Centrifugal Pump and Heparin Coating Improves Cardiopulmonary Bypass Biocompatibility

Transcription

1 Centrfugal Pump and Heparn Coatng Improves Cardopulmonary Bypass Bocompatblty Oddvar Moen, MD, rk Fosse, MD, PhD, nar Dregeld, MD, Vbeke Brockrneer, MD, Conny Andersson, CCP, Kolbjorn Hog,sen, MD, PhD, Per Venge, MD, PhD, om rk Mollnes, MD, PhD, and Peter Kerulf, PhD Departments of Cardothoracc Surgery, Anesthesology, and Clncal Chemstry, Ulleval Unversty Hosptal, Oslo, Norway Background. Centrfugal pumps are beng used ncreasngly for short-term extracorporeal crculaton purposes such as durng heart operatons. Whether the centrfugal pump mproves the cardopulmonary bypass bocompatblty has not been fully documented. Methods. A roller pump (n = 2) was compared n vvo wth a centrfugal pump (n = 2) n groups of patents n whch cardopulmonary bypass crcuts that were ether totally heparn coated (Carmeda BoActve Surface; n = 2) or uncoated (n = 2) were used. We expected the heparn coatng to attenuate blood actvaton, thus possbly makng the comparson of the two pumps easer wth respect to ther dfferent blood actvaton potentals. Samples of blood plasma, obtaned durng cardopulmonary bypass from low-rsk coronary artery bypass graftng patents, were analyzed for hemolyss (plasma hemoglobn), complement actvaton (C3bc and the termnal complement complex), a complement lytc nhbtor (v- tronectn), coagulaton actvaton (fbrnopeptde A), granulocyte actvaton (lactoferrn), and platelet actvaton (/~-thromboglobuln). Results. he concentratons of termnal complement complex, lactoferrn, and fl-thromboglobuln were sgnfcantly lower n assocaton wth heparn-coated surfaces. he concentraton of plasma hemoglobn was sgnfcantly lower n assocaton wth the centrfugal pump. In uncoated crcuts, the l~-thromboglobuln level was sgnfcantly hgher n assocaton wth the roller pump than wth the centrfugal pump, but ths sgnfcant reducton n the l~-thromboglobuln level dd not hold true for the heparn-coated crcut group. Conclusons. A heparn-coated cardopulmonary bypass surface reduces the blood actvaton potental durng cardopulmonary bypass, and the centrfugal pump causes less hemolyss than the roller pump. (Ann horac Surg 1996;62:1134-4) he nonocclusve centrfugal pump was orgnally constructed for long-term extracorporeal crculaton, but has ncreasngly been used durng heart operatons. hs s probably the result of safety consderatons [1] and also ts mproved blood handlng ablty [2]. Results from several cardopulmonary bypass (CPB) model studes have ndcated blood actvaton was reduced n assocaton wth the use of systems wth a centrfugal rather than a roller pump, and hemolyss was especally reduced n some studes [2, 3]. Reduced complement and platelet actvaton has also been observed durng open heart operatons n whch centrfugal rather than roller pumps were used [4, 5]. A problem experenced wth the centrfugal pump durng sustaned extracorporeal membrane oxygenaton s hemolyss, whch has been attrbuted to the negatve pressure on the nlet sde [6]. hs problem s avoded when a flled venous reservor s used. he advent of heparn-coated CPB surfaces has been regarded as an mprovement n CPB bocompatblty [7]. hus, a sgnfcant reducton n complement and granulocyte actvaton has been demonstrated for the Carmeda BoActve Surface heparn-coated CPB [8]. Accepted for publcaton Mav 14, Address reprnt requests to Dr Moen, Department of Cardothoracc SurgeD', Ullev~l Unversty Hosptal, N-47 Oslo, Norway. he prmary goal of the present study was to compare the effect of the use of a roller or a centrfugal pump on blood actvaton markers. We expected that the heparncoated CPB surface would cause blood actvaton to be attenuated and that lower "background" blood actvaton would clearly pont up dfferences between the pumps. o study such blood actvaton, partcularly that caused by the pumps, we have assessed heparn-coated and uncoated systems usng the followng plasma varables: plasma free hemoglobn, reflectng hemolyss; complement actvaton (C3b, C3b, and C3c collectvely called C3bc, and the termnal complement SC5b-9 complex [CC]); levels of the complement lytc nhbtor vtronectn; coagulaton actvaton (fbrnopeptde A [FPA]); granulocyte actvaton (lactoferrn); and platelet actvaton (/3-thromboglobuln [/3-G]). Materal and Methods Forty consecutve patents accepted for electve coronary arter bypass graftng were ncluded n the study after gvng nformed consent. he excluson crtera were (1) left ventrcular ejecton fracton of less than.4, (2) any concomtant surgcal procedure, (3) chronc obstructve pulmonary dsease, renal nsuffcency, lver dsease, or nsuln-dependent dabetes melltus, (4) a known coagulopathy or ongong antcoagulaton therapy, (5) actve 1996 by he Socety of horacc Surgeons /96/$15. Publshed by lsever Scence [nc Pl[ S3-4975(96)492-4

2 Ann horac Surg MON AL ;62: CARDIOPULMONARY BYPASS BIOCOMPAIBILIY nflammatory dsease or nfecton, and (6) use of sterods, nonsterodal antnflammatory drugs, or acetylsalcylc acd wthn 8 days of operaton. he patents were placed randomly nto one of four groups, wth 1 patents n each group: Group l: he extracorporeal crcut comprsed a roller pump (Gambro, Horten, Norway) and an uncoated oxygenator (Maxma; Medtronc Cardopulmonary, Anahem, CA). Group II: he extracorporeal crcut comprsed a Gambro roller pump and a heparn-coated oxygenator (Carmeda BoActve Surface heparncoated Maxma; Medtronc), wth heparn coatng of the entre blood-contact surface. Group III: he extracorporeal crcut comprsed a centrfugal pump (Bomedcus; Medtronc) and an uncoated Maxma oxygenator. Group IV: he extracorporeal crcut comprsed a Bomedcus centrfugal pump and Carmeda Bo- Actve Surface heparn-coated Maxma oxygenator, wth heparn coatng of the entre bloodcontact surface. An arteral lne flter and a cardotomy reservor were used n all patents. We appled the Maxma hollow-fber membrane oxygenator (model 138; Medtronc). he cardotomy reservors were a Medtronc Intersept SK 1351, and the venous reservor, a Medtronc MVR 16. he arteral flters used were the 2-/xm Medtronc Intersept and the prebypass flter, a Medtronc Intersept PBP. In all patents, Medtronc Intersept PVC Class IV tubngs were used; the aortc cannula was an AA 24-C and the venous cannula, a R (Research Medcal, Salt Lake Cty, U), wth ether a BoMedcus centrfugal pump (model 54) wth an external drve unt (model 54 ) and the Bo-Pump Head (BP 8; Medtronc) or the nonpulsatle Gambro roller pump. he roller pump was adjusted to low occluson (pressure reducton from 3 to 2 mm Hg n 1 seconds). he temperature control unt was a Gambro Hyper-hypotherma unt (Hyp 1-2; Gambro). Heparn was admnstered ntravenously before the onset of CPB at a rate of 4 IU/kg of body weght (heparn 5, IU/mL; Leo, Ballerup, Denmark). Addtonal heparn was gven to acheve a mnmum actvated coagulaton tme (AC) of 48 seconds (reference range, 7-12 seconds). he AC was measured wth a Hemochrome 4 (Internatonal echndyne, dson, NJ). he operatons were performed under moderate general hypotherma (28-32 C) wth topcal coolng accomplshed by ce slush n addton to cold St. homas' cardoplegc soluton. After CPB was ended protamne sulfate (1 mg/ml; Leo) was admnstered to reestablsh the preoperatve AC level. Medastnal shed blood was retransfused. he amount of heparn and protamne admnstered, the AC values, the medastnal blood loss, and the retransfused blood volumes durng the frst 12 postoperatve hours were recorded n all patents. A baselne sample of blood was obtaned from the arteral lne at the start of extracorporeal crculaton. he test samples were drawn 3 mnutes after the start of bypass, 1 mnutes after release of the aortc cross-clamp, 1 mnutes after the admnstraton of protamne, at skn closure, and 6 hours postoperatvely. he blood was sampled n an ethylene-damne tetraacetc acd vacutaner for routne hematologc analyss, ncludng measurement of the levels of plasma hemoglobn, complement actvaton products, vtronectn, and lactoferrn. he plasma samples were stored at -7 C before analyss n batches. Samples for analyss of FPA were collected n specal vacutaners wth a 1/1 volume (.2 ml) strong nhbtor:.15 mol/l of NaC1, 1, IU/mL of heparn, and 1, IU/mL of aprotnn (rasylol; Bayer AG, Leverkusen, Germany), centrfuged at 4 C (1,9 g for 3 mnutes), and the plasma was stored at -7 C before analyss n batches. Samples for ]3-G analyss were drawn n specal vacutaners, whch were ce cooled before samplng and contaned.2 ml of antcoagulant from Datube H (Stago; Boehrnger Mannhem, Mannhem, Germany). Plasma for/3-g analyss was obtaned from the mdlayer to avod collectng lght platelets, and the resultng samples were centrfuged (1,9 g for 3 mnutes) and stored n the same way as the FPA samples. Analyss of Samples Routne hematologc varables were determned usng a echncon H.2 analyzer (echncon Instruments, arrytown, NY). he plasma hemoglobn level was quantfed n a Htach U-2 spectrophotometer (Noka Works Htach, okyo, Japan) accordng to a prevously descrbed method [9] (reference value, <.2 g/dl). he C3 actvaton product C3bc was measured n a doubleantbody enzyme mmunoassay usng the monoclonal antbody bh6 reactng wth a neoeptope expressed n C3b, C3b, and C3c, but not n natve C3, as the capture antbody [1]. A zymosan-actvated human serumpool (n - 8), specfed to contan 1, arbtrary unts (AU)/mL of C3bc, was used as the standard (reference range, AU/rnL). he CC was quantfed n a smlar double-antbody enzyme mmunoassay usng the monoclonal antbody a11 specfc for a C9 neoeptope expressed n CC, but not n the natve C9, as the capture antbody [11] (reference range, AU[mL). he standard was the same as the one descrbed for the C3bc assay. Vtronectn (S-proten) was also quantfed n a double-antbody enzyme mmunoassay [12]. he coatng antbody was a monoclonal antbody to vtronectn, and the secondary antbody was a rabbt polyclonal antbody to vtronectn produced n our own laboratory (reference range, g/l). Fbrnopeptde A was quantfed n a modfed radommunoassay (IMCO, Stockholm, Sweden) [13] (reference value, [SD] ng/ml). Lactoferrn was quantfed n a radommunoassay as descrbed [141 (reference value, 385 ± 153 [SD] 1 6 g/l). /3-hromboglobuln was quantfed n an enzyme rnmunoassay (Dagnostca Stago IA kt Asserachrom ]3-G; Boehrnger Mannhem) [131 (reference value, [SD] ng/ml).

3 1136 MON AL Ann horac Surg CARDIOPULMONARY BYPASS BIOCOMPAIBILIY 1996;62: able 1. ssental Varables n the Four Patent Groups Studed Varable No. of patents Age (y) (range) Female/male Dstal anastomoses Mnutes on cardopulmona D, bypass Aortc cross-clamp tme (ran) Heparn ( 1 IU/kg) Actvated clottng tme (s) (medan} ~ Protamne (nag) Medastnal blood loss (ml) Retransfused volume (ml) Roller Pump a Centrfugal Pump b Uncoated CBAS Uncoated CBAS (group I) (group ll) (group III) (group IV) (42-67) 55 (43-76) 64 (37-75) 59 (45-74) 2/8 1/ " Gambro ruller pump (Gambro, Horten, Nur~vay). t, Bomedcus centrfugal pump (Medtronc CardopulmonaD, Anahem, CA). were not sgnfcantly dfferent wth respect to these clncal data. CBAS = Carmeda BuActve Surface (Medtronc). he groups Statstcal Methods Nonparametrc analyss was used because of the small sze of the groups. Intergroup comparsons were based on the sum of medan values n each group, or between peak values when approprate (Kruskal-Walls test) [15]. he Fredman test was used to dentfy tme-dependent changes wthn groups. Results are presented as medan values and nterquartle ranges. A p value less than.5 was regarded as sgnfcant. Results he age dstrbuton dd not dffer among the four patent groups, and although female patents were underrepresented, the male-female rato was smlar for the four groups. he number of dstal anastomoses, the extracorporeal crculaton tme, the aortc cross-clamp tme, the medan AC, the medan protamne dosage, and the postoperatve blood loss dd not dffer among the groups (able 1). Plasma Hemoglobn he plasma hemoglobn concentraton ncreased n all four groups from the value at the start of CPB and reached maxmum values 1 mnutes after the admnstraton of protamne n the roller pump groups and at skn closure n the centrfugal pump groups (Fg 1). he maxmum concentratons were sgnfcantly hgher (p -.2) and the sum of the concentratons was sgnfcantly hgher (p.4) n the roller pump groups than n the centrfugal pump groups. he plasma hemoglobn concentraton dd not dffer sgnfcantly between the heparn-coated and uncoated groups. C3bc In all four groups the C3bc concentraton ncreased from the value at the start of CPB to reach a maxmum at the end of operaton. Intal values were almost reestablshed 6 hours postoperatvely (Fg 2). In all four groups the C3bc concentraton was sgnfcantly ncreased 3 mnutes after the start of the CPB (p <.7) compared wth the baselne value. here were no sgnfcant dfferences among the four groups wth respect to the C3bc concentraton. ermnal Complement Complex he CC concentraton ncreased n all four groups from the value at the start of CPB. he maxmum values were,_ ~ O e-.2 ('o CPB Start - ~" CU- '~ CC I I l t I 3 Post Post Skn 6h MnutesACC protamneclosed PO Fg 1. Medan eoncentratons wth nterquartle range of plasma hemoglobn n patents undergong coronary artery bypass graftng (n 4), comparng the level n those n whonl the Bomedcus centrfugal pump was used wth the level n those n whom the Gambro roller pump was used, and also comparng the Carmeda BoActve Sur~we wth the uncoated CPB surface, for a total of four groups Cn 1 n each group): centr!f~gal pump, uneoated (CU); centrfugal pump, coated (CC); roller pump, uncoated (RU); and roller pump, coated (RC). he plasma was sampled at the start qf cardopulmonary bypass (CPB), after 3 mnutes, 1 mnutes after release qf the aortc cross-clamp (post ACC), 1 mnutes after protamne admastraton, at skn closure, and 6 hours postoperatvely (PO).

4 Ann Yhorac Surg MON AL ;62: CARDIOPULMONARY BYPASS BIOCOMPAIBILIY,.,J t~ o'3...i I J.75 ~3 t--.6 t- o.45 >.3 - t,,- CU- "" CC ~'~'~"~-- q~k /4,t'~ y. " X F x x x x x / I I.15,,,,, CPB 3 Post Post Skn 6 h Start Mnutes ACC protamne closed PO Fg 2. Medan plasma concentratons wth the nterquartle range of the C3 complement actvaton products C3b, C3b, and C3c (C3bc), the termnal complement complex SC5b-9 (CC), and the complement lytc nhbtor vtronectn n groups of patents undergong corona~ artery bypass graftng, as defned n the legend for Fgure 1. (AU - arbtnz~ unts; other abbrevatons are as n Fy.ure 1.) reached 1 mnutes after the admnstraton of protamne n the centrfugal pump, uncoated group and at skn closure n the other three groups (see Fg 2). In both of the uncoated groups the CC concentraton compared wth the baselne value was sgnfcantly ncreased 3 mnutes after the start of CPB (p =.6 n the roller pump group; p =.9 n the centrfugal pump group). In the two heparn-coated groups the CC concentraton compared wth the baselne value was sgnfcantly ncreased 1 mnutes after the admnstraton of protamne (p =.3 n the roller pump group; p =.1 n the centrfugal pump group). After 3 mnutes of CPB the CC concentraton was sgnfcantly hgher n the roller pump, uncoated group than n the roller pump, coated group (p =.2), and 1 mnutes after release of the aortc crossclamp, t was sgnfcantly hgher n the centrfugal pump, uncoated than n the centrfugal pump, coated group (p.2). he formaton of CC was not sgnfcantly dfferent between the two roller and the two centrfugal pump groups, but the heparn coatng sgnfcantly reduced the CC concentraton n each pump group: In the roller pump, coated group, the sum of CC was sgnfcantly lower (p -.6) and the maxmum value sgnfcantly lower (p =.3) than those n the roller pump, uncoated group. In the centrfugal pump, coated group, the sum of CC was sgnfcantly lower (p =.1) and the maxmum value sgnfcantly lower (p =.4) than those n the centrfugal pump, uncoated group. Vtronectn he vtronectn concentraton decreased from the value at the start of CPB to reach mnmum values of about 5% of the ntal concentratons after 3 mnutes on CPB n the roller pump groups and 1 mnutes after release of the aortc cross-clamp n the centrfugal pump groups (see Fg 2). he ntal concentraton was not reestablshed 6 hours postoperatvely. In all four groups the mnmum vtronectn concentraton was sgnfcantly lower than the level at the start of CPB. he lowest concentraton of vtronectn was observed n the centrfugal pump, coated group, but the mnmum values dd not dffer sgnfcantly among the groups, and the decrease n the concentratons was smlar for all groups. No sgnfcant dfferences n the vtronectn concentraton were observed between the pump groups or between the heparn-coated and uncoated groups. Fbrnopeptde A he FPA concentraton ncreased from the value at the start of CPB to reach maxmum values at skn closure n all four groups (Fg 3). he maxmum values were sgnfcantly hgher than the baselne concentratons n all four groups (p <.5). he groups dd not dffer sgnfcantly wth respect to the sum of the measurements of FPA. jb- hromboglobuln he ~-G concentraton ncreased from the value at the start of CPB to reach the hghest values 6 hours postoperatvely n all groups (see Fg 3). In both the uncoated groups the /3-G concentraton was sgnfcantly ncreased after 3 mnutes of CPB compared wth the concentraton at the start of CPB (p -.2 n the roller pump group; p =.4 n the centrfugal pump group). In the two heparn-coated groups the ]3-G concentraton dd not ncrease sgnfcantly compared wth the baselne value before 6 hours postoperatvely (p =.3 n the roller pump group; p =.1 n the centrfugal pump group). In the roller pump, uncoated group, the hghest /3-G concentraton was sgnfcantly hgher (p -.4) and the sum of the concentratons sgnfcantly hgher (p =.8) than those n the roller pump, coated group. In the centrfugal pump groups the heparn coatng dd not lead to a sgnfcantly lower/3-g concentraton. he sgnfcant reducton n the /3-G concentraton n the roller pump, coated group versus the roller pump, uncoated group dd not reach statstcal sgnfcance when

5 1138 MON AL Ann horac Surg CARDIOPULMONARY BYPASS B1OCOMPAIBILIY 1996;62:1134-4,..I 75 o~ 6 - < "o 45 ~- 3 Q. o 15 t" "r".q "~ I. - ~ O t,,- h- I ~" CU " ~" CC.--o--. RU RC #~ I I I I I x -. - " ", CPB 3 Post Skn 6 h Start Mnutes protarnne closed PO Fg 3. Medan plasma concentratons wth the ntenluartle range qf fbrnopeptde A and f3-thromboglobuln n groups of patents undergong coronary artery bypass gn~fh'ng, as defned n the legend.#or Fgure 1. (See Fgure I for abbrevatons.) both the roller pump groups were compared wth both the centrfugal pump groups. Lactoferrn he lactoferrn concentraton was almost unchanged n both the coated groups, and t was sgnfcantly ncreased n the two uncoated groups (Fg 4). he hghest lactoferrn concentratons were measured 1 mnutes after release of the aortc cross-clamp n the two uncoated groups. In the roller pump, uncoated group, the hghest lactoferrn concentraton was sgnfcantly hgher (p =.3) and the sum of concentratons sgnfcantly hgher (p -.6) than those n the roller pump, coated group. In the centrfugal pump, uncoated group, the hghest lactoferrn concentraton was sgnfcantly hgher (p.6) and the sum of concentratons sgnfcantly hgher (p -.8) than those n the centrfugal pump, coated group. he lactoferrn concentraton dd not dffer between the two pump groups. Comment he present study was desgned to evaluate dfferences n blood actvaton between a roller and a centrfugal pump durng routne coronary procedures, as well as the effect of the Carmeda BoActve Surface heparn-coated as opposed to the uncoated CPB surface. hs was prompted by conclusons from earler studes that blood handlng s better when a centrfugal pump rather than a roller pump s used [1-5]. On the bass of earler reports, we expected the heparn-coated CPB surface to reduce complement and granulocyte actvaton [8]. If the centrfugal pump used n the present study should prove to reduce blood actvaton, we wanted to evaluate ths effect n addton to the well-known and expected effects of heparn coatng. he combned use of these varables was based on the stll unproven relatve mportance of the CPB bocompatblty ndces--of blood-foregn surface propertes as opposed to mechancally and rheologcally or hemodynamcally nduced effects. he ncreased plasma hemoglobn concentratons observed n the roller pump groups ndcate hemolyss s ncreased n these as opposed to the centrfugal pump groups. Increased red blood cell destructon gves rse to an ncreased plasma hemoglobn concentraton, whch results n hemoglobn-haptoglobn complexes that are quckly removed by hepatocytes. Hemolyss durng CPB may result from dfferent mechansms, but mechancal destructon of the red blood cells s probably of major mportance [16]. he extent to whch factors other than mechancal factors contrbute to hemolyss durng CPB remans uncertan. Based on fndngs from an n vtro study, t has prevously been suggested that mechancally damaged erythrocytes are more prone to complement lyss [17]. he mportance of heparn coatng was observed also n the present study, because the CC concentraton was sgnfcantly reduced n the heparncoated group rrespectve of the pump type. he amount of crculatng CC should reflect the extent of complement "bystander lytc attack" on cells [18]. he adhesve proten vtronectn s an mportant nhbtor of bystander lyss [19-21]. In the present study we found about a 5% reducton n the vtronectn level durng CPB. However, we could not demonstrate a sgnfcant effect on the vtronectn decrease attrbutable to the pump type. he two pumps dd not operate dfferently n terms of ~ 2 3 o 15.. " 1 o -~ 5 O " -~ CU -~" CC "-o-" R U "--'-- RC,f ',, I I I l I CPB 3 Post Post Skn 6 h Start MnutesACC protamneclosed PO Fg 4. Medan plasma concentrah'ons wth the nterquartle range of lactoflerrn n groups qf patents undergong coronary artery bypass graftng, as d fned n the legend for Fgure 1. (See Fgure I for abbrevatons.)

6 Ann horac Surg MON AL ;62: CARDIOPULMONARY BYPASS BIOCOMPAIB1LIY coagulaton actvaton, nor dd the heparn coatng n the present study cause the FPA concentratons to be reduced. hs corresponds wth our n vtro fndngs [17]. In ths context t should be ponted out that n the present study, the systemcally admnstered heparn doses were smlar for all four groups, leadng to smlarly prolonged ACs n all groups (see able 1). hus, the major antcoagulant effect appeared to be related to the systemcally admnstered heparn. It has been demonstrated that blood coagulaton actvaton occurs durng CPB despte ntense antcoagulaton wth heparn [22]. On the other hand, t has prevously been shown that end-pontmmoblzed, unfractonated heparn wll adsorb factor XII [23], nhbt factor Xa through ts nteracton wth antthrombn [23], and thus lead to less thrombn formaton on surfaces coated by ths technque. On the bass of these fndngs t appears that the net antcoagulant effect durng CPB s dependent on the concentratons of mmoblzed heparn as well as on the amount of systemcally admnstered heparn, the latter overshadowng the former when ntense. It may be debated whether the use of full versus reduced systemc heparnzaton s preferable n evaluatons of the bocompatblty of entrely heparn coated CPB crcuts. In some prevous studes [8, 24], the combnaton of heparn coatng and reduced systemc heparnzaton has been found to sgnfcantly reduce granulocyte actvaton, compared wth the granulocyte actvaton seen for uncoated crcuts and full heparnzaton. he use of smlar systemc heparnzaton n both the heparn-coated and uncoated groups probably confers an advantage for the evaluaton of the heparn-coated crcuts n the present study. Our comparson of centrfugal and roller pumps n the presence and absence of entrely heparn coated surfaces n the CPB crcut was especally useful for the evaluaton of platelet actvaton. Prevous studes have ndcated platelet actvaton s reduced when centrfugal pumps are used durng open heart operatons [4, 5]. he ]3-G concentraton was sgnfcantly hgher n the roller pump, uncoated group than n the centrfugal pump, uncoated group, but the dfference was not sgnfcant when the coated groups were ncluded n the comparson. On the bass of the fndngs n the present study, heparn coatng may have a much greater nfluence on platelet actvaton than the pump type. he mechansms for platelet actvaton durng CPB are not clear [7]. he observed dfferences cannot be explaned by dfferences n the exposure tme to the foregn surface, as the CPB tme was smlar for the four groups. If the roller pump more than the centrfugal pump results n mechancally nduced actvaton or destructon of the platelets, ths may explan the observed dfferences between the uncoated groups. It should be ponted out, however, that complement actvates platelets, and possbly the reduced complement actvaton n the heparncoated groups may contrbute to the reduced release of ]3-G. Our fndng that the ~-G levels were sgnfcantly lower n the roller pump, coated group than n the roller pump, uncoated group ndcates that mechancally act- vated platelets may be more prone to complement attacks. he reduced lactoferrn concentratons observed n the heparn-coated versus the uncoated groups reflects reduced granulocyte actvaton, as prevously documented both n vvo [8, 24] and n vtro [17]. here was no dfference between the roller and centrfugal pump groups wth respect to ths granulocyte actvaton varable. Blood actvaton products, generated durng CPB, may exert several effects n vvo through ther nteractons wth varous cell types and through complex amplfcaton systems. Our study fndngs ndcate that the centrfugal pump causes less hemolyss (plasma hemoglobn concentraton) than the roller pump and that heparn coatng reduces complement actvaton (CC), granulocyte actvaton (lactoferrn), and platelet actvaton (/3-G). hey also ndcate that the combned use of a totally heparn coated CPB surface and a centrfugal pump can lead to mproved blood compatblty, durng heart operatons. We greatly apprecate the excellent techncal assstance provded by the staff at the partcpatng laboratores. he study was fnancally supported by grants from he Norwegan Councl on Cardovascular Dsease. References 1. Bolles R. Centrfugal pumps for routne cardopulmonary bypass: St. Jude Lfestream M centrfugal pump system. In: Pathophysology & echncs of Cardopulmonary Bypass, 13th Annual Meetng, San Dego, CA 1993: Horton AM, Butt W. Pump-nduced haemolyss: s the constraned vortex pump better or worse than the roller pump? Perfuson 1992;7: Moen O, Fosse, Br~ten J, et al. Roller and centrfugal pumps compared n vtro wth regard to haemolyss, granulocyte and complement actvaton. Perfuson 1994;9: Wheeldon DR, Bethune DW, Gll RD. Vortex pumpng for routne cardac surgery: a comparatve study. Perfuson 199; 5: Jakob HG, Hafner G, heleman C, et al. Routne extracorporeal crculaton wth a centrfugal or roller pump. ASAIO rans 1991;37:M Pedersen H, Karlsen H, Wolden R, et al. Does negatve pressure on the nlet sde cause hemolyss durng extracorporeal crculaton wth a centrfugal pump [abstract]? In: Pathophysology & echnques of Cardopulmonary Bypass, 13th Annual Meetng, San Dego, CA 1993:2. 7. Van Oeveren W, Wldevuur CRH, Kazatchkne MD. Bocompatblty of extracorporeal crcuts n heart surgery. ransfus Sc 199;11: Fosse, Moen O, Johnson, et al. Reduced complement and granulocyte actvaton wth heparn-coated cardopulmonary bypass. Ann horac Surg 1994;58: Harboe M. A method for determnaton of hemoglobn n plasma by near-ultravolet spectrophotometry. Scand J Cln Lab Invest 1959;11: Garred P, Mollnes, Lea. Quantfcaton n enzymelnked mmunosorbent assay of a C3 neoeptope expressed on actvated human complement factor C3. Scand J Immunol 1988;121: Mollnes, Lea, Fraland SS, et al. Quantfcaton of the termnal complement complex n human plasma by an enzyme-lnked mmunosorbent assay based on monoclonal antbodes aganst a neoantgen of the complex. Scand J lmmunol 1985;22:

7 114 MON AL Ann horac Surg CARDIOPULMONARY BYPASS BIOCOMPAIBILIY 1996;62: Hog,sen K, Mollnes, schopp J, et al. Quantfcaton of vtronectn and clustern. Ptfalls and solutons n enzyme mmunoassays for adhesve protens. J Immunol Methods 1993;16: Skjonsberg OH, Kerulf P, Fagerhol MK, et al. hrombn generaton durng collecton and storage of blood. Vox Sang 1986;5: Olofsson, Olsson I, Venge P, et al. Serum myeloperoxdase and lactoferrn n neutropena. Scand J Haematol 1977;18: Mattews JNS, Altman DG, Campbell MJ, Royston P. Analyss of seral measurements n medcal research. Br Mecf J 199;3: Salama A, Hugo F, Henrch D, et al. Deposton of termnal C5b-9 complement complexes on erythrocytes and leukocytes durng cardopulmonary bypass. N ngl J Med 1988; 318: Moen O, Fosse, Brhten J, et al. Dfferences n blood actvaton related to roller/centrfugal pumps and heparncoated/uncoated surfaces n cardopulmonary bypass model crcut. Perfuson 1996;11: Morgan P. Complement membrane attack on nucleated cells: resstance, recovery and non-lethal effects. Bochem J 1989;264: Podack R, Kolb WP, Muller-berhard HJ. SC5b-7 complex: formaton, solaton, propertes, and subunt composton. J Immunol 1977;119: Dahlback B, Podack R. Characterzaton of human S- proten, an nhbtor of the membrane attack complex of complement demonstraton of a free reactve thol group. Bochemstry 1985;24: Murphy BF, Saunders JR, O'Bryan MK, et al. SP-4, 4 s an nhbtor of C5b-6 ntated haemolyss. Int Immunol 1989;1: Gravlee GP, Haddon WS, Rothberger HI<, et al. Heparn dosng and montorng for cardopulmonary bypass: a comparson of technques wth measurement of subclncal plasma coagulaton. J horac Cardovasc Surg 199;99: lgue G, Sanchez J, gberg N, Olsson P, Resenfeld J. ffect of surface-mmoblzed heparn on the actvaton of adsorbed factor XII. Artf Organs 1993;17: Borowec J, heln S, Bagge L, et al. Heparn-coated crcuts reduce actvaton of granulocytes durng cardopulmonary bypass--a clncal study. J horac Cardovasc Surg 1992;14: Bound volumes avalable to subscrbers Bound volumes of the 1995 ssues of he Annals of horacc Surgery are avalable only to subscrbers from the Publsher. he cost s $99. (outsde US add $25. for postage) for volumes 59 and 6. ach bound volume contans a subject and author ndex, and all advertsng s removed. he bndng s durable buckram wth the name of the journal, volume number, and year stamped on the spne. Payment must accompany all orders. Contact lsever Scence Inc, 655 Avenue of the Amercas, New York, NY 11; or telephone (212) (facsmle: (212) ).