular disease. Cirrulnruun 48, I167-IIFR 11973). 19. Astrup. P.. H<Ilung-Larsen. P.. Kjeldsen. 1C. and Slellemgaard. K_ The eRact of lohacco smoking on the dissociation curve of ozyhemoglobin_ Insestigations in patients with ocdusice aneral diseases and in normal suCjens. Scaud. J. Clin. Lnh. lncest. 18, 450-457 (19661. 20. Ayres. S. \I., Evans, R.. Licht. D., Griesbach, 1.. Reimeld. F.. Ferrand. E. F.. and CnscitirJlo. A. Health effects of exposure to high concentrations of automotive emissions: Smdies-in bridge and tunnel workers in New' York City. Arrh. Enriron. Health 27, 168-178 (19731. 21. Asres. S. 61., Giannelli. S.. Jr.. and Mueller, H. S. Effem of low concentrations of carbon monoxide: hlvocardial and systemic responses to earboxyhemoglobin. Ann. .\'.)'. Arnd. Sri. 174. 268-293 (1970). - 22. Ayras, S. M.,_Mueller. H. S.. Gregory, J. 1.,-Giannel6, S.. Jr., and penny. J- L. S)stemic and mocardial hemodl namic responses lo relatively small concentrations of carbox)hemoglobin tCOHB )- Arch. Enciron. Hcalth 18, 699-709 (1969). 23. Barnard. R. 1.. Gardner. G. W.. and Diaco. N. V.-"Ischemic" heart discasc in fire fghters with normal coronary aneries- J. Orrup- dfrd- 18. g18-820 (1976). 24. Birnstingl, M. A.. Bnnson. K., and Chakrabani, B. K. The effect of shnn-term exposure to carbon monoxide on platelct stickiness. Brir. J. Surg. 58. 837-839 119711. 25. Bimstingl, id., Hawkins. L, and McEw'en. T. Experimental atherosclerosis during chronic expo- sure to carbon monoxide. Er.r. Surg. Rer. 2, 91-93 (19701 (Abstract). 26. Brown. S. M., Marmot. M. G., Sacks. S. T., and Ksvok, L. W. Effect on monality of the 1974 fuel msis. A'arure (Londant 257. 306-307 (I975). 27. Coburn. R. F.. Forster. R. E.. and Kane. ?. B. Considerations of the physiological variables that determine the blood carbox)htmoglobin concentration in man. J. Clirrt fmrsr. 44, 1899-1910 (1965)- 28. Cohen. S. 1.. Deane, St., and Goldsmith. J. R. Carbon monoxide and survival from m}ocardial infarction. Arch. Enriron. Health 19; 510-517 (1969). 29. Cohcn, S. f., Perkins, N. M.. Cry. H. K.. and Goldsmith. 1. R. Carbon monoxide uptake in eicareue smoking. Arrh. Enriron. Henlrh 22, 55-60 (1971). 30. DeBias. D. A., Banerjce. C. St., Birkhcad, N. C.. Grecne, C. H.. Scott, S. D., and Hamer. \\'. V. Effects of carbon monoxido inhxlatiun on ventricular fibrillation. ArrL. Emfron. Hrnfrh 31. 38-42 (1976). - 31. D<Bias. D. A., Banerjee, C. M., Birkhead. N. C., Harrar, W. V., and. Kazal, L. A. Carbon monoxide inhalation effeas following myo©rdial infarction in monkeys. Arrh. Emiron. Hrnlrh 27, 161-167 (1973). - - 32. Fortuin, N. J., Anderson, E. W.. Strauch. J. M., and Knelson. J. N- Effects of lowlevel carbon monoxide exposure on human cardiac funetion. 1. Normal subjects. "Prcliminary paper:' Environmental Protection Agency and the C. V. Richardson I-aboratory, November 24, 1972. 33. Harke,FL P.ZumProblemdes"Passiv-Rauchens."Afunch w'ocRensrhr. 112,2328-2334(1970) 34. Harmsen, H.. and Effenberger, E. Tabakrauch in VerkehrsmittFln, Wohnund Arbeitsraumen. Arrhir.Hvg. BnAreriof. 141, 383-400 (1957). 35. Hcrnbcrg, S., KarBva. R.. Koxkda, R., and Luoma K. Angina Pcctoris. ECG findings and blood - pressure of foundry vworkers in relation to carbon monoxide exposure. Srnnd. J. SS'orl Enriron. Hralrh 2. Suppl. l, 54-63 (1976).. ,J - - . 1--_- -- --f°-- - --I ~

eRr\ sr srtnutnt 8, t-3?-Ot10ft979) 'I,1 a .>r~ ,:a~k~•~ f.` ,, C, ~'' ;-z3 21 t379 This set of . . ~' ~ Ar Queti=s ~ _' ` - rk^ ..~-~ ^........ ;. . ..r ., icat a/l cxrec;i : .., :: is a ~. ~e Effect of Carbon Monoxide on Cardiovascular Disease' RrILBERT $. ARONOwe Car6mcsnJar Scrtinn. Lnnp Brnch {'rlnsnt idntfnivtrnlimr Huepirnl. Lnqc Brtrrh CclJorcio anJlhe L'nlserfir. nlCcli/nrnin. Inine. CnLfornin 97654 - Recei.ed losccb<r 27, 1978 ~~ Carbon mor.oaiLe esposure from hcas. scoki-_ or heasy atmo<phrric carhun munosidc peaution depresses mocardizl function in p_ricr.ts aith coronary heart disease.aggrasates an^iaa pecsoris. acgrasates intermiucnt claoCicaGon of the calf or thigh, increases mpocar- dial ischemia in p:icr.ts with clinical and subclieic:a coronary hean disease. and contributes lo an in.rea•ed incidtnce of nonfatal and fa;aJ mi ncardial infarclion and sudden death from eoron~T heart d:sease. Carbon monoxide coc:nFutrs to the increase in non(atal and faral my oardial icfarction and in sudden death from coronary heart disease in cigarette smokers bg tat carbexsbemog!obin interfering with m}ecardial oxygen deliserp at the time nicotine - Las caused an iraease in m) ocardial oan gen de r..and. ag¢ras'ating an episode o( m) ocardial ischemia. (b) the ret•ative inotropic effect of czrbntchemoglobin aggravating an attack of r..,~ardial ischemia. [el earbox) hemegto'~in reducing the threshold for centricutar Gbrillatioa d.tring an episode oC myotardial ischemia. a.d (d) earboxyhemoglob in incre asing plate let stickinets, theret.. inaeasing a thrombotic ter.dency. Furthermore, experimental data indi- eate that exposure to carbon monoxide in con<eotrations found in heavy tobacco smokers or in Fer.ons uith heas-) occupational exposcre to carbon monoxide plays a role in the pa:hc_en<sis oCeardiosascular disease. Smoking high-nicotine, low-nicotine. or nonnicotine cigarettes causes an in- creased carbox .hemoglobin level (5. 7, 8. 13, 28), which reduces the amount of oxcgen available to the myocardium. As cigarette smoke exposes the pulmonary r,.apillarv blood to at least 400 ppm of carbon monoxide, smokers who inhale develop high earboxyhemoglobin levels. Increased carboxyhemoglobin levels may also result from exposure to passi.e smoking (3. 27. 33. 34, 40_ 43, 47). Heat}atmospheric carbon monoxide pollution may also lead to increased car- box}hemoglobin levels. A major source of carbon monoxide in the urban atmo- sphere is automobile exhaust, in which carbon monoxide emission is greatest during idling and deceleration. Peak atmospheric carbon monoxide exposures have been reponed to reach as high as 1.7 ppm in Los Angeles freeway traffic and 141 ppm in New York expresstt'ay, traffic (41), 135 ppm at traffic intersections in Dayton. Ohio (42). and 217 ppm for 1 hr in a loll booth at the Queens midtown tunnel in New York (20). R'e obsened that patients v,rith angina pectoris uho were driven for 90 min in peak early morning freeway traffic in Los Angeles county during ninter months increased their mean arterial carboxyhemoglobin level from 1.12 to 5.08q (1-0). T_- ----- - -- I 'Prcsented at a µbrkshop on Carbon ]fonotidc and Cardiovascular Disease, sponsored bp the . Amer"ca, Health Foundation and the Federal Hes)th Office. Federal Rcpvblic of Gcrmany, Berlin, tXtober 10-12. 1978. ^ Reauests for reprints should be addressed to: Nil;+crt S. Aronow, St-D.. Chief, Cardiovascular Section_Veterans Adm.inistration Hospital, Long Bcach. Calif. 90822 - - 0091-7415.'79.0063-OOOOSO'_sya'o CoC>~+fA r 19ri hY A..Aemk Rnt 1.[. AII rilvr d rtpmdur~lon in.nr 4+m rtmn.J W,,R q.c d . (i" Y '