Document 6J8DNR01e9dL8V6dmz7r38J6

We^le.v' /f*J-/AS3U h, r -x-- a The Influence of Polyvinyl Chloride (P.V. C.) Tubing on the Isolated Perfused Rat's Heart By K. L.jlUKyusa, 31.D., A. F. Wii.iajihamw, 3J.Sc., J). 31.J). 1l'i//i //if technical ttssiatuurc of V. Grniijf mi<l G. ]. ho Perfusion nf the isolated rat's heart through certain types <>I' polyvinyl chloride tailing results in a deterioration <if cardiac performum-c. Since plastics are commonly used ju henrt-lung machines and transfusion-gcta, this observation tuny he of some importance. HE isolated heart of the rat perfused Wy cnmmla (C, tig, 1) in the aorta of the aiustln- Tthe Langeiulorfi: toelmie1 can he kept beat* tized mid heparinized animal, tlic heart was i". jug for many* hours. Over a period of several moved and connected to Hie perfusion apparatus. The jerfusion fluid was innlrhcd as closely as po>. years we have performed hundreds of such sible to the coinjssilioi of the e.vf ivieoJhilnr fluid experiments without difficulties. of the nit,3'7-* The perfusion fluid was saturated In `20 consecutive perfused heart experi with 5 per cent CO in oxygen (.1, tig, l). The ments, the electrocardiograms and imhictoeardiograms3 of the isolated heart were found unchanged for periods of 4 hours or more. Subsoipient expansion of our lalioratorv facili ties made it necessary to rebuild our perfusion pir of the perfusion fluid was 7.5.V Has hithhhs were evacunh-d by huhlilc traps (H, tig. 1). The jwfusirm fluid reached the Jieart b.v 2 iden tical circuits, one including a bottle of 750 ml. eonbiining 500 ml. glass pearls, the other nit idea* tiesd tattle containing 50 ml. of P. V. C. slices with apparatus. After this, over 50 successive per a thickness of 2 to 4 mm. and a diameter of S to fusions proved to he unsuccessful. Premature eardiae .arrest mid ventricular fibrillation oc curred. Calcium. epinephrine, strophanti)in and mniuophylliuc, added to the perfusion 12 turn. Before every cxperimeul the P. V. ('. slices ami the glims pearls wen- rinsed with dis tilled wafer. J'effusion pressure was regulated by altering the height of perfusion fluid container'. Every experiment was started by perfusing the fluid, were ineffective in combating tbc de heart via the glass circuit for 10 to 211 min. Simul terioration. A thorough investigation of the perfusion fluid did not reveal any change in ehemieal composition. Perfusion pressure was constant throughout all experiments. It taneously the ]M`i`fii.siou fluid was allowed to pass through the 1*. V. C. eireuil. The perfusion ve locity' in both circuits was about 2l> nil.miii. The fluid siMikisl about 15 min. through the I'.V.C. be fore it leached the heart. This was estimated with seemed possible, therefore, that the polyvinyl tlie use of methylene blue, liy means of the stop chloride tubing which had been used instead of the glass tubing in the original set-up could he the responsible factor.4** Experiments were therefore designed to test cock (K, lig. 1), perfusion of the heart through glass or plastic was alternated. The glass spirul.(S. lig. 1) Were Used to nuiintnii) the fn'i-iu-im, fluid at the desired temperature of 5S* C, The mechanical activity of the heart was re this possibility*. corded by means of a small Tiennal niagnel (.V. Methods White rats weighing about 25U Cm. were used lbr Hie experiments. The j>eifu*ioij apparatus is depict'*! in figure 1. After the insertion uf a fig. 1) attached to tin* ajs-x of the heart (//.tig. I) ami placed in the con* of a coil. Cardiac mntfac tion caused (he magnet to move up ami down. The resulting potentials in the coil induced by the movements of the magnet were amplified ami re. From tin* I'niversity of Amsterdam, Department of Cardiology, Willielmiiiu (histUnix, Amsterdam. Supported in part liy grants from Hie Netherlands Organization for Pure Heseareli (Z.W.O.), The Hague, Tlic Ncllierlari'ls. rnrdcd by an ordinary direct-writing eleetrocardingraph. The record was called "imhictncanlio. gram.''* Results and Discossion 'I'he passage of perfusing llniil through the Iteeeived for publication July SO, 1959. polyvinyl chloride tubing resulted in a <!*- VIII. Jw `i'v 20544001 BFG03832 T PVC Ttim.VG OX PERFL'SED HEART Kina f e.v.c. !nvf*tiiralefl: Table 1 A it e D K Toi 11I Xmn l>r of lic:i rts : Xiuiilicr of investigation:!: Cnriliotoxic effect: *"*'positive within 15 min. 7 `J *J "J 4 14 4 4 4 (i 14 (J 0 17 Dhtf/nimmatu! representation nf the set-up used to iUrestif/ate the influence of pnlyriuirt chloride on the inechnuhttl activity nf the isolated perfused rat*s heart. For details see text. terioratioit of the heart contractions within 10 min. (.1, table 1). Figure 2 shown the induetocardiogram of a heart perfused in suc cession via the glass ami the P.V.C. circuit. During P.V.C. perfusion the contractions of the heart diminished considerably and be came irregular. After restoring glass per fusion. the mechanical activity increased but did not attain the previous level. Perfusion with fluid from the P.V.C. reser voir {.l, table l) caused a progressive deteri oration of contraction. Resumption of per fusion with Huid from the glass container did not restore the mechanical activity of the heart. The effects of P.V.C. perfusion were additive. Circulation Reteareik. Volume VIII. itawnt IHO A total of 17 Hearts was US4d to investigate "> different types of polyvinyl chloride tubing and the results are sunmiarized in table 1. Chemical analysis of sample A (which is .strongly toxic to the'heart) ami of sample 11 (non-toxic) revealed the following: P.V.C. brand: .1. Plastic: Polyvinyl chlor ide; Plasticizer: Content--W.7 per cent. The plasticizer concerned is an ester of phthulicaciii, probably di-2 ethylhcxyl-plitlmlate: Sta bilizer: An orgnnie tin compound. The organic part .f the moleeule is unknown. About 1 per cent of this stabilizer was used. P.V.C. brand: ft. Plastic: Polyvinyl chlor ide. Plasticizer: Content--per vent. An ester of phtlmlie. arid, probably di-2 ethylhcxylphthalate. Stabilizer: A Imrinm--emlmintn stabilizer, with an excess of barium. This means that a mixture of barium and cad mium salts of fatty acids was used for stabili zation. Prom the above data the following eonclusious were drawn: The polymer proper (polvvinyl chloride) common to ls>th samples is not responsible for the eardiotoxie effect because only sample A is deleterious to the heart. The plasticizer does not cause the effect either. It should bo noted thut in case the plasticizer were the cause, it would rapidly be extracted by the salt solution from the more elastic tube with tin* higher content of plasticizer, ami mueh more slowly from the hard tula* with the lower plasticizer content, in the latter ease, i.e. if the plasticizer were the cause, the effect would also Is* olwcrved at tin* harder tube in a retarded way. As this was not observed, the plasticizer cannot be the cause either. ;V ; -f ;z i f i4 i'% ji 8 *-s 4* H rf* .. i 8 BFG03833 T I 4G ISmlfi 40ml it IS min Figure 2 The indw (oettnlbifirnin of on isolated rut's heart, perfused su<ees$iee)ti riu the <thixs circuit. the ]dttviu</l chloride ein-uit "nil the //hiss /ircuit uguin. Paper speed JO tutu./see. The remaining possible cause is the stabi lizer. It appears tliat the barium-cadmium stabilizer has no disturbing effect, whereas the organic tin compound has. Furthermore the e.xtractability of the compounds in question with a salt solution can play an important role. It is possible that tooth materials may )e toxic but only the latter can be extracted by the perfusate. If in both cases one added chemical would be concerned, the extractability is larger in the soft elastic product. It is possible that traces of an emulgator likewise play a part in tlic process. Further tests arc necessary in order to obtain better understanding of the mechanism that is responsible for cardiac de pression. Summary Some brands of polyvinyl chlorides inter fere with cardiac contraction, whereas other brands do not. Chemical investigation showed that tlie stabilizer is most probably responsible for the cardiotonic effect, it is suggested that wiij.kp.k.wds, ihkkku all types of polyvinyl chloride nsofl ft,r (nodi cal and 1 )iohioir;d applieai ions should be tested with this tochiih-. Acknowledgments The |1 resent itiiilmi- :in vii> grateful in Mr, K. Tmth-ler, i,h,ni. dr*., I lireetyr the I * L;< -(i<* < tie search Institute T.N.O., Pelft. t'ur hi- a"i'tnrn'e :iiul advice. W`o arc indebted li> tin- 1 *11i 1 i[ s *'u., Ki mUicneii, Holland, for providing us with t Uo rleet r<*rn oiin Knijili. Summario in Interlingua Forte typos iti* ctiliiriii'o pnly vinylic interfere hcentmetion c:inliao durante ipio atlrres tin milh* to] cflYcfo. Fn investigation ehimic prmnv.i con ;i11< grados de probabilitnte ipio )< slabilisator es rcsptmvibile (r< Ic elTcrto rjirdiuloxic. Ks proponitt' ipie oninc typos ile rlilnruro polyvinylic usutr in applica tiono* medical i* biologic deliercn Osser testate per lr tecliniea hie describin'. References 1. 1,a.v<;>:.vik>nk>', O.; Utjlersiichungen am ii<ciK*In den Situgcthierhcrzi'ii. i'lliigers Arch. 61: l!9l. 1895. 'J. MrYLER. F. I,., Ilona, Clir.. anp OrtKKUNS, F. I*. J.: A simple method for ttu* reeunliny of the cunt met ion* of the isolated rat's heart, if necessary together with tin* rhvl rin ardiugi am. Arch. lut. Physiol. I'Uiehrm: 66: thfl. lt'.'s. Meyleh, F. J,.. opfKin.i.v.s, F. c. j., tvmr llftANDS, A. I'\, ANU liKOKV. ,1.: Col't I'iirt ir tiK'Chniiisiiu* cn cluktrotyHiiiisliiuidini; v;m hel geisolccrde, ovcrlevcmle rattehart, mode in \er- band met dc working van in.sulinc. Nel. T. I'ti.-jieeskninh'. 103; ]47!, ]<>n9. 4. MaI.TKN. K. K.: lSorocpscksiTin bij hel vru m ken van kunststotTeii in hot biezondor van Oliverzadigde polyester harseii en ncthoxylino liaison. Thesis, Amsterdam. It'.'ii. NriCWAKT, .1, W., AND STl'HkMxa-, M. Hemol ysis eaused by tubing in extrncnrporenl *-ir rutation. The Taneft : 1: :',4tt. IP.'ii, li. Srt:ar,c. t*. K.: Tetters to the J'Miloc; ''Tubing materials." Tin- 7,ai.....I; 1: 419. li.`P. 7. WTstkkink, l)., (im:iti.ixs, F. ti. \yn Wn.i.r iiiUNns, A. IV invt.....1 van Kalinin *leti eientio o]j hot gehnlle nan water en elect rulyten in serum on .spierwerfsel bij Jc mi. Ned. T. (teneeskunde. 99; Vdi-py 195.5. M. CUrKHUNs, K. <i. Over hot verlunul tu--ej, K'nliumdeliciont ie, s]>i:rpara lyses en insuline. Thesis, Amsterdam, 1955. Cirriilatiun HiKMircA. \'olnmr I'Jlf, Juntntry H`ki) 20544003 T