In Vivo Image-Based 4D Modeling of Competent and Regurgitant Mitral Valve Dynamics.

BACKGROUND: In vivo characterization of mitral valve dynamics relies on image analysis algorithms that accurately reconstruct valve morphology and motion from clinical images. The goal of such algorithms is to provide patient-specific descriptions of both competent and regurgitant mitral valves, which can be used as input to biomechanical analyses and provide insights into the pathophysiology of diseases like ischemic mitral regurgitation (IMR). OBJECTIVE: The goal is to generate accurate image-based representations of valve dynamics that visually and quantitatively capture normal and pathological valve function. METHODS: We present a novel framework for 4D segmentation and geometric modeling of the mitral valve in real-time 3D echocardiography (rt-3DE), an imaging modality used for pre-operative surgical planning of mitral interventions. The framework integrates groupwise multi-atlas label fusion and template-based medial modeling with Kalman filtering to generate quantitatively descriptive and temporally consistent models of valve dynamics. RESULTS: The algorithm is evaluated on rt-3DE data series from 28 patients: 14 with normal mitral valve morphology and 14 with severe IMR. In these 28 data series that total 613 individual 3DE images, each 3D mitral valve segmentation is validated against manual tracing, and temporal consistency between segmentations is demonstrated. CONCLUSIONS: Automated 4D image analysis allows for reliable non-invasive modeling of the mitral valve over the cardiac cycle for comparison of annular and leaflet dynamics in pathological and normal mitral valves. Future studies can apply this algorithm to cardiovascular mechanics applications, including patient-specific strain estimation, fluid dynamics simulation, inverse finite element analysis, and risk stratification for surgical treatment.

Patient-specific CFD models for intraventricular flow analysis from 3D ultrasound imaging: Comparison of three clinical cases.

BACKGROUND: As the intracardiac flow field is affected by changes in shape and motility of the heart, intraventricular flow features can provide diagnostic indications. Ventricular flow patterns differ depending on the cardiac condition and the exploration of different clinical cases can provide insights into how flow fields alter in different pathologies. METHODS: In this study, we applied a patient-specific computational fluid dynamics model of the left ventricle and mitral valve, with prescribed moving boundaries based on transesophageal ultrasound images for three cardiac pathologies, to verify the abnormal flow patterns in impaired hearts. One case (P1) had normal ejection fraction but low stroke volume and cardiac output, P2 showed low stroke volume and reduced ejection fraction, P3 had a dilated ventricle and reduced ejection fraction. RESULTS: The shape of the ventricle and mitral valve, together with the pathology influence the flow field in the left ventricle, leading to distinct flow features. Of particular interest is the pattern of the vortex formation and evolution, influenced by the valvular orifice and the ventricular shape. The base-to-apex pressure difference of maximum 2mmHg is consistent with reported data. CONCLUSION: We used a CFD model with prescribed boundary motion to describe the intraventricular flow field in three patients with impaired diastolic function. The calculated intraventricular flow dynamics are consistent with the diagnostic patient records and highlight the differences between the different cases. The integration of clinical images and computational techniques, therefore, allows for a deeper investigation intraventricular hemodynamics in patho-physiology.

Patient-specific CFD simulation of intraventricular haemodynamics based on 3D ultrasound imaging.

BACKGROUND: The goal of this paper is to present a computational fluid dynamic (CFD) model with moving boundaries to study the intraventricular flows in a patient-specific framework. Starting from the segmentation of real-time transesophageal echocardiographic images, a CFD model including the complete left ventricle and the moving 3D mitral valve was realized. Their motion, known as a function of time from the segmented ultrasound images, was imposed as a boundary condition in an Arbitrary Lagrangian-Eulerian framework. RESULTS: The model allowed for a realistic description of the displacement of the structures of interest and for an effective analysis of the intraventricular flows throughout the cardiac cycle. The model provides detailed intraventricular flow features, and highlights the importance of the 3D valve apparatus for the vortex dynamics and apical flow. CONCLUSIONS: The proposed method could describe the haemodynamics of the left ventricle during the cardiac cycle. The methodology might therefore be of particular importance in patient treatment planning to assess the impact of mitral valve treatment on intraventricular flow dynamics.

Fully automatic segmentation of the mitral leaflets in 3D transesophageal echocardiographic images using multi-atlas joint label fusion and deformable medial modeling.

Comprehensive visual and quantitative analysis of in vivo human mitral valve morphology is central to the diagnosis and surgical treatment of mitral valve disease. Real-time 3D transesophageal echocardiography (3D TEE) is a practical, highly informative imaging modality for examining the mitral valve in a clinical setting. To facilitate visual and quantitative 3D TEE image analysis, we describe a fully automated method for segmenting the mitral leaflets in 3D TEE image data. The algorithm integrates complementary probabilistic segmentation and shape modeling techniques (multi-atlas joint label fusion and deformable modeling with continuous medial representation) to automatically generate 3D geometric models of the mitral leaflets from 3D TEE image data. These models are unique in that they establish a shape-based coordinate system on the valves of different subjects and represent the leaflets volumetrically, as structures with locally varying thickness. In this work, expert image analysis is the gold standard for evaluating automatic segmentation. Without any user interaction, we demonstrate that the automatic segmentation method accurately captures patient-specific leaflet geometry at both systole and diastole in 3D TEE data acquired from a mixed population of subjects with normal valve morphology and mitral valve disease.

Evaluation of isovolumic relaxation phase in the process of ventricular remodeling following myocardial infarction.

The course of cardiac remodeling after an acute cardiac MI, might affect the orientation of the cardiac muscle fibers as well as their contraction behavior. This may result in alteration of the untwisting during isovolumic relaxation phase, which might have effects on rapid early filling phase. In the present article, the variation of the time constant of isovolumic pressure drop (tau) has been studied during the course of cardiac remodeling after different types of induced myocardial infarction (MI) in sheep. The results for each group show different patterns of change in tau. The normalized tau curve in all three groups of anteroapical, anterobasal and posterobasal MI group show a rise 30 minutes after infarction. Two weeks later, the pressure drop constants decline to a lower level than baseline and by eight weeks after infarction, the time constant reached around the baseline level.

New paradigms and improved results for the surgical treatment of acute type A dissection.

OBJECTIVE: To examine the effect of an integrated surgical approach to the treatment of acute type A dissections. SUMMARY BACKGROUND DATA: Acute type A dissection requires surgery to prevent death from proximal aortic rupture or malperfusion. Most series of the past decade have reported a death rate in the range of 15% to 30%. METHODS: From January 1994 to March 2001, 104 consecutive patients underwent repair of acute type A dissection. All had an integrated operative management as follows: intraoperative transesophageal echocardiography; hypothermic circulatory arrest (HCA) with retrograde cerebral perfusion (RCP) to replace the aortic arch; HCA established after 5 minutes of electroencephalographic (EEG) silence in neuromonitored patients (66%) or after 45 minutes of cooling in patients who were not neuromonitored (34%); reinforcement of the residual arch tissue with a Teflon felt "neo-media"; cannulation of the arch graft to reestablish cardiopulmonary bypass at the completion of HCA (antegrade graft perfusion); and remodeling of the sinus of Valsalva segments with Teflon felt "neo-media" and aortic valve resuspension (78%) or replacement with a biologic or mechanical valved conduit (22%). RESULTS: Mean age was 59 +/- 15 (range 22-86) years, with 71% men and 13% redo sternotomy after a previous cardiac procedure. Mean cardiopulmonary bypass time was 196 +/- 50 minutes. Mean HCA with RCP time was 42 +/- 12 minutes (range 19-84). Mean cardiac ischemic time was 140 +/- 45 minutes. Eleven percent of patients presented with a preoperative neurologic deficit, and 5% developed a new cerebrovascular accident after dissection repair. The in-hospital death rate was 9%. Excluding the patients who presented neurologically unresponsive or with ongoing cardiopulmonary resuscitation (n = 5), the death rate was 4%. In six patients adverse cerebral outcomes were potentially avoided when immediate surgical fenestration was prompted by a sudden change in the EEG during cooling. Forty-five percent of neuromonitored patients required greater than 30 minutes to achieve EEG silence. CONCLUSION: The authors have shown that the surgical integration of sinus segment repair or aortic root replacement, the use of EEG monitoring, partial or total arch replacement using RCP, routine antegrade graft perfusion, and the uniform use of transesophageal echocardiography substantially decrease the death and complication rates of acute type A dissection repair.

Application of "double bridge mechanical" resuscitation for profound cardiogenic shock leading to cardiac transplantation.

BACKGROUND: In patients with acute profound cardiogenic circulatory failure unresponsive to conventional resuscitation, we instituted immediate aggressive application of extracorporeal membrane oxygenation (ECMO) to restore circulatory stability. Long-term hemodynamic support was accomplished with an early "bridge" to ventricular assist device (VAD) before definitive treatment with cardiac transplantation. METHODS: A respective review of ECMO and VAD data registries was instituted. RESULTS: From May 1996 to July 2000, 23 patients were placed on ECMO support for profound cardiogenic circulatory failure. Eleven patients (47%) were withdrawn from support due to severe neurologic injury or multisystem organ failure. Three patients (13%) were weaned off ECMO with good outcome. Nine patients (39%) were transferred to a VAD. Two patients expired while on VAD support, and 7 of the VAD-supported patients (78%) survived to transplantation. Overall survival was 43%. CONCLUSIONS: Emergent ECMO support is a salvage approach for cardiac resuscitation once conventional measures have failed. In neurologically intact patients, the early transfer to a VAD quickly stabilizes hemodynamics, avoids complications, and is essential for long-term circulatory support before definitive treatment with cardiac transplantation.

Circulatory management of the unstable cardiac patient.

The objective of this article is to provide an orderly and concise approach to the treatment of the unstable cardiac surgery patient. The common causes of hemodynamic instability in this patient population are reviewed. The various pharmacologic, mechanical, and electric therapeutic options available for each clinical situation are explored, and a sequential treatment algorithm is developed.

Glycoprotein IIb/IIIa receptor antagonist tirofiban inhibits thrombin generation during cardiopulmonary bypass in baboons.

Platelets play a major role in coagulation mechanisms and anti-GPIIb-IIIa antibodies inhibit tissue-factor induced thrombin generation in in vitro studies. Tirofiban, a nonpeptide selective glycoprotein (GP) IIb/IIIa antagonist, preserves platelet number and function during cardiopulmonary bypass (CPB) in baboons. We tested the hypothesis that platelet inhibition by tirofiban inhibits thrombin generation in vivo. Four groups of baboons (n = 7-12) were perfused for 60 min; all groups received heparin (300 units/kg). The controls received only heparin. The low dose (0.1 microg/kg/min) and high dose (0.3 microg/kg/min) infusion groups received tirofiban for 60 min before and 60 min during CPB. The bolus plus low dose infusion group received a 15 microg/kg bolus before starting CPB and a low dose infusion (0.1 mg/kg/min) only during CPB. At end of CPB, compared to control group (2.99+/-0.36 nM), prothrombin fragment F1.2 levels were lower (p<0.05) in low dose infusion group (1.65+/-0.14 nM, mean +/- SE) and high dose infusion group (1.71+/-0.19 nM), but not bolus plus infusion group (2.69+/-0.49 nM); they remained significantly lower after protamine administration. At end of CPB, thrombin-antithrombin complex levels were lower in high dose infusion group (40.0+/-11.2 ng/ml, p<0.05) compared to control group (76.2+/-7.3 ng/ml). These studies indicate that tirofiban inhibits not only platelet aggregation but also thrombin generation in vivo during CPB, and that this effect is demonstrable even in the presence of intense heparin anticoagulation. They underscore the important inhibitory effect of GPIIb-IIIa antagonists on thrombin generation.

Restraining infarct expansion preserves left ventricular geometry and function after acute anteroapical infarction.

BACKGROUND: Expansion of an acute myocardial infarction predicts progressive left ventricular (LV) dilatation, functional deterioration, and early death. This study tests the hypothesis that restraining expansion of an acute infarction preserves LV geometry and resting function. METHODS AND RESULTS: In 23 sheep, snares were placed around the distal left anterior descending and second diagonal coronary arteries. In 12 sheep, infarct deformation was prevented by Marlex mesh placed over the anticipated myocardial infarct. Snared arteries were occluded 10 to 14 days later. Serial hemodynamic measurements and transdiaphragmatic quantitative echocardiograms were obtained up to 8 weeks after anteroapical infarction of 0.23 of LV mass. In sheep with mesh, circulatory hemodynamics, stroke work, and end-systolic elastance return to preinfarction values 1 week after infarction and do not change subsequently. Ventricular volumes and ejection fraction do not change after the first week postinfarction. Control animals develop large anteroapical ventricular aneurysms, increasing LV dilatation, and progressive deterioration in circulatory hemodynamics and ventricular function. At week 8, differences in LV end-diastolic pressure, cardiac output, end-diastolic and end-systolic volumes, ejection fraction, stroke work, and end-systolic elastance are significant (P<0.01) between groups. CONCLUSIONS: Preventing expansion of acute myocardial infarctions preserves LV geometry and function.

Are vitamin B12 and folate deficiency clinically important after roux-en-Y gastric bypass?

Although iron, vitamin B12, and folate deficiency have been well documented after gastric bypass operations performed for morbid obesity, there is surprisingly little information on either the natural course or the treatment of these deficiencies in Roux-en-Y gastric bypass (RYGB) patients. During a 10-year period, a complete blood count and serum levels of iron, total iron-binding capacity, vitamin B12, and folate were obtained in 348 patients preoperatively and postoperatively at 6-month intervals for the first 2 years, then annually thereafter. The principal objectives of this study were to determine how readily patients who developed metabolic deficiencies after Roux-en-Y gastric bypass responded to postoperative supplements of the deficient micronutrient and to learn whether the risk of developing these deficiencies decreases over time. Hemoglobin and hematocrit levels were significantly decreased at all postoperative intervals in comparison to preoperative values. Moreover, at each successive interval through 5 years, hemoglobin and hematocrit were decreased significantly compared to the preceding interval. Folate levels were significantly increased compared to preoperative levels at all time intervals. Iron and vitamin B12 levels were lower than preoperative measurements and remained relatively stable postoperatively. Half of the low hemoglobin levels were not associated with iron deficiency. Taking multivitamin supplements resulted in a lower incidence of folate deficiency but did not prevent iron or vitamin B12 deficiency. Oral supplementation of iron and vitamin B12 corrected deficiencies in 43% and 81% of cases, respectively. Folate deficiency was almost always corrected with multivitamins alone. No patient had symptoms that could be attributed to either vitamin B12 or folate deficiency Conversely, many patients had symptoms of iron deficiency and anemia. Lack of symptoms of vitamin B12 and folate deficiency suggests that these deficiencies are not clinically important after RYGB. Conversely, iron deficiency and anemia are potentially serious problems after RYGB, particularly in younger women. Hence we recommend prophylactic oral iron supplements to premenopausal women who undergo RYGB.

Enoxaparin suppresses thrombin formation and activity during cardiopulmonary bypass in baboons.

OBJECTIVE: This study tests the hypotheses that enoxaparin, a low molecular weight heparin and potent inhibitor of factor Xa, alone or in combination with standard heparin, inhibits thrombin formation and activity and modulates complement activation and neutrophil elastase release during cardiopulmonary bypass in baboons. METHODS: After preliminary studies to determine doses and possible species differences to anticoagulants and protamine, 27 anesthesized baboons had normothermic cardiopulmonary bypass with standard, unfractionated, porcine intestinal heparin, enoxaparin, or a combination of heparin and enoxaparin. Protamine in appropriate doses was used to reverse anticoagulation. Blood samples were obtained at 6 time points. Activated clotting times were monitored; template bleeding times were measured before and up to 24 hours after cardiopulmonary bypass. RESULTS: Hemodynamic measurements were not affected by the anticoagulant. Activated clotting times remained above 400 seconds throughout bypass, and no clots were observed. The anticoagulant did not alter platelet count, aggregation to adenosine diphosphate, release of beta-thromboglobulin, release of neutrophil elastase, or complement C3b/c and C4b/c. Enoxaparin alone, but not in combination, significantly reduced plasma levels of prothrombin fragment F1.2, fibrinopeptide A, and thrombin-antithrombin complexes but prolonged template bleeding times for more than 24 hours. CONCLUSION: Enoxaparin significantly reduces thrombin formation and activity during cardiopulmonary bypass but does not suppress complement activation and neutrophil elastase release and is not adequately reversed by protamine after bypass.

Prophylactic iron supplementation after Roux-en-Y gastric bypass: a prospective, double-blind, randomized study.

OBJECTIVE: To determine whether prophylactic oral iron supplements (320 mg twice daily) would protect women from iron deficiency and anemia after Roux-en-Y gastric bypass. DESIGN: Prospective, double-blind, randomized study in which 29 patients received oral iron and 27 patients received a placebo beginning 1 month after Roux-en-Y gastric bypass. SETTING: Tertiary care medical center. PATIENTS AND INTERVENTIONS: Complete blood cell count and serum levels of iron, total iron binding capacity, ferritin, vitamin B12, and folate were determined preoperatively and at 6-month intervals postoperatively in 56 menstruating women who had Roux-en-Y gastric bypass. MAIN OUTCOME MEASURE: Incidence of iron deficiency and other hematological abnormalities in each treatment group. RESULTS: Hemoglobin, hematocrit, and vitamin B12 levels were significantly decreased compared with preoperative values in both groups. Conversely, folate levels increased significantly over time in both groups. Oral iron consistently prevented development of iron deficiency in the iron group. Ferritin levels did not change significantly in the iron group. However, in placebo-treated patients, ferritin levels 2 years postoperatively were significantly decreased compared with preoperative levels. There was no difference in the incidence of anemia between the 2 groups. However, the incidence of microcytosis was substantially greater (P=.07) in placebo-treated than iron-treated patients. CONCLUSIONS: Prophylactic oral iron supplements successfully prevented iron deficiency in menstruating women after Roux-en-Y gastric bypass but did not consistently protect these women from developing anemia. On the basis of these results we now routinely recommend prophylactic iron supplements to menstruating women who have Roux-en-Y gastric bypass.

Infarct size and location determine development of mitral regurgitation in the sheep model.

OBJECTIVE: This study tests the hypothesis that neither small nor large myocardial infarctions that include the anterior papillary muscle produce mitral regurgitation in sheep. METHODS: Coronary arterial anatomy to the anterior left ventricle and papillary muscle was determined by dye injection in 41 sheep hearts and by triphenyl tetrazolium chloride in 13. Development of acute or chronic mitral regurgitation and changes in left ventricular dimensions were studied by use of transdiaphragmatic echocardiography in 21 sheep after infarction of 24% and 33% of the anterior left ventricular mass. These data were compared with previous data from large and small posterior left ventricular infarctions. RESULTS: Ligation of two diagonal arteries infarcts 24% of the left ventricular mass and 82% of the anterior papillary muscle. Ligation of both diagonals and the first circumflex branch infarcts 33% of the left ventricle and all of the anterior papillary muscle. Neither infarction causes mitral regurgitation, although left ventricular cavity dimensions increase significantly at end systole. After the smaller infarction, the left ventricular cavity enlarges 150% over 8 weeks without mitral regurgitation. CONCLUSIONS: In sheep small and large infarctions of the anterior wall that include the anterior papillary muscle do not produce either acute or chronic mitral regurgitation despite left ventricular dilatation. In contrast large posterior infarctions produce immediate mitral regurgitation owing to asymmetric annular dilatation and discoordination of papillary muscle relationships to the valve. After small posterior infarctions that include the posterior papillary muscle, mitral regurgitation develops because of annular and ventricular dilatation during remodeling.

Papillary muscle discoordination rather than increased annular area facilitates mitral regurgitation after acute posterior myocardial infarction.

BACKGROUND: Acute posterior myocardial infarction that produces immediate mitral regurgitation alters the mitral annulus and its spatial relationship with both papillary muscles. The precise deformations that cause valve insufficiency are not understood and impair efforts to repair the valve. METHODS AND RESULTS: In six Dorsett hybrid sheep, sonomicrometry transducers were placed around the mitral annulus (6) and at the tips and bases of both papillary muscles (4). Two weeks later, three branches of the circumflex coronary artery were occluded to infarct approximately 32% of the posterior left ventricle. This infarction produced acute 2 to 3+ mitral regurgitation in all animals, as determined by color flow Doppler velocity mapping. Before and after infarction, distance measurements between sonomicrometry transducers were used to produce the three-dimensional coordinates of each transducer every 5 ms. After infarction, the area of the annulus increased only 9.2+/-6.3% at end systole (ES). In addition, the normal shortening of the posterior papillary muscle was obliterated to allow its tip to move 1.4+/-0.6 mm closer to the centroid of the annulus at ES. After infarction, the anterior papillary muscle continued to shorten normally, but at ES, its tip and base were 0.9+/-0.7 mm and 1.3+/-0.7 mm farther from the centroid, respectively. CONCLUSIONS: These deformations tend to produce a relative prolapse of leaflet tissue attached to the posterior papillary muscle and restriction of leaflet tissue attached to the anterior papillary muscle. This papillary muscle discoordination with minimal annular dilatation distorts leaflet coaptation sufficiently to produce severe mitral regurgitation.

Distortions of the mitral valve in acute ischemic mitral regurgitation.

BACKGROUND: In the absence of papillary muscle rupture, the precise deformations that cause acute postinfarction mitral valve regurgitation are not understood and impair reparative efforts. METHODS: In 6 Dorsett hybrid sheep, sonomicrometry transducers were placed around the mitral annulus (n = 6) and at the tips and bases of both papillary muscles (n = 4). Later, specific circumflex coronary arteries were occluded to infarct approximately 32% of the posterior left ventricle and produce acute 2 to 3+ mitral regurgitation. Before and after infarction, distance measurements between sonomicrometry transducers produced three-dimensional coordinates of each transducer every 5 ms. RESULTS: After infarction, the annulus dilated asymmetrically orthogonal to the line of leaflet coaptation, but the annular area increased only 9.2% +/- 6.3% (p = 0.02). At end-systole, posterior papillary muscle length increased 2.3 +/- 0.9 mm (p = 0.005); the posterior papillary muscle tip moved closer to the annular plane and centroid, and the anterior papillary muscle tip moved away. CONCLUSIONS: Small deformations in mitral valvular spatial geometry after large posterior infarctions are sufficient to produce moderate to severe mitral regurgitation. The most important changes are asymmetric annular dilatation, prolapse of leaflet tissue tethered by the posterior papillary muscle, and restriction of leaflet tissue attached to the anterior papillary muscle.

A baboon model for hematologic studies of cardiopulmonary bypass.

Objective investigation of new inhibitors of blood protein or cellular systems that are activated during cardiopulmonary bypass (CPB) is impeded by the absence of a satisfactory animal model. Because most baboon hematologic proteins immunologically cross-react with those used for human assays, we developed a robust, reusable baboon model of CPB. Blood samples were obtained from adult baboons at six time intervals before, during, and after 60 minutes of partial CPB at 37 degrees C with peripheral cannulas. Both membrane (n = 7) and bubble oxygenators (n = 7) were investigated. We measured platelet and white blood cell counts; platelet response to adenosine diphosphate and release of beta-thromboglobulin; fibrinopeptide A, prothrombin fragment F1.2, thrombin-antithrombin complex, D-dimer, and plasmin-antiplasmin complex; activated complement (C3b/c and C4b/c); elastase-alpha1 proteinase inhibitor complex; and bleeding times. Adherent glycoprotein IIIa antigen in Triton X-100 washes of the perfusion circuit was also measured. Markers of baboon platelet, complement, and neutrophil activation and thrombosis significantly increased during CPB with bubble oxygenator systems but did not change appreciably in membrane oxygenator circuits. Markers of fibrinolysis, D-dimer, and plasmin-antiplasmin complex did not change with either oxygenator. The baboon model of CPB, when a bubble oxygenator is used, is a robust, reusable animal model for evaluating inhibitors of platelet, complement, and neutrophil activation and thrombosis during and after CPB.

Tirofiban provides "platelet anesthesia" during cardiopulmonary bypass in baboons.

OBJECTIVE: Tirofiban (Aggrastat) is a reversible, nonpeptide inhibitor of platelet glycoprotein II/IIIa receptors. We tested the hypothesis that tirofiban preserves platelet number and function and shortens postoperative bleeding times in baboons after cardiopulmonary bypass. METHODS: Four groups were studied: control, n = 12; low-dose tirofiban (0.1 microg/kg per minute), n = 7; high-dose tirofiban (0.3 microg/kg per minute), n = 7; and bolus tirofiban (15 microg/kg) followed by 0.1 microg/kg per minute during cardiopulmonary bypass, n = 7. After heparin, animals were perfused for 60 minutes at 50 ml/kg per minute and 37 degrees C with a bubble oxygenator, roller pump, and peripheral cannulation. Hemodynamics, platelet count, platelet aggregation to adenosine diphosphate, and release of beta-thromboglobulin were measured before tirofiban infusion, before heparin, after heparin before bypass, after 5 and 55 minutes of bypass, after protamine, and 60 minutes after protamine. Template bleeding times were measured at the same times except during cardiopulmonary bypass and 120 and 180 minutes after protamine administration. Platelet glycoprotein IIIa antigen was measured in Triton X-100 washes (Sigma Chemical Company) of the perfusion circuit after bypass. RESULTS: High-dose tirofiban completely prevents platelet loss during cardiopulmonary bypass. beta-Thromboglobulin release and sensitivity to adenosine diphosphate are significantly less than control at the end of bypass in all tirofiban groups. Template bleeding times return to preoperative values in both the low- and high-dose tirofiban groups 180 minutes after protamine administration and are significantly less than control bleeding times at both 120 and 180 minutes after protamine. Surface glycoprotein IIIa antigen does not significantly differ between groups. CONCLUSION: High-dose tirofiban completely preserves platelet number and improves platelet function during cardiopulmonary bypass in baboons and significantly accelerates restoration of normal template bleeding times after bypass.