Indicators of fibrinolysis during cardiopulmonary bypass after exogenous antithrombin-III administration for acquired antithrombin III deficiency.
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Antithrombin III↗
Biomedical subjects
R P Cochran
Publications and source records attributed to R P Cochran.
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↗
Characteristics, management, and outcome of patients with acute myocardial infarction treated with bypass surgery. Myocardial Infarction Triage and Intervention Investigators.
BACKGROUND: Although multiple studies have addressed the efficacy of bypass surgery in patients with stable angina, there are relatively few studies that have evaluated the optimal timing, risk of hospital mortality, and long-term outcome for patients with bypass surgery performed in the setting of acute infarction. METHODS AND RESULTS: With data collected from all admitted patients with acute myocardial infarction to 19 Seattle-area hospitals between 1988 and 1994, we studied the characteristics, hospital course, and long-term outcome in 1299 patients who underwent bypass surgery. There was no difference in hospital mortality in patients operated on during the first 24 hours after admission compared with those operated on later in the hospital course (8.3% versus 7.2%; P=.60). Factors that predicted hospital mortality in those who underwent bypass surgery included increased age, prior bypass surgery, infarct extension, and stroke. Long-term outcome in those who underwent bypass surgery was excellent, with low rates of subsequent coronary angiography (7.4% at 3 years) and coronary angioplasty (2.6% at 3 years). Three-year survival was better in bypass recipients than in those treated medically (83% versus 66%; P < .0001), and this difference remained after multivariate adjustment for baseline differences (hazard ratio, 0.68; 95% CI, 0.55 to 0.85). CONCLUSIONS: Patients can be safely operated on early in the course of acute infarction, risk factors for hospital mortality are not substantially different from factors identified in the noninfarct setting, and bypass surgery in select patients after acute infarction is associated with low repeat procedure use and excellent long-term survival.
Adult↗
Evaluation of laboratory coagulation and lytic parameters resulting from autologous whole blood transfusion during primary aortocoronary artery bypass grafting.
STUDY OBJECTIVE: To determine if autologous blood reinfusion influences overall hemostatic function following aortocoronary artery bypass graft (CABG) surgery, and if so, where the predominant area of this influence lies. DESIGN: Prospective, with control values on each patient. SETTING: Cardiac operating room of a major university-affiliated county hospital. PATIENTS: 20 patients undergoing elective CABG surgery. INTERVENTIONS: Following heparinization, and prior to cardiopulmonary bypass (CPB), venous blood (average 4.9 ml/kg) was removed via an indwelling internal jugular catheter into a preservative-free plastic transfer pack unit and stored without agitation at room temperature. This autologous whole blood was reinfused after systemic protamine reversal of heparin. Blood samples for analysis were drawn immediately before and 5 minutes after completion of the reinfusion. MEASUREMENTS AND MAIN RESULTS: Autologous blood reinfusion appears to be significantly related to increased hemoglobin, hematocrit, platelet count, fibrinogen, plasminogen, and antiplasmin levels. The prothrombin time and activated partial thromboplastin times decreased significantly, whereas activated clotting times and D-dimer levels were unchanged. Significant increases occurred in the following thromboelastography parameters: maximum amplitude, amplitude 60 minutes after the maximum amplitude, and whole blood clot lysis index. Reaction time and coagulation time were not statistically different from control values. CONCLUSIONS: Significant improvements in coagulation and lytic parameters occur following CPB after the infusion of autologous blood. These improvements in coagulation indices may be the result of the infused blood or hemoconcentration, which is also known to occur during this period. Additional control studies are needed to differentiate these effects.
Anticoagulants↗
Perfluorocarbon emulsions and cardiopulmonary bypass: a technique for the future.
Artificial blood has been sought for a considerable period of time and two major lines of research have led to FDA testing of some possible compounds. The two major types of compounds are polymerized hemoglobin moieties and perfluorocarbon emulsions (PFC). Polymerized hemoglobin preparations have the ability to carry oxygen and release it in a manner similar to the oxyhemoglobin dissociation curve of whole blood. PFCs carry oxygen, nitrogen and carbon dioxide, as well as all other non-polar gases, by enhanced chemical solubility. Therefore, all dissolved gases are available for metabolic utilization and no sinusoidal release curve of oxygen is encountered. Early PFC emulsions had problems with toxicity of the emulsifier and were difficult to get into their emulsion for infusion. Furthermore they were very dilute in the active ingredient for gas transport. Today there are second generation PFCs becoming available that have a 40% concentration of the PFC and therefore the potential for gas transport is greatly increased. The PFC emulsions have a very small size, 0.1 microns, so the surface for gas exchange is massively increased as well as the potential increased for perfusion into areas of potentially sludged erythrocytes. Work with the PFCs has shown them now to be able to carry adequate oxygen to work as blood substitutes. They have shown protection from air embolism in a number of animal and end-organ models. What makes the PFCs unique is their ability to carry/absorb nitrogen and therefore protect from gas embolization. There are data in animal models showing significant cerebral protection in cardiopulmonary bypass models. The new PFCs should sometime in the not-too-distant future be tested in human bypass with assessments of neuropsychiatric dysfunction and stroke.
Animals↗
The effect of chordal replacement suture length on function and stresses in repaired mitral valves: a finite element study.
BACKGROUND AND AIMS OF THE STUDY: Replacement of ruptured mitral valve chordae using expanded polytetrafluoroethylene (ePTFE) sutures is becoming an increasingly utilized repair technique. However, setting the proper length of the replacement suture is technically challenging, and the effect of a non-optimal suture length is undefined. The purpose of this study was to assess how varying the length of replacement sutures affects mitral valve function and stresses. MATERIALS AND METHODS: We employed a finite element model of the mitral valve used extensively in our laboratory. Seven different valve conditions were simulated using this model: (i)normal valve, (ii) chordal rupture without repair, and (iii-iv) chordal replacement using ePTFE sutures that were equal in length to the replaced chordae (equal length), 10% longer (Long10), 3% longer (Long3), 3% shorter (Short3), and 10% shorter (Short10) than the replaced chordae. Each model was loaded to physiologic pressures. RESULTS: Both the Long10 and chordal rupture models achieved complete valve closure, but chordal stresses were nearly double normal values. The Long3 model also demonstrated complete valve closure, but chordal stresses were increased to only one-third more than normal. Using sutures equal to or shorter than the length of the replaced chordae prevented complete valve closure, and produced stress concentrations at the anterior leaflet free edge. The resulting gaps and stress concentrations were most significant in the Short10 model and least significant in the equal length model. CONCLUSIONS: These models demonstrate that replacement sutures equal to, or slightly longer than the replaced chordae optimize function and stresses in the repaired valve.
Biomechanical Phenomena↗
Aortic valve sparing in aortic root disease.
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Aorta↗
Modified conduit preparation creates a pseudosinus in an aortic valve-sparing procedure for aneurysm of the ascending aorta.
Mechanical valved conduit replacement of the aortic root is a durable and appropriate procedure for many diseases of the ascending aorta, but may sacrifice an anatomically salvageable aortic valve. For young active patients and for patients with "systemic" arterial disease (atherosclerosis, Marfan's syndrome) who may require future operations, life-long anticoagulation with its attendant thromboembolic versus hemorrhagic risks is not ideal. Several techniques have been suggested as aortic valve-sparing options. Recently, a procedure was described that combines the freehand homograft techniques with the standard Bentall techniques (David procedure). This innovative technique replaces the ascending aorta with a Dacron cylinder, spares the aortic valve, and restores competence and thus offers an excellent alternative. The durability of this procedure that places the aortic valve inside a cylindrical conduit without sinuses of Valsalva is unknown. In selected patients, we have used this technique to spare the aortic valve. On the basis of experimental data and preliminary computer modeling, with the hope of improving the durability, we have modified the conduit to create a "pseudosinus" in our most recent nine patients. We have done the David procedure in 10 patients. The pseudosinus modification was done in the most recent nine patients. Patients' ages ranged from 37 to 71 years (mean 49.9 years). There were five female and five male patients. Five patients had Marfan's syndrome and five patients had annuloaortic ectasia. There has been no mortality and all patients have had both early and late follow-up echocardiography. Five patients have zero to trace aortic insufficiency, four patients have trace to mild aortic insufficiency, and one patient has mild or "1+" aortic insufficiency. Aortic insufficiency has not progressed in any patient during the 18 months of follow-up. The patient with 1+ aortic insufficiency has no activity limits, good ventricular function, and no evidence of congestive symptoms. One patient who had extensive thoracoabdominal aneurysmal disease has undergone subsequent replacement of the descending aorta to the level of the renal arteries and has done well. Aortic valve-sparing replacement of the aortic root is an excellent procedure for any patient with an ascending aortic aneurysm and an anatomically salvageable valve. We believe that by modifying the proximal conduit and creating a "pseudosinus" into which the leaflets can retract without contact of the cylindrical conduit we may increase the longevity of the native aortic valve in this procedure.
Aorta↗
A perfluorocarbon emulsion prime additive improves the electroencephalogram and cerebral blood flow at the initiation of cardiopulmonary bypass.
Depression in electroencephalogram (EEG) has been documented clinically and is reproducible in swine at the initiation of cardiopulmonary bypass (CPB) utilizing a crystalloid prime. The physiological cause of this transient alteration in electrical brain activity appears to be associated with the transient drop in arterial pressure. The etiology is unknown but may be attributable to the bolus of the crystalloid prime or micro emboli, either air or fibrin-platelet. Thirteen swine (17-26 kg) were anesthetized and received 4 mg/kg dexamethasone, and following a tracheotomy were ventilated with halothane in 100% O2. Surgical preparation included: sternotomy and preparation for right atrial-aortic CPB. The CPB circuit consisted of a hollow fiber membrane oxygenator, a hard-shell venous reservoir, a roller pump, and PVC tubing. The circuit was randomly primed with either 1200 ml Plasmalyte-A or 10 ml/kg perfluorocarbon emulsion (PFE) and Plasmalyte-A to total 1200 ml. The animals were monitored continuously for systemic hemodynamics and electrocardiogram, and cerebral monitoring included blood flow and bitemporal EEG. Arterial blood gases were measured and PaCO2 was kept between 30-45 mmHg both before and during CPB. Cerebral blood flow (CBF) was measured pre-CPB and at 10 minutes after initiation of CPB. Bitemporal computerized EEG was analyzed every 60 seconds. Total power of each hemisphere, power in frequency bands, and spectral edge were recorded. All animals demonstrated a relative decrease in EEG total power at the onset of CPB. Animals that received PFE demonstrated a more stable arterial blood pressure, an increased CBF, and a lesser decrease and an earlier recovery of the EEG power.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Changes in cardiovascular surgical approaches to achieve early extubation.
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Cardiac Surgical Procedures↗
Individual variations in the fibrinolytic response during and after cardiopulmonary bypass.
The purpose of this study was to determine whether individual patients show different patterns of fibrinolytic response to cardiopulmonary bypass (CPB) and whether preoperative or intraoperative parameters were predictive of these different patterns. Active t-PA, active PAI-1 and total t-PA antigen were measured in plasma samples obtained from 38 subjects, age 32 to 85 (median 69 years), before, during and after CPB. Four patterns of fibrinolytic response were noted: 1) 40% of patients showed the "typical" response, a rapid rise in active and total t-PA during CPB followed postoperatively by elevated PAI-1 and reduced t-PA, 2) 10% showed no change in t-PA or PAI-1 during or after CPB, 3) 24% showed no change in t-PA with an increase in PAI-1 postoperatively, and 4) 26% showed an increase in t-PA during CPB with no change in PAI-1 postoperatively. When present, the t-PA response was rapid, occurring within the first 30 min of CPB and was more common in patients undergoing valve surgery than in coronary artery bypass grafting (p < 0.005). Increased levels of PAI-1 postoperatively were associated with ischemic times greater than 70 min (p = 0.003) but not with the total length of CPB. Age, sex, CPB temperature, total CPB time and preoperative levels of t-PA and PAI-1 were not associated in the intra- or postoperative fibrinolytic response pattern. We conclude that the fibrinolytic response to CPB is heterogeneous. Further studies will be needed to determine whether different response patterns are clinically significant.
Adult↗
Schwannoma of the left atrium: diagnostic evaluation and surgical resection.
A case of primary benign schwannoma of the left atrium is reported. A 35-year-old man presented with new onset atrial fibrillation. Noninvasive evaluation revealed a 4 x 7-cm mediastinal mass either directly posterior to or involving the left atrium. The histologic diagnosis and specific location of the mass were established by incisional biopsy through a left thoracotomy. On cardiopulmonary bypass the tumor was resected by widely excising the posterior left atrium. The residual 20-cm2 left atrial defect was patched with pericardium. This unusual case illustrates that left atrial tumors originating near the pulmonary veins may be nonmyxomatous neoplasms of neural origin. Diagnosis may be difficult and require a surgical transthoracic approach.
Adult↗
Anatomic basis for mitral valve modelling.
The increasing popularity of mitral valve repair and current interest in replacement with a mitral homograft or heterograft warrant a new look at the normal functional anatomy of the system. We conducted a detailed review of the anatomic structure of both the intact and excised mitral apparatus of porcine and human species. The following intact structural dimensions were measured: total annular length, anterior and posterior annular length. Excised measurements included: total annular length, anterior and posterior annular lengths, leaflet edge lengths, leaflet heights, and anterolateral and posteromedial commissural heights. Leaflet area was calculated from planimetric measurements. Chordal lengths were measured and distribution recorded. The majority of leaflet measurements were not statistically different between groups. For both groups, the measured annular length increased significantly upon valve excision. In both groups, the posterior leaflet area was significantly larger than the anterior leaflet area, and the area of each leaflet alone was significantly greater than the calculated orifice area. Chordal length was not significantly different between groups, however, distribution varied slightly with the ratio of origins to insertions being 8:1 (porcine) and 5:1 (human). The results are consistent with previous studies of the human mitral valve. This study showed little difference between human and porcine data, and the porcine valve was identified as an appropriate model for further investigation of the mitral valve system.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Aortic root and valve relationships. Impact on surgical repair.
A surgical procedure has recently been described for patients with aortic incompetence caused by annular dilation, but with normal aortic leaflets. The dilated aortic root is replaced with a Dacron graft, and the native aortic valve is resuspended within the graft. Matching the size and shape of the graft to the size of the leaflets may have significant effects on valve closure and leaflet stress and thus on the longevity of the repair. To define the relationship of native aortic root structure to leaflet size, we morphologically examined normal human aortic roots (n = 10) and valve leaflets and applied mathematic analyses to the results. Our data show that the root has a consistent shape with varying size and that there is a definable mathematic relationship between root diameter and clinically measurable leaflet dimensions. We derived an equation that allows calculation of the appropriate diameter of the root at the sinus of Valsalva level from leaflet heights and perimeters. The diameter of the graft at the sinotubular junction and base should follow the relationship of the normalized root dimensions, either by tailoring of the graft or by new graft design. The current data imply that the graft should incorporate sinuses for proper valve closure and for sharing stress with the leaflets. Application of these results will allow prosthetic graft design to more closely resemble the native aorta. These new grafts should improve physiologic function of the valve, reduce leaflet stress, and increase the durability of the repair.
Adolescent↗
Differential collagen distribution in the mitral valve and its influence on biomechanical behaviour.
Surgical repair of the mitral valve primarily involves endogenous valve tissue, however, the intrinsic mechanical behaviour of the tissue is not well described. To address this issue, porcine mitral valve leaflets were examined histologically and engineering concepts were applied to understand the mechanical behaviour of the layered tissue. Rectangular portions were excised from the anterior and posterior leaflets, either parallel or perpendicular to the annulus, and sections were stained for collagen (Masson's trichrome). The cross sectional layers of the valve (atrialis/spongiosa, fibrosa, and ventricularis) were identified by differences in cellularity and collagen density. The fibrosa is composed of dense collagen, while the atrialis/spongiosa and ventricularis are composed of loose collagen. Layer thicknesses were recorded digitally across the section. These values were averaged within tissue groups to determine changes in layer thickness over the length of the sample and average thickness of each layer. In all tissue groups, the fibrosa was the thickest layer, and the atrialis/spongiosa layer was thicker than the ventricularis layer. The total and fibrosa layer thicknesses of the anterior leaflet were significantly thicker than in the posterior leaflet. Mechanical engineering analysis of the layered structures under tension indicated that the anterior leaflet would be able to support greater tensile loads than the posterior leaflet. The layered arrangement was then examined as a beam in bending, and was shown to decrease the resistance of leaflets to bending, and decrease the overall bending stresses on the leaflet. This type of analysis may be extrapolated to gain insight into changes in function in diseased valves as well.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Finite element analysis of the mitral valve.
A finite element model was developed to examine deformation and stress patterns in the mitral valve under systolic loading conditions. This is the first three-dimensional finite element model of the mitral valve, incorporating all essential anatomic components, regional tissue thickness, collagen fiber orientation and related anisotropic material properties. A non-linear, transient, dynamic analysis was performed which included time-dependent loading, leaflet and chordal mass inertial effects and chordal element bi-linearity. The model was first analyzed without either annular or papillary muscle contraction and then with either or both. The hypothesis was that the combination of annular and papillary muscle contraction would have a beneficial effect on valve function. In all models, the computed anterior leaflet principal stresses were tensile and of greater magnitude than those in the posterior leaflet. The principal stress directions were observed to correlate well with collagen fiber orientation. Earlier leaflet coaptation was demonstrated with annular contraction, promoting valve closure, while papillary muscle contraction increased the stress on the chordae tendineae and both leaflets, tending to pull the latter apart. The combination of the two combined these effects, and showed the most even stress distribution. The effects of annular and papillary muscle contraction on valve function were shown to be beneficial by this model, and they can be further elucidated by varying the extent and timing of the individual contractions. This model can be used to examine the effects of pathologic changes, surgical manipulations and proposed material replacements. It can thus aid both the surgeon and the biomedical engineer in improving the materials and techniques available for the repair and/or replacement of mitral valve system components.
Animals↗
Stress/strain characteristics of porcine mitral valve tissue: parallel versus perpendicular collagen orientation.
Mitral valve tissue was analyzed in uniaxial tension testing. Rectangular strips were excised from fresh, whole, porcine mitral valve leaflets, with the long axis in the following orientation: perpendicular to the annulus (posterior [PPERP] and anterior [APERP]), parallel to the annulus (posterior [PPAR] and anterior [CAPAR]), and parallel to the annulus and involving chordal insertions (anterior [MAPAR]). Basal and marginal chordae were also tested. These samples were tested in uniaxial tension (INSTRON Model 1000) at deformation rates of 5 and 10 mm/min, the load applied along the long axis of the strip. The specimens were preconditioned by cyclically loading from 0 to 4.0 g for five cycles, and then applying a final 50-g load. Whole excised porcine mitral valves were previously examined by small angle light scattering, polarized light microscopy, and routine histologic examination in order to ascertain the collagen fiber orientation throughout the valve. Groups tested in uniaxial tension with collagen fibers parallel to the applied stress are significantly stiffer than those with perpendicular fibers (p less than 0.001). Collagen fiber density is greater in the chordae than in the leaflets, and a corresponding increase in stiffness is demonstrated. This indicates that the mitral valve tissue behaves as a classic fiber reinforced composite, i.e., increasing mechanical stiffness (modulus) is related to density and direction of fibers. This information can be applied to the design of biosynthetic valve substitutes with a similar fiber reinforced composite structure.
Animals↗
Splanchnic blood flow response to intraaortic balloon pump assist of hemorrhagic shock.
Hemorrhagic shock results in marked changes in splanchnic arterial blood flow. We studied the effects of intraaortic balloon pump assist (IABP) upon splanchnic blood flow during sustained hemorrhagic shock and following volume resuscitation. Hemorrhagic shock was induced (mean blood pressure = 30 mm Hg) for 120 min in 20 dogs. Controls (n = 11) underwent resuscitation with shed blood and lactated Ringers solution only. In the study group (n = 9), IABP was begun after 60 min of hemorrhagic shock and continued throughout a 90-min period after resuscitation. Hemodynamic parameters were assessed and splanchnic blood flow was estimated (radioactive microsphere technique) at baseline, through 120 min of sustained hypotension, and during the resuscitation period. Splanchnic blood flow was significantly reduced in both the control and the IABP groups during the period of hemorrhagic shock. Interestingly, the IABP group was found to have a return to preshock splanchnic viscera perfusion without the hyperemic reperfusion phenomenon seen in control animals resuscitated with shed blood and Ringers lactate alone. IABP assist of hemorrhagic shock appears to improve vasomotor control of splanchnic blood flow in this experimental preparation of shock. This may result in less reperfusion injury to the splanchnic viscera during the resuscitation of severe hemorrhagic shock.
Animals↗