Thrombogenic Performance of a St. Jude Bileaflet Mechanical Heart Valve in a Sheep Model WEI YIN,* IRVIN B. KRUKENKAMP,† ADAM E. SALTMAN,† GLENN GAUDETTE,* KRISHNAMURTHY SURESH,† OSCAR BERNAL,† JOLYON JESTY,‡ AND DANNY BLUESTEIN* The sheep model is preferred for chronic evaluation of pros- thetic heart valves, surgical techniques, and endocardio- graphic studies. A bileaflet mechanical heart valve (MHV) was implanted into a sheep model to study its in vivo perfor- mance and to evaluate the thrombogenic potential of the valve. Transesophageal echocardiography and transcranial Doppler ultrasonography measurements were conducted be- fore and after the valve implantation. Platelet activity state (PAS) assay measurements were also conducted before and after the implantation surgery. After sheep euthanasia, the MHV was explanted and scanning electron microscopy (SEM) was performed on the explanted valve to examine changes to the MHV surface. Tissue blocks were taken from the sheep brain, left ventricle, aorta, spleen, and lung lobes for histo- logical examination. Our results indicated that after the MHV implantation, more embolic signals were detected in the sheep carotid artery, increasing monotonously as a function of implantation time. Echocardiographic parameters includ- ing blood aortic velocity, transvalvular pressure gradient, and velocity time integral increased. PAS increased significantly after valve implantation. SEM pictures demonstrated calcium and phosphate deposition on the valve surfaces. Histological examination demonstrated hemorrhage in the lung tissue, pulmonary thrombosis, and osteogenesis in heart tissue. ASAIO Journal 2006; 52:28–33. V alve replacement is sometimes an essential treatment for pa- tients with severe heart valve diseases. About 60% of the pros- thetic heart valves being used are mechanical ones. St. Jude Medical bileaflet mechanical heart valves (MHVs) are widely used in the United States, and clinical studies indicate that they have good hemodynamic performances in vitro and in vivo. 1 However, the nonphysiologic flow patterns induced by MHVs may cause platelet activation and lead to thromboembolism and the attendant cardioembolic stroke, which are among their major complications. 2 The most common complications related to MHVs are major bleeding 3,4 and thrombosis. 5,6 Interestingly, car- diovascular osteogenesis is not uncommon after cardiovascular surgery. 7,8 In this study, sheep were chosen because they tolerate cardiac surgery well, and their cardiovascular anatomy is similar to that of humans. In recent years, many research groups have demonstrated that the sheep model is for chronic evaluation of prosthetic heart valves (PHVs), surgical techniques, and endocar- diographic studies. 9 –14 Compared to dogs, pigs, and calves, sheep have a relatively large aorta, which makes them technically better animal models for MHV studies. Anesthetic doses for sheep are similar to those for humans, and general anesthesia is well tolerated without any respiratory complications after exudation. Sheep also have a blood coagulation profile similar to that of humans, 15–17 which was another important consideration with regard to the sheep platelet activity measurements performed in our study. Ruel et al. 18 used a sheep model to study the knotless suture welding techniques for the mitral valve replacement and con- cluded that the sheep model was very reliable, and it provided a promising method to model valve surgery procedures in human patients. Wheatley et al. 19 chose sheep to study and compare the in vivo performance of MHVs, tissue valves, and polymeric heart valves. They implanted ATS MHVs in 10 sheep, polyurethane valves in 8 sheep, and Carpentier-Edwards porcine valves in 10 sheep, and found that the porcine valve and the polyurethane valve had lower thrombogenicity than MHVs. Hofman et al. 20 used sheep to study the safety issues related to silicone-polyure- thane valve implantation. They implanted polyurethane mitral valves in six sheep and studied the biodegradation and failure rate of the valve, demonstrating again that sheep were good in vivo models for mitral valve replacement studies. The aim of this study was to establish the thromboembolic risk and the thrombogenic potential of a St. Jude Medical bileaflet MHV implanted in the aortic position in a sheep model. Transcranial Doppler (TCD) ultrasonography was con- ducted to measure the microembolic signals (MES) in the sheep carotid artery. Transesophageal echocardiography (TEE) was performed to study the changes in cardiac parameters in the sheep before and after MHV implantation. Blood samples from sheep were taken before and after MHV implantation and platelet activity state (PAS) was measured using a modified prothrombinase assay. 21,22 Preoperative to postoperative com- parison established the platelet activity in the presence of MHV. Tissue samples were taken for histological and patho- logical examinations after the sheep euthanasia. Scanning electron microscopy (SEM) pictures were taken to study the surface changes of the MHV. Materials and Methods The animal studies conducted and described herewith were approved by the Stony Brook University Institutional Animal Care and Use Committee. From the Departments of *Biomedical Engineering, †Surgery, and ‡Medicine, Division of Hematology, Stony Brook University, Stony Brook, NY. Submitted for consideration June 2005; accepted for publication in revised form November 2005. Reprint Requests: Dr. Wei Yin, Ph.D., Weill Medical College of Cornell University, New York, NY. DOI: 10.1097/01.mat.0000198123.42686.ca ASAIO Journal 2006 28