Scientific Report 2003-2004 - Cleveland Clinic Lerner Research ...

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THE W. SMITHLABORATORYNanette Businger, B.S.Fernando Casas, Ph.D.Dave Dudzinski, B.S.Lei Gu, D. Eng.Christine Flick, B.S.Ryan Klatte, B.S.Lei Gu, D. Eng.Markus Lorenz, M.S.Wenfeng Lu, M.S.Viviane Luangphakdy, M.S.Andrew Reeves, M.S.John Sankovic, M.S.Stephan Weber, M.S.COLLABORATORSH. Ming Chen, Ph.D. 1Ji-Feng Chen, B.S.Brian Duncan, M.D. 2Brian Farrell, M.S. 3Kiyotaka Fukamachi, M.D., Ph.D. 3Jai Kadambi, Ph.D. 4Raymond J. Kiraly, M.S, .M.E.Patrick McCarthy, M.D. 5John Player, M.S. 3Nicholas Vitale, M.S.M.E. 1Qun Zhou, B.S.1Foster-Miller Technologies,Inc., Albany, NY2Dept. of Pediatric andCongenital Heart Surgery3Foster-Miller, Inc., Boston, MA4Case Western ReserveUniversity5Dept. of Thoracic andCardiovascular Surgery,CCFCase Western ReserveUniversity24BIOMEDICALDEVICESBlood Pump Technology Leads toDevelopment of a Familyof Blood Pumping DevicesPrior research at The Cleveland ClinicFoundation has shown that chronic survival withnonpulsatile blood flow is possible. Thepurpose of this research is to explore engineeringtechnologies that will advance the design, developmentand application of this new form of cardiac assistdevice.One aspect of the program is development oftest methods to accurately and repeatably characterizenonpulsatile blood pumps.Determination of the “index ofhydrolysis” is one important test.Unfortunately, comparing resultsfrom laboratory to laboratory (oryear to year within one laboratory)is difficult because the criticalparameters and tolerances havenever been quantified. To create atest standard with a scientific basis,we are working to determine howvariations in test characteristics mayaffect pump results. A morefundamental understanding offactors relating to blood fragilitymay also be obtained.Another research area ispump design technology. Industrial rotary pumptechnology was developed based on water as theworking medium. Blood is a significantly differentfluid. Blood pumps are also in a very different range ofpressure and flow, as compared to commercial pumpapplications. The goal of this research is to develop arational design philosophy for rotary blood pumps.The ultimate goal is to achieve a balanced optimum ofperformance, efficiency, size, low hemolysis andminimal deposition.A third research area is diagnostic monitoringof blood pumps. Permanent blood pump implantswill require means to detect failures well before theyoccur, so that replacement can be arranged in goodLorenz, M., and W.A. Smith (2002) Rotodynamic pump scaling. ASAIO J. 48:419-430.Doi, K., Smith, W.A., Harasaki, H., Takagaki, M., Ochiai, Y., Howard, M.W., Weber,S., Byerman, B.P., Massiello, A.L., Vitale, N., Donahue, A., Hirschman, G., and K.Fukamachi (2002) In vivo studies of the MagScrew total artificial heart in calves.ASAIO J. 48:222-225.McCarthy, P.M., and W.A. Smith (2002) Mechanical circulatory support—a long andwinding road. Science 295:998-999.Smith, W.A., Fukamachi, K., Weber, S., Harasaki, H., Doi, K., Schenk, S., Vitale,N., Hirschman, G., and A. Donahue (2002) The Cleveland Clinic/Foster Miller Mag-Screw pulsatile blood pump program. Annu. Int. Conf. IEEE Eng. Med. Biol. Proc.2002, vol. 2.Weber, S., Doi, K., Massiello, A.L., Byerman, B.P., Takagaki, M., Fukamachi, K.,Donahue, A., Chapman, P., Hirschman, G., Vitale, N., and W.A. Smith (2002) Invitro controllability of the MagScrew total artificial heart system. ASAIO J. 48:606-611.The Department of Biomedical Engineeringtime. The laboratory is part of an effort to developacoustic methods to detect the early stages of pumpmalfunction.Device Design and DevelopmentTotal Artificial Heart. The total artificial heart(TAH) program at CCF is the continuation of a longtermeffort. The CCF’s TAH design uses pusher-platepumps with biolized surfaces. A continuouslyreciprocating actuator is packagedbetween the two ventricles. The rate isvaried to maintain the left ventricle at anominal 90% of full stroke. An internalbattery provides short-term power, anda transcutaneous energy transmissionsystem (TETS) provides primarypower from a wearable external batterypack.The CCF’s TAH uses theMagScrew system of Foster-MillerTechnologies, Inc., the latest generationof blood pump driver. In operation,the MagScrew system is similar inconcept to an ordinary nut-and-screwsystem, except force is transmittedWilliam A. Smith, D.Eng., P.E.magnetically rather than by threadcontact, thus eliminating friction and wear. A thinsealing wall can also be interposed between “nut” and“screw,” permitting the motor and bearings to behermetically sealed in their own compartment.Combined with the CCF pumps, the system has provencapable of 9 L/min with 15 mm Hg atrial pressure.Ventricular Assist Devices. Our program ispursuing a number of approaches to a ventricular assistdevice (VAD). The MagVAD (based on the MagScrewactuator described above for the TAH) uses the rightpump changer of the TAH. However, the MagVAD is asingle-chamber assist system that will unload a failingventricle. Like the TAH, the MagVAD shows very highsensitivity to inlet pressure and can, if necessary, entirelyreplace the function of one ventricle.The inherently controlled bearing (ICB) pump isa VAD that uses a magnetic-bearing-supported rotaryblood pump. It promises to provide a simple, reliableapproach to an LVAD for those hearts that need asignificant increment of flow to support a satisfyinglifestyle.The “MiniMixedFlow” pump technology is ahighly miniaturized magnetic bearing rotary bloodpump technology, which is being pursued to developpartial assist adult LVAD’s, RVAD’s, and implantablepediatric pumps.Support Pumps. A number of external supportpump systems are being developed. These includean emergency cardiopulmonary bypass/extracorporealmembrane oxygenation system, funded by theDepartment of Defense; a catheter pump forminimally invasive surgery; and an external-useversion of the ICB system. Each of these pumpsfills a particular and crucial niche in the medical/surgical armamentarium.
The Department of Biomedical EngineeringHealing of Prosthetic Vascular GraftsCARDIOVASCULARBIOENGINEERINGSynthetic grafts are used widely in vascularreconstructive surgery, but their long-termpatency, especially in small-vessel or lowflowapplications, is limited. Smooth-muscle-cellaccumulation and matrix deposition adjacent tothe anastomoses mayprogress to intimalhyperplasia and graftfailure. We haveshown that smoothmuscle cells onprosthetic grafts arecharacterized by asynthetic, proliferativephenotype that isdistinctly differentfrom the contractilephenotype of arterialsmooth muscle cells.The graft smoothmuscle cells producehigh levels of growthfactors, and this maystimulate the ongoingmigration of arterialsmooth muscle cellsonto grafts as well assmooth-muscle-cellproliferation in thearea of the anastomosis.In addition, thegraft smooth musclecells secrete higher levels of collagen than aorticsmooth muscle cells. We are currently investigatingthe regulation of collagen synthesis. Prostheticgrafts in humans, unlike in experimentalanimals, never develop a complete endotheliallining, and therefore, they remain relativelythrombogenic compared with normal bloodvessels. Low-density lipoprotein (LDL) oxidizedLinda M. Graham, M.D.by Dacron graft-activated monocytic cellsinhibits endothelial cell migration in vitro, and theinhibition can be prevented by certain antioxidants.We are currently investigating themechanism by which oxidized LDL inhibitsendothelial cell migration,focusing on the effect ofoxidized LDL on intracellularcalcium concentration,cell membranefluidity, and cytoskeleton.In addition, the effect ofhypercholesterolemia, andthe effect of antioxidants,on endothelial cellingrowth onto prostheticgrafts in vivo is beingstudied. Identification ofthe mechanisms by whichhypercholesterolemiaimpairs prosthetic grafthealing will allow developmentof effective therapiesto improve graft patency.Active areas ofinvestigation include: 1)the molecular mechanismsinvolved in the posttranscriptionalregulationof collagen secretion bygraft SMC, 2) the mechanismby which oxidizedLDL inhibits endothelial cell migration, and 3)the effect of hypercholesterolemia on endothelialcell ingrowth onto prosthetic grafts in vivo. Abetter understanding of the changes in cellfunction on prosthetic grafts will be used todesign a better vascular graft using tissueengineering principles.THE GRAHAMLABORATORYPROJECT SCIENTISTScott M. Colles, Ph.D.POSTDOCTORAL FELLOWSAmitabha Chakrabarti, Ph.D.Pinaki Chaudhuri, Ph.D.Dongmei Zhang, Ph.D.TECHNICIANSAmanda FinanXuemei GaoJunqing Shen, B.S.STUDENTSNamisha JainCOLLABORATORSDerek S. Damron, Ph.D. 1Paul L. Fox, Ph.D. 21Center for AnesthesiologyResearch, CCF2Department of Cell Biology,CCFvan Aalst, J.A., Pitsch, R.J., Absood, A., Fox, P.L., and L.M. Graham (2000) Mechanism of Dacron-activatedmonocytic cell oxidation of low density lipoprotein. J. Vasc. Surg. 31:171-180.Absood, A., Furutani, A., Kawamura, T., and L.M. Graham (2002) Differential PDGF secretion by graftand aortic SMC in response to oxidized LDL. Am. J. Physiol. Heart Circ. Physiol. 283:H725-H732.Ghosh, P.K., Vasanji, A., Murugesan, G., Eppell, S.J., Graham, L.M., and P.L. Fox (2003) Membrane microviscosityregulates endothelial cell motility. Nat. Cell Biol. 4:894-900.Chaudhuri, P., Colles, S.M., Damron, D., and L.M. Graham (2003) Lysophosphatidylcholine inhibits endothelialscell migration by increasing intracellular calcium and activating calpain. Arterioscler. Thromb.Vasc. Biol. 23:218-233.25
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