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Biomedical subjects

R P Cochran

Publications and source records attributed to R P Cochran.

At least 19 recordsLinked to original sources
PubMed2001

Mechanisms of aortic valve incompetence: finite-element modeling of Marfan syndrome.

OBJECTIVES: Progressive aortic root dilatation and an increased aortic root elastic modulus have been documented in persons with Marfan syndrome. To examine the effect of aortic root dilatation and increased elastic modulus on leaflet stress, strain, and coaptation, we used a finite-element model. METHODS: The normal model incorporated the geometry, tissue thickness, and anisotropic elastic moduli of normal human roots and valves. Four Marfan models were evaluated, in which the diameter of the aortic root was dilated by 5%, 15%, 30%, and 50%. Aortic root elastic modulus in the 4 Marfan models was doubled. Under diastolic pressure, regional stresses and strains were evaluated, and the percentage of leaflet coaptation was calculated. RESULTS: Root dilatation and stiffening significantly increased regional leaflet stress and strain compared with normal levels. Stress increases ranged from 80% to 360% and strain increases ranged from 60% to 200% in the 50% dilated Marfan model. Leaflet stresses and strains were disproportionately high at the attachment edge and coaptation area. Leaflet coaptation was decreased by approximately 20% in the 50% root dilatation model. CONCLUSIONS: Increasing root dilatation and root elastic modulus to simulate Marfan syndrome significantly increases leaflet stress and strain and reduces coaptation in an otherwise normal aortic valve. These alterations may influence the decision to use valve-sparing aortic root replacement procedures in patients with Marfan syndrome.

Aortic Valve↗
PubMed2001

Finite-element analysis of aortic valve-sparing: influence of graft shape and stiffness.

Aortic valve incompetence due to aortic root dilation may be surgically corrected by resuspension of the native valve within a vascular graft. This study was designed to examine the effect of graft shape and material properties on aortic valve function, using a three-dimensional finite-element model of the human aortic valve and root. First, the normal root elements in the model were replaced with graft elements, in either a cylindrical or a "pseudosinus" shape. Next, the elements were assigned the material properties of either polyethylene terephthalate, expanded polytetrafluoroethylene, or polyurethane. Diastolic pressures were applied, and stresses, strains, and coaptation were recorded for the valve, root, and graft. Regarding shape, the cylindrical graft models increased the valve stresses by up to 173%, whereas the root-shaped graft model increased valve stresses by up to 40% as compared to normal. Regarding material properties, the polyurethane models demonstrated valve stress, strain, and coaptation values closest to normal, for either root shape. Graft shape had a greater effect on the simulated valve function than did the material property of the graft. Optimizing the shape and material design of the graft may result in improved longevity of the spared valve if a normal environment is restored.

Aorta↗
PubMed2000

Mechanisms of aortic valve incompetence: finite element modeling of aortic root dilatation.

BACKGROUND: Idiopathic root dilatation often results in dysfunction of an otherwise normal aortic valve. To examine the effect of root dilatation on leaflet stress, strain, and coaptation, we utilized a finite element model. METHODS: The normal model incorporated the geometry, tissue thickness, stiffness, and collagen fiber alignment of normal human roots and valves. We evaluated four dilatation models in which diameters of the aortic root were dilated by 5%, 15%, 30%, and 50%. Regional stress and strain were evaluated and leaflet coaptation percent was calculated under diastolic pressure. RESULTS: Root dilatation significantly increased regional leaflet stress and strain beyond that found in the normal model. Stress increases ranged from 57% to 399% and strain increases ranged from 39% to 189% in the 50% dilatation model. Leaflet stress and strain were disproportionately high at the attachment edge and coaptation area. Leaflet coaptation was decreased by 18% in the 50% root dilatation model. CONCLUSIONS: Idiopathic root dilatation significantly increases leaflet stress and strain and reduces coaptation in an otherwise normal aortic valve. These alterations may affect valve-sparing aortic root replacement procedures.

Aortic Valve↗
PubMed2000

Re-creation of sinuses is important for sparing the aortic valve: a finite element study.

OBJECTIVE: The treatment of choice for aortic valve insufficiency due to root dilatation has become root replacement with aortic valve sparing. However, root replacement with a synthetic graft may result in altered valve stresses. The purpose of this study was to compare the stress/strain patterns in the spared aortic valve in different root replacement procedures by means of finite element modeling. METHODS: Our finite element model of the normal human root and valve was modified to simulate and evaluate three surgical techniques: (1) "cylindrical" graft sutured below the valve at the anulus, (2) "tailored" graft sutured just above the valve, and (3) "pseudosinus" graft, tailored and sutured below the valve at the anulus. Simulated diastolic pressures were applied, and stresses and strains were calculated for the valve, root, and graft. Leaflet coaptation was also quantified. RESULTS: All three root replacement models demonstrated significantly altered leaflet stress patterns as compared with normal patterns. The cylindrical model showed the greatest increases in stress (16%-173%) and strain (10%-98%), followed by the tailored model (stress +10%-157%, strain +9%-36%). The pseudosinus model showed the smallest increase in stress (9%-28%) and strain (2%-31%), and leaflet coaptation was closest to normal. CONCLUSION: Valve-sparing techniques that allow the potential for sinus space formation (tailored, pseudosinus) result in simulated leaflet stresses that are closer to normal than the cylindrical technique. Normalized leaflet stresses in the clinical setting may result in improved longevity of the spared valve.

Aorta↗
PubMed1999

Acute renal failure after cardiopulmonary bypass in related to decreased serum ferritin levels.

Acute renal failure (ARF) requiring dialysis occurs in up to 4% of patients after cardiopulmonary bypass (CPB). CPB leads to the generation of intravascular free hemoglobin, resulting in increased endothelial and renal tubular cell free iron, which is associated with renal injury. Conversely, renoprotection is conferred by processes that upregulate heme and iron sequestration pathways, such as ferritin. This study evaluates the influence of free hemoglobin generation during CPB and the capacity to sequester free iron on the occurrence of post-CPB renal insufficiency. Thirty consecutive patients undergoing CPB were enrolled in the study. Serum creatinine, free hemoglobin, and ferritin were measured preoperatively, at the end of bypass, and 24 and 48 h after surgery. Renal injury, as determined by an increase in the serum creatinine of > or =25% (ARF) by 48 h after surgery, occurred in 40% (12 of 30) of patients, and dialysis was necessary in 6.6% (2 of 30). Free hemoglobin levels increased in all patients but did not correlate with postoperative ARF. However, patients with preoperative serum ferritin levels < or =130 microg/L, the median value for the group, had a sixfold greater likelihood of developing ARF compared to patients with levels above this value (P = 0.03). Lower serum ferritin levels appear to be associated with the development of ARF. Serum ferritin levels may signify intravascular as well as endothelial and renal epithelial cell ability to bind free iron generated during CPB-induced hemolysis, and thus may help provide information regarding the risk for ARF.

Acute Kidney Injury↗
PubMed1999

Mechanisms of aortic valve incompetence in aging: a finite element model.

BACKGROUND AND AIM OF THE STUDY: The effect of aging on aortic valve and root function was examined using a three-dimensional finite element model of the aortic root and valve. METHODS: Three models representing normal (< 35 years), middle (35-55 years) and older (> 55 years) age groups, were created by assigning tissue thickness and stiffness that increased with age (using ANSYS software). Diastolic pressure was applied; stresses and strains were then evaluated for the valve and root, and percent leaflet coaptation was calculated. RESULTS: Leaflet stresses were increased with aging, whereas leaflet strain and coaptation were decreased with aging. Specifically, leaflet stresses were increased by 6-14% in the middle-age model, and by 2-11% in the older-age model, as compared with normal in specified leaflet regions. Conversely, leaflet strains were decreased by 27-41% and 42-50% in the middle-age and older-age models, respectively. This reduced strain resulted in markedly decreased coaptation (9% and 30% reduction for middle- and older-age models). In the root, stress remained fairly constant with age, but strain in the root was progressively reduced with age (11% and 35% reduction for the middle and older-age models, respectively). CONCLUSIONS: In these models, increased stiffness and thickness due to aging reduces leaflet deformation and restricts coaptation. Clinically, valvular regurgitation may result due to leaflet thickening and stiffening with normal aging. Our model can now be utilized to evaluate the root-valve relationship in the presence of bioprosthetic valves or root replacements.

Adult↗
PubMed1999

Acute mitral valve regurgitation created in sheep using echocardiographic guidance.

BACKGROUND AND AIM OF STUDY: This study was designed to determine: (i) Whether acute mitral valve regurgitation (MVR) due to chordal rupture can be reproducibly created under echocardiographic guidance; (ii) what degree of MVR can be created; (iii) what degree of acute regurgitation is survivable; and (iv) whether acute MVR due to chordal rupture progresses over time. METHODS: In a pilot group of six juvenile farm-bred sheep, selected chordae tendineae were ruptured using either a biopsy needle or endoscopic scissors under echocardiographic guidance, without need for cardiopulmonary bypass. Sheep were sacrificed acutely (n = 2), and at six weeks (n = 2) or eight weeks (n = 2). When the technique was optimized, five sheep entered a study group in which chords were ruptured using endoscopic scissors; the sheep were sacrificed 16 weeks after surgery. RESULTS: In the pilot study, acute MVR (grade 2-4+) was produced in all sheep, normal ventricular wall motion was maintained, with minimal progression of regurgitation over time. In one pilot sheep which did not survive, grade 4+ MVR was created acutely. Use of endoscopic scissors was preferable to the biopsy needle. In the study group, acute MVR (grade 2-4+) was produced in all five sheep, and was still present at 16 weeks, with progression in only one animal. CONCLUSIONS: This pilot study demonstrated that controlled degrees of survivable acute MVR due to chordal rupture can be created under echocardiographic guidance, with minimal progression of MVR over time. This animal model can be applied to investigate the pathogenesis of clinical MVR, and to suggest appropriate medical or surgical intervention.

Acute Disease↗
PubMed1998

Prospective trial of catheter irrigation and muscle flaps for sternal wound infection.

BACKGROUND: Sternal wound infection is a relatively rare but potentially devastating complication of open heart operations. The most common treatments after debridement are rewiring with antibiotic irrigation and muscle flaps. Here we present the results of a prospective trial to determine the appropriate roles of closed-chest catheter irrigation and muscle flap closure for sternotomy infection and to assess the effect of internal mammary artery bypass grafting on the outcome of each treatment modality. METHODS: Between 1990 and 1994, 5,658 sternotomies were performed at the University of Washington Medical Center. Sternal dehiscence occurred in 43 patients, 25 of whom had infection (overall incidence, 0.44%). Because of the infrequency of this complication, a prospective, randomized trial was developed in which the initial approach to sternal dehiscence was rewiring and catheter irrigation. Muscle flaps were used as the primary treatment if the sternum could not be restabilized or as secondary treatment if catheter irrigation failed. Wound resolution, length of hospital stay, and complications were evaluated. RESULTS: Sterile dehiscences were successfully closed with irrigation in 17 of 18 patients; the other patient required flap closure. Of the 25 patients with infection, 19 had irrigation and 6, closure with flaps primarily. In the group of infected patients, 17 of the 19 who received irrigation also had internal mammary artery bypass grafting. Irrigation failed in 15 (88.2%) of these 17 patients, and salvage was accomplished with muscle flap closure. All 6 patients with infection who were closed primarily with muscle flaps had a successful outcome. Hospitalization averaged 10.2 days when muscle flaps were used primarily and 14.3 additional days for unsuccessful irrigation. When irrigation was successful, the hospital stay averaged 11.2 days. CONCLUSIONS: Catheter irrigation should be reserved for patients without infection or patients with infection but without internal mammary artery bypass grafts in whom dehiscence occurs less than 1 month after sternotomy. All others should have closure with muscle flaps.

Anti-Bacterial Agents↗
PubMed1998

Effect of papillary muscle position on mitral valve function: relationship to homografts.

BACKGROUND: We used a finite element model to determine the effect of papillary muscle position on the stress distribution in the mitral valve. METHODS: A normal model was modified to move the posteromedial papillary muscle outward by either 2.5 mm or 5.0 mm. Next, the thickness was increased by 20%, simulating diseased tissue. Physiologic loading pressures were applied, and leaflet stress, chordal stress, and coaptation results were analyzed. RESULTS: Displacement of the posteromedial papillary muscle increased the leaflet stresses and altered the normal stress patterns. The displacement also restricted the leaflets from closing completely, allowing regurgitation. Combining increased thickness with papillary displacement decreased the stresses slightly. However, the amount of leaflet coaptation was further decreased, creating larger gaps for regurgitation. In all models, the stresses in the chordae were increased in the marginal chordae and decreased in the basal chordae, demonstrating a transfer of stress. CONCLUSIONS: Papillary muscle displacement creates abnormal valve stresses, and the potential for significant regurgitation. Papillary-chordal-leaflet geometry must be maintained in partial or complete mitral homograft replacement.

Blood Pressure↗
PubMed1998

Altered collagen concentration in mitral valve leaflets: biochemical and finite element analysis.

BACKGROUND: Ischemic mitral regurgitation or ventricular wall motion abnormalities will alter the stress distribution in the mitral valve. We hypothesize that in response, the regional collagen concentration will be altered and will significantly impact the stress distribution in the mitral valve. METHODS: Two sheep served as normal (sham) controls. Two other sheep had coronary ligation resulting in abnormal ventricular wall motion. Four sheep underwent ligation to infarct the posteromedial papillary muscle, resulting in ischemic regurgitation. After 4 or 8 weeks, the mitral valves were excised, and the anterior leaflet sections were subjected to an assay for collagen concentration. Next, in a finite element model, to simulate changes in collagen concentration, the tissue stiffness was increased by 20%, and then decreased by 20%. In another model, the thickness of the tissue was increased by 20%, and then combined with decreased tissue stiffness. Physiologic loading pressures were applied, and leaflet stress, chordal stress, and coaptation results were analyzed. RESULTS: The average collagen concentration in the normal sheep leaflets was 59.2% (dry weight), 50.6% in the ischemic controls, and 45.8% in the papillary muscle infarct group. Collagen concentration was greatest at the midline and decreased toward the commissures. Increased tissue stiffness resulted in increased leaflet and chordal stresses, as well as reduced coaptation. Decreased stiffness resulted in the opposite. Increased tissue thickness reduced leaflet and chordal stresses, but also reduced coaptation. The combination of increased tissue thickness and decreased stiffness demonstrated the greatest reduction in leaflet and chordal stress, while maintaining normal leaflet coaptation. CONCLUSIONS: The observed changes may demonstrate an early effort to compensate for increased leaflet stress. Microstructural alterations may demonstrate an early effort to compensate for altered physiologic loading to reduce stress and maintain coaptation. It is crucial in repairing or partially replacing thickened tissue that normal geometry and physiology be restored.

Animals↗
PubMed1998

Heparin-coated bypass circuits (Carmeda) suppress the release of tissue plasminogen activator during normothermic coronary artery bypass graft surgery.

OBJECTIVES: To study fibrinolysis in a homogeneous first-time coronary artery bypass surgery (CABG) population in whom heparin-coated circuits were used. DESIGN: A prospective, blinded, randomized, placebo-controlled study. SETTING: A university hospital, tertiary care, intraoperative and postoperative intensive care unit. PARTICIPANTS: Twenty-one adult elective primary CABG patients. INTERVENTIONS: Randomized circuit-type centrifugal pump, membrane oxygenator, rigid cardiotomy reservoir, either placebo (n = 10) or heparin-coated (n = 11) (Carmeda; Medtronic Inc., Anaheim, CA). MEASUREMENTS AND MAIN RESULTS: Blood samples were analyzed for tissue plasminogen activator (TPA) activity, TPA antigen, plasminogen activator inhibitor-1 (PAI-1) activity, prothrombin complex F1.2, and antithrombin III (AT-III) at the following times: before cardiopulmonary bypass (CPB), during CPB (30 and 60 minutes), post-CPB, and day 1 postsurgery. TPA activity and antigen increased fivefold in the placebo group during CPB, whereas it did not even double in the heparin-coated group. PAI-1, F1.2, and AT-III were not different between groups. CONCLUSIONS: Heparin-coated CPB circuits reduced TPA release in this homogeneous CABG population with routine heparin/protamine management.

Adult↗
PubMed1998

A second-generation blood substitute (perfluorodichlorooctane emulsion) does not activate complement during an ex vivo circulation model of bypass.

OBJECTIVES: To examine whether a second-generation perfluorocarbon (PFC) blood substitute added to the cardiopulmonary bypass (CPB) prime influences complement production. DESIGN: A prospective, randomized, single-blinded, ex vivo model. SETTING: A university hospital, laboratory, and clinics. PARTICIPANTS: Ten healthy adult consented volunteer blood donors (five men, five women). INTERVENTIONS: Ex vivo closed-loop extracorporeal circuit including membrane oxygenator, tubing, and filter primed with crystalloid or crystalloid plus PFC was circulated for 1 hour with the addition of 500 mL of heparinized fresh human whole blood. MEASUREMENTS AND MAIN RESULTS: Laboratory specimens were drawn from the circuit at 10-minute intervals for 1 hour and measured for complement (C3a, Bb fragment) concentrations, blood gases, fibrinogen concentration, platelet count, and hematocrit. In the PFC group, C3a and Bb fragments were equal to or less than those in the group that received crystalloid alone. CONCLUSION: The second-generation PFC added to the prime of a CPB circuit does not independently increase complement production.

Adolescent↗
PubMed1998

Angiographic and histological evaluation of porcine retinal vascular damage and protection with perfluorocarbons after massive air embolism.

BACKGROUND AND PURPOSE: We have previously shown that perfluorocarbon emulsions (PFEs) reduce the severity of cerebral injury (indicated by infarct, reduced blood flow, and depressed EEG) induced by air embolism during cardiopulmonary bypass (CPB). This study used retinal fluorescein angiography to define the mechanisms of cerebral injury and to determine the efficacy of PFEs in cerebral protection. These angiographic findings were correlated to previously reported histologic findings. METHODS: Twenty domestic pigs underwent CPB with a prime of standard crystalloid or PFE (5 mg/kg) and crystalloid. After 10 minutes on CPB, a single (5 mL/kg) or double (2x2.5 mL/kg) bolus of room air or saline (control) was delivered via the right carotid artery. Retinal fluorescein angiograms were captured at 4 time points: baseline, air insult, postbypass, and postreperfusion. Following euthanasia, both eyes were removed and the retinas isolated for histological analysis with horseradish peroxidase (HRP), as previously reported. RESULTS: In control pigs, postreperfusion angiograms showed small nonperfused areas, and retinal whole mounts demonstrated vascular damage as previously reported. In 5 PFE-primed animals, postreperfusion angiograms showed hyperfluorescence, but angiograms and HRP mounts were otherwise not significantly different from baseline. Severely hyperfluorescent vessels observed angiographically also showed a correlation with HRP extravasation but were not consistently indicative of severe vascular damage. CONCLUSIONS: Retinal fluorescein angiography and retinal staining with HRP indicate that mechanisms of cerebral air embolism include nonperfusion, vascular leakage and spasm, red blood cell sludging, and hemorrhage. Priming with PFE prevented many of the sequelae associated with air embolism.

Animals↗
PubMed1998

Flexible versus rigid ring annuloplasty for mitral valve annular dilatation: a finite element model.

BACKGROUND AND AIMS OF THE STUDY: The study objective was to compare coaptation, and leaflet and chordal stresses in normal and dilated mitral valves (18% annular dilatation) versus valves with flexible (Duran) and rigid (Carpentier-Edwards classic) ring annuloplasty, using a computer model. We have developed a 3D finite element model which allows us to evaluate valvular function in terms of coaptation and stresses in both leaflets and individual chordae. METHODS: The mitral valve was simulated using ANSYS 4.4A software. Normal model geometry, collagen fiber orientation, tissue thickness and material properties were determined from fresh porcine valves. For annular dilatation, the annular circumference was increased by 18% versus normal. For annuloplasty, a simulated flexible ring was attached to the annulus, and a simulated rigid ring then attached. Valves were evaluated during systolic pressure loading, after which timing of coaptation and leaflet and chordal stresses were determined. RESULTS: In the normal valve, the anterior leaflet was subject to higher tensile stresses than the posterior leaflet which was under compression. With annular dilatation, all stresses were increased, particularly in the posterior leaflet. The flexible ring returned leaflet and chordal stresses closer to normal than did the rigid ring. Leaflet coaptation began at 5 ms in the normal state, was delayed by dilatation, and returned towards normal with both rings. The flexible ring returned coaptation and stresses closer to normal than did the rigid ring. CONCLUSIONS: Ring annuloplasty reduces the stresses and improves coaptation relative to annular dilatation. The success of mitral annuloplasty is likely due to the re-establishment of posterior leaflet compressive stresses and near-normal coaptation.

Biomechanical Phenomena↗
PubMed1997

Perfluorocarbon emulsion in the cardiopulmonary bypass prime reduces neurologic injury.

BACKGROUND: Perfluorocarbon emulsion has proved beneficial in the prevention and amelioration of experimental air embolism. We examined whether the addition of perfluorocarbon to the prime solution could lead to a reduction in the incidence and severity of neurologic injury after the formation of a massive air embolism during cardiopulmonary bypass. METHODS: Fourteen pigs underwent bypass in which either a crystalloid prime solution or a perfluorocarbon prime solution (10 mL/kg) was used. Ten minutes into bypass a bolus (5 mL/kg) of air or saline (control) was delivered via the carotid artery. The resulting cerebral infarcts were graded on the basis of the findings in triphenyltetrazolium chloride-stained cerebral sections. Colored microspheres were used to measure cerebral blood flow. Bitemporal electroencephalography was used to evaluate cerebral function. RESULTS: Cerebral infarction was not found in the perfluorocarbon-air group (0 to 5 animals), as compared with its occurrence in 3 of the 5 animals in the crystalloid-air group. Cerebral blood flow was also maintained or increased in the perfluorocarbon-air group (p < 0.05), and the electroencephalogram total power showed less of a decrease and recovered more completely (p < 0.05) than it did in the crystalloid-air group. CONCLUSIONS: The addition of perfluorocarbon emulsion to the cardiopulmonary bypass prime solution leads to a reduction in the incidence and severity of neurologic injury after the formation of a massive air embolism during bypass.

Animals↗
PubMed1997

Annular dilatation increases stress in the mitral valve and delays coaptation: a finite element computer model.

The purpose of this study was to examine the effects of annular dilatation on coaptation, and leaflet and chordal stresses, using a three dimensional finite element computer model. To do this, the whole mitral valve was simulated using ANSYS 4.4A software. Normal model geometry, collagen fiber orientation, tissue thickness, and material properties were determined from fresh porcine valves. For annular dilatation, the annular circumference was increased by 18% versus normal. Isovolumic contraction and rapid ventricular ejection were simulated. Data showed that, in the annular dilatation model, the stress magnitudes increased more than two-fold compared with normal in both the anterior leaflet and posterior leaflet. Coaptation was greatly delayed in the dilatation model, and the leaflets never fully coapted. Chordal stresses were also greatly increased in the dilatation model. In conclusion, increased stress due to annular dilatation may lead to tissue disruption, further dilatation, delayed coaptation, and increased regurgitation, in a 'closed-loop' degenerative process.

Animals↗
PubMed1997

Horseradish peroxidase as a histological indicator of mechanisms of porcine retinal vascular damage and protection with perfluorocarbons after massive air embolism.

BACKGROUND AND PURPOSE: This laboratory has previously shown that a second-generation perfluorocarbon emulsion (PFE) reduces the severity of cerebral injury induced by air embolism during cardiopulmonary bypass (CPB). Horseradish peroxidase examines vascular permeability and was used in this study of the mechanisms of cellular protection afforded by the PFE. METHODS: Twenty domestic pigs underwent CPB with a prime of standard crystalloid or PFE (5 mg/kg) and crystalloid. After 10 minutes on CPB, a 5-mL/kg bolus of room air or saline (control) was delivered via the right carotid artery. The air insult was delivered as either a single bolus or double bolus. After 1 hour of CPB and 1 hour of spontaneous reperfusion, horseradish peroxidase was injected intravenously and circulated for 15 minutes. After euthanasia, both eyes were removed, and the retinas were isolated for histological analysis. RESULTS: Total length of retinal vessels exhibiting horseradish peroxidase extravasation was significantly less in PFE pigs (P < .05). Vascular spasm and red blood cell hemorrhages were unaffected by PFE. PFE pigs exhibited mild to moderate vascular nonperfusion and red blood cell sludging; crystalloid groups demonstrated severe nonperfusion and sludging. CONCLUSIONS: Histological staining with horseradish peroxidase indicated that mechanisms of cerebral air embolism include vascular endothelial leakage, vascular nonperfusion, and red blood cell sludging and hemorrhage. Pretreatment with PFE prevented some sequelae associated with massive air embolism and CPB.

Animals↗