CARDIOPULMONARY BYPASS, MYOCARDIAL MANAGEMENT, AND SUPPORT TECHNIQUES

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1 CARDPULMNARY BYPASS, MYCARDAL MANAGEMENT, AND SUPPRT TECHNQUES BDY TEMPERATURE NFLUENCES REGNAL TSSUE BLD FLW DURNG RETRGRADE CEREBRAL PERFUSN Akhko Usu, MD a Kej ohara, MD a Fumhko Murakam, MD b Hdek oshma, MD b Mtsuo Kawamura, MD b Mtsuya Murase, MD a bjectve: Ths study compared the cerebral mcrocrculaton durng retrograde cerebral perfuson wth that durng antegrade cardopulmonary bypass under normothermc and hypothermc condtons. Methods: Bran tssue blood flow was measured wth the hydrogen-clearance and colored mcrosphere (15 and 50 gm) methods durng antegrade cardopulmonary bypass and retrograde cerebral perfuson. Measurements were performed durng normotherma (37 C), moderate hypotherma (28 C) and deep hypotherma (20 C) n groups of mongrel dogs (n = 8). Results: Durng antegrade cardopulmonary bypass, the mcrosphere method showed a sgnfcant decrease n cerebral blood flow as body temperature decreased ( ml/mn/100 gm at 37 C, 16.2 ± 18.0 ml/mn/100 gm at 20 C wth 50 ~m mcrospheres) At 20 C, the cerebral blood flow measured wth the 15/.tm mcrospheres was sgnfcantly lower than that assessed wth the hydrogen-clearance method ( vs ml/mn/100 gn). Durng retrograde cerebral perfuson, the mcrosphere method also showed a sgnfcant decrease n cerebral blood flow wth coolng. At 37 C, the cerebral blood flow measured wth the 15 /.tm mcrospheres (0.8 _+ 0.7 ml/mn/100 gm) was sgnfcantly lower than that assessed wth the hydrogen-clearance method (10.1 ± 3.5 ml/mn/100 gn). At both 28 and 20 C, the hydrogen-clearance method showed sgnfcantly hgher cerebral blood flow (10.1 ± 5.8 and ml/mn/100 gn) than dd the 50 #m mcrospheres (1.8 ± 0.6 and 1.0 ± 0.8 m!/mn/100 gm) and 15 /.tm mcrospheres (0.23 ± 0.14 and 0.18 ± 0.15 ml/mn/100 gn). Concluson: (1) Cerebral blood flow that shunts to capllares s ncreased durng antegrade cardopulmonary bypass under deep hypotherma. (2) Durng retrograde perfuson, the majorty of the blood flow shunts away from bran capllares, even under normothermc condtons, and blood flow through large venoarteral shunts ncreases as body temperature decreases. Although the cerebral mcrocrculaton durng retrograde perfuson s decreased, retrograde perfuson provdes some degree of oxygenaton to the body. (J Thorac Cardovasc Surg 1997;114: 440-7) From the Department of Thoracc Surgery, Nagoya Unversty School of Medcne, Nagoya, ~ and the Cardovascular Center, war Prefectural Hosptal, chnomya, b Ach, Japan. A Grant-n-Ad for Scentfc Research and a Japan Heart Foundaton Research Grant for 1990 supported ths study. Receved for publcaton May 15, 1996; revsons requested July 16, 1996; revsons receved Jan. 27, 1997; accepted for publcaton Feb. 13, Address for reprnts: Akhko Usu, MD, Umegaoka, Tenpaku-ku, Nagoya, Japan 468. Copyrght 1997 by Mosby-Year Book, nc /97 $ /1/81118 R etrograde cerebral perfuson (RCP) s a new and smple technque used to protect the bran aganst nterrupton of the cerebral crculaton durng aortc arch surgery. As shown n prevous studes, RCP can provde blood and oxygen to the bran, mnmze the decrease n cerebral tssue adenosne trphosphate levels, and mantan bran coolng. RCP also can mnmze schemc damage and extend the duraton of safe cerebral crculatory nterrupton. 1-4 The dstrbuton of perfused blood has been measured wth the colored mcrosphere method, 440

2 The Journal of Thoracc and Volume 114, Number 3 Usu et al. 441 and t has been observed that RCP can perfuse the whole bran wthout lateralzaton of perfuson or sgnfcant areas of nadequate cerebral perfuson. 5 Retrograde perfuson s not a physologcally usual condton, however, and the regonal mcrocrculaton durng RCP remans to be clarfed. n ths study, we measured regonal tssue blood flow (TBF) wth small (15 /xm) and large (50 /xm) colored rncrospheres, as well as wth the hydrogenclearance method. Small mcrospheres are trapped only n capllares, allowng evaluaton of capllary blood flow. Large mcrospheres are trapped n vessels smaller than 50/xm n dameter, whch nclude capllares and arterovenous shunts. The hydrogenclearance method measures regonal blood flow. Dscrepances among TBF measured by each method can yeld nformaton about the condton of the cerebral mcrocrculaton. We therefore compared the cerebral mcrocrculaton durng RCP wth that durng antegrade cardopulmonary bypass (CPB) by means of both the colored mcrosphere and hydrogen-clearance methods. Materals and methods All anmals receved humane care n complance wth the "Prncples of Laboratory Anmal Care" formulated by the Natonal Socety for Medcal Research and the "Gude for the Care and Use of Laboratory Anmals" prepared by the Natonal Socety for Medcal Research and the "Gude for the Care and Use of Laboratory Anmals" prepared by the nsttute of Laboratory Anmal Resources and publshed by the Natonal nsttutes of Health (NH Publcaton No , revsed 1985). Anmal preparaton and RCP method. Sxteen mongrel dogs weghng 13.0 _+ 1.1 kg (11.5 to 15.0 kg) were used n ths study. Eght underwent RCP and the other eght underwent antegrade CPB as control anmals. Anesthesa was nduced wth ketamne hydrochlorde (10 mg/kg) gven ntramuscularly and thopental sodum (5 mg/kg) gven ntravenously. After endotracheal ntubaton, each anmal was mechancally ventlated wth 100% oxygen. The ventlator rate and tdal volume were adjusted to mantan the arteral carbon doxde tenson at approxmately 35 mm Hg by the alpha-stat method of ph control. Anesthesa was mantaned wth ntravenous ketamne hydrochlorde (2 mg/kg/hr) and pancuronum bromde (0.1 mg/kg). Catheters were placed n the nternal carotd or femoral artery, the rght external jugular ven, and the rght femoral ven to montor blood pressures. A perfuson cannula (8F) for RCP was placed n both nternal maxllary vens. Temperatures were recorded by a thermstor placed n the nasopharyngeal cavty. Cerebral blood flow (CBF) was measured by both the colored mcrosphere method and the hydrogen-clearance method. Hydrogen-producng electrodes were nserted nto the rght paretal cortex through a burr hole placed n the skull. A rght thoracotomy was made through the fourth ntercostal space. Heparn (300 U/kg) was gven ntravenously. The ascendng aorta was cannulated wth a 16F metal-tpped perfuson catheter. The rght atrum was cannulated wth two separate venous cannulas (28F), and vena caval tapes were appled before clampng of the azygous ven. CPB was establshed at a flow rate of 1000 mg/mn under oxygenaton wth pure oxygen at 1.0 L/mn. Mechancal ventlaton was then dscontnued and a crossclamp was appled to the ascendng aorta. The heart was arrested, and ntermttent cold crystallod cardoplega was appled. RCP was then establshed by perfusng blood through blateral nternal maxllary ven cannulas by a small roller pump through a Y-shaped connector. The aortc cannula was opened, and blood was drected by gravty to the cardotomy reservor after blateral clampng of the caval cannula. The pump crcut conssted of a membrane oxygenator (D705 MDFL; Ddeco, Mrandola, taly) wth a cardotomy reservor (3L CARDF PLUS; Mallnckrodt Medcal TP, nc., rvne, Calf.) prmed wth electrolyte soluton and 500 ml blood obtaned from another dog to prevent hemodluton. No nterventon to control blood pressure was made durng each study. Expermental protocol. n the RCP group, CPB was establshed at a flow rate of 1000 ml/mn under normothermc condtons (37 C). Ten mnutes after aortc crossclampng, after stablzaton of the vtal sgns, the perfuson was swtched to RCP. A nasopharyngeal core temperature was mantaned at approxmately 37 C wth ntermttent core heatng. After ths, rapd core coolng was nduced to reduce the nasopharyngeal core temperature to approxmate 28 C and then to 20 C whle remanng on RCP to avod the release of any mcrospheres trapped n capllares. Durng RCP, the external jugula r venous pressure was mantaned at approxmate 25 mm Hg whle the perfuson flow rate was vared. Nasopharyngeal temperatures of 37, 28, and 20 C were each mantaned for 10 mnutes. At the end of each 10-mnute perod, colored mcrospheres were njected through the cannula placed n each nternal maxllary ven, and the blood pressure n each catheter was recorded. Blood samples were wthdrawn from the nflow and outflow cannulas, and return blood flow rate was measured drectly from the aorta. The hydrogen clearance was measured smultaneously. n the control group, CPB was establshed at a flow rate of 1000 ml/mn, and a nasopharyngeal temperature of 37 C was establshed by ntermttent core heatng. Core coolng was appled to reduce the nasopharyngeal temperature to 28 o C and then to 20 C. The same measurements performed n the RCP group were obtaned at 37, 28, and 20 C (nasopharyngeal temperatures) and compared wth those obtaned durng RCP. The anmals of both groups were klled mmedately at the end of the study to avod releasng any mcrospheres from the tssue to the crculaton. Analyss. Blood pressure was measured wth a blood pressure montor (HP7835; Hewlett Packard Co., Palo Alto, Calf.) wth dsposable transducers (SCK7178; Vggo Spectramed PTE Ltd., Sngapore, Sngapore). The zeropressure level was set at the level of the operatng table. Perfuson flow was calculated from the pump rotaton

3 442 Usu et al. The Journal of Thoracc and September 1997 rate, whch was calbrated for each pump crcut after each procedure. The blood samples were drawn nto heparnzed syrnges and analyzed mmedately at 37 C (the alpha-star ph control) for ph, oxygen tenson, carbon doxde tenson, oxygen saturaton, oxygen content, total carbon doxde, and hemoglobn (ABL-300; Radometer A/S, Copenhagen, Denmark). Cerebral TBF was measured wth the hydrogen-clearance method (RBF-2; Bomedcal Scence, nc., Kanazawa, Japan). 6' 7 Cerebral TBF was calculated by subtractng the baselne value measured durng total crculatory arrest. Colored merosphere method. TBF was also measured wth the colored mcrosphere method, whch allows calculaton of TBF from the number of mcrospheres trapped n the capllares) Nonradoactve colored mcrospheres (E-Z Trac, Los Angeles, Calf.) are made of a polystyrene-dvnylbenzene brdgng complex and labeled wth chemcally stable dyes. 8 Two szes (15 and 50 txm) and three colors (red, blue, and green) were used n ths study. Salne soluton (10 ml) contanng 200 thousand counts of 50/xm mcrospheres and 4 mllon counts of 15 /xm mcrospheres of each color was njected at a constant rate over 1 mnute through the nflow cannula at the end of each 10-mnute study perod. The anmals were klled at the end of the study and ther skulls were opened. Blood was perfused through each nternal maxllary ven to verfy that there was no nterference by any venous valves. The whole bran and portons of the upper and lower spnal cord were dssected for analyss. The cerebrum was dssected blaterally nto frontal, paretal, and occptal lobes. Each part was dssected nto whte and gray matters. The bran stem was dssected nto the thalamus, putamen, pons, and medulla oblongata. From each specmen a 2 to 3 gm sample was separated, weghed, and processed by enzymatc dgeston and centrfugaton. The number of mcrospheres n each sample was determned wth a hemocytometer. TBF n each sample was calculated accordng to the followng formula: TBF = A (Mo/M) (Q/W) (ml/mn/100 gm), wherea s a constant (2381), Mo s the number of observed mcrospheres, M s the number of njected mcrospheres, Q s the perfused flow rate + 10 (n mlllters per mnute), and W s the weght of the tssue sample (n grams). Total CBF (TCBF) was calculated as the sum total of blood flow n each specmen (TBF W/100 ml/mn). Calculaton. Total vascular resstance (R) was calculated accordng to the followng formula: R = (P - Po)/Q(dynes sec cm-s), where durng RCP, P s the external jugular venous pressure, Po s the nternal carotd arteral pressure, and Q s the blood flow (n mlllters per mnute) returned through the aortc cannula, and durng CPB, P s the femoral arteral pressure, Po s the central venous pressure, and Q s the perfuson flow rate. Wholebody oxygen consumpton (Vo2) was calculated from the followng equaton: Vo 2 = (Cao 2 - Cvo2) Q/100 (ml/mn), where Cao2 s the oxygen content of the perfusate blood, Cvo 2 s the oxygen content of returned blood, and Q s ether the blood flow (n mlllters per mnute) returned through the aortc cannula durng RCP or the perfuson flow rate durng CPB. Results are expressed as means plus or mnus standard devaton. Statstcal sgnfcance was determned wth the pared t test after confrmng normal dstrbuton. The p values on multple comparson were corrected by the Bonferron method, and a p value less than 0.05 was determned to represent sgnfcance. Results Perfuson flow rates, vascular resstance and oxygen consumpton. Antegrade CPB was performed at a perfuson flow rate of 1000 ml/mn. Vascular resstance dd not change sgnfcantly durng antegrade CPB as the body temperature decreased (Fg. 1). However, Vo2 decreased sgnfcantly as the body was cooled. xygen consumpton was 54.5 _ ml/mn at 37 C, 37.5 _ ml/mn at 28 C, and ml/mn at 20 C. The dfference between oxygen consumpton at 37 C and at the lower temperatures was sgnfcant (Fg. 2). Retrograde perfuson flow rates were 335 _+ 64 ml/mn at 37 C, ml/mn at 28 C, and 277 _+ 60 ml/mn at 20 C. Retrograde perfuson flow rates appeared to change slghtly at dfferent temperatures; however, these changes were not sgnfcant. Vascular resstances ncreased when the nasopharyngeal temperature decreased to 20 C; a sgnfcant dfference compared wth the value at 37 C (4817 _ vs 3035 _ dynes sec. cm-5; Fg. 1). xygen consumpton durng RCP also decreased as the body temperature decreased. However, there were no sgnfcant dfferences among these values. xygen consumptons durng RCP were one sxth and one fourth those durng CPB at 37 C and at 20 C, respectvely (Fg. 2). Dstrbuton of TBF accordng to colored mcrosphere method. The average rates of bran blood flow n the whte matter, gray matter, bran stem, cerebellum, and spnal cord measured wth the 50 /~m mcrospheres durng normothermc RCP were 7.5 _ 7.0, 4.7 _+ 4.5, 12.0 _+ 10.0, 9.7 _+ 8.3, and 9.7 _+ 5.9 ml/mn/100 gn, respectvely. These values were 18.7%, 13.3%, 24.5%, 22.7%, and 20.4%, respectvely, of the values measured durng normothermc CPB (Fg. 3). There was no lateralzaton n the dstrbuton of blood flow and no sgnfcant dfferences between the frontal, paretal, and occptal lobes n the whte and gray matters of cerebrum. The average bran TBFs assessed wth the 15 ~m mcrospheres were extremely low, measurng 0.8 _+ 0.7, 0.9 _+ 0.8, 1.5 _+ 1.0, and 0.5 _+ 0.4 ml/mn/100 gm n the whte matter, gray matter, bran stem, and cerebellum, respectvely. These values were only 3.1%, 3.4%, 3.7%, and 1.6% of the respectve blood

4 The Journal of Thoracc and Volume 114, [',lumber 3 Usu et al '2 --D--, Antegrade Perfuson Retrograde Perfuson 6000' E o u w 4000 'o o 3000 c "J mmmmmrmmm n" 2000' o > [ p= C 28 C 20 C Fg. 1. Vascular resstance durng antegrade CPB and retrograde perfuson under condtons of normotherma, moderate hypotherma, and deep hypotherma. Error bars represent standard devaton. flows measured wth the 15/xm mcrospheres durng normothermc CPB (Fg. 3). Cerebral TBF measured by colored mcrosphere and hydrogen-clearance methods. Durng antegrade CPB, TBF n the cerebral cortex measured wth both the 50 /xm and 15 /xm colored mcrosphere decreased sgnfcantly as body temperature decreased[. There were sgnfcant dfferences between the CBF measured at 37 C and at 20 C wth both types of mcrospheres, However, the hydrogenclearance method dd not show a sgnfcant change n cerebral TBF as body temperature decreased. At a body temperature of 37 C, the CBF measured wth the 50 /xm mcrospheres was sgnfcantly hgher than that measured wth the hydrogen-clearance method. Durng deep hypotherma (20 C), the CBF measured by the 15 /xm mcrospheres was sgnfcantly less than the blood flow measured wth the hydrogen-clearance method (Fg. 4). Durng RCP, the cerebral TBF measured by the hydrogen-clearance method dd not change sgnfcantly wth change n body temperature. Cerebral TBF measured wth both the 50 and 15 /xm mcrospheres, however, decreased sgnfcantly as the body was cooled. There was a marked dfference n results between the methods durng RCP at 28 and 20 C. At 37 C, the CBF measured wth the 15/xm mcrospheres was sgnfcantly less than the CBF measured wth both the hydrogen-clearance method and the 50 /xm mcrospheres. At 28 and 20 C, CBF measured by the hydrogen-clearance method was sgnfcantly greater than the values obtaned wth ether the 50 or 15 /xm mcrospheres (Fg. 4). TCBF and whole-body blood flow. Durng antegrade CPB, the TCBF, calculated as the sum total of the blood flows measured wth the 50 /xm mcrosphere, were 33.7 _ ml/mn at 37 C, 24.3 _ ml/mn at 28 C, and 14.5 _ ml/mn at 20 C. These values sgnfcantly decreased as body temperature decreased and were 3.4%, 2.4%, and 1.5% of perfused blood flow rate at 37 C, 28 C, and 20 C, respectvely. TCBFs measured wth the 15 /xm mcrospheres were ml/mn at 37 C, _ 11.0 ml/mn at 28 C, and 10.4 _+ 6.2 ml/mn at 20 C, representng 2.2%, 2.4%, and 1.0%, respectvely, of the perfused blood flow. The TCBF was sgnfcantly decreased at 20 C; however, there were no sgnfcant dfferences between the values measured wth the 50 and 15 /xm mcrospheres at any temperature. Durng RCP, the TCBFs measured wth the 50 /xm mcrosphere were 6.1 _+ 5.5 ml/mn at 37 C, 2.3 _+ 1.2 ml/mn at 28 C, and ml/mn at

5 444 Usu et al. The Journal of Thoracc and September " Antegrade Perfuson --[3-- Retrograde Perfuson p= A 60" e". m E E 50 c- ~= e~ 40- E u~ e o~ 20 >, x 10 p= gl_.... [] 37 C 28 C 20 C Fg. 2. xygen consumpton durng antegrade CPB and retrograde perfuson under condtons of normotherma, moderate hypotherma, and deep hypotherma. Error bars represent standard devaton. 20 C, whch were 1.8%, 0.9% and 0.34%, respectvely, of the perfused blood flow rate. The TCBF and the percentage of TCBF decreased sgnfcantly as body temperature decreased. TCBFs measured wth the 15 /xm mcrosphere were extremely low, only 0.71 _ ml/mn at 37 C, 0.24 ± 0.13 ml/mn at 28 C, and 0.20 ± 0.16 ml/mn at 20 C, or only 0.21%, 0.10%, and 0.07%, respectvely, of the perfused blood flow. Dscusson Retrograde perfuson through a superor vena caval cannula has been reported as a new technque for bran protecton durng crculatory arrest. We also have reported the results of several experments wth RCP. n a prevous study, we found that RCP can provde blood and oxygen to the bran; however, t s nsuffcent to mantan full bran functon. 2 Nonetheless, RCP can mnmze the oxygen debt and schemc damage to the bran and extend the duraton for whch cerebral crculaton can be safely nterrupted. 3 Blood flow to the bran and bran oxygen consumpton do not ncrease once venous pressure exceeds 25 mm Hg. 4 n our most recent study, we measured the dstrbuton of regonal blood flow durng RCP wth the colored mcro- sphere method) We concluded that RCP can perfuse the whole bran wthout lateralzaton of perfuson, causng no sgnfcant areas of nadequate cerebral perfuson. We also found that regonal blood flow measured by the colored mcrosphere method vared accordng to the body temperature and wth the sze of mcrospheres. n ths study, our am was to further defne the varatons n regonal blood flow assocated wth changes n body temperature. We used the mcrosphere method wth two dfferent szes of mcrospheres (50 and 15/xm) and also used the hydrogen-clearance method to measure regonal blood flow durng normotherma (37 C), moderate hypotherma (28 C,) and deep hypotherma (20 C). The colored mcrosphere method measures TBF by countng the mcrospheres trapped n capllares, s f mcrospheres crculatng n the body are not be trapped by capllares, the TBF may be underestmated. The small mcrospheres tend to dstrbute n a fashon smlar to that of red blood cells but are subject to shuntng, partcularly when physologc changes n vascular tone occur. TM n the other hand, the larger lncrospheres are preferentally trapped n areas of hgh flow because of ther axal dstrbuton n the bloodstream M-

6 The Journal of Thoracc and Volume 114, Number 3 Usu et al. 445 Antegrade Perfuson whte matter gray matter cerebellum Bran stem spnal cord whte matter gray matter cerebellum 37 (2 ~ 28 C [ 1 ' 1' 'o' ~o ~o ~o' ~o 6o' 40 o ~o' ~o 30' ~o ~o ~o Tssue Blood Flow (ml/mn/t g) B-~ 37o(; Retrograde Perfuson!! 28 (3 ] ooc ~' o' ~o' go' 40' 50 mcron mcrosphere 15 mcron mcrosphere V C Bran stem spnal cord o so 2o ~o Tssue Blood Flow (ml/mrdl00g) 0';o' ~0 Fg. 3. Regonal blood flow measured wth 15 and 50 /xm mcrospheres durng antegrade CPB and retrograde perfuson on normotherma. Error bars represent standard devaton. crospheres 50 /xm n sze are easly trapped n capllary beds that the 15 /xm mcrospheres run through. The dfference n the regonal blood flows measured wth 15 /xm and 50 /xm mcrospheres should therefore represent blood flow that s shunted away from capllares. We also measured regonal blood flow wth the hydrogen-clearance method. Ths method measures regonal blood flow of 100 mg wet volume by evaluatng the clearance curve of tssue hydrogen concentratons. 6' 7 The tssue hydrogen content should be cleared by capllary blood flow; however, t may be cleared by blood flow that shunts away from capllares. t s therefore possble that the hydrogen-clearance method overestmates regonal blood flow. When dscrepances between the regonal blood flows measured wth 50 /xm mcrospheres and the hydrogen-clearance method occur, the dfferences represent shunt blood flow through vessels larger than 50/xm n dameter between the arteral and venous systems. Comparson of the regonal blood flows measured wth these methods therefore can yeld more accurate nformaton regardng the regonal mcrocrculaton. We summarze our results as follows: (1) Durng antegrade CPB, CBF decreases as body temperature decreases, and the CBF shunted away from capllares ncreases at deep hypotherma. (2) Durng retrograde perfuson, the majorty of the CBF s shunted away from capllares, even durng normotherma. The amount of blood that runs through larger shunts ncreases as body temperature decreases. There have been several reports regardng the mcrocrculaton durng normal perfuson. t has been reported that blood flow that s shunted away from capllares ncreases durng deep hypotherma ~2 as arterovenous shunts open. ur results concur wth these reports. Blood flow at 20 C measured wth the 15/xm mcrospheres was sgnfcantly lower than that measured by other methods. Ths ndcates that arterovenous shunts larger than 15/xm are open at 20 C. The study of the mcrocrculaton durng retrograde perfuson has not been well defned. Theoretcally, blood perfused n a retrograde manner runs from the venous system to the arteral system through capllares. There s, however, no evdence to support ths theory. Ths study ndcates that most blood perfused retrogradely may be shunted away from capllares, runnng through larger venoarteral shunts n the bran tssue. Ths conjecture s based

7 446 Usu et al. The Journal of Thoracc and September 1997 E M. "0 0 0 W = 8 60" " 20-10" 20 10" p= p= p= C 28 C 20 C p=.006 p= p= p=.03 ' p ~ p=.001 Antegrade Perfuson [~ Hydrogen Clearance ] 50 mcron mcrosphere[ 15 mcron mcrosphere J Retrograde Perfuson 0- L p= :)= p= Fg. 4. TBF n cerebral cortex measured by the hydrogen-clearance and 15 and 50 /~m mcrosphere method durng antegrade CPB and retrograde perfuson durng normotherma, moderate hypotherma, and deep hypotherma. Error bars represent standard devaton. on the fndngs that the 50 ~m mcrospheres were trapped and the 15 ~m mcrospheres passed through durng normothermc RCP. Durng hypothermc perfuson, even the larger mcrospheres (50 ~m) were not trapped. Ths ndcates that large venoarteral shunts, through vessels greater than 50 txm n dameter, may open durng hypotherma. The phenomenon may be related to functonal arterovenous shunts wth a dameter of 70 xm n the pa mater and spnal cord descrbed n studes of prmates. 13 Retrograde perfuson s entrely dfferent from antegrade perfuson. There s a small possblty that mcrospheres wll not be trapped even when the mcrospheres run through capllary beds. t s, however, more probable that the majorty of the blood runs through venoarteral shunts. Boeckxstaens and Flameng 14 reported that sgnfcant CBF could not be detected by mcrosphere methods and less than 1% of the RCP nflow returned to the aortc arch durng hypothermc RCP n a baboon expermental study. They concluded that RCP does not perfuse the bran because of venovenous shuntng. They performed RCP through blateral nternal jugular vens wth the nferor vena caval dranage. The nferor vena caval dranage durng RCP s subject to venovenous shuntnga; n ther study, however, mcrospheres were traced even n returned blood to the aortc arch. Arterovenous shunts n the bran are therefore probably responsble for ths shuntng durng RCP. RCP can provde some oxygen to the bran tssue and reduce the decrease n tssue adenosne trphosphate levels. t s not clear, however, whether retrograde perfuson provdes suffcent bran protecton because the mcrocrculaton durng RCP s totally dfferent from the physologcally normal crculaton. The dog may not be a good model for RCP studes because t has a small nternal jugular ven and also has many cervcal venous valves. 15 Human bengs, n contrast, have large nternal jugular vens and few jugular venous valvesj 5 Venous valves

8 The Journal of Thoracc and Volume 114, Number 3 Usu et al nterfere wth retrograde perfuson. We observed both nternal maxllary vens after each procedure to confrm that there was no nterference caused by venous valves. The cerebral mcrocrculaton durng retrograde perfuson s stll not fully defned; however, the majorty of blood perfused n a retrograde fashon tends to shunt away from capllares of the bran. The effcacy of the blood shunted away from capllares s also unclear; however, retrograde perfuson provdes some degree of oxygenaton to the body. t s stll unclear whether retrograde perfuson provdes suffcent bran protecton because of extreme dfferences between the mcrocrculaton durng retrograde perfuson and that under physologc condtons. Further expermental and clncal studes are necessary to clarfy how long RCP can prolong the tme durng whch crculatory arrest s safe. The study was prepared n consultaton wth the statstcan, Nobuyuk Hamajrna, MD. REFERENCES 1. Usu A, Hotta T, Hroura M, Murase M, Maeda M, Koyama T, et al. Retrograde cerebral perfuson through a superor vena caval cannula protects the bran. Ann Thorac Surg 1992;53: Usu A, Hotta T, Hroura M, Murase M, Maeda M, Koyama T, et al. Cerebral metabolsm and functon durng normothermc retrograde cerebral perfuson. J Cardovasc Surg 1993;1: Usu A, ohara K, Tong-ln L, Murase M, Tanaka M, Takeuch E, et al. Determnaton of optmum retrograde cerebral perfuson condtons. J Thorac Cardovasc Surg 1994;107: Usu A, ohara K, Tong-ln L, Murase M, Tanaka M, Takeuch E, et al. Comparatve expermental study between retrograde cerebral peffuson and crculatory arrest. J Thorac Cardovasc Surg 1994;107: ohara K, Usu A, Murase M, Tanaka M, Abe T. Regonal cerebral tssue blood flow measured by the colored mcrosphere method durng retrograde cerebral perfuson. J Thorac Cardovasc Surg 1995;109: Doyle TF, Martns AN, Kobrne A. Estmatng total cerebral blood flow from the ntal slope of hydrogen washout. Stroke 1975;6: Pasztor E, Symon L, Dorsch NWC, Branston NM. The hydrogen clearance method n assessment of blood flow n cortex, whte matter and deep nucle of baboons. Stroke 1973;4: Hale SL, Alker K J, Kloner RA. Evaluaton of nonradoactve, colored mcrospheres for measurement of regonal myocardal blood flow n dogs. Crculaton 1988;78: Phbbs RH, Dong L. Nonunform dstrbuton of mcrospheres through a medum-szed artery. Can J Physol Pharmacol 1970:48: Ypntso T, Dobbs WA Jr, Scanlon PD, Knopp TJ, Bassngthwaghte JB. Regonal dstrbuton of dffusble tracers and carbonzed mcrospheres n the left ventrcle of solated dog hearts. Crc Res 1973;33: Marcus ML, Hestad DD, Ehrhardt JC, Abbound FM. Total and regonal cerebral blood flow measurement wth 7-, 10-, 15-, 25- and 50-/zm mcrospheres. J Appl Physol 1976;40: gura K, Takayasu M, Dacey RG Jr. Effects of hypotherma and hypertherma on the reactvty of rat ntracerebral arteroles n vtro. J Neurosurg 1991;75: gata J, Fegn. Arterovenous communcatons n the human bran. J Neuropathol Exp Neurol 1972;31: Boeckxstaens CJ, Flameng WJ. Retrograde cerebral perfuson does not perfuse the bran n nonhuman prmates. Ann Thorae Surg 1995;60: Mller MM. The venous system. n: Mller MM, edtor. Anatomy of the dog. Phladelpha, London: WB Saunders; p