AXTELL, HK

HERMANN, G

MARCHIORO, TL

STARZL, TE

WADDELL, WR

English

PubMed

Starzl, TE

Hermann, G

Axtell, HK

Marchioro, TL

Waddell, WR

Name not available

Failure of sino-atrial nodal transplantation for the treatment of experimental complete heart block in dogs

D-Scholarship@Pitt

FAILVRE Ob' SINO-ATRIAIJ NODAL TRANSPLANTATION FOR T H E  TREAT3II':NT OF EXPERIRIENTAL CORIPIJETE HEART BLOCK I N  J)O(iS '1'. E. STAXZI,, LI.1). G. HERMANN,  MI). H. IC. ,lSTET,IA, R1.U. T. T,. RZARC'IIIOIZO, K T ) .  ant1 IT. R. IV\'AI)I)ET,L, M.U. Deliver, Colo. From the Departments of Surgerj ,  Ilni\erslty of Colorado Me~lical Center. an,( the \'eterans A d m ~ n i s t r a t ~ o n  Hospital Reprintecl from THE JOURNAL O F  TIIORACI(' ANI)  CARI)IOVAISCUTAXR SURGERY St. LOUIS ITol. 16, No. 2, I'ageu 201-206, August, 1963 (Copyright 0 1 9 6 3  by The C V Mosby Cornpany) ( P r ~ n t e d  in the IT S A ) FAILURE OF  SINO-ATRIAL NODAL TRANSPLANTATION FOR THE TREATMENT OF  EXPERIMENTAL COMPLETE HEART BLOCK I N  DOGS '1'. E. Starzl, M.D.,* G. Hermann, M.D. ,  H .  K.  Axtell ,  M.D.,  T .  L. Marchioro, M.D., and W .  R. Wadde l l ,  M.D.,  Denver, Colo. W ITH sy~xiptor~latic c0111pIete heart block, the principal circulatory derange- rilents are secondary to braclycarclia.?, "ffefeive therapy, therefore, do- pends on iilcreasi~ig the ventricular rate. This has been achievcd with pharn~w- cologic agents or  with electrical stinlulatiorl of the veritriclcs with internal o r  esterrial pacemalters. Recently, a different approach has been snggcstcd by Ernst,' based on the proposition that  anriculo-ventrict~l~~r conduction can be rcstorcd by transplaii- tation of the sino-atrial (SA) tiocle into the ventricular niyocardium. Although the results of his stuclics with clogs supported the potential clinical use of this technique, Ernst took care to point out that  he had not 11cea able to carry out the crucial espcriment necessary to  establish its ralne. Such an experinlent woulcl necessitate the procluction of proved permanent co~nplete heart block, and its subsequent effective treatment with SA nodal transplantation. I n  the present study, SA nodal transplantation was carricd out under. circumstances in which success or  failure coulcl be ascertained with certainty. Complete heart block was established in 9 dogs. 2 to 9 weeks before nodal transplantation, to establish the fact that  the heart block was permanent. Thc SA node \\-as then traiisplanted, and the animals were observed for as long as 3 months for evidence of restored aariculo-ventricular conduction. Thirty-screii mo~igrel dogs, weighing from 10 to 20 kilograms, were usecl. With the use of a previously described t e c h n i q ~ e , ~  complete heart block was produced (Fig. 1) with placement of the atriotonly so as to avoid the nutrient artery to the SA node. Postoperatively, the a ~ l i ~ ~ ~ a l s  were allowed to recover for an average of 28 days (range, 14 to 66 days) during which time daily pulse rates were From the Departments pf Surgery, University of Colorado Medical Center, and the Veterans Administration Hospital, Denver, Colo. Aided by Grants A-634 1 and A-6283 from the I:. S. Public Health Service. Received for publication Feb. 18, 1963.  'Markle Scholar. STARZL ET AL. J. T!~oracic and Card~ovas.  Surs. counted and electrocardiographic confirmation of the complete heart block was obtained a t  intervals. I n  those ariinials with permanent idioventricular rhythm, SA. nodal transplantation was carried out. The original iricision through the right fourth intercostal space was re- opened with the animal under Pentothal anesthesia. The technique of SA nodal transplantation was essentially the same as that described by Ernst.* The SA node arid its inferiorly based pedicle wcrc drawn into a noncrushing clamp , Rt. ventricle 4Pericardium OriEice of coronary stnus Fig. 1.--First operation. Production of complete heart block by incision of the bundle of His (luring temporary inflow occlusion. Atrial incision is kept away from prospective pedicle. (Fig. 2, A ) .  After dissecting thc pedicle free, the resulting defect in the atrial wall was closed with continuous 5-0 arterial silk (Fig. 2, B) .  To insure com- pleteness of excision of the SA node, a portion of the wall of the superior vena cava was included. This invariably produced narrowing of the inflow tract of the superior vena cava which was well tolerated. Vigorous bleeding from the tip of the pedicle was always observed. After noting the presence of auricular contractions throughout its length, the tip of the pedicle was implanted beneath the epicardium or within the myocardium of the right ventricular wall and fixed with a few 6-0 silk sutures (Fig. 2, C ) .  The chest was closed with water-seal drainage. After SA nodal transplantation, pulse counts were obtained daily. Electrocardiograms were obtained every 7 to 10 days until the animals either died or were sacrificed. Complete autopsy was performed in every case. Particular attention was directed to the site of SA nodal transplantation, where multiple sections were obtained and stained with henlatoxylin and eosin as well as trichrome stains. 101 46, \ o  ? Augo't, 1063 EXPERIMESTAL COMPLETE IIEART BLOCK RESULTS Experinzental Success Rate.-Of the 37 dogs originally entered in the ex- periment, all but 9 were eventually eliminated for two reasons. (1) I n  20 ani- mals complete heart block either could not be produced or, more commonly, reversion to a sinus rhythm occurred subsequent to the original operation. (2)  Eight additional animals died during or within a few days after the SA nodal transplantation. Period of Observation After SA Nodal Transplantation.-The 9 dogs meet- ing the full criteria of the experiment were followed (Table I) for an average of 65 days (range, 11 to 97 days). Six of the dogs were eventually sacrificed, and the other 3 died spontaneously. Fig. %.-Second operation. Technique used for S 4  nodal transplant. 28 38 24-30 Yes 30 I1  50-55 Yes 19 77 32-44 Yes 14 78" 35-55 Yes 14 97* 48-54 Yes 66 76* 35-55 NO 28 59* 48-50 Yes TABLE I. -. - ~ 8 27 66* 45-55 No NO 9 24 84% 50-65 Yes No DAYS BETWEEN SA TRANS- IIEART RETURN OF PLANT AND 1 RATE HEART A-V CONDOC- DEATH PER MINUTE FAILURE TION - SO.  DAYS BETWEEN HEART BLOCK A S D  SA TRANSPLANT STARZL ET A L .  J .  Thoracic and Cardiovns. S l ~ r c .  Varintio?zs in Idioventriculur Rhyt1zm.-Idioventric~ilar ratcs ranged from 24 to 65 per minute, and in  most dogs was 40 to 55 per minutc. I n  a givcn ani- mal, the rate varied little from day to day during the rest of its life. Similarly thcre was no electrocarcliographic evidence in any dog oC a change in  the idio- ventricular rhythm after SA nodal transplant. The dissociation of auricular and ventricular beats was complete even after 97 days. F~K. : .-Dog. S o .  7, 8 \vcvl<.s a i t v r  SA noclal trnnsl)lantntion. Section through the tr.ans- plantntion s i tc  in thv r i s l ~ t  \'entri(,lc. rl Pi11,kinje flbrl-s o C  SA node. b ,  Viable aur iculnt  musrriu. c, Ventt.icular myocardium. d. Fibrous'union. e .  Sut r i t ' n t  ar tery .  A u t o p s y  Findings.-Seven of tile 9 animals had gross and/or ~nicroscopic evidence of various stagcts of l r f t -  and right-siclcd heart  failure. The SA nodal transplant was always easily seen (Fig.  3 ) ,  and att;lched to the surrounding tissues with a fibrous union. Amicular inuscnlar or conduction tissue was iden- t~fiable, but sometimes strophic. Thc s u b j a c ~ n t  myocardium often had some evi- dence of degeneration. IIyaline cartilage forlnation was occasionally observed. Cont1-01 P1-oceduj.es.-Five dogs not included in  the dcfinitite series were studied to determine ( a )  the effect of procainization and remo-cal of the pediclc tip and (b )  the possible role the contracting pedicle might have in mechanically stimulating the vent~icle.  I n  3 dogs, the SA nodal pedicle was prepared as described above. The tip naq first injected with 1 per cent procaine and then excised. I n  one dog, the p Val. 46, No ? EXPERIMEh-TAI, COMPLETE IIEART BLOCK August, 1963 waves disappeared for several hours, in another the amplitude was diminished, and, in the third, the auricular rate slowed. Similar alterations have been ob- served by Riberi and his associates2 with injection of procaine into the SA node. I n  2 dogs, an auricular sling was devised (Fig. 4) immediately after the produc- tion of complete heart block. The ventricular contractions followed the auricular beat for 24 to 48 hours, at  which time the idioventricular rate returned. At autopsy the auricular sling had become attenuated which accounted for the loss of mechanical stimulation. Fig. 4.- -Formation of auricular sling which a t  first mechanically stimulated ventricular beats. As the sling became attenuated, the idioventricular beat returned. DISCUSSION The recent ingenious experiments of Ernst,l if confirmed, would have a far-reaching practical significance in the clinical therapy of complete heart block. EIowever, two considerations have made it neccssary to subject the method to further analysis. First, the concept that conduction can occur across the scar of the implantation site is contrary to well-accepted opinion on the requirements for cardiac excitation. Second, the experiments cited, while suggestive, did not conclusively prove the therapeutic value of SA nodal transplantation. Aside from providing firm evidence that SA nodal transplants are not capable of ventricular stimulation, the present experiments indicate how easily systematic artefacts could be introduced into an evaluation of this sort. I n  order to perform a complete experiment in 9 animals, a total of 37 dogs were used. I n  20 of these, permanent complete heart block could not be obtained. The usual sequence was the initial production of heart block with reversion to a sinus rhythm hours or days later. If the SA nodal transplant had been previously done, it might have been concluded that its presence accounted for the resump- tion of a sinus rhythm in two thirds of the animals studied. An additional potential source of error could be mechanical stimulation of the ventricle by the mechanical tug of the transplanted pedicle. Although short- lived, this effect was demonstrated in the present study with the use of an auric- ular sling. SUMMARY SA nodal transplantation, for use in the treatment of complete heart block, has been evaluated. Complete heart block was surgically produced weeks or months before SA nodal transplantation. After transplantation, the animals were STARZL E T  AL. J. Thoracic and Cardiovas. Surg. observed for as long as 97 days. Transplantation of the SA node had no in- fluence on the pre-existent idioventricular rhythm. I t  is concluded that there is no justification for a clinical trial of this technique. REFERENCES 1. Ernst, R. W.: Pedicle Grafting of the Sino-Auricular Node to the  Right Ventricle fo r  the  Treatment of Complete Atrioventricular Block, J. THORACIC SURG. 44: 681, 1962. 2. Riberi, A., Shumacker, H .  B., Jr., Kajikuri, H., Grice, P. F., and Boone, R. D.: Ventric- ular Fibrillation in the  Hgpothermic State,  Surgery 38: 847, 1955. 3. Starzl, T. E., Gaertner, R. A., and Baker, R. R.: Acute Complete Hear t  Block in Dogs, Circulation 12: 82, 1955. 4. Starzl, T. E., and Gaertner, R. A4.: Chronic Hear t  Block in  Dogs: An Experimental Study, Circulation 12: 259, 1955. 

FAILURE OF SINO-ATRIAL NODAL TRANSPLANTATION FOR THE TREATMENT OF EXPERIMENTAL COMPLETE HEART BLOCK IN DOGS.

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FAILURE OF SINO-ATRIAL NODAL TRANSPLANTATION FOR THE TREATMENT OF EXPERIMENTAL COMPLETE HEART BLOCK IN DOGS.

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