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

CARDIOVASCULARBIOENGINEERINGTHE GREENBERGLABORATORYINVESTIGATORKenneth Ouriel, M.D.Dept. of Vascular Surgery, CCFRESEARCH FELLOWSStephan Haulon, M.D.Jamal Khwaja, M.D.Ellis Sampram, M.D.Gene Tanquilut, MDTECHNICAL SUPPORTTamara BurtonDaniel YoungENGINEERSJames Foster, B.S.M.E.Davorin Skender, B.S.Karl WestRoy K. Greenberg, M.D.Vascular Surgery Focuses on theEndovascular Treatment ofAortic Aneurysms and Aortic DissectionsThe Vascular Surgery Laboratory, which hasrecently expanded, focuses on twoapproaches to endovascular treatment:mechanical devices and drug therapy fordissolving thrombus.Endovascular grafting of the aorta hasemerged as the treatment of choice for certainpatients with an abdominal aortic aneurysm. Therisks associated with open surgery are exponentiallyincreased with the number and severity ofmedical comorbidities, to the point where therisk of open operation is prohibitive. The use ofendovascular technology to site an aortic grafteliminates many of the risks ofopen abdominal surgery, inparticular, the physiologicalstresses associated with aorticcross-clamping.Currently being developedare endovascular branch vesseldevices for the repair of aorticaneurysms involving thehypogastric, renal, SMA andceliac arteries. Universalapplication of endografttechnology is limited by theanatomy of aorta, especially theextent and distribution of theaneurysmal disease itself.Aneurysm repair requires anappropriately designed deviceand technical maneuvers tailoredto the individual patient’s need.Considering the wide variety ofaneurysm anatomy, branched stent grafting forthese complex aneurysms is now a valuableoption for patients who are deemed to be at highrisk for conventional aneurysm repair. Thesedevices are being developed and prototyped withthe aid of solid and surface modeling using Pro/E, along with analytical calculations andGreenberg, R.K., Srivastava, S.D., Ouriel, K., Waldman, D., Ivancev, K., Illig, K.A.,Shortell, C., and R.M. Green (2000) An endoluminal method of hemorrhage control andrepair of ruptured abdominal aortic aneurysms. J. Endovasc. Ther. 7:1-7.Greenberg, R.K., Lawrence-Brown, M., Bhandari, G., Hartley, D., Stelter, W., Umscheid,T., Chuter, T., Ivancev, K., Green, R., Hopkinson, B., Semmens, J., and K. Ouriel(2001) An update of the Zenith endovascular graft for abdominal aorticaneurysms: initial implantation and mid-term follow-up data. J. Vasc. Surg. 33(2Suppl):S157-S164.Greenberg, R.K. (2002) Abdominal aortic endografting: fixation and sealing. J. Am.Coll. Surg. 194(1 Suppl):S79-S87.Ouriel, K., Greenberg, R.K., and D.G. Clair (2002) Endovascular treatment of aorticaneurysms. Curr. Probl. Surg. 39:242-345.Kwan, D., Dries, A., Burton, T., Bhandari, G., Young, D., Green, R., Ouriel, K., andR.K. Greenberg (2003) Thrombus characterization with intravascular ultrasound: potentialto predict successful thrombolysis. J. Endovasc. Ther. 10:90-98.The Department of Biomedical Engineeringexperimental data collection and interpretation usingMatlab. Specific interest in device development willbe in the effects of pulsatile flow on the device’sgraft material/alloy construction.The laboratory has also worked with theBiological Resources Unit (BRU) to institute acompliant setting in which Good LaboratoryPractice (GLP) studies can be conducted in a fullyequipped animal angiography suite with state-ofthe-artfluoroscopic imaging and intravascularultrasound. A Quality Assurance (QA) office wasestablished to independently monitor each GLPstudy to assure the quality and integrity of thedata in conformance with 21CFR Part 58. StandardOperating Procedures wereestablished, implemented and areregulated by the QA office. Wehave completed three GLPstudies working with companieson developing innovative stentsand stent grafts and are planningon performing more GLP studiesthis year.The other focus of thelaboratory is the study of drugtreatment for thrombusdissolution. Administration ofthrombolytic agents intooccluded arteries and veins hasbecome one of the mostfrequent methods to dissolvethrombus. Along with lyticregimes used in the clinicalmanagement of peripheral arterial ischemia, newdrugs and catheter devices are being explored andcompared within in vitro and in vivo models.We have developed an in vitro perfusionsystem, simulating the human arterial system in aclinical setting. Thus we are able to control suchvariables as the size and consistency of thethrombus and the hemodynamic conditionspresent while maintaining flow rates, meanpressures and temperature. Our goals are todetermine the speed of flow restoration, quantifyembolic debris and evaluate the chemicalcompleteness of thrombolysis. Some of ouranalysis is performed with the use of radioactivematerials, 125 Iodine-labeled fibrinogen and111Indium oxyquinoline, to label platelets andanalyze the effects of lytic agents on the thrombus.The laboratory has also created a reproduciblechronic thrombus in vivo model in the caninesarteria system. Both in vitro and in vivo models willallow for future research of innovative thrombolyticdrugs in conjunction with device cathetersfor studying thrombolysis.Roy K. Greenberg, M.D.26