TABLE A17 .-Incidence of new coronary heart disease by smoking category and behavior type for men 59-49 years of age (Numb-m in pnrentheses are number oC CHD cases in each aubnroup) Smoking group NW.3 smoked Currot and former pipe and ciynr only I-16 Cigarcttez 16-25 2C rnd over TOtAl 1.6(l) 15 8(15) 14.9(16) 9.3(461 1.3(J) 3.1 (3) 4,9 (0 3.3(18) 4.3(5) 9.3(18) 10.4(20) 6.2(63) --- -- Analysis of variance Iable Source Sum of sauark-0 d.C. `Eater nre sue-adjusted nnnual incidence per 1,000 men. *Mean SQUH~TI for "betwccm smoking groups" and "between behavior Iypea" are each computed eliminating the general mean and the other main effect but ignoring interaction. thus yicldine m eatimak al each main o f- feet unconfounded by other significant main ef?~ta. SOUKCS: Jcnkino. C. D. et al. (90). TABLE AlS.-Incidence of new coronary heart disease by smoking category and behavior type for men 50-59 years of age (Numbera in psrcntheaes are number of CHD cylea in cacb nubgroup) Former Current and Cigarettes BehaVlOr Never cigarette fOiTlCl' DiDC tYDC amokcd amoken and cigar only 1-16 16-25 26 and over TOlal A . ** . . . .~. .., . . . . . .,.. `12.4(K) 18.6(B) 21.8 (8) 16,4(6) 21.5 (9) 30.0(14) 20.4 (43; B .*....... . . . . . . . . . . ...,., 10.0(4) 6.1(I) 6.4 (3) 4.7(l) 21.1 (I) 19.1 (51 12.0(21) Total . ., . . . . , ., 11.1(g) 14.2(9) 14.9(!1) 11.6(6) 21.3116) Z&0(19) 16.8(70) - Analysis of variance table Wltbin eclb . . . . . ., ,#I......,.. ,....,. ,.. . . . . . . . . . . ..,. 63.627 911 0.070 Regreuion on age . . . . . . . . ..*..*.*..* ,..... ..,.,... . . . . . . . . . 0.117 1 0.171 2.64 0.111 Dctwctn smoking groupa: . . . ,.. . . . . . . . . . ., . . . .., , ~, . . . , 0.522 6 0.104 1.496 0.188 Between behavior typea 2 ..,...~.....,., . . . . . . . ,.,... .,..,,...... 0.296 1 0.296 4.24 0.040 hkr.ction . . . . . . . . . . . . . . . . . . . . . . . . . ..I . . . . . . I ,....,,.,..,.,, 0.129 6. 0.026 0.37 0.870 IFLaLpl are age-hdjuattd annual incidence per 1.000 men. cflect buL ignoring interaction, lhur yielding an catimate of each mnln rf- `Yew ~puarea for "between smoking groups" and "between behavior feet uncanloundL4 by other significant rn~~in ellectr. trpn" are each computed eliminating the general meon and the other msin SOURCE: Jenkins. C. D. et nl. (901. TAULE .420.-Expcrinrents concwning the cffccts of swoking ant1 nicotine on animal cardiovascttlar function West cl nl.. 33 norm01 1958, ndult rn0ngrcl U.S.A. rlous. (:`OS) COIOn&I-Y intro- ortcrinl nicotine: 1. 0.2-2.2 uz./ka. II. 0.04-i )ig./ks. Dttli"iW incrensc (ey3lolic). (Tctrnuthylammonium chloride b!ockcd CUF In- crcnsc.) The authors found no evidence of coronary YLBD. mnalriction In tbeuc healthy rnimala. TABLE ABO.--Ezperiments concerning the efects of smoking and nicotine on animal cardiovascular function (cont.) Author, YCIT. Number and Smoking Heart Blcmd Cardiac CCTO"tIW EO""tcJ, type of DKXCd"~C rate DXW"R OUtPUt blood Commenld rdcrence DoDulnlio" flow Forte 27 obscrvn- intravenous Definite No cbanw. No signlflcant change I" either left ventricular et nl., tiono on 8 nicotine up initial work or myocardlal oxygen extraction. 1060, dogs. I3 21.6 "lg. increase U.S.A. given 83 6-16 then 165). !.w./kg./ dccroase. minute. - Kicn and 21 adult doas Ciasrette Definite Definite Increase ERccts of cigarette smoke were duplicated by In- Shrrrod, 1960. U.S.A. IlIP). smoke under positive pressure via tracheostomy. Nicotine 20 pg./kg. intrs- ve"ou8Jy. Epinrphrine 6 w./kg. intra- ve"ausly. increaae. i"crea8e. followi"g trnvenous nicotine and eDi"eDbrl"C. incrcnse During cigarette smoke Inhalation. it WBI noted in blood that without blood pressure or output chanp+a, prC*s"rC coronary blood Row did not Incrrnse and tbnt and cardiac while adverse EKG changea were noted they COP 0"tD"t. related Marc claaeiv with decreued cardinc OXY- gel, utilization than with actual cardiac wGrk. TraVCll 14 norm"1 intravenous DCli"itC Nicotinc.induced coronary blood flow and heart CL RI., rabbits nnd nicotine increase rate increase in the atheroeclulotic nnlmals re- IICO. 1C rabbits 0.01-0.1 mg. in normals. auirrd 10 times and 2 timn. ~IIB~C~LIVCI~. thr U.S.A. with severe emwnta rwuircd in the norms1 animula. flS9). cholratwxzl- induced ather- sclerosis. TADLD A20.--6zpcrimcnts concerning the cflccts of smoki,tg nud nicofinc on animal cardiovnecular function (cont.) Numbrr and type oc raopulntion Smoking proccdurc Comments Dellet I. 10 narmol dose l"trevcnaus 1.126 percent The nuthors noted that: et al.. 11. 9 dous at nicotine. increase 1, The rCBPO"Se of coron.ry blood flow to "ica- 1962, varying in- 20 ug./kg./ II. 82.6 percent line resembled that of anoxtmia I" t(c Drrs- U.S.A. tervnls Iol- minute for l"CV?WX cnce of eoronsry i"3ufllciency. (22). lowing core- 15-20 mi"ute3. 111, 83.3 DE'K'Znt 2. The grater the induced coronary imwlrment nary artery increase the smaller the increment in coronary blood ligation. Row. III. 7 dogs with varying grndcn of srtificinlly- induced corcw nary artery narrowing. Leaders 16 adult Left anterior Nicotine and norcyinrphrine both ir\crcnacd corc- and mongrel descending nary vascular rcsiotance and myucnrdinl contrsc- Long. dogs. i"tracoro"nrY tile force (the formor mcanurcd by e. conalant- 196?, injection of volume variable~prcssurc rystem). The action of U.S.A. niwtinc or nicotine was blocked by prrtrcatment wilh hcx- (125). norepincphrine. amethonium, pmtolinium. rcsrrpinc. or I(U&~C tbidinc. Lk?-Wll 13 rdult Intravenous Definite Definite Systemic vnscular rrsiatnnce ond pulmonnrr nrten et al.. mongrel nicotine, incrcasc. incraw. and left atria1 ~rr~surca show4 biphnaic rr 1965. duga. 0.02 mg.lke.1 ?~ponoen of increase followed by drcrcsac. U.S.A. minute for (JZJ). IO-12 minutes. P TABLD A20.-&p&??~nt8 concerning t/te eflecls of smoki~tg wd nicotine ox anirrla~ cafdiovQscU~ar flt?Iction (cont.) 0 m Author. yr.r. Number and Smukina cuuntry, type of ptOC`%lUtC C"mlne"tl refrrencc population FOIL? 7 dog-a of 30 inveatleated et al.. (Rcmoinder expcrirnced 1966, cntbcterizntion fnilurra). U.S.A. (64). h'adcau and J&mm. 1961. U.S.A. (144). 26 dogs 1. Cigarette smoke inhnlntian to isolated left lower lobe and then blood perfused coronary srtcries. 11. Cunrctte smoke to rest of lunu and then blood pnascd to gcnrral cireullltion. III. Nicotine perfuocd directly into left coronary nrtery. Nicotine 0.01-10.0 pg. into sinus node artery. I. No change in cor~n&ry vw~lnr resistance. II. S/G show~~i increase in c~r~ne.ry va~ulor tesiatance due, actordine to the author. to gcncral aympathetlc nervou~l ayatem stimulation. IIt. 415 showed ~nrrcn~e in corunnry vascular rnisldnce. The authors eon- cldc that the cnrdiac eflcct~ of tobacco arise nlmotlt entlrcly from thr extracnl.rlinc actiona of smoking instend of the direct reaponae of the 111.nrt. HeurL rate showed initial slowing (due probably to vnaal stimulation) fol- lowed by r.ccelcrntiun (due probably to vagnl pnrnlyais and cntecholamine reluse~. No systrrnic blood pressure changes nuted~ 22 monurel dopa I. (IO Intrnvcnour nicotine cnrct. I. Nlcotinr pruduccd B dclinitc incrcnre In the force and vt~l~~city of left 50 irr./kg.lminutc fur 3-4 \L.~IIIC~II;II. c\jnt~actiun. minutes II. Prrtrcntmcnt with proprsnolol produced (r&live to rP3u1IP Of Group 1): II. (8) Prcpranolol pretreat- (a) A further increase in left vrntriculsr ayatolic prrsnlrr. ment, then 50 hK./kg./minute (b) A dccrensc in velocity of shortening. nicotine fur 3-d minutes (c) A aignificxnt incrtnae in lrft vrntrirular cnd.diwtolic prc*rurc. The authors CO~CIUIIO thnl proprnnolol probably lmpnira the no,rcpinrpbrirl~ like cfIccts of nicotine on the myocardium while cnhrnclng ita wriphrral ve.*oprcssor enecta. TASLD AZO.-Ezpetiments concerning Llle eflccts of smoking a,td nicotine on atiirttnl cardiovascdar function (cont.) Author, YC`T. Number end Smoklna cuuntry. type of ptOCCdUre Comments l-dcrcncc populntlon D1Iaza Bcaule dona with lesions 1. Normsb (3-6 per exveriment): I. (a) No evidence of arrhythmias; (b) A ainele or ~1 few ectopic brats Cl al.. Induced in myocardium by (a) 4 PK./kg. intravenous in Z/3 normal dogs. 1969. either: (1) IaavroierenOl nicotine. lb1 40 ,%/kg. II. Extrnsystoles noted in 2/3 animals during the firat dny nftcr cesantlon U.S.A. vrctrcatmcnt. or (2) intravenous nicotine. of the arrhythmia induced by the lesion alone. but not thcrenfter, (Id). ligation of the anterior II. Experimentnl (3), 4 )iK./kg. These and nicotine-induced arrhythmias wcrc of II abort clurution. descending ecmnar~ artery. intruvenoua nicotine Greensvan Cardiac muaeleisalated from Nicotine Z-100 ~~p./cc. in Nicotine perfusion produced: Cl 81.. the right vcntriele of 10 Tyrode'n solution verfuunte. (I) An increase In myocnrdlnl contractile force avusrently indrvcndrnt 1969. adult dogs. of adrcnergic innervation. U.S.A. (2) An increased automuticity of the Purkinje Aber ~ystcm ~lvpe.rently (74). due to release 01 catecholamin& from chromnmn tissue ~turn. (3) A dccresse in conduction velocity. The authors conclude that the latter two eirectn vrobnbly predispose to nr. rhythmia formation. Swhlr and RaPSPOrt. 1969. U.S.A. (166). 88 mongrel cats Nicotine 6-12 pg./kg. injcctrd lntrnarterially to mesenterie circulatio". I. hlesenteric injection of nicotine WLI followed with 1-2 secunda by: (a) Increased left ventricular ayatalic prcasure (LVSP). (b) Increased systemic resistance. (c) Enhanced myocvrdial performance. II. Left ventricular injection of nicotine WBB followed by: (a) Increased LVSP. (b) L1radycardia. (c) Enhanced myocardisl pcr!ormnnce grcnter than that wxn in mcrenterir-injected group. 111. Prctrcntmcnt with phcnoxybcnznmine diminished the incrcnlc in LVSP while pr~~pl`nnoli~l prctrrutmcnt diminiJhcd the tnhnncrmcnt of my- ocardial perfurmnncc while LVSP still showed D. niKnif~cnnt IIIC~PU~~. 1V. MNrntvrie sympsthctic ncrvc section led to a diminished rc*i,on~u. The nuthurs ctmeludc thnt the cnrdiovnsculnr IC'IPO~BCB to nlcntinc m&y be ncurogenic in nature with receptors distributed in ccrtnin abdominal srterica. TABLD A20.-Ezpsriments concerning the etfects of smoking and nicotine on animal cardiovascular function (cont.) Smoking procedure Comments Lrb ct al., 12 mon~rcl dov and Nicotine 100 u#.lkt. for Effecelive Corunary Flow (ECF) 11 that part of the totnl COTU"*T) IloW 1910. CBF measured with UIC of 2 mln!lLC Intravenously. (TCF) which il "ellcctivelr ' involved In nutria1 exchonec. U.S.A. Rb" and digital counter. Nicotine injection WM followed by: (J,6). (11 96.6 gcrccnt increase in TCF. (2) 61.1 percent lncrense in ECF. (3) 73.1 percent increase In mwcardial oxysen ccnaumption and annl~aia revealed that capillav flow increased almost ptovortimatcly to my- wardial oxygen consumption whereas the increase in TCF W~LI f&r In CXCCJ8. (4) Definite increases In cardiac output, hesrt rate. left ventricular work, and oorlic pressure. Ross rnd BIna. 1970, U.S.A. (160). 10 does undergoIng inatrntulcwJs COlO"r.ry arrerinl flow meuurement. Nicotine lC-100 BB. lntra- coronary injection. Nicotine injection was followed by: (11 Increurcd tontractilc force. (2) Decreawl myocardial cuntrnction time. (3) Dccrensed time RCCCJI~~Y to reach peak tension. (4, Dccreucd total stroke ustolic CBF. (5) Incrcwcd total stroke dirutolic CBF. (6 I Increased total stroke CBF. (7) Changes similar to intraarterial rDin&rine. (8) Changes blocked by pentolinium pretreatment. (9) No change in heart rate or blood ~r~rure. The authors conclude that eatecholamines released from the ventricular mywardium mediated thrae I~~FIOIIIFI to nicotine. TABLE A21.- Experiments concerning the efects of smoking. and nicotixc on the cardiovascular system of humana Author, Year. Nypy;;nd Smoking Heart Blood Electrocardiogram Stroke Cnrdiac %%" eounlry, procedun rate PttBY"te ballistocard~ugrsm volume OutDUt Commenta referrnee DODUhth, Row Rusaek I. 28 healthy 1 standard and 1 I. Incresae. Incrcaee. EKG: Denicotinircd cign- et al., male amokera denicotlnired I. 16/29 showed rettes evoked changes 1955. 21-60 yearn cigsrettc. significnnt of R lesser dcgrcc U.S.A. of age (aver- chnnaex. in normnle and CliD (ISi). ape 42). II. No sis- subjoeU, but in the II. 37 male patients II. Increeae. 1ncre.s.w. nineant latter group thcr'e with overt chansce. wc,s no aiguiflcnnt clinical CHD BCC : dilTcrcnce between 42-10 yeara of I. these change+.. .-ge (bvenge II. 18/37 showed 64) ( 6 were aiKnificnnt nonsmokers. chnnue. DIrgeron 14 of 30 healthy 1 cigarette Insinnilicsnt Increase. Dcnnite Coronary vrl8cIIIflr et al.. adult mnle vol- inhaled at increase. increase. re3i3tBncc fill 1967. untccr smokera intervals of si!pificelrtly. U.S.A. and nonrmokers 20 aeconda. Myacerdinl O3 fJ71. who underwent usage unllcrwc"l no BUCCeSSfUl aienlfirsnt chnnac. catheterization Pyruvnte extrnction 18-63 years fell slightly. of age. Authora conaldrr lack of incrcnw in heart rate u due to bascllne nl>prrhcnsive tschyrardia. F 0 TABLE A21.- Expriments concerning the eflects of smoking and nicotine on the cardiovascular s@?T?t of humans (cont.) Author, Y-r. cou"trY. NUt~pbc"o;"d Smoking Heart Dlood Elcctrocardiopram Stroke Cardiac prowlure rate pre49urc b@lliatocardloprrm volume output cYl"Y reference potNlstio" nOow Comment4 Repm et al.. 1860, U.S.A. (IS4). 7 mnlca with 2 standard DCA"lte Dcnnite Incrcaac. No aipnl- Myocsrdlal 0, conaump- bintory of cirarettn In Increase. increcae. licnnt tlon row sliuhtl,`in EKC.DWWl 26 minutes change. 3outof7. myocsrdial inhaled at The author considcra Inf~rctlo" minute that the EKG chsnrca undergoing Intervals. notrd on amokinw are cardiac ~a- probably due ICYS to theteriration. decreased coronor~, blood Row than to incrcawd worklond (oxygen "red) where oxygen supply dwcs not incrcwe. Noted no cvidrnce of myocardirl irchcmla during anwkinp. Thomas and 113 clinlcallu One rtandard Definite Definite Definite Definite Pulse yrcsaurc ahowed MUWhY, healthy young cigarette increase. increase. incrcaae. increase. a decrease. 1960, males. smoked at Smokers rrr~mnded U.S.A. own pace. slightly but sisnl- (166). Acantly more actively lhan "on- smokrra. BCC change were incrcnninfly common with incrraaing ale. wright, and serum ehulcaterol. TADLE AZl.--Experin~ents concerning the effects of smoking and nicotine on the cardiovascular system of humans (cont.) Author. YCBT, country. retcrencc Number nnd type of Dopulnlion Smoking Heart procedure rate Blood Electrocardiosram Stroke Cardiac lltC33"t.? bnllirtocardioyrnm v0lume output cti:o":w timmcntd now Von Ah", The author Cigarette Increase. EKG: Slight ST EKG changes more 1960. reviews * smoking. HCg"lC"t prominent in younr, SWCd?" arries of denreeaion clinicnlly healthy (POZ). expcrimenta nnd T-wnve aubjccla than /II performed nattc"i"c. older. hltbitunl IJCLWCC" amokcrs. Intro- 1944-1954. venou nicutinc end smuki"K ahuwrenses not de. (b) Non-inhalation lb) No No change. (IJ) No cbrnge. No change. dilutwn tvchniwc. Ennlnnd fined. 19-66 yesra smoking. change. (89). ol nw. all mod- (c) 2 standard (c) Definite Widened (c) DefiniLe DeAnire ernte-heavy cigarettes in increase. vulse, increaaae. increase. cisaretti smokers. 10 minutes. pressure. (d) NicotineO.6 (d) Definite Definite (d) Dcfinlt-e Dellnit- mg. intra- increase. increase. i"CV3.W. change. Ye"ousIy. TAOLE A21.--6ccpcri~~~ents concerning the efects of smoking and nicotine on the cardiovascular system of humans (cont.) Author. Year. country. rclercnce Prntrcost Nut$r;nd Smoking Heart Blood Eleclrocardiosrnm Stroke Cardiac DhXFSi!J~~ rate PRSl"W ballistocnrdloeram volume OUtDUt C"d;o,n;lY Comment.8 pODUt`,tiO" How I. 14 volunteers Single ciKarette Definite Definite I. 10 21 DerCe,,t ;b"J with clinical Shelling- CIID, 13/14 l~,ril, smokers, 11164. averape *pe U S.A. 39.6. (149). II. 6 patients with angina pCCtAri.3. &it1 smokers, ave. rage age 43.4. 111. 14 Datk"tS with history ol definite myo. cnrdinl infsrc- tlon, all smok. em *"eraBe age 64.1. smoked at own increase increase geW"t incrcaw. rate in 6-l in all in all increase, minutes. ITOUDI. !JrO"DS, II. Inter- Interme- medipte dlnte change. change. III. a DCP 1 D~rG?r,t cent incresac. decreaae. Frulikl 6 male and 3 2 rtandsrd Definite No signih- No signifi- The author contrnnta P! HI., female Datients cigarettes in incrense cant changes cant this rnponse with lcKJ5, u*ith healed 10 minute3 at al rest at rest or chnngL-3 that LI~C" amo,,p U.S.A. myocardisl inlarc- rest and under and at during at rest or hcnlthy you"&! (ti?). tion 48-69 years graded exercise. exercise. exercise. during individuals. 01 age Z/8 non- exercise. smokers. TABLE A21.- Experiments concerning the e&Tech of smoking atld nicotine on the cardiovascular system of hman8 (cont.) AUlbW, year. Number and Smoking lienrt Blood Electrocardiocrnm Stroke Csrdinc CO"IltlY, 1ype of procedure rate pWSs"rC bnllistocnrdiogram volume cK,"d"v output ^ C4mmentc reference populntion 1lLlW Allison 30 healthy male 2 standard ciga- Definite Increase. Increase fol- Definite drercnac in and Roth, aubjectr. retta smoked Increase. lowed by pulmonary blwd 1969. 1949 years of In 12-16 minute decrease wulume 83 indicated U.S.A. (3): nge. period. within 20 minutes. by impwloncc mc\boda of thorocic PUIX volume. Aronow and 10 male patienta 1 low nicotine Definite Definite All patients dcvclopcd SWltOOD. with classical cigarette in increase. increase. angina moner if 1969. fingina pectoris. 6 minutes. they amoked bclore U.S.A. 32-59 yeara of exercising. (7). aye. Aronow and 10 male patients 1 non-nleotlne No chanw. No chance. No dlfiercncr natcd Swanson. with claraical cigarette in In time or onset 1969. anpina pectaria. 6 minutea. of excrcistcinduced U.S.A. 32-69 yeara of *ngir,0 bctwe,n (6). ape. anwkina and non- rmoklng prucrdurca. Mershsll et III., 1969. U.S.A. (129). 42 normotenslvc 314 of one standard Insignificant lnsignificnnt Blood prr-srurc rrB"onle healthy male cigarette. increase. increanc. to cold prwsor teat prisoner8 noled to Lw grcntrr in 13-50 yean of heavy amokcra. a!ze. Prc5~n~opnl rcnctiona 13 nonsmokera. to 40 dcgrre bced-up 16 moderate till moi-c Irruucn1 smokers. in smokers. 13 heavy smokers. TABLE A22.-.?hpeti?ncnts concerning the cgcct of nicotine or smoking on cutcchoht~inc lcuch WMlfril 22 mongrel doga Clgnrette smoking via Ile~uler ciunrette smoke evoked a atatlatically aignlflcent incrcndc In nilrrnnl vein. md Watta, trneheal cnnnula: vena cave. and femoral artery levels of eDinepbrine. CornsIlk cigarcttc amukr woked 1063, 1 cigarette/8 minutea no chnnse. U.S.A. for 36 minutes. (ZIO). Wes1fall 21 male volunteers 3 ciunrettcs smoked in Smoking nt rnte noted for 2',4 hours evoked B signlficnnt Incrcn8c In urinnry cplnc- and Wntta. ap~roximnlely 26 SO minulca. phrinc. but not norcpincphrlne Irvels. 1ec4, yenre of n*e; U.S.A. 11 nonsmokers, (II!). 10 amokem. wmtfsll et al., MOnkTVZl dOK8 Standard cigarette amokc Smoke inhalntian cvoknl R r/Be In cardloc output. atrokc volume. blood nrrw\!rc, nnd 1966, cxwsure vin cndotrnchcnl plarmn catccholnminc levels. Prctrcntmcnt with prvprnnolol diminial~cd the cnrdinc U.S.A. tube. Smoke lnhnlntion output and ntrokc volume reeponsn but increased the blood prcsaure rrsponsc-the (209,. every third inspiration for latter cflect llue to the release of alpha-receptor activity by betn.bloekade. 3 minutes. E TABLE A23.-Experiments concerning the atherogenic eflect of nicotine administrution m Author. ye.,, couotn. Number and tyDe Procedure Results rercrciee cl mlmal~ Adler et al.. Rabblb Nlcotlne 1.6 mg. IntravenouaLv in 6 oercent The authors noted an artcrionecrosir of the aorta. anectins mainly the 1906, U.S.A. (2). mlutlo" 6 O! 7 dnya per week for more than 4 munthr. inner muscular 18ycrs. hlocrorcopicslly. early changa consisted Of ,mall nrens of calcnrcuus ridging nnd aneur~smsl dilatation without notable fatty degeneration or intimnl discontinuity. hlicroucopicnlly. rarly changes appeared in the muscle cells of the media. and "chalky" depositi wcrc noted between the elastic Rbcn. HUWW. 1943. U.S.A. (SS). I. 6 moni~el donr. Nicotine subcutaneously. lncreaaing dosage up I. O/G ~njmn1s died of infection nnd showed marked cdcmo. n!ld f0Cnl UP to 2.6 cc. 013 percent solution fur 1 hynlinizntion of the mcdin of the e.ojin and lnrgc clustic nrtvriL*. month. 216 nn,mnls wcrc sncrificed and show4 thickcninn and hynlinizo- tion of the WSH~ of the mronory artcries nnd cdcmn uf the mcllin BP well as ondothclial prulifelntion of other aIzc.ricB, II. 60 rati. Increaalne doses UP to 1 cc. of 1 percent II. Much It-15 *ortic involvement than that found in thr doga: inlrc- solution for 1 month. quent r,rteriolnr changes consisting of Rbrosia and thickcninu of the media. MS6lOVa, Rabbi& I. (10) Nicotine aubeutaneously 1 percent I. Aorlic wall---acute swelling of claxtic fibem with loco1 frognlenta- 1966, solution 0.2 cc. daily for 116 days. lion and partial disintegration-no intimal lot deposits SCC~. USSR Coronary vessels-thickening 01 thr vessel wall-no fat deposits. (130). II. (14) Nicotine ~1~s 0.2 grams cholesterol II. Aorta-"massive" deposits of "cholesterol" in the intlma nnd YLLSIL per day. vniorum with "lcmsening" of the aotiic wall. Cotonnry VMSVII- the larger vcsscl~ showed mticrntc fnt depositlou nnd the ~mllllcr ve~scls showed swelling of the cliuLicn. III. (IO) Cholesterol only. III. Aorta--i.olatd lipid deyusition in the arch snd a.vccndinv. portiune only. Coronary vessels-no fat dcpusitiun. -- Czochra- Rnbbita I. (10) 1.0 g. cholesterol/day for 100 ln~irx uf nul-tic lnion density (cholesterol inr~ltrstion): Lysanowicr dnye. I. 2.5. et al., Il. (10) Cholesterol plus 0.0015 g. nicotine/ II. 3.4. 1969. day intrnvenourly. U.S.A. 111. (4) Nicotine only. III. Nu nurtic lcsiono noted. (46). Author, year, CO""lrY. Number and type I'rllcrilurc RcvultJ rcfcrrncc of nnimnl -- Wcnzrl Pl al.. Rabbits I. (12) C,~ntwl untlcntod. Gcncrni Rn~l!n~`s: Mnrkul .sorlic nntholonic involvrmrnt w'ns noted in nil 1050. II. fl U.S.A. (frn7). III. IV. V. 12) Cs~ntrul ,licl plu3 I percent cholcstcrl,l nnd 5 ,icrccnt cuttanseed oil nddcd 12) Cnnlrol diet plus oral nicotine 2.2H mp./kC./dny. 12) Rraimen 11 plus oral nicotine 2.2R ma./ha./day. 12) Regimen 11 plus oral n&line I.42 mu./ks /~lny. Thicncs 1960, U.S.A. VI. (12) IleKimcn II plus oral nicotine 0.57 mg /ka./dey. Newborn rata nnd Nicotine subcutnncousiv un to 5 mg./kg. No nnrrini pathology noted. hledinl dwrnwntion wcn more Irn~unltiv mice. twice daily by the end of 1 month. Animals autonsied at 1 year. hlale rabbits I. (10) Nicotine subculnncounlv 0.16 Sicnilicont diflcrcncn in aorlic subrndothrilnl fibrail brtwwn control Sncrificcd at GO days. i= TABLE AZ?,.--Eccperimenls concerning the QtherOgeniC cfCct of nicotine administration (Cont.) OJ Author. year, countw, Number and type Procedure Reaulb rcfewnce of animrl Hua cl al., Male rabbits Nicolinc Diet Vilomin D 1966, I. (8) Conlrol CO"ltOl Control I. Infrwucnt medial calcific disease without llpid localization. U.S.A. 11. 17) Control Cholrsterol Cuntrol II. No medial calcific disease but Ireguent intimal atherurna formation. (80). III. (14) Nicotine CU"ttOl CO"ttUl III. Rare cnlcilic medinl degeneration; no intimal athcro"bntous dlscost. IV. (15) Nicotine Cholcslerol Control IV, The Iaw=t number of ntheromataus lesions. V. (91 Control Cholesterol Vitamin D V. No medial calcific diseaae. VI. (14) Nicotine Cholesterol Vitamin D VI. Conslrtent medial calcific disease. (Sacrificed at various times) Control-no treatment. Nicotine-subcutaneous injectiona in oil- increasing amounts 2 times per week. Vitamin D--subcutanwus injections up Lo 6-8 x 1w III. Cholesterol--260-500 mg. cholesterol sdded per 100 g. diet. Choi. Albino rabbita I. Nicotine l-5 mg./kg.lday intraperi. I. Increasing nicotine dosages were aswciatcd with dccrcnscd athcroma 1961. t0"MllY. formation (findings not statistically significant). Korea Cholesterol 1 g.1dr.y (in varying II. Nlcotinc ulone prcduccd no nthcruma formation bul WBJ usur,ciatI prOCCd"rC fatty ncidr cholrstclol triglyccridcs ottlcr Comments rerrrcnce wpulotiou hlurchiron 0 melt and 4 2 cigarettes I. Dclinitc Nu rhngc. Nu chan~c. Uoth regular nnd sham amokers and fcmnle mod- in 15 minutes. incwose. shawcd significant incrcn.4cs FYIIZ, mate smokers I. Lit-cign- II. No change. No ClLmKe. No chnnw, in conccntrntion of IcNm I'JGC. with various rc1tes. oieic acid nnd SLgnlfirnnt Scotland discnses 31- 11. Unlit-cign- dccrcnars in conuvlltrl~tion of (139). 67 ycnrs of rettcs. ~crum Pnllnitic acid. age. Kerrhbaum 6 normal et .I., heavy 106i, cipnrette U.S.A. amukcrs (105). 20-15 years of nE!e. Vnrlous types of cigarettes of known nicotine content. llrsulai. cigarcttrr. filtrr ciKnrrttes. chmcllnl-filtP, ciunlcttcs. pipe tobnccn PI\B cignreltes nil showed similnr increiw in FFA. Lcltuce Ical cimrettes hnd negligible eRect. ANIMAL AND IN VITRO STUIlIES Kerrhbaum 20 adult I. 0 reccivcd I?4 nicotine et al., 1 II c 5 , U.S.A. (107).