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11. Cnrt>tiorrtarrtfnr Slrttlir. "1NFI UFNCE OF ANTIARRIIYTHMIC AGFNIS ON MY(K'ANI)Inl. ('ON I RACT 11.1 TY." Ily F. T AnRelakos, Mh, Phl), Ikparlnxnt nf Physi- olnRy, Ho-tton I/niversity School of Medicine, Massachusetts. "MecMnisms and lherapy of ('ardiac Arrhylhmias," 141h Flahnemann SymMosium, Phila- detphia, April 26 29, 1965. Published by (3rune & Stratton, 1966 , lhe ultimate therapeutic aim In the suppression of arrhythmias with an antiarrhythmic agent is to improve cardiac dynamics. I( this aim is to he rerved, It is essential to know any direct effects that anliarrhythmic agents may have on myocardial contractkrn. Tests with the classical antiarrhythmks r,uinidinc and prrrcaineamitk, and with the newer ant.rnlinc, .II showed a distinct drlnession of myocardial tcnsion I his depression of contractility seems to be a direct eRrct of the drugs on the myocardium. Various mechanisms are proposed which could account for Ihis dc- prcssant ertrcl Ilnwever, the lundamcntal mechanisms which are actually respcrosibk fnr the eflect have txN been identified Practically all antiar- rhylhmres (when given in suRicicnl dnus and studied with appropriate Icchnics). have heen shown tn have a myr.cardial depr"sanl efiect Aa present it is nnt ckar whether this priri.rrly is inherent in anliarrhythmic activity or is a"sitk eflect" relatrd in simrlnilies in thc chemical nxrictics resfxmsthie for cach action In cithcr ca~c, stncc high hharmacnlnRic spcci- ficity is rnost desirahlc frnm a Ihrral.curic rwttnt td vrcw, tlte scarch must cnntinue for the development of mrrrc active, mnre sf.ccihc and kss rk- pressanl antianhylhmic agents OtArr Rr.nter.r National Science Fnundation and the 11 S Public Ikatth Service. "A[)RFNFRGIC FFFFCTS OF NICOTINF. ON CORONARY IIL.(x)h F•I.OW ANI) B1.(X)1) LIPII)S ` By Samucl fkllct, MI), 1)ivisinn of Cardiolt.Ry, Philadelphia (ieneral Ilrnpital, Pennsylvania. ('hapter IX (pp 74-8, ) in "Prevention of Ischcmic Ikart Uiscase." W. Raab, editor, ('harlcs C. Thomas, Springfield. Illinais, 1966. 7 he effects of nicotine and Inhaccn srrnrkc on certain rhysinlnr.ic raranxtcrs, n.nxly coronary hhxxl flow and hlrwxl lipids, tc Arscutiscd in lhis haper Fttlxriments with dogs showed that the nicotinc indtK'ed .uRmcnlation of coronary hirnrd flow was considerably Icss markrd in aninuls with artih- cially produced cnronary insufficicncy Ihan in cnrresfxrndins cnnutrls Fkctr<a-ardinRraphic changes were nnted, and the reslxrnsc of nther param eNers, such as cardiac oulfrut, nxyRcn cnnsumldiun and crrrnnnry a v th/lcr- cncc was >tlin alterrd 7hese findings wnuld npl+car tn have a hcarinR nn the ~linii al I r„hlrm rrl.lr.r t.. Ilrr rrTrr t~ 1 nu ntinc an0 of nrrr linr iitx'ratcd 1inn. an ror.•nary alirrv rh%r.ltr A rapid and consistent rise in serum free-fatly acids was prrxluced by nicotine in dogs and snx,kinA in humans. Patients with'myraardial infarclurn developed an elevation morc than twice that of normal subjects and non- coronary patients l)ther Arantor.r National Lnslitutes of Heallh and the Foundation for ('ar dioiascular Research. "[)IFFF.REN('FS IN FFFFCTS OF CIOAR AND CICiARF ITF. SM( )K- 1N(i ON FRF?E FAl-I Y ACID MOBILIZAI ION ANI) ('A 11 ('!1OI.A. MINE F:X('RF.7ION." By Alfred Kcrihhaum, MI), Samuel Ifellct, MU, lose liminer. MI), ark) I,erroard 1. Feinber`, Phl), 1)ivision of ('ardioluRy, Philadelphia (iencrd Ilcnpilal, Pennsylvania. luurnof of the Arnnrrun AlrJicol AtsrNiannn 193/1):1(/9S-I(We, March 28. 1966 ((irantrc: Belkl) lo eaperiments conducted among 43 normal mak subjccts who werc habitual moderate or heavy smokers of either cigars or ciRaretlcs, the com- parative effect of cigar anG cigarette smoking on free fatty acid (I;I;A) mnbilitalion and catecholar.ane eacrelion was observcd nd the influence of inhaling and diflerenccs in absorption of smoke contents was dctcrntined. Results showed that there was agrealer increase in FFA concentration in the serum with cigarette than with cigar smoking. Inhaling during sn>,rkinR caused a greater FFA response than nc( inhalinR, with InNh ciRars and ciRar- cltes. With tobacco containing glucose randomly labeled with radivactive carbon ("C), there was a greater absorption of '•(' with cigarette snNrkinR. Eacrelion of catccholamines followed the same pattern. The differences observed with the two forms of smoking prul.ably result from Ihe tendency to inhak with cigarette and not with cigar srnokinR and from the effcct of this on nicotine absorption. Otflrr Rrantor.r American Medical Association Fducalion and Rcscarch Foundation and the National Institutes of I leallh. "MODIFICATION OF NICOTINE-INDUCED FIYPFRI.IPII)FMfA l1Y ANTIAI)RFiNFR(iIC A(iFNTS." By Alfred Kcrshhaum, MD, losr limenez, MI), Samuel Belkt, MI), and 1). Tanullini, I)ivisiun af ('ardial)Ry. Philadelphia Grrn•ral llospilal, Pennsylvania lrrurnal of ,lrhrrnt, fnour Rirrmc)r 6i24-5 10, Nnv.-1)cc. 1966. ((iranlce: Ilkllcl ) In .n atlcmpl to elucidate the rolc uf sympathetic and carrt hulanune activity in the alteration of plasma fire fallr acid levcls. Ihe rllcrt uf a (I-adrenerRic rccelNUr hkrckin6 agent (ncthal~ak), an . rerclrtra hhxkinR agent (phenoxyhcnraminc), and a central suplnessur of adrencrRic activity (chlorrromarinc) nn the lipid response to nicutine was sludred in ancsthc lired dogs. Nicotine alnrx, in control c.heriments in 211 doRs, gave a rna.im:J rrvr in FFA ennccnlrntinn of 14 - 4'!~, Whrn the druRs wrtr given wtthoul m(t) 19 M

line to determine their intrinsic cffect on serum I'I A concrntritirrn., nr,hi lide and phennxyhenraminc pnxtuccd a vRnilicanl rise in I I A Icvcl. whtrcas chlnrPrnmatinc had no tiFnificant elfccl After ncthalide, there was a signlli cant suppressinn nf the I I A resryrnse tn nicrllinc Illc nther crrmlwrunds did not affect the nicnlinc induced ITA resfw,nsc. Nicotine caused a rise in serum IriRlyceridc levels in eight d•1Rs which was diminished by pre-Ircalment with nethalitk. The results nf tlxse eaperiments eml+hasi?e Ihe role of the tymnathn- adrenal systcnt in the hyrerlrpklemk effects of nicotine and suRgetl they arc mcdiated by /i adrencrRlc receptors. Other Rranrorar National Inslilules of Ilealth and the 11 S 1'uhhc llrallh Service. "SMOKINO AS A FA("TOR IN AIIIFROSCI.FROSIS: A RF.VII:W OF FP1UFM1O1(X;l('Al., PAlllOL.(X:I('AL, ANI) 1'XPFRIMI?NIA1. SI l1I)IUS " fly Alfred Kershhaum, MI). and Samuel Ilellel, MI), I) visitln of ('ardinlnRy, Philadcll+hia General Ifnspital, Pcnnsylvania. (:rrinr.ir t 21/12 15S 17l), Ikcemhcr 1966 ((Jrantee: Ilellel) The rnk of tobacco smoking in the Rerxsis and development nf athcrr/ aekrosis is e.amined by revicwinR epirkmalh,yical, rathulrrRical and ctlrcri mental sludies OulstandinR anxonR the firxhnRs in thls invectiRatum atc the fnlhlwinR 1 FpidcmirdnRical studirt have shrrwn, wilh little crmtridictr+ry evi- dence, a siRmficant assrx'iaUon hrtwr cn rlParctlc smnkrnR arld the nunlnJily nd mortality rll coronary hearl dl.cat 2. Pathological studies of the curnnary arterics in cnnsrcutivr rnutine autof+sics showed an association t.ctwcrn cigarette smnkinR antl Ihe stvcrlly of coronary alherosclcrosis. 3. lhe relatively fcw sludies of the cficcl of nicotine on cRf+rrltucrltal atherosclerosis have shown inconsistcnt resulls. lhcre is need frlr more investigation of lhis probkm, using newer techniques and other slrct'ics. Recently, much has bcen karrxd concrrninR the effect of smokinR :rnd nicotine on various melaholic, hemalologic, hormonal, and circulatory prnc- esses involved in alheroRenesis Some of these biological effects ctwld cnn- tribute to the initiation and progression uf atherosclcrnsis. (/rArr wrantnr.r Amerkan Medical Assrrcialitrn Fduc-alinn anrl Rc.rartlt Foundatinn and the National Institulcs uf Ilcahh "A NFW 111A(iNOSi IC 11~S1' FOR ('ORONARY AR 11'R1' I/1`VACI " fly Alherta ('ohen, MI), F.ide l)ilmar I.uFs, MI), I Jward 1 7alc%ki, MI), and Richard I fling, MI), Wayne Slate University Schrwd rrl Mcdicinc, Ikttoit, Mich A(rnnrtrNO tilrAirinr 19/1 17_2I, )anuary 1966 ((iranlcr RinR) Ihc thaRnrnuc prrardure here rl fluenliatcs rahully Irtwrrn the esl.1h lishcd thmlrnRs that niur.RlVtrrm rrKrra.rt twrlnarv hlN"l flow in nnrrnal individualt hut nnt in palienls with cornnary artery diseasc, hy the usc lrf a IMnitnm emitter and a coincidence counlinR system I he tcsl it Iechnit:Jly simple and ah)etlive, and is made without calhelodi7atiun, invrrlvinR only intravcnuus infu.nln nf ruhidium'• and an arterial f/unclore lu draw hI/MK1 through the cnunlcr I he dala are then processed by ulmpulcr, whic h caltu lales hhwHl flnw in nd/min, together with the slandard devialirlns and Ihc siRnificance of the change in flow prior to and following the suhlinRual aJ ministration n/ nitrnRlyccrin. It permits differentiation of patients with and without coronary artery disease with a reasonable degree of accuracy f)tAer Rrontnr.r ll. S. Public Ileallh Strvice, lhe John A Ilartfnrd Founda tion, and the Arnerican Mcdical Assxxialinn - 1 ducalion and I(esrarth Fnundaliun "A('ltll! ITIT('fS O/: AL('OHUI. ON THI? Ffl/MAN MYOt'AR- Ily V. 1?. Wendt, R. Aljuni,'f. A. hruce, A. S. Prasad and Richnrd 1. fling. Amrricon lournol of C'mdirdoRy 17/6:e01-It 12, June I96(h lhe effect of acute akohol ingeslion.(6 oz of RI proof V<afka/ was stut:icd ir I I patients with a known history of chronic alcohulisnl None had any evidence of vitamin rkficicncy nor of heart or liver discase No significant changes appeared in pulse rale, blood pressure, cardiac output, slrnke volume, arlcrial venous o>tyRen estraclinn or respiratury yuolicnt Iksllne the lack of Ihcse hemodynamic altcrations, flattened and invertcd 1' wavcs occurred in the clcclrocardioRrams of Iwo paticnls 10 minutes after Ihc ingestion of alcohul. 'I he significant metabolic findings included  rise in hhwal lactate, a decline in arterial hyruvate, a marked lall in blood Rlucose, a decGrre in frre rally acids and a rise in triRlycctides one half hour allcr Ihe inRcstion u/ alcohnl. 7inc was lihcratcd by the heart in Ihe majority of palicnls, and serum alcoholic dchydroRcnase activity cloaly followed that of hhtiKl rinc 1'hns phnlipid blood Icvcls rcmained unchanged It is tuPRcsted that rcpealyd esf+osurc to acute akoholism could result in permanent allcratirrns in myo cardial mclahnlisrn which could kad to the devchrrrncnl uf irrcversihle alcoholic cardiumyupathy. Other Rrnntora: l).S Puhlic Nealth Service, American Ilearl Assrxialinn, MichiRan Ilcarl Associatinn, Life Insurance Medical Rrsearch I'unJ, Ilur ruuPhs WellcrrnK• 1 und, Ihc ltlhn A Ilallfntd Puundaurrn and the Ilcuhlcln ('nmhany I "SI IM111 A1ION (1F R1TARAIIVI'. PR(X'I:SSI:% I(11 1OWINI: I X 1'ItItIMI NIA1 MY(I('ARI)1AI. INFAI(('IION" Ily S(:urlbl.unaarn lrrhn (' I•crdon, I'.lul I Wolf and Rithard l FlinR Arrlrncrr ./ Mrrrn,d lfr•duinr I I8/ 1: 11-16, July 1966 the reparative processes in cardiac muscle falluwinR eat•crimcnlal myrxordiil infarctir/n prrxlured in dr1Rs hy IiRalinn of Ihe crurm.lry artcrrrs wcre stimulatcd with anaht/lic hormrncs I rcalmcnl wilh insulin incrcaurl Ihe irxnrlMUatinn ltt Rlycinc 2"(' intu prulrrn ur inlarctcd u~suc hy )4':., 21 ?I/

/tralmrnl with Lnvine growth hrnmone raiut) Ihc incorfa.ratir n hy 16R^~, and trcatmcnl with Mah insuhn and Rrrtwlh Mnmrnrc rarticrl the intnrrurri- tion by 2S 1^, all witlrn 24 hnurs rd trcalmcnl Treatment with an inuavennus infusion of Rlucose, inarlin, K(1, cnervymcs and vitamins incrcasrd I+rrrtcin syntheais in infarc'tcJ musclc 7 hnurs after infarction by 171^L.; repeated infucinn led tn a further rice within 24 hnurs after infarction Ascorbic acid rncreaad protein synthesis in the center cd infarclcd area by 122% and Ihe anaMdic slernid methandro- slcnolonc auRrrxnted irxorporation into the center of infarct by 249%. 1 onR term treatment with Insulin or the anaholic sternid prevented development of aneurysm, whereas animals fed a protein free dicl had a siRnificanlly thinner scar and frequent development of aneurysm It should he rcemphasited that the biochemical tlemnnslratinn of protein synthesi; in Ihe infarctcd myncardium does not Imply synlhesis of prulein by necrotic heart muscle, hul is due to fibroblastic proliferatinn in thc injured area Othrr Rr.ntorar 11 S. Puhlk Hcalth Service (2). Ihc John A. Ilartfnrd Foundation, MichiRan Ncart l4.sociation, and the American Medical Acso- ciation Uducation and Research Fnundatinn. (hher (+arers published by Dr fling and asascialcs since Ihr 1965-66 Report of the Scientific hireclor, with credit for support by 1 he Council for Tobacco Rcscarch - II S A, follow Other Rraninrs are noted between parenlhcses "TI11' MV rAh(11.ISM O!' THf: IIFAR I' IN FAII IIRI: " Ry S Gudhjarn- ason and R. 1 HinR Ar ra (-mdurhoRir a 2/) 'S. 111 1Rt), 1965 ( PI IS, M(IIA, 1-IMRI', 11WI, AMA fRl' and 1A11F) "METABOI.I(' FACTORS IN ll)!' CUNIROL OF ('ARI)IA(' O11f- PITT." fly V. f Wendt, C. Wu. R Flalcon and R 1 IlinR ('h:rpter in "ShocA and 11YPrrrrnrirrn," puhl 1965. (irune b Stratton IPIIS, AIIA, M('IIA, I.IMR1;, I1WF, )Atll;) "CIR('ULAIORY CHANGhS FO1.1.OWIN(7 MY(X'ARI)IAL. INFARC'- TIUN." Hy V. 1? Wendt, R 1lalum, 1. Rihcilima and R. J. fling ('haptcr in "Shock and ll vpr,rrminn " puhl 19hS, (irunc & Stratton 11'l IS, AI IA, M(11A, I.IMR1:, I1WF, lAllF) "MP.IAIIOLISM OF TfIF lIFAR U IN hA11 I IRF " fly John (' Urnton, Symundur (iudhiarnason and Richarrl /. Ilin/ Amrrigon llrrnf Arv'ruirrn 11fnnoRrnph Nn /, Second Vditirrn, April 1966 12 411 (1'1I%, r•1( IIA, I.IMRF-, HWF, AMA-FiRh, /Alll-'/ "HYPOXIA IN /l(R GFNFSIS OF C'ARI)IA(' ARRIIY I IIMIAS " Hy luhn (' Fentnn, S(iudhjarnason and Richard I HinR Iroun "Mrrhanirmr and 7 hrnrpy n/ ( ardia' A rrh yfhmrat," 14th Ilahncmann Sym/nium, puhl 19h6. Grunc & Stnalton SR 61 IF'IIS, M('11A, IIWI:, A( S. AMA FRI', 1nI11 ) I "('APlI.I.ARWS IN IIFART ANr)SKFI.FTAI. M(1S('1.1: ()1: IXXi ANI) RAIlN1I-." Dy K. Rakusan and W. du Mesnil de Rochemont ((irantce: R. 1 F1inR ). 1'rrx rrdrnRa of fhr.fr>r irt y/rn F i prrfnvntal /1rn)n4 v and A1rJr rinr 124/3:R1R 940, March 1967. (PIIS, )AIIF, M('IIA, AMA fRf, Ixi1IR(') "FFFFCTS OF AI.PFIA-METfiYI-DOPA ON TTIF MY(X'ARUTAI. HLOOU Fl.OW, IITILIZIN(3 111E COIN('IUENCI? ('O(/N I ING MF-TFU)D" fly Alberto ('ohen, 1. S. Maxmcn, M. RaRheb, I1 1laleiron, E. 1. 7.kski and R. 1. HinR. lournd of l l.nical PharmaufuRy and lournof of New l)rurs 7/2:77-R3. March-April 1967. (MSI)RI., 1'IIS, IKiIIR(') "MI?AS(1RF?Mf?NT' OF Tl1E SHORTENING OF ('ARI)IA(' I-IIII:RS IN MAN." fly Richard 0. Madcira, Wolfgang du Mcsnil de RrxficnMmt, ('harks W. Oadd,1 homas B. Stock and Richard 1. Hin6 . Amr.i, nn luurrwl of C'ar4ioloRy 19/S:6R(~691, May 1967. (MCHA, IXi11R(') "PFRSISTC•NCE OF REFLEX SYMPATHETIC NFRVO(IS SYSfFiM ACTIVITY IN MAN ON GUANETHIUINE OR RI;SF.RPINF " Ity Jay 1). Coflman, MI), Department of Medicirx, Noslon Oniversily Medical C'enter, Massachusells. Ctrcularlon 35/2:319-346, February 1967. The eRect of oral Ruanelhidine or reserpine on the refkn vasoconstric- Iion in Ihe calf and foot resulting from a prolonRed. Reneralved sympathetic stimulus (body cooling) was studied In 12 normal suhjects. I.arRe daily clinical-doses of guanethidine or reserpine were given for 2 and 3 weeks, respectively. Fcxrt and calf blood flows were measured by venous ncclusion water pklhysmt>Rraphy. Two control studies were performed on each sub ject, one before and another long a/ler administration of the JruR. Flody cooling produced significant decreases in cal/ end foot bh>iK1 f ow and increases in vascular resistance in both conlrol stuJics. Suhjrcts evidenced drug eflects by a significant decrease in pulse rale, postural hyht tension, hypotcnsion following e.crcise, and bhx:kade or altcntuatUnn of the Valsalva maneuvcr "ovcrshoo/." 'ihe altenuatiun ol the syntpathetic nervnus-system vasoconslrklor rtflea to general FxKly cooling was nut stalis tically significant. Since large clinical doses of Ruanelhidine or reserpirx admini.trrcd orally for 2 or I weeks, respeclively, did nM inhihil Ihe rc0et va.rKirnutittrrr effccl of total IwKly coilinR, functional sympathetic neurulransrnittrr .ub starx•e cannot tre said tr) he absent (ItArr Rr.ntor r National Institutes of I/ralth. "REAPPRAISAI. OF PFIYSIOL(xil(' PRIN('IPI FS IN I lIr r Rf A 1 M!?NT (/F IS( IIIiMICHI?ART 1)ISFASF" Hy (?ril f: ('tn+t and 1'rtrr F. Sahsbnry, MI), Ihpartments of Medical Re%cernh anJ Mcrhtmc, St Joseph Ilospital, nnthank, C.lihnnia lnrernol Alr.trd rnc I)rReu 1 1') 14, February 1966 ((irantee: ('toss) ~' 21 ~~ 2 2 cT~

...3. .f.. 0 ~ m (-n .- 4e~t:f m .S.J~ m (T A course of treatment of ischemic heart discase hased ularn the main- tenance of hl(xxl pressure at the Irlwcat kvel compatible with normal funclum of the palicnt's vital nrRans is hreantcd in this paper I he recrrnuncndcd treatment is fnrmnlated upon a review of the current atalua nf kmrwtcdRe of the coronary circulatinn, consideralinn of recenl discovcrics and a reap- praisat of the rhysinlnRicat principles involved in acute, severe coronary disease. In order to understand the Impc»tant physirdr.Ric mechanisms involved, studies were undertaken of the interaction of cornnary pressures and flows with the function of the heart. When coronary htrxxl flow was measured in anesthclired doR., the resistance of the coronary vessels remained cnnstanl within the "normal" ranRe or cardiac outputs and of hkxxl pressures 1 he coronary vessels did not dilate when the work of Ihe heart incrrasrd nnr did they constrict when the work or the heart decrcascd Active curnnary vessel conslriction or dilalinn was obxrved only when highly abnormal slatrs of the circulation (for esampk, Intentionally produced high pressure in the aorla) were present The physiologic ohunatinns and clinical nxssures noted here suRRect the Ixnsihifity rd a future increace in Ihe survival rale in i%chcmic heart disease . /)rA.r Rr.nrnr.r National Ileart Institute, (/ S Public Ilcalth Service and the I ife Irnurar.ce Medical Rcscarch I und "('(/MP1 r('I11I(1NSl>F: ATFIFROMA1O(IS PI.AQl1FS" Hy Ira Gore, M[), lkpartment n/ PathnluRy, Ftnstun Univercity Medical Ccntcr, Massa- chusells At la ( a.dinlnRrr a X I R9 I IIR, 1966 In this revkw paf.rr, the complications of atheromatous playucs, namcly, thromhrnes, hcrnonhaRe, ancurysms, ulceratiun, cmlxdizatron and calcrfi- cation, are considcred in light of their relationship to the athcrnwlerolic process. Studics of coagulation and platelet utilization cited in this review favor the concept that alherosenesis and occlusive thromlxnis complicating intimat disease re both related to  common coagulative dislurf.ance. A frxal hns of the normal acid mucopolysacchatide determined anlicoaRulant finq,crties of the intima, which it produced by the atherosckrotic process, complements the action of systemic influences in facilitating IhromMNic comfdi( atinns. larcalization of plp ues, at Ieast Ihose formed by IhromMNic (klx/srt., is dependent u/xtn the hydraulks of hhxxl flow. IlcnwrrhaRe from ttrm wnikd inlimal eapiilarics aphean to be an early event in aherr.RrrKSis, lusl as lheromalous uiceration, entbrlism, aneurysm and cakilicatir,n alqx ar. Inr various remons, to be dependent ulxxt the growth and earnt ut athr r(r..le- rotic ptaques Ihfirr 1fr.nrorz N.Nnnal Ikart Inslihrtc "1-IItRINOl1'II(' A("IIVIIY //1 IIIt: . UNIH111II:I IItM" Ry Inkar) I ujinami, MI), anJ Ira (:orc M11, tlrlr;rrtmcnl yd ('ath(rLrRy. Iln vcr%rty ?.1 Flocpital, Boston University Medical Center, Massachusetts Japanese ('i.- culannnlournol )1/2:267-27), February 1967. ((;rantee: (:rae) Chemical and histological rnethods were used to study the fibrinolylic activity of the endothelium of blood vessels in guinea piRs, rals and rabbits Fihrinolytic activity was demonstrated in rats and guinea pigs but not in the rabhit, which is the most susceptibk animal to eaperimental atherosclennis. The observed lytic activity might have been due to plasmin aclivator (rum the vessels, since the endotheliurrt did not show anr aclivity wilh heated fibrin. Activity was weak in the I+roaimal .rxta (which is the prevalent area frx atherosclerosis in roaknts), and became proltressively Stronger down the length of the arxta 'Ihe strongest activity was observed in the inferiur vena cava 'ihese 6ndinRs suggest that fibrinolylic activity of the enduthehum may be one of the Important intrinsic faclcxa in alherrrytenesis. /)tlker gr.nterr National Fleart Institute. "INFIIfi1TION OF DIETARY AT1i'P-ROSCLFROSIS IN RAIIOITS BY NORETNYNOI)RFL." By Ita Gore, Y. Iwanaga and Harcl Gore, Bostnn University Medical C'enter. loun.al of ArAerotclrrozif Rerrarrh 7: J61-J66, 1967. Norethynodrel administered to rabbits reduces the athcrnRenicity of a cholesterol diet in part through its eRect on serum cholesterol I here is n increase of the aortic acid mucopolysaccharides of the treated animals, an observation which contradicts the thcory that such accumulations predis- pose to the occurrence and kxalizalion of lipid deposits. Other Rr.ntort National Fleart Institute. "AN UNUSUAL VFNOCONSTRICTION INDU('FI) IiY ACI:hYI,- CHOLINE." By A. 1. Rice and 1. P. Lon6, PhD. lkpartment of F'harma- colo6y. College of Medicine, ltniversit~ of lowa, Iowa ('ity. 7 hr Inurnal of 1'harmaolr.gy and F-~rptrinKnrol Thtraprurict I51/):42)-42Y, March 1966. ( Grantee : I .on` ) "LOCALIZATION OF VFNO('ONSTRICTOR RFSPONSFS " hy A. 1. Rice, C. R. F.eeson and 1. P. Long, Phl), Ihpartments of PharmacoluRy'n'1 Anatomy, ('o1kRe of Medicine, University of lowa, Iowa ('ity 7hr lournal of Phannocnlngy and Erprrimrnral Thrrapewicr I54/1:S19-S45, Ikccm- ber 1966. ((kantee: lAinR) Fsperinxntal ubservalkro of n unusual drug induced ven(.coostrie litxt, made whik studying the nteehanism of vencx:onstriclion InrwhKrd by aeetykholine (A('h), stimulated an invesliRatirrn of the site of thcsr vcnrr eons.rklor resfatnses lklails of these studies uf the mcctunisrn of vrnrcon striction are given in the present papers In esperinxms designed to study the In vivo eflect of /5( Tr (,n thc acccs urry, cerhalic vein of the d(rR, it was noted thst injccti(tns rrf MRh drnrs (,/ A(?r dtreclly inlu Ihr rerfu.ed vein prtxluceJ  nurked risc rn /-rrfumon pressure. The site of this A( h induced vcn(rconsuicti(m was I(Kalircd at 25 J

C) f5r1 :z .~ the reRion of venous bifurcatir.ns Several eitl+erimcnls suRRcatrd Ihal the vennconstriction did not result front a compcnsalnry rc11cit 1 hr prccan resfonse to A('h was blocked by auopine and hhcnlnlaminc and if was antaRnnired by rcurpinc (iuanelhiclirx, hcsamcthr+nium or chrrrnre syml.a- thectomy did not aflecl the resronse I he potenhaurrn of the Pressor reshrrnce by coc'aine and dircct assay of the venous hlrxxl on the chick cccum help support the conclusion that the fxessor resPrrnu is mediated by ^ relcase of catccholamines from eslraneural atores. Further investigation of this original observatirrn was carried out by correlative tests of the responses of four veins in the dog to several vaso constrictor stimuli lhe aRents used includcd nicotine, acetylchrrlinc, nnre- pinephrine and srmpalhetic nerve stimulation Nicutine did not pioduce venodmslriclion in any of the pre srations. I.crcaliycd reslxmses were in- duced by scetylcM,line, ncwepinesrine and vasrxonstriclor nerve stimu- lalion In the accesuxy ctf+halic and latcral saphemrus veins IlistolnRic eaaminatinn of these regions showed an area that contained valves and was richly invested with smcxrh muscle. Valves were present also in the creternal iliac and the spknic - the non-resclivc veins; however, these veins lacked ^ny appreciahk amount of snxxilh muscle fibers in the tunica media It would aMxar. Ihen, that vcnncnnstriction in Ihcse veins involved Incalired areas ccx+taininR valves and rich in smooth muscle OtArr Rranlnr: American Medical AS«sciatinn -- Fducatirrn and Reuarch Foundation "Slllhlf:S ON Illfi AltRl( 111 nR SIIM111 AI1N(; A('1I(1N OF NI('OI INF " Ily ) I' I unR. I'hls. end IG ( irr-%%, I>, h.utunrnt if I'h.uma- eoloRy, College of Medicine. lhuvcrcrty if tnwa, 1r,wa ( rty .4n hr.•n rnrrr- nofionofrr de phurnvandvnomrr rr di rhrrarrr Ihl 1 111 17, Mry IVhh ((irantee: I.onR) lhis erperinxnt was undertaken to study The mechaniam by which nicotine produces an increase in aurrcular rate and force of contraction In one phase of the eRperiment, ixrlated cat auricks were susf,enrkd in Locke-RinRer's solution, allowed to stahilite for at kast 15 minutes, and then wbjccled either to variation of the pll o( the medium or to vagal nerve rlimulalion. In another phase of the eRperirnenl, hemicholinium was admin- istered intravenously to 1) cats, and auricular activity was compared in cats suhjeeted to a) the action of hemicholinium, b) vaRid nerve stimulatiun, or c) the combined sction of hemichnlinium and vagal nerve stimulation Data prestnted In this paper supfxxts the fulhrwinR ohscrvaturns 1. the stimulating actirrn of nicotine is present at plf's of R I arid 7 4 1 he stimulatinR aclinn appears to he more marked in a more alkaline nrcdrum but this was accompanied by an ahered restinR auricular rate. 2. VaRsl nerve stimulation with the electrodes placed distally on the nerve in the iarleted cat auricle prrparatinn rrrxluced significant increase in the suricular ratr hnt not a sir.mhcant intrease in the force of eontraction 26 3 When hemicholinium was administered to cats in vivn and accom f+anied with right vagal nerve slimulation. the auricular slimulalinR actiuns of nicotine in the isolated auricular preparation was siRnificantly antaRonired 1 he evidence presented suggests nicotine acts on the Parasyrnrathetic nerves within the auricks and directly or indirectly produces release of norepinc phrine from the sympathetic nerve terminals. (RRrr Rrentnr: American Medical Association - I'ducation and Research houndation. "(Y)MPARATIVF Sllll)IFS OF ATRIAI- RF?SPONSIS FO1.1.(-W- IN(i NI('UfINF AND TRANSAlR1AL SIlMl/1.All(1N." fly F(; ('rruss, T S. Whitacre and J. P. InnR, Phl), (kparlmcnt of PharmacrrluRy. University of Iowa ('ollc6e of Medicinc, lowa ('ity. Archivrs Inrrrna-irrnnln de I'hornrocadVnamir rt de Thlrapir 166l2:273-21110, April 1967 ((:ranlec l.onR ) Atrial reactivity to nicotine and Iransatrial stimulation was evaluated in eight species (cals, dcW, (roRs. Ruirxa prRs, lurtks, chickens, rats and rabbits). Wide species variatinns were olnerved following ealxtswe to either nicotine or Iransatrial stimulation. Only the cat and rabbit rknx,n slrated both positive and negative chronolr( {+rc and inotropic reslxrnscs to nicotine. lhe cat, alone, demonstrated hiphasic resfxrnses to transatnal stimulation. 1-itllc, if any, correlation was noted in reslxmsivcncss whcn comparinR nicotine and transatrial stimulation. lbe great spccies variation recorded here sugifest that care musl be observed in evaluating the activity of compounds on isolalcd atria Other Rrr.ntorr Amcrican Medical Asurciation - Fducaliun and Rcscarch Foundalion. I "7IiF IIF.MOf)YNAMIC CONSFOl1(iN('FS OF ARRIIY f1IM1AS " Hy Flenry 1). Mcinlosh and James J. Morris, Jr., ('ardiovascular I aMaatmy, 1)uke University Medical (enler, Durham, N('. PruRrrrr in ('ardirrvar, ular f)irrasr R/4:)10-)67. January 1966. ((irantce: McIntosh) The rate of an arrhylhmia regardless of the type can he rrf siRnificance at either erttrrrne of the rate scale 1 he relation of atrial systole to vcnrricutar systole tktcrmines if the normal alrial transport function will tx• Ivcacnt as wcll as determininR the efficiency of atrioventricular valvr chnurr I he virr of migin and tylvc of cundur lion of The pacing stinwlus ate imlwrrt.rnr rlctrr minants of the eflecliverxss of venlricular systok ^nd atru,vcnlnruLv valvr cnrwlretency. '1 he patholoRic state of the heart as a pump ckterminrs how cflrctivrly and how long the ^dverse eRecls of ^rrhythmias may be trderatcd I tre intcRrily uf the vasonxNor cnnlrol mechanism serves as,hc final aiu- If aJfuvt mcnt to maintain adrquate perfusion of the vital center of the tural ouRaimm Associated tliaeases delermine how well a eomprnmiard circulation rn:ry be tnkralcd Ulhcr farturs inllucncc each of the alxwc mcntnrncd paramctrrs 27

1 hr final hemtxlynamic e/iect of the arrhythmia, Iherehnc. ArlrcnJk tin the summatiun of the eRecls n/ numcrnm chinycs of vatymr rnywut.rntc (lth.r Rrenrnr.: Natinnal FBcart Institutc ( I). John A. 1lartlrrrd I rrunrli lion, and the I ife Insurance Medical Rccearch I und "r:VFT .(-rS OF IIYPfRDARI(' nXYGI:NA 11ON ON CORONARY ARtURY (K'('LI/SION IN PI(iS." By Robert 11 Peler, MI), Ronald W Rau, (1S1?R, Rohert F. Whakn, M[), Mark 1. I ntman, MI) anJ Ilcnry 1) Mclntosh, MI), hurham, NC. C-rrru/o(irrn Rrvor,h IR,'I R9 96, lanuary 1966 ((iranlee M(intnsh) Tn evaluate mo(e precisely the possibk prntective effect of hypcrhatic osyRenalion in eaperitnental myncatdial Inf.rction, Rradual cn•cluuun of a coronary artery was produced in the piR Ameroid constrictors tksiRncd tn produce compkte occlusicm within 4R hours were placed on the left anlerinr dexendinR coronary artery of 24 young farm piRs Of these, 12 wcre placed In a hypcrbaric chamber at 1 25 atmospheres absolule and al'owed to breathe I(M)'76 oxyRen for  ma>;imum of )2 hcwrs For control studres 12 other rigs were handkd in a similar manner outside the chamber while breathing air at normal atmnspheric pressure Pigs treated with hyperharic nxyRenalinn outlived the untrealed piRs. Palhnlrrsical and hishuhemical studres of the hearls revealed that piRs treated with hypcrharic u.yRenathnn had a hiRh incidence of tnytrcatdral infarction, whereas only Iwn prRs in thc untrealcJ prnrp aht.wed iny evrdcnce of myncardial damage ihesc hndrnRc .uy'cst that nwxkrate hut )rrrrlunRed hyperbaric nryRenatian may IrnRthtn h/e rlurrnR and after trunnity trcclu sinn lhis prnlrrnRatu.n rd life may Lermrt Ihc dc.clr,l+rncnt rrf p:,th(JtrRrc'ally detectable myocardial infuctinns Other Rr.ntor.: U S. Puhlic Health Servicc, Nnrth ('aralin:t Ilcart Aaarci dinn, American Ifeart ASHK/aUnn, and l.ifc IrKurancc Mcnccil Rctcarch Fund. "POSIPERICARI)IOTOMY SYNDRUMF AS A ('OMPLICAIION 01: PFRCll1ANEOUS LE:Ff VIiNIRI('111.AR PI/N('1l1Rli." Dy Robert !1. Peter. MI), Robert F. Whakn, M(), Fdward S. Orgain, MI), and Iknry 1). Mclntosh, MI), Cardiovascular L ahnralnry, 1)cparlmcnl nf Medicine, 1)uke University Medical Center. Uurham, N(' Anvriron lnrumd t,/ ( nrdr- oGrRy 17/) R(i-9(), January 1966. (Grantee' Mclntosh) 1 wo caus of pt»Iperkardittlnmy syndrome fulluwinR pcr(ulancuus k/l venlricular puncture have been reported 11uth had symlrlnms irkntit a with the nther "c'atditNnmy" syndrrnucs and reafwrnJed prnmlNly trr adrennl slernld therapy. Ihe fact that one nf Ihe patiems had a acct,ncl clriatMk of pericarditis four weeks following open heart stnRery may nrcan that thc devehrprrsenl (rf Ihis syndrnme following k/t ventri(ular Irunclutc may lre assnciated with the develtrpnxnt of the (.rttllrcricardirrlrrmy ayndrrrmc (nllrrw- inR c11rthar 1rnRrry llthir /rwnf.v ~J.rurul IIr.r1 In~lrlulr 1! 1 "111F; IIFiMO1)YNAMIC FFEFCfS OF THE W IN1P('II(1N OF ('ON- 'IRASf M11)II1M (IS(1PAQllF:)." Dy Henry Mclnt.osh, MU, Victor . Hurst, MI), Iloward I(. lhompson, lr , MU,Ulamcs 1 Morris, lr , MU, and Robert F:. Whalen, MI), Cardiovascular l.ahcsralnry, Ikparlment of Mcdicine. Duke lJniversity Medical ('enter, hurham, Nurth ('aruhna ^nRrrrlrrRy IR/5:)1)6-)15, May 1967, (Grantee: McIntosh) h.ninR studies evaluating the hemodynamic changes (ulluwinR the intravascular injection of a new contrast aRent, sodium and N-mclhylRluca mine me/ri?nate ( Isnpaque ), it was found that within seconds after inlectiun of the contrast medium into the heart and great vessels there was a prnmhl decrease of hcmatocrit, due to Ihe loss of red cell water and a(educrinn of red cell volume Observalions br light microscopy of the eflnl of cuntrasl medium on ted cells indicated Ihat these changes occurred rapidly enough to he compkted dutinR the initial transit of the cont.ast-medium hlocKl misture. lhese agents alter the permeability of the cell membrane to patas- sium. Such changes in pcrmeability were not produced by 5'9o sodium chloride, despite a similar rapid reduction of cell volume. It is suggeated that similar changes may occur in endolhelial cells It is possible that the eftlu>t of ions from these cells may have an effect on the downstream "receptor" cells and be responsible for certain of the herrNr dynamic changes observed following the injection of contrast medium. (hh.r Rranrnr.: National Fleart Institute (2), the John A Hartfurd Foundation, and the Winthrop Lahoralotics. Other paPcrs published by [h. McIntosh and aasnciatea since the 1965-66 RryKxl of the Scientific Directnr, with credit for sulyytrl by Ihe ('ouncil for Tohacco Research - U S A., follow Other Rranluts are rwled between parenlheses. "INFIINI)IH(ILAR P111.MONICSTENOSIS hIII? 10 A 1TRI('ARUTAI DANI)." American Jaurnal of Cor4irrlaRy 16/2:21r2-266, AuRust 1965 (NIII) "TIIF. ASS(X'IATION OF N(X'TURNAI. ANGINA PE(-1ORIS W1111 I1RF.AMIN(i." Annoh of Internal Afrdicinr 61/ 6: 1114t/ 11/46, 1)ecernher 1961 (NIII(2), AIIA) "FI F('I RI(' SI I(X'K IIA7ARDS IN RADIOI (x iY 1)1 1'AR I MI N I S" Amrrir on Irnnnrrl rr/ RrrrnlRrrtrrMRy 95/4 976 9110. 1)ct cmlw r 1')A1 ( NI11, N('lIA ) I "1111 AIFRAI I IIN('II(/NAI.SIIIIAOR11('S11 Nt/SISIN 1111 Al 1 I ( aAIOR " l rnn tur Irnnt n/ rlhr Anvrrr rtn ( Irnn .rl nn.l ( Irrrr.rl.rL rRrr .d ,1 r r.r rionnn7R 119 1)R, 1966 (N111, )AtIF) "111F. MANA(7f'Mf_N1' OF SIIPRAVFNIRI('UT AR nRO(II\ 111 MIAS° Mrdrnnl .Innnlt trf Ilrr 1)rvrirl rr/ (nlumM1r,r 1% S2% S2), 5Jh 1966 (NIII, JAlll , I IMRF ) 29

III~M()1)1'NAMI(' RI'Sf'(1NCI C I()I 111 WI I I111m I11 (N/11 " 1 II,nJ Inlcrn:ninnal ( nnlrrrncc rm Ilyla•th:n,c M,Jn rnr. I)mlram N(, I'rf.C ) Nohnndl Rr,rnr, Ir (.rnnr rl I'uhhr rur..n 01404 1'1f.1. ( NI IA( )), A 1IA, N( IIA, I IMR1 ) "('INI ANG I(K'ARI)I(1(;RAI'IIY " 7irr /l,v,rr I'rn,rrrr nl Afr.brinr V 11, I')(r(r "IIIIi PROIf('IIVF FFFFCT OF ilYPFRIIARI(' OK1'(:1 NnII()N IN ('FRFHRAI. ANO)(IA" Arrhivrt of Nru.oh-Rv 14 I 15 2f). 1:mu:vy 1966 ( PItS( 1), N( l(A, AFIA / °FFFF'(-TS Or' 1(YPFRIIARI(' OXYGFNAIION ON VK( I S; I A( IA1V I'ROU(/('llON IN I XI R( ISIN(; I)(K;S" Arnrrirrrn Jnurnnl rrf I'hy+rnlnRy 21(1/1 471 477, March 1966 (NHI(1). N( IIA, AIIA) "RI I.ATIONSIIIP OF FIRRII (.AIURY WAVVS ANI) P WA'JI-S IN 11(1. FI F:(-IR(X'ARI)IO<iRAM "l r.rnlonnn 11'4 S99 MMr, Arrrl IV(,(. (NFII, N('IIA, I.IMRF) "TI(F PRF('(1R1)IAL IIONK ".Inrrarurr /rrurnol rrf ( mdud,rRv 17 . 4 5//9-515, April 1)(,6 (PIIS121. AIIA. N( I(A) "ATRAIIMAI I(' RIGII I VI-Nf 41( 1/1 AR ANf(IRYSM RI P(1R1 OF A('AS1: "( irculaliun 14 7 121 126. )nly IV(,h INIII( 1). 1A111 , N( IIA/ "F.LFC1 RI('AI. ('ONVI:RSI()N ()1 A I RIAL I IIIRII I A I IUN IMMF- 7) I)IATI: ANl) L.ON(i-11-RM RI S(II.IS ANI1 SI L/ ( II(/N (1F 1'A- '1 IVN I S" rl nnolt of Inrrrnn/ Mrdr, rnr hS 2 216 211, Aufu.t I'/A(, (NIII(2), NCIIA) "'i f+~ ..+1. "VI?NiRI('UI.AR VUL(IMF SIIIhIFS IN A PA1lFNi WI I11 IfYP1:R- 7 ROPIII(' S( /IlA( )R 11(' S I FN( )SIS "( irr ulannn 14 i 4: 5 79 SN4, ( klr+lrcr 1966 (NIFI, AITA, NCIIA) "A ('LINICAL AND iIFMOhYNAMIC EVAI.(IATION O1- A NFW (Y)NiRASf MFI)IIIM: ISOPAU(1F. 440 (SO1)IIIM ANI) N MF.I IIYI - .}~... GI.II('AMINii MF T R17OA 1 I/." An+rrir on lr,rr.nnf rrf RnrnrRrn,dr'Ry 0 1(X//2:4(tR 471., lunc 1967 (NIII, lAllV) "A(;F. AN(1 I)ISI?ASFi-RFI.AII:1) AI.IFRAIIONS IN 1•11fRINtH;1-N ftt(7LO11111 IN (FIIIRINUI.Y I I(') III IIAVIOR " Ify Krnncth M m ~ M,xcr, MI), and (;rurRe ('. Ilajjar, M1), 1)c(~artmrnt of Mccficinc, (;rurRc- luwn l/nivrrsity Mcdical Schrwd and Ihc I~nyyrnc Rctcarch I atH,raHny, 1) (' (;rncral IlnsPhal, WashinRton, 1) (' Ihr .Omrriran lrrurnnl rf rhr ~ t9 Afn/rru/ "irrrn,rr 251/S S16 544, May 1906 ((irantce: MnscrI ~ Studirs,d IA.r,rw.Ren crrnccntr.tum .nd fihrinnlyuc activiiy (ruRlnhulin w +. ~ ,r. lytic r,n,r ) wrrr r arrr,l r-ul tn J,Ilrrrnl I'aurnt Rr,n,l'c If waa caahl,thcd ~ til J © C III that thcrc it n,r cnrrelatiun hetwcen lihrinosen cnnccnU:duwn anJ hhrma,lync activity Attempts to dcfinc the day-to-day reproducihility of (ihrinulytic activily and fihrinuRcn mcasurcrrxnts indicated that fihrinuRcn (evrls rcmain y,nte stahle and that cnrresl>,rndinR meaturct of lihrinolyiic activity arc a,lryuatrly rehrnducihlc, althnuRh hhrinolylic aclivity, in gcncral, increascs dunaR thr I+crirKllxtween V INI a m and 2.(M) p m. Comparisrtn of lihrirndylic Ir•havuu in Rrnups of young, nld and intermediate age rnrrmajs, cinholics and dia hctics ditchncd thal tuch activity was tiRni/rcanlJy greater in Ihc cirrh,rtict, nNtst labile in the young normals FibrinoRen levels in Ihc dialretics wrre consislenlly higher than lhose in the (Nher Rroups, while old nrnmals had hiRher levels than young rw,rmals. 'Ihe fihrirNVRen and frhrinolytic behavior observrd in Ihetc .tudics may have inq+(icationt with respect lu thromlxrathcro6cnetis and the physiuluRy of /ihrinolysit which mcrit further investiRation. (/tA.r Rrnntor.: -1 he Natiopal Institule; of ileallh and 'ihe Office of Naval Research. "TFIF?RAPY OF ATRIOVFNTRICULAR NODA1. fA('IIY('ARI)IA " Ry l.ouis A. Srs1oR, MI), and William S. Frankel, MI), ('ardiovascular Uivi sion, 1)cpartmenl of Medicine, Temple Universily Medical SifirKd 1'hda- rklphis, Pennsylvania. From "Mechanisms and lhcrapy of ('ardiac Anhy- thmias," 14th Ifahnemann Symposium, Philadclphia, April 2(r 29, 19hS Puhlithed by Crune & Stratton, 1966. ((Iranlee: Sololl) Atrinventricular nodal lachycsrdits are usually separated into parn.ys- mal and nnn-paro>tysmal types. uistinction of these two types is worthwhile txcause the first is usually benign and easily reca.Rnired, while the seconJ is usually serious and hard to diagnose on clinical Rrounds Ihcrapy nl the parotysmal type is best accomplithed by mechanical measures whic h increne vaRal tone, sedalion or diRilaliratinn. bisital4aticm is also indicated for non paroxysmal arrhylhmias e><cepl when they occur in the diRitalvrd patient In lhis case, Ihc specific treatmcnt is discontinuance of drFilalie trlus the rotsihle use of anli-arrhythmia dnrRs such as pryx-aincamiJc ru .IurniJinc sulfate. (hlirr Rrnntnr.: I/.S Public Nealth Service and the Arlrne Ihcklrr (;rass Foundation, Ilrart Asa+ciation of Snutheaslcrn Pemnylvania "RI?I.AIH1NS1111' III?IWI'FN (:111('OSI? ANI) FAI IY A( II) IN MY(K'ARI)IAt. INVAR('11ON." Ily Lrruis A tir,lull, K11), rnd /lrrnr Schwar'r, MI), 1'h/), I)ivisiun of ('ardiohrRy, lcmhk Ilmver.ny Mrd,ral ('enler, Philadrll+hia, ('rnnsylvania l.onrre 1'44V 452, 1 cbruary lh, Ivnh ((Jrantce: Srrlull ) l he Rlueox and fatty acid resfainses to Rluco.c hradinR were Jrrrr mined in 15 Patients who were eonvrlrscinR frnm myrKardial infarcLi,rn, in 15 trealment-rk(~cn,knt dialxtics, nd in I S patienrt rrn healthy v,duntrrrs who had no evirkncc of hcart disca%e or of Jiatx•tcs 11

All ischemic ratitnls satisfitd the criteria rd chemical dialKles Fivc had :r falty acid res(x,nsc to Rlucnac similar In, hut actually Frcatcr than, the ntxmal and Itl had a fally acid respnnce simdar to the dialx•tics lhtsc 1(/ Palients were also charac'ICr'vtd by a diminishcd inhibition of slcaric acid rekasc provuked by Rlucnse Furthermtirc, all coronary palicnls. the second mup more than tlu first, had a diminishcd capacity tu liberate linn leic acit~on demand. Ortirr Rrenror r l I S. Public Ilcalth Service. "ON MFASl1RIN(i I.FFT VENTRICl1LAR VOI.UMIi" Hy Itruis A. SnhoR, MI/ 1)crarlmcnt of Mrdicine, t)ivision of ('ardiohrRy. Irmple lIni versily Mediral Schcxil, Philatklphia, Pennsylvania llrr Amr.n an h,urnal rr/ ('rndirrfnRy I R/ I 2 S, July 1966 lhe institution of a satislactory technic of tklcrmininR left ventricular volume in man is t.trenxly imfusrtant, for without it orx cannot tktcrmine thc over all (Krwer snd performance of the heart muxlc. Such a definitive technic, howcver, has rxA been rkvehq.rd as yet In Ihis review of the past M) years' eflnrts to measure the volume of the heart as  whole and of llx left vcnlrick, many technics are Ji.cusad. Methods cc.nsidtrcd include rrantRernrhrRy; anRi.carJioRra(+hy, direct vnlumciric mcaiuremenl by indicalws. Ihe cnmhinatit.n tit radirrpryuc dilu- litm curves snd anRinRraphy, snd the use af chanRc in a diameter nr circum- ferencc as an indcR nf change in volume I his la.t mclhtrl apl,•ars Lrnmis- inR but it rrmarni fnr the fulure tit drtrrmint if such fnrmulia are rlyplicahlc to the mormal human hcart and alan to clinical cardiac dnnrtkrs Othrr Rrenter: ll S Public Ilcalth Service. "CAROIAC Ol/IP1/T-, FIL.(N)O PRhSSIIRF ANI) FRFf. FA1-IY ACII) RFSPONSES TO SMOKIN(i IN l 111: NONIIASAL S 1 A 1 F" fly William S. (=rankl, MO, MS. Ronald hriedman, MI), and l.ouis A Schrfl, MI), tkrartrrxnl of ('ardioloRy and the ('ardiovascular Research ('rntcr, I cmlrle Unrversity Medical ('enter, Philacklphia, Pennsylvania. Amr.uun lrrurnnl of rhr Mrdn al St irrxrr 2 S2 / I:)9-44, July 1966. ((7rantoc : Stdu/l ) Other studica have shown cardiac output, cardiac inder, sunle volume and (ree fatty acids to rise after smukinR in the reslinR, hasal sfalr, hul Ihc /xcsent studies were matk in individuals in a nnn hasal state to dctcrmine the validity tit amtikcrs' claims that temions arc rascd hy InwrlinR SiR healthy younR hshitual SnNflcrs, all famthar wilh the inrravascular procedures used, were cmphryed in these tests After riRhl hcart cathrtcrira lion and hrachisl arterial purclure, each suhject smt+kcd 2 standarJ s'veA filter liP ciRarcttrs within 10 minutcs ('ardiac anJ circulatnry paramelrrs were mtasured l.efort snxikinR, durinR smtikinR, anJ I S, lU, /.l/, and 91) min utrs thereafter l'srtlinc ntnpul antl frrr fatty acirls were elrvatt'rl laim tti smokinR In nr,nr id Ihr ~ul,lrrts wat thrrr a ~iPnihtant huthrr ri+c in cardiac rnrtl.ut or I free fatty acids after smoking (except for a hnrdcrline sipnilicant rise in carJiac indc immcdiatcly aflcr complelinn of smoking ) 1 Irc cr hndmRs cast uimc Jrwht on whcthcr tohacco actually escrls any siRnitrc:rnt cflccl on cardiac nutput, stroke volume or hlaxl(rcc fatty aciJs in (hc non basal statt Orhrr Rrenrar: ll. S. Public Flcalth Service. "('IR('IILA'TY)RY VALIIES ANI) NI?MOI.YSIS 1)l1RING PVNIO RARIIIIAI. 1)IA1.-URIi1HANIi ANESIIIf.SIA IN INK7S 1'R1 M11)I ('AII U WIIFI MORI'111N1:." liy C. A. Papacostas, 1. Wciss anrl 1. A Solofl, I)epartmtnts of PharmaculnRy and ('ardioluRy, Icmple Ilniversily Medical ('enter, 1'hilarklphia, Pennsylvania. l.ifr .Scurnr rr 6111 1 1195 - 1199, June 1967 ((7ranlce: Scdufl) l hirty four adult rrxtngrel dogs were given morphine sul/ate su1K utanr- oucly anJ 1(1 minutes later were anesthct'vcd with a miraturc tit /Kntub:uhital and dial urethane From these doRs, control valucs were ubt:rinrd hir nxan arterial Pressurc, heart ratc, cardiac output, stroke vnlumc anJ Iwal IK•ri. pheral resistance. All vcnous blood samples taken in this scrirs showed evidence of nxxlcrate to marked htmolysis. Mechanical fathrrs did ntrt ap pear to he resPtinsihle and hcrrxrlysis apparently resulted frum the usc uf this often employed special anesthetic mi><ture. Orh.r Rrantor.: 11.S. Public Ilcalth Service anJ thc National Ilcart Institute. 111. CnrcinoRentlossiu Stl.diPa "('AR('IN(xiFNIC A(TIVITY OF ISONIATIt)t?, IIYI)RA7.IN1? ANI) IIYURA7.INF. 11(:RIVAIIVt=S." tly ('csare Iliancifitni, MI), Urvisinn of ('ancer Research, l)niversity of Pcrugia, Italy. Annari drrla ra,oha rli M.Jr cina rChirurRia drlla Univrr+ita drRli ,Srudr di l'rruRra 57/ 1 152-159, March 1966. "'iltf RI?LATION OF ISONIAT.11) (INII) ANI) A1 1.11:1) ( UM POIINUS IO ('ARCIN(X:TiNUSIS IN SUMI? SI'U('II?S OF SMA11. I.AIIORAIURY ANIMAIS: A RI-.VIIiW." fly Cesare Iliancdwri, M11. antl I ut'in Srvrri. MI), 1)ivisinn n/ ('ancer Rrsrarch, (lrrivrrsrty r I Pnu~i.t, Italy. Ihrnth lnu.nal of ('anrrr 211/):52R 51111. Srplcrnher 1966 "ISt)NIA711) AN11 AI I.IFI) ('OMPOI/Nl)S AS RF1 A 11 1) 10 1 l/N(i 111M(/RS IN ANIMAI.S" fly I ucro Stvcri. MI), snd ('csarr Ri.tn rh"rr MI). Uiviiirrn of ('anccr Researth, llniversity of I'cnrRra. I/.ily (:.-rh 10/ 4: 167 1R2, I)ccemher 1966. lhcsc,hrct Palars summarin the present stn,r tit scirntih, Arn,v.IrdRc conccrninR thr ihrssihlc carcinrrRcnic aclivily rrl i.r ni;riiJ I INI11, a rhuR used widcly in thc trt•atment trf tulrcrculusis 11 12

r o, I~nniarid and it1 allies, hydrarinc and other hydrarinc Jrrivitives, havc induced lung and liver tumcas in various cancer caaceptihlc and rraiclint strains nf nvice and rats, thus provinR thcmulves to be very cflcclrve carcinn Rens in ccrtain small laboratnry animals Initial labnratnry demonstrations were mark of the carcinogenic action 44 iaoniarid ( IN1I ), after which studies were instituted to identify the mcla- Milic drrivalivcs f•f INII nd to determine whether INII is carcin<+Rcnic in ilwlf or via its metabolites. INII, itself, hrts been shown to Induce lung tumnrs in "alhino," R111, IfAl.11/c, ('57H1 and CBA mice, and to enhance the development of Htown Pearce tumors and Itachcobronchial papillomas in rabbils. Since mer.bolic breakdown of INII resulls in the production of iami- cotinic acid and hyr)rarine (which in turn is converted to ammonia ), ctperi- mental investirations of hydraiine were underlaken These studies demon- straled the ertectivcness of hydrarinc in the production of tumors of the IunR in RALH/c/(b/Se, RAI 11/c/An/Se, ('HAi( b/Sc mice and ('b 1-on- don rats and tumors of the liver in Cf1A/('b/Sc mice. With the implication of hydrarine as a polential carcinogen in man, efforts were made to determinc the biological characteristics of hydrarine- induced lumors In various etperiments, induction time was determined, dose response was demnnstrated, influence of roule of administration was shown to hc neRliRibk and metaslasis and malignant invasion of vessels by these tumors was ethibiled The effrct of hydrarine sulfate on resistanl %pecies was tested in an eriperinKnt conducted with (Z+/Sc slrain rals, a suain noted for its low incidence of pulmonary tumors Of 32 treated rats, 25% had pulmonary tumors and 21% had adenomalous changes by the end of the etpenmenlal period. Other hydrarine derivatives have been shown to induce tumors of the lung and leukemia in HALH/c/Ct+/Se mice, lumors of the lung and ,eukemia In ('f),Fl mice and tumon of the mammary gland in (hlx.rne Mcndel rats. The summation of these es(+c rinxntal facts plus some disturtinR clin- ka1 nburvations suggest that INI1 and irs allied compounds may he related to the deveMprrrcnt of lung tumors in man. In this connection, other e.peri- menlal observations have introduced the possibility that the hrrrrnones of the adrenal cortes are involved in the origin of lung lumnrs. Other Rranrorr Anna Fulkr Fund, New Ifaven, ('nnnecticut. "(;I'Nl:.fl(' S111DIFS ON TNE f?l 101 (1(iY AN11 MORPIIOI.(XiY OF MAMMARY I IIMORS IN MI('F. " fly Wrlliam S Murray, 'nce 1ack.rrn I aMrratnry, Her N.rlKx, Maine. lournal of rhr National ('on4 .r Irnrrrul• 3M1/2:249 257. Fchruary 1966. Ptpcrimrntal use of hyhridiratinn, one of the more effrctive methods for the aturly (if the mammary lumorigenic cnmplct, is harnltcreJ bv sevcral c0rnlrl,c.rinR fa(ror. 1 hc hrrcrnl slurly dcils wilh two of ,hrsc fa(lrrrs: I) I the control of viral uansmission, and 2) the relationship of etiology to lumor morphology. llsinR mice of the strains C3H/Hel (a slrain highly susccprihlc to mouse mammary tumor virus (M1 V) and known to carry the viral prin- ciple in active form), C3NeH/Fe (a strain highly susceptiblc to M I V but one that has a low mammary tunwsr incidence), and MA/My (a strain highly susceptible to MTV but one which has been observed to have no mammary tumrrrs), four reciprocd crosses were carried out lhc first filial generation femaks of these crosses were then bred and observed until they developed mammary tumor or died. F.aaminalion of the dislribulion and morphokgy of the observed tumori led to the following conclusions: 1) The milk-transported M 1 V slimulates the development of A and B type mammary adcnrxarcinomas in early age and early middle age. 2) The other mammary tumors found - lype C, fibrosarcoma, heman- RirxndrNhelioma, and adenoacaothoma, which characteristically develop in Lte middk age and old age aod are independent of the direction in which reciprocal crosses are made - have a aeparate eliolosy. 3) The parallel between the lirne of occurrence of the late mammary tumors and the time spread of appearance of rumors in other organs suP,gesti a common ctioloRy for all late-appearins lumors. Otflrr Rranrorr National Cancer Institute. "GENETIC STUDIPS OF CARCINOGENESIS IN MI('E." fly William S. Murray, ScD, and Clarenoe C. Lillk, ScD, The lackscxt I atwrratory, liar f larbor, Maine. lournal o/ the Notional Cancer Institute 3R/5:619 656, May 1967. (Grantee: Murray) T1re reactions of physiolo6ks produced by various Rcnomet to the presence or absence of the mamm.ry lumor virus ( M I V) were studied throughout the lifespan of 3,630 F, femak mice. Particular atlenliun was paid to the relationship of age and of reproductive eaperience to the rxcur- rerxe of various types of mammary lumon. l)sins mice of the three aforementioned strains ((',11/11e), (',11rH/I-r, and MA/My) plus ('57H1/6 (a strain highly resistant to, and IKlievcd free of. M 1 V), anJ A/I le (a strain highly susceptible to M I V and one which carries Ihe virus in aclive form), seven reeiprrKal ctosses were carrierl rw 'Ihe first filial generation females of the 14 erosus were hrcd aoJ rhrn obxrvrd until they developed manmury lunMrr or dicd Results showed that there was a great increaae in tumru proJorwrn when M 1 V was inurrduced by the lrmale 7 he re%ulrs al.rt ohrrwrJ , I.rr ly that genetically di0crenl physrnloRies, when suhjecred to M I V.uirnul.uun, developed their tumors over eharacteristic age spreads that cnrrnnh:n.rd rhr 41h through 19th month; those phyainlrrRies which received no M I V ttimu lation devehrped thc great bulk of Ihrir Iumrna at aOcs rrf 211 nurnrhe rrr mruc lherefore, ap,e dittrihulirm of earty turnurs alqrars to dclrcnd un f41I V ,j (D 14 15 r j

i ~r I s ~ .+., ~..r ~ ,., rn .- ~ m Q, ird J e t.~ ttimulatinn and (m mcthrK) of tranamistinn I atc alqpc:rtinp turnnrs :ur indc- rcndcnt n/ these factors. Ccrtain s/*cculatinns and hylMithrtcs arc Incu'ntcd Jcalirnr, with malc trantmissinn (•f the mammary tunxrr virus and rtt rcl:rtinn trr thc nudulrr'cnic virus. ()tt1er Rranrnr: National ('ancer Institute. "INTRINSIC FACTORS OF PULMONARY ('AR('IN(NiI NFSIS U1= Tllli MUUSF: 1?FFECTS OF NliONAfAI- IIIYMF-("IOMY." Hy Rtxlolfn Rihacchi, 1)M, AV, and (iaetann (:iraltb, 1)M, 1)ivition o( ('anccr Rcsearch, llnivcrsity of PeruRia, Italy I avuri d.lflv,rur.r dr nna- Inrnra r itfnLrRia (.arnln><rca drlto (InivrrfTrd drRlr Srudr dr I'nuitro 2lr/ I 1: 127-1)6, 1966. ((iuntee: L. Severl ) In Ihii study of the eRctis of thyrnectomy upon lung tumor development. 204 male and femak BA1.8/c/Cb/Sc mice were divided into three groups. One group was Ihymrctomited at birlh, one "sham nrcratcd" and one kept as a cnntrol All mice, treated anJ untrcated, rcccived a sinRle intral.cri- toneal injcctimon td 9 mg urrthanc at 10 14 days (if aRc Arprrrzimatrty 17 mice from each pnur were then tacrifsccd at St), 70. 91/ or I I11 rliyt after treatment Among the mice sacrificrd at SO d.ys, I11O^;, (if the Ihymccl4rnrin-d mice had multiple IunR tum,rrs, whrIr only r,r, h"- rf thc "shim nlti r.rt,.1" and 64 7'"n of thc cnnUol< <hrr.. iI tutnl.ir I,n,hnp. I hrt rn,u.rl Aill, rcncc rlia- arrcared tatrr, snne atl msrc krllcrl ,r It,, vn I tU ,L,yc h.u1 mnll,l-lr lung tumors Ilnwcver, thr avrrarr nruntrr „/ luny tnrn„rv IMr m,.ucc wet always higher in the thymct tomvcJ rrmnlr thin rn rrthcr Ihc ',h.nn rqK•r:urd" animals or thc crrntrolt The results of this e>t(•crinxnt shaw that nennatal thymcctnmy favors the antet and development of urethane-induced lung lumrrrs Since thyrnec- tomy acls to reduce or inhibit the imrnuno(rrietic capacity (if the mrruse, it is eonsitkred that immumx/erentknce constitutes a new in,rinsic f.rctrrr which. k+nR with Rerxtic, environmental and pnssihle hurmtrnal facttns, infhrcnccs pulmonary tumor development. IV. Srttrl«, at thP Cr'llrtlrrr 1,err'l "PFIOSPIIOI.IPlI) SYNIIIFSIS IN 1111' I.AR(lli P(1I MONARY A1.- V1:OL.AR 11-S RI?I.A 1'1ON lO L.l /N(1 Sl /RFA('1 AN I S" Ily Sue 1luckinRham, MI), 11 (1. llcincmann, MI), Sheldon (- Srrmmcrt, MI), and William F. McNary, Phi). I)rpartmcnls n/ I'rdintrics. Mcdreinr and PathnHoRy, Columhia Oniversity ('olleRe (if l'hysiciant arrd SurRcnnt, and Francis I)elafic/d ifntrilal, New York. N Y., and the 1)chartnrent of Anatnmy, flr+atnn Univertity Sch4wrl of Medicine, Matt. Amerrr an lnurnal rrl I'nrhrb,rv 4R 6 11127 11/4I, lunr 1966 ((;rantcc' S 1luckinpham) lr, . 1 In an attempt to confirm the preferential incorlroralitrn trf acrtatc and pilmitalc into lung kcithin and to ckmtmslrate Ihc hrcah.-aturm (if Ihcse reactions in the large pulmonary alvcolar cellt, the uptakc and dnuihuthrm of lahclcd acetatc and ralrniule into lipid fractions of IunR wcre studied in rahhits, and the cellular kocali»tinn of the synthetic reactirrns was csamincd by means of scrial autoradiographs. Similar studies were carried uut on corresl.nndinR liver tissue for comparison. 7 hrcc groups of three White New Zealand rabbits each were treated respcclively with Iritiatcd sodium acetate (specific activity, 145 nK per mM ), tritrum lahekd palmilate (256 mc per mM) and (rilium Iahekd palmitate ( 21)0 mc per mM ). 1 he animals were sacrificed 15 to 90 minutes after intravenous injrclion and lung and liver specimens were subjrctcd to micra scnpic r.amination, auttxadia6raphy and lipid analysis. Onc half as much palmilate was taken up by lung as by liver (Rrarn (tx Rram ). In lunR, howevcr, palmitate was rapidly and preferentially incorrtr rated into phrnpholipids (>1S% ), mtnt of it (60% ) into lecithin In the liver, the label was equally distributed between the neutral and Irhosphulipid fractions. t.unR tissue per unit weight was twice as active as liver in incur(arrating 'If acetate into lipids Acetate was also metahulired rapidly into phntrhr, lipids in the lung (90%), cspccially into kcilhin (h(1`)'~ ): the liver uulrnd acetate to form varinus lipid components. Within the phnsphatitks of lung, the C,. (palmitalc) fraction accunro- latcd nearly all the label following either acetate or ralmrt:rtc, in the liver phns(rhatirks. both precursors were distributed ur cunvcrtcd into varirrus ratty acids. Autoradingraphic sludics of lung tissue Irom trcaled rahhitt shuwrJ silver Rranulet, indicating radioactivity, in the cytoplasm of the large alver,lar crlls by )t) minutes after injeetion. No other lissuc ekments, eaccht (ur an oecasional alveolar macrorhaRe, preuntetl evirknce of rarlinictive lahrl ing I hete silvcr grains were found bctwcen, hut nul intidc ol. Ihc tharai ter istic eylorlasmic inclusions of these cells. 'Ihesr findings are discussed with reference tr, the frrrmitirrn and turn over of lung surfacunt phospholipids. I)rhrr Rrantor: United States Public Health Service. "/'lll M(1NAR1' AL.VI'OIAR LFSIONS IN VA(i()1'()MI/1 I) RAIS" Ny Victor 1: (lnhknhrrR, MI), Suc lluckinrharn, M11, and ShrlJnn (' S.rro mcrs, MI), 1)r(rartrncnts of 1'alhuloRy anrl 1'cdiari, t, ('nlumhre IInrvcrarty ('ollrRe of rhyticians anJ Surgcont, and francis (h•L.JocId Ilrnhnal, New York, New Ynrk /oh.rrarury lnrrttrRorirrn 16/ti 691 IUt, M.ry /9hl .(Grantce: DuckinRham) I.unRt of rats wcrr studicd hy IiPht and elcctrrrn micrrracrqry at I tr) h hnurs alter vaRutr,my I he sahent hndinRt in thc rutrnunary alvrr,h ul Ihrsr 17