Reduction of the Oxygen Utilization of the Heart by Left Heart Bypass

Transcription

1 Reducton of the Oxygen Utlzaton of the Heart by Left Heart Bypass By Clarence Denns, M.D., Ph.D., Davd P. Hall, M.D., Juan R. Moreno, M.D., and Ake Sennng, M.D. Downloaded from by on January 2, 219 Keports of support of the heart n acute falure both n man 1 and n expermental anmals 2 " 12 have been publshed. The means nvestgated nclude: (1) heart-lung bypass, from the cava through an oxygenator and pump to the aorta; 1 ' 1 " 12 (2) veno-arteral pumpng wthout oxygenator ; 2 ' 3 ' 7 ' 13 ' 14> (3) aortc synchronzed counter pulsaton to lower the pressure durng left ventrcular ejecton and to rase t when the valves are closed; 8 and (4) left heart bypass, from left atrum to aorta. 8 The studes here reported have been done smultaneously wth our development of a smple method of nearly complete left heart bypass wthout thoracotomy, adaptable to clncal acute left heart falure whether from coronary occluson, mtral dsease, or aortc stenoss too severe to respond to the usual conservatve measures. 15 It s essental, therefore, to settle the dsputed queston as to whether partal cardac bypass can reduce the oxygen utlzaton of the heart. Left heart bypass has been nvestgated here for the further reason that t s bascally less complcated than heart-lung bypass, 11 or the Harken method, more physologcal than veno-arteral pumpng, 7 ' 14 and appears to us more susceptble to performance under precse control n the laboratory. Methods Seventeen mongrel dogs (18 to 27 Kg.) were anesthetzed wth ntravenously admnstered tho- From the Thoracc Surgcal Research Laboratory (former Assocate Professor Ake Senng, former Head) and the Thoracc Surgcal Clnc (Professor Clarence Crafoord, Head,) of Karolnska Insttuted Stockholm, Sweden. Dr. Denns' present address: Department of Surgery, College of Medcne, Downstate Medcal Center, Brooklyn, New York. Supported n part by grants and fellowshps from the Natonal Heart Insttute, Bethesda, Maryland, and by a grant from the Amercan Heart Assocaton. Presented at the meetng of the Amercan Heart Assocaton, Mam Beach, Florda, October 21, Receved for publcaton September 12, pental sodum (3 to 4 ng.), supplemented us needed wth thopental or pentobnrbtnl sodum, and placed on the left sde. Thrty to 5 per cent Oo was gven wth an Engstrom resprator. The establshed technque conssted n securng 1 a cannula n the coronary snus by a lgature just dstal to the vena magna, cords, from whch a Y-tube led ether back to the rght atrum or to a condom attached at the level of the top of the atrum and supported dstally by one pan of a balance. Snus blood flow was measured by stopwatch and clamp occluson of the atral return tube at physologcal pressures (6 mm. I.D. throughout cnnnul.-, and 4 cm. of tubng) (fg. 1). For the bypass crcut, blood was draned from the transseptal cannula, 15 a cannula n the left atral appendage (abandoned because of poor maxmum flows), or a cannula, n the upper end of the left atrum (abandoned because of ar embolsm). It passed by sphonage through an AGA flowmeter* to a flexble-walled chamber placed 8 to 9 cm. below the atrum, from whch a, roller pump returned t to a proxmal femoral artery (fg. 1). A large sde tube permtted rapd addton or removal of blood. There was no bloodar contact. Blood and blood crcuts were prepared aseptcally; the surgcal technque was clean, not aseptc; and penclln and streptomycn were gven before dssecton. Heparn (3 mg./kg.) was gven after prelmnary dssectons. A mercury manometer was used for arteral blood pressure eght tmes, an Elema Mngograf 42B wth 1-rnn. polyethylene cannulas, nne tmes; the latter was also used for left ventrcular and left arteral pressures four tmes. A water manometer permtted mantenance of central venous pressure durng experments always wthn 3 cm. of the control, and always below 1 cm., except once when t was delberately rased. Temperature was held between 36 and 39 C. The electrocardograph was used to record pulse rates at tmes. Coronary snus blood samples were taken through a stopcock n the tube to the condom after two or more flow measurements. Arteral samples were drawn through a 1-mra. polythene catheter n the aortc arch. Blood was drawn nto standardzed slconzed syrnges, whch were sealed and l-efrgerated untl O2 determnaton (maxmum three hours). Although early exper- "Aktebolaget Gas Accumulator, Ldngo, Sweden. Crculaton Research, Volume X, March 1962

2 LEFT HEART BYPASS 299 Coronary snus dranage 7 CONTROL OBSERVATIONS Iwl/aul by past) EFFECT OF CHANGE IN BLOOD PRESSURE 16 - kg. t th*pt*rd dog m I' 3 Clamp & stopwatch for flow measurement 11 s 1 'n ' ' Downloaded from by on January 2, 219 Roller pump Flexble sphon chamber (SO cm. below atrum) FIGURE 1 Extracorporeal crcuts. A aannula s secured n the coronary snus by a snug purse-strng suture just dstal to the vena magna cords. Blood from ths returns to the rght atrum. A Y-connecton wth condom attached permts flow determnaton by balance, stopwatch, and occluson of return to the rght atrum. The major crcut drans the left atrum through a> transseptal jugular cannula, through an AGA. flowmeter, to a flexble-walled chamber 8 to 9 cm. below the left atrum. Blood s pumped back to a femoral artery wthout contact wth ar. Transfuson connecton not shoun. merts used the Kpp method, 111 all conclusve ones employed the Van Slyke 17 or the speetrophotometrc method (Beckman). 18 All blood O 2 determnatons were n duplcate; all flow determnatons were multple (two to fve runs, usually three). Observatons were dvded nto two categores. Tr category I, all preparatons were made, but no bypass was used; the effects of changes n blood pressure secondary to wthdrawal or addton of blood, and the effects of mnute gas embolsm and of manpulaton were assayed. In category II, observatons were made n pars, one durng bypass and the other wthout t. Except for two nstances (see table 2), the control ether mmedately preceded or followed the expermental run. Control and expermental runs were less than 1 mnutes apart n half the experments, as long as 26 mnutes once, when flows wore run n qnntuplcate (here controls both preceded and followed the expermental run). The mean blood pressure was held nearly constant n the two runs of each pared observaton, that n the expermental run lyng below the control fve tmes (maxmum 4 mm., mean 2 mm. Hg), and never more than 8 mm. Hg above the control. All data were contnuously dctated nto a tape recorder to permt a tmed full record. The same Crculaton Research, Volume X, March 196X SO SO 7 so SO too no UO ISO ISO BLOOD PKSSUK - m > FIGURE 2 Effect of changes n blood pressure on coronary snus blood flow and oxygen utlzaton of the coronary snus dranage area. Blood pressure changes were produced by addton of blood to, or removal of blood from, the crculatng blood volume. The hghest ttvo flow rates are the fnal observatons, and the numbers ndcate the order n whch the oxygen utlzaton data were ganed. O 2 determnaton method was used for both the expermental and control determnatons of each pared run. Results CATEGORY I Coronary snus flows were not detectably altered by changes n level of the juncton of tubng to condom between 3 and +3 cm. above the top of the rght atrum. Resstance to flow through the crcut or nto the condom at the rates measured was less than 1 cm. In the absence of bypass, both coronary snus flow and O 2 utlzaton vary wth changes n blood pressure brought about by alterng the blood volume (fg. 2). There was slow varaton n control coronary snus flows and O2 utlzaton rates done serally wth ntervenng bypass runs even though the blood pressure was held constant (table 1). On the other hand, O2 utlzaton was ncreased followng mnmal ar embolsm (25 per cent on two observatons), manpulaton of the heart (25 per cent once), or fbrllaton and defbrllaton (15 per cent once), even though the blood pressure was controlled. CATEGORY II In sx dogs, experments were performed on bypass wth orderly control of all factors. In all of 21 pared observatons, the oxygen utlzaton of the porton of the heart draned

3 3 DENNIS, HALL, MORENO, SENNING TABLE 1 Decrease n Oxygen Utlsaton Par Passu wth Increase n Bypass" TABLE 3 Effect of Interatral Shunt from Accdentally Torn Septum (22-Kg. Bog) Downloaded from by on January 2, 219 Tm s (mn.) SO ) c 1 u Bypa«(ml c 'E Puls us 112 nary 3 flow /mn.) Coro snu (ml %%& %m O *Male shepherd dog, 26 Kg. Coronary snus flow: moan of four or more determnatons. Ths preparaton was used thereafter for studes of effect of blood pressure wthout bypass shown n fgure 1, and remaned relatvely stable throughout. TABLE 2 Absence of Dependence of Oxygen Upon Pulse Pate (27-Kg. Dog) n.) ss Kg./m Bypa (ml./ rate mn.) nary blood mn.) Coronary snus flow (ml./ blood sure Hg) Mean press (mm s* 3 Arter oxyge satur Utlzaton en aton Slyke) mn.) Oxyg utlz (Van (ml./ * *Blood, 1 ml., was removed on nsttuton of bypass to mantan the blood pressure at the control level. by the coronary snus was reduced below the control levels by nsttuton of bypass (fg. 3). Coronary snus blood oxygen saturaton was hgher on bypass than on control n 17 experments, lower n four. Strkng effects of bypass on coronary flow and on O<2 utlzaton were observed wthout sgnfcant pulse rate changes (table 2). In one experment, manpulaton caused a septal tear suffcent to permt rght-left shunt and a drop n arteral oxygen saturaton on hgh rates of bypass flow. OL. utlzaton by the heart fell sharply here, but rose wth the Bypass (ml./ Kg./mn.) Coronary snus blood flow (ml./kg./mn.) Arteral oxygen % saturaton Oxygen utlzaton* (ml./mn.) 2.6 B 6.1 B 2.9 B 6. B 6.6 V 3.7 V 5. V 5.3 V *B=Beckn lan blood oxygen analyss; V=V:m Slyke blood oxygen analyss. arteral Oo saturaton when a lower rate of bypass pumpng reduced the nteratral gradent and shunt (table 3). A smlar, but unproved, shunt may have occurred n another experment, n whch arteral saturaton of 83 per cent was noted (61 nl./kg./mn., fg. 3). In all other dogs (except one observaton of 92 per cent n a control run), the arteral saturaton was 94 per cent or above.* Tracngs made on hgh bypass show an aortc pressure curve wth complete left ventrcular pulse defct, and reflectng only the pulsatons from the pump. The left ventrcular systolc pressure was only a fracton of the aortc, whch was sustaned by the pump (fg. 4) (14 ml./kg./mn.,fg. 3). Of the 17 experments wth arteral oxygen saturaton of 94 per cent or above, the 9 wtl low b3^pass flow (below 61 ml./kg./mn.) had a mean O2 utlzaton of.24 ml./kg./mn., n contrast to a mean for the controls of.29 ml./kg./mn. The 8 experments wth hgher bypass had a mean O L. utlzaton of.21 ml./ Kg./mn., n contrast to a mean for controls of.34 ml./kg./mn. In 4 dogs, the O 2 utlzaton on bypass appeared to drop n lnear relaton to the ncrease n bypass flow (table 1)- The lnearty of reducton of Oo utlzaton *The manpulatons of defbrllaton faled to enlarge the septal perforaton n a clncal patent for whom ths technque was employed, apparently due to the tougher structure of the fossa ovals n man. Crculaton Research, Volume X, March 196S

4 LEFT HEART BYPASS 31 EXPERIMENTAL OBSERVTIONS - - CO J5 6, j S '5-2 to ART,oo % JO SAT. so 9 A-V 1 11 I j 1 : 1!!! I k I < j III % Downloaded from by on January 2, SO SO no LEFT HEART BYPASS - ml./kg./mn FIGURE 3 (raphc presentaton of 21 determnatons of oxygen utlzaton on left heart bypass. The adjacent control determnaton (wthout bypass) s ndcated n sold black just Io the left of the expermental value f t preceded t, just to the rght f t followed t n tme. The overlad lower graph ndcates arteral oxygen per cent saturaton and also the arterovenous dfference n volumes per cent, for each expermental observaton and for each control. Flow rates as such are not presented, but may be calculated. wth ncreasng bypass flow s demonstrable n the entre data by expressng each expermental determnaton of! OL> utlzaton as a fracton of the adjacent control, especally f one consders only the.17 observatons wthout arteral desatutaton (below 94 per cent) (fg. 5). The 9 runs wth bypass below 61 ml./ Kg./mn. present a mean CK. utlzaton of 82 per cent of the controls, and the dfference of ths mean from the controls s statstcally sgnfcant (P <.1). The 8 bypass determnatons above 61 ml./kg./mn. present a mean On utlzaton of 67 per cent of the controls. The mean O2 utlzaton of the hgh bypass group s sgnfcantly less than that of the low bypass group (P <.4). The 5 determnatons wth hghest bypass flows have Crculaton Research, Volume X, March 196S a mean utlzaton sgnfcantly less than the next 5 or the next 8 observatons, suggestng a somewhat greater On-sparng as nearly total bypass s acheved (P <.1).* The mean of control values of O2 utlzaton for hgh bypass runs was hgher than that for the low bypass experments. Controls mmedately followng perods of hgh bypass showed no elevaton above controls just precedng (three of four runs). The dfference between means of low flow controls and of hgh flow controls s, therefore, concdental. 'Probabltes of statstcally sgnfcant dfferences calculated both by " ch-square" test and by calculaton of relatve devates on the normal frequency curve.'

5 DENNIS, HALL, MORENO, SENNING 32 I I J! '! ' I ' M M I j j I I 1 [ j J J ] j 1 j In ' j 11 ( 1 1 1! M " ' j j Left ventrcle yvvww^pwwwwwwww^^ 1p mrnhg Left atrum Isec. COMPLETE LEFT VENTRICULAR PULSE DEFICIT Downloaded from by on January 2, 219 TOTAL LEFT HEART BYPASS BY JUGULAR VEIN-SEPTAL PUNCTURE (open chest) ROUTE FIGURE 4 (Upper) Pressure tracngs taken durng the measurements of flow and oxygen utlzaton of the experment vth bypass at 14 ml./kg./mn. shown n fgure 3. Left atral pressure s lov, and left ventrcular pressure does not rse to the level of the aortc pressure, whch s mantaned by the pump. (Lower) Tracngs taken a few moments after upper tracngs at 25 mm. per second paper speed. The aortc pulsatons n the frst one-thrd of the record are clearly not ventrcular n orgn. The rse n left atral pressure when the pump support s stopped s assocated wth a drop n aortc pressure, whch n ths nstatce s temporary. In two dogs, the "tme-tenson ndex" (T.T.I.) of Sarnoff et al.2 was determned. The areas were measured under the left ventrcular pressure tracng on paper movng 1 mm. per second. The T.T.I, showed no decrease on partal bypass untl dsappearance of the left ventrcular component from the aortc pressure tracng (table 4). The slope of the steepest porton of the ascendng lmb of the systolc rse changed smlarly wth ncrease n bypass flow. Oxygen studes were not done on these dogs. Dscusson The mechansm by whch reducton n left ventrcular work s accomplshed by left heart bypass appears to be through reducton of left atral pressure to such a level that left ventrcular fllng s reduced or elmnated (fg. 4). That left ventrcular fllng does not occur under full left heart bypass wth the transseptal cannula n the absence of thoracotomy s demonstrated by angocardographc studes to be reported.23 Late n some experments, there was dffculty n holdng Crculaton Research, Volume X, March 1968

6 LEFT HEART BYPASS 33 TABLE 4 Effect of Left Heart Bypass on Tme-Tenson Index and on Slope of Ascendng Lmb of Left Ventrcular Pressure Curve* Downloaded from by on January 2, 219 Bypass flow (L./mn.) Pulse (per n.) ate Slope of left ventr contracton curve (mm. Hg/.1 s T.T.I, mm. Hg/sec Pulse defct No Yes No No No 5% Yes *Mlo shepherd dog, 19.5 Kg. tt.t.i, calculated from the area under the left ventrcular pressure tracng, usng the end-dastolc pressure as baselne. the blood pressure up durng control perods, even wth transfuson of 1 to 2 ml., so that wthdrawal of blood was then necessary to mantan constancy of blood pressure when generous bypass was nsttuted. The blood pressure drop seen for a few seconds durng termnaton of hgh bypass may be due to the loss n systemc blood volume ncdent to refllng of the pulmonary vens and left heart suffcently to lead to effectve left ventrcular ejecton nto the aorta (fg. 4 lower). The rapdty of ths response s a good ndex of the stablty of the expermental preparaton. 15 The senstvty of the O2 utlzaton rate to multple factors (ar embolsm, manpulaton, tme) led us to the employment of the parng of expermental runs wth adjacent controls whch we have descrbed. The possblty that ar mero-embol mght be a factor n rasng cardac O 2 utlzaton confrmed our decson to use left bypass, and therefore no oxygenator, and to use a completely closed system, for ths study. As defned by Sarnoff: et al., 2 "the tmetenson ndex (T.T.I.) per beat n mm. Hg seconds was obtaned from the area under the systolc porton of the aortc pressure curve and s equal to the mean systolc pressure tmes the duraton of systole." They Crculaton Research, Volume X, March 19GS 11 S ' to 2 3 to so to TO LEFT HEART BYPASS FLOW M a B O D S FIGURE 5 Data of fgure 3 plotted vth each expermental observaton as a proporton of the adjacent control(s). Parentheses brace data n runs wth arteral unsaturauon and are omtted from statstcal studes. The drop n O t utlzaton s steeper than that of coronary snus flow. concluded that '' n any gven functonal state of the beatng heart, the T.T.I, (mean systolc pressure tmes duraton of systole) s the prncpal, f not the sole, determnant of myocardal O2 utlzaton." Ther work was concerned wth cardac outputs of 1 L. per mnute or more, whereas ours n consderable measure has nvolved bypass flows suffcent to reduce the calculated left ventrcular mnute output to less than 1 L. In some of our experments, bypass flow was suffcent so that some or all left ventrcular contractons faled to eject blood nto the aorta, a stuaton n whch Sarnoff's T.T.I, would be zero, but n whch the oxygen utlzaton s more than half the control level. We have, therefore, calculated the T.T.I, from the area under the left ventrcular pressure tracng, usng the end-dastolc pressure as base lne. Although full bypass produces comparable decreases n Oa utlzaton and n T.T.I., our results show defnte and consstent reductons n O2 utlzaton at lower bypass flow rates not accompaned by drops n T.T.I, (cf. fg. 3,fg.5, table 4). The mechansm of decrease n O2 utlzaton n the absence of decrease n T.T.I, s not

7 34 DENNIS, HALL, MORENO, SENNING Downloaded from by on January 2, 219 clear. Sarnoff et al. 2 suggest that varatons n Oo utlzaton mght arse from changes n the rate of development of systolc tenson whle holdng the other hemodynamc factors constant. Measurements of the slope of the steepest part of the rsng lmb of the left ventrcular tracng also faled to show correlaton wth oxygen utlzaton, as t dd not drop wth ncreasng bypass untl the left ventrcular component partally or wholly dsappeared from the aortc pressure curve (full bypass), whle O 2 utlzaton decreased wth less than 25 per cent bypass (table 4). We have not measured mean dastolc left ventrcular volume durng left heart bypass. It s possble that nsttuton of bypass may dmnsh ths value and, therefore, fber length and thus favor a decrease n 2 utlzaton, as Sarnoff suggests. In spte of the conclusons of others that bypass less than the full cardac output does not reduce 2 utlzaton by the heart, 8 ' 1 ' 12 ' 2 our use of left bypass wthout the complcatons of an oxygenator, the precson of our control of varables such as respraton, blood volume, blood pressure, venous pressure, temperature, and manpulaton, the elmnaton of gaseous mcro-embolsm, and the statstcal sgnfcance of our fndngs, lead us to the belef our conclusons are vald. We have measured total coronary snus flow only. It s suspected that the reductons n Oo utlzaton, here reported, mght be more strkng f one could measure blood draned from the left ventrcular muscle only, wthout admxture of blood whch has perfused the rght ventrcle, whch s reported to use approxmately as much ^ as the workng left ventrcle. 22 It s possble, on the other hand, that the proporton of total coronary flow draned by the coronary snus vares wth nsttuton of left bypass, and ths s a possblty we have not yet studed. We are proposng to use left heart bypass wthout thoracotomy by means of atra] septal puncture for such catastrophes as major coronary arteral occluson, or severe mtral dsease or aortc stenoss Avhch cannot be handled more conservatvely wth success. The method has been used for 24-hour runs wth survval of 9 of 1 dogs. n The results here reported ndcate a reducton n oxygen need on left bypass wth an ncrease n oxygen tenson n the myocardum (as reflected by that n the blood from the coronary snus), a drop n left atral and pulmonary ven pressure (antcpatng relef of pulmonary edema), whle mantanng a sound arteral blood pressure to assure good perfuson of the stll patent coronary arteral tree. Whether a few hours of support mght permt enough muscular recovery for patent survval wthout defnte surgcal procedure, as past experence suggests, 1 or whether left bypass be used a few hours as preparaton for defntve operaton, as we have once so far employed t clncally, 15 s a queston whch must awat further experence for resoluton. Summary Full left heart bypass reduces the oxygen utlzaton of the heart to about half the control levels, as measured by coronary snus flow and arterovenous oxygen dfferences. All measured lesser degrees of bypass reduce the oxygen utlzaton less markedly, but wth hgh statstcal sgnfcance of the reductons below controls. The reducton n oxygen utlzaton upon nsttuton of partal or complete left bypass s usually the result more of a decrease n arterovenous oxygen dfference than of a decrease n coronary sums blood flow. These results support the thess that left heart bypass should be benefcal n reducng the nternal work of the left ventrcle n acute left heart falure wth competent aortc valve. Acknowledgment The authors wsh to express tler thanks to Dr. Wllam Dock, Professor of Medcne, State Unversty of New York Downstate Medcal Center, for hs many valuable suggestons n the preparaton of ths manuscrpt. References 1. STUCKEY, J. H., et.al.: Use of the heart-lung machne n selected cases of acute myocardal nfarcton. Forum Am. Coll. of Surgeons 8: 342, CONNOLLY, J. E., BACANER, M. B., BRUNS, D. L., LOWENSTEIN, J. M., AND STORLI, E. : Meclan- Crculaton Research, Volume X, March 19GS

8 LEFT HEART BYPASS 35 Downloaded from by on January 2, cal support of the crculaton n acute heart, falure. Surgery 44: 255, KUHN, IJ. A., GRUBER, F. L., FRANKEL, P., AND KUPFER, S.: Use of closed-chest extra-corporonl crculaton wthout oxygcnaton n acute myocardal nfarcton wth slock. Forum Am. Coll. Surgeons 1: 6.1, THROWER, W. B., VEITIT, F. J., LUNZER, S., AND HARKEN, D. E.: Effect of partal extracorporcn.1 bypass on sodum excreton n normal dogs and n those wth heart falure. Surg. Gynec. & Obst. 11: 19, I96. WALLACE, H. W., SUOARMAN, H. J., AND RHEIN- TANDER, H. F.: Effects of cxtracorporcal crculaton on myocardal netabolsn. Proc. Soc. Artf. Internal Organs 6: 2S2, 196. STORM, E. A., CONNOLLY, J. E., BACANER, M. B., AND BRUNS, D. L.: Relatonshp of coronary blood flow to the effectveness of mechancal support of the crculaton n acute heart falure. Forum Am. Coll. Surgeons 11: 214, 196. PATT, H. H., CLIFT,.T. V., LOH, P. B., BOA, T. C, WEXLER, J., AND SKLIGMAN, A. M.: Vcno-arteral pumpng n normal dogs and dogs wth coronary occluson. J. Thoracc Surg. 39: 44, 196. SALISBURY, P. F., CROSS, C. E., RIEBEN, P. A., AND LEVVIN, R. J.: Comparson of two forms of mechancal assstance n expermental heart falure. Crculaton Research 8: 431, 196. CI.AUSR, R. H., BIRTWELL, W. C, ALBERTAL, G., LUNZER, S., TAYLOR, W. J., FOSBERG, A. F., AND HARKEN, D. E.: Asssted crculaton: Arteral counterpulsator. J. Thoracc Cardovas. Surg. 41: 447, SALISBURY, P. F., BOR, N., LEWIN, R. J., AND RIEBEN, P. A.: Effects of partal and total heart-lung bypass on the heart. J. Appl. Physol. 14: 458, GALETTI, P. M., HOPF, M. A., AND BRECHER, G. A.: Problems assocated wth long-lastng hea't-lung bypass. Proc. Soc. Artf. Internal Organs 6: 18, GEREIN, A. N., JONES, B. A., AND CROSS, F. S. : Cardac bypass wth the pumpoxygenator for crculatory support durng cardac decompensaton. Forum Am. Coll. Surgeons 11: 216, HAMER, N. A. J., DICKSON, J. F., AND DOW, J. W.: Effect of prolonged venoartoral pumpng on the crculaton of the dog. J. Thoracc Surg. 37:,19, RUTHERFORD, R. B., AND SWAN, H.: Expermental partal perfuson. Forum Am. Coll. Surgeons 11: 212, I SENNING, A., DENNIS, C, HALL, D. P., AND MORENO, J. R.: Atral septal puncture for total left heart bypass wthout thoracotomy. To be publshed n Acta chr. scandnav. 16. ZYLSTRA, W. G.: Manual of Reflecton Oxmotry. Assen, VAN SLYKK, D. D., AND NEILL, J. M.: Determnaton of gases n blood and other solutons by vacuum extracton and manometrc measurement. J. Bol. Chem. 61: 623, DRABKIN, D. L., AND SCHMIDT, C. F.: Observaton of crculatng blood n vvo and the drect determnaton of the saturaton of hemoglobn n arteral blood. J. Bol Chem. 157: 69, BANCROFT, H.: Introducton to Bostatstcs. New York, Harper & Bros. (Hoeber), SARNOFF, S. J., BRAUNWALD, E., CASE, R. B., WELSH, G. H., AND STAINSBY, W. N.: Henodynamc determnants of oxygen consumpton of the heart. Am..1. Physol. 192: 148, 195S. 21. MORENO, J. R., SENNING, A., OVENFORS, C.., DENNIS, C, AND HALL, D. P.: Angographc studes durng total left heart bypass. To be publshed n Acta radol. 22. LITWAK, R. S., MEYER, W. H., JR., SLONUI, R. J., SLOTKIN, M. B., AND OCA, C.: Studes n dvded coronary blood flow; left, and rght ventrcular dynamcs n the bypassed rght heart. Forum Am. Coll. Surgeons 9: 175, Crculaton Research, Volume X, March 1962