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1.
Protamine sulfate is routinely administered after cardiopulmonary bypass to reverse systemic heparinization, but may cause a severe hypotensive reaction in as many as 2% of patients. Research Medical, Inc., has developed an extracorporeal venovenous heparin removal device (HRD) for use in patients at high risk for a protamine reaction. Circulation through the HRD removes heparin by hollow fiber plasma separation and selective sorption of anionically charged heparin to a polycationically charged poly-L-lysine ligand coupled to a agarose substrate. The heparin depleted plasma then reenters the whole blood pathway and is returned to the patient through the double lumen catheter in the right atrium. To evaluate the HRD in a clinically relevant model, cardiopulmonary bypass was performed in pigs using RA-Ao cardiopulmonary bypass (120 min) with systemic heparinization (300 IU/kg), a nonpulsatile pump with a membrane oxygenator, and systemic hypothermia (28 degrees C). Group 1 (HEP n = 7) had no intervention to neutralize the heparin; Group 2 (HRD n = 7) used the HRD. After 19.7 +/- 4.2 min of circulation through the HRD, the activated clotting time had returned to baseline, whereas the pigs in the HEP group were still anticoagulated (activated clotting time = 396 +/- 152 sec; time to baseline was 124 +/- 9 min). There were no significant differences between groups with respect to hemodynamics, hematocrit levels, leukocyte profiles, or platelet counts, HRD is an effective heparin removal device in a pig model of cardiopulmonary bypass and awaits a phase I clinical trial in humans.  相似文献   

2.
A 74-year-old man underwent elective coronary surgery under cardiopulmonary bypass. A few minutes after the protamine administration was started, he suddenly developed a severe hypotension necessitating cardiac massage and recannulation for pump assistance. A further test dose of protamine provoked an identical reaction. We installed a Heparin Removal Device, which allows for ex-vivo deheparinization. In 35 minutes ACT decreased from 480 sec to 180 sec and clots appeared in the operating field. This system provides an excellent alternative to protamine in patients with an adverse reaction to protamine.  相似文献   

3.
Hypusine formation on the eukaryotic initiation factor 5A (eIF-5A) precursor represents a unique posttranslational modification that is ubiquitously present in eukaryotic cells and archaebacteria. Specific inhibition of deoxyhypusine synthase leads to growth arrest and cell death. The precise cellular function of eIF-5A and the physiological significance of hypusine modification are not clear. Although the methionyl-puromycin synthesis has been suggested to be the functional assay for eIF-5A activity in vitro, the role of eIF-5A in protein synthesis has not been established. Recent studies have suggested that eIF-5A may be the cellular target of the human immunodeficiency virus type 1 Rev and human T cell leukemia virus type 1 Rex proteins. Motif analysis suggested that eIF-5A resembles a bimodular RNA-binding protein in that it contains a stretch of basic amino acids clustered at the N-terminal region and a leucine-rich stretch at the C-terminal region. Using Rev target RNA, RRE, as a model, we tested the hypothesis that eIF-5A may be an RNA-binding protein. We found that both deoxyhypusine and hypusine-containing eIF-5A can bind to the 252-nt RRE RNA, as determined by a gel mobility shift assay. In contrast, the unmodified eIF-5A precursor cannot. Deoxyhypusine-containing eIF-5A, but not its precursor, could also cause supershift of the Rev stem-loop IIB RRE complex. Preliminary studies also indicated that eIF-5A can bind to RNA such as U6 snRNA and that deoxyhypusine modification appears to be required for the binding. The ability of eIF-5A to directly interact with RNA suggests that deoxyhypusine formation of eIF-5A may be related to its role in RNA processing and protein synthesis. Our study also suggests the possibility of using a gel mobility shift assay for eIF-5A-RNA binding as a functional assay for deoxyhypusine and hypusine formation.  相似文献   

4.
Postoperative heparin rebound was investigated in 50 adult patients undergoing cardiopulmonary bypass with the use of the Hepcon heparin analyzer. Prior to bypass each patient received 2 mg/kg of heparin. During bypass, the activated clotting time (ACT) was utilized to assess the need for additional heparin to maintain the value between 300 and 400 seconds. The average amount of heparin given was 160 mg. Once cardiopulmonary bypass was terminated the Hepcon unit was employed to determine the actual amount of active circulating heparin and to calculate the dose of protamine sulfate. The average amount of protamine administered intraoperatively was 200 mg. The overall mean ratio of protamine-to-heparin was 1.25 : 1. Once hemostasis was achieved, no circulating heparin was measured with the Hepcon unit, and the ACT value had returned to its baseline, the incisions were closed and the patients were transferred to the intensive care unit. One hour later a blood sample was obtained and analyzed by the Hepcon unit for any heparin rebound. We found that 26 patients (52%) had circulating heparin and required an additional dose of protamine, averaging 70 mg. Drainage from the thoracotomy tubes averaged 400 cc in the first 24 hours, and a mean of 2 units of packed cells was infused. Three patients (6%) did not require any blood transfusions. The use of the Hepcon unit has produced a safe and expedient method of analyzing and neutralizing active circulating heparin in patients following cardiopulmonary bypass. It is a useful adjunct in blood conservation because it reduces excessive postoperative blood loss associated with heparin rebound.  相似文献   

5.
BACKGROUND: Peripheral arterial and venous cannulation for cardiopulmonary bypass is used increasingly for patients undergoing minimally invasive cardiac operations, complex reoperations, or repair of aortic dissection or aneurysm, and for patients with extensive arteriosclerotic aortic disease in whom aortic cannulation is a prohibitive embolic risk. The common femoral artery and vein are most commonly used for peripheral cannulation, but these sites may be predisposed to complications, primarily because the femoral vessels are commonly involved with arteriosclerotic disease. We have recently begun to use the axillary artery and axillary vein as alternative cannulation sites, achieving full cardiopulmonary bypass, providing antegrade aortic flow, and avoiding many of the complications associated with other sites. METHODS: Seven patients with peripheral vascular or aortic disease, or both, prohibiting safe aortic or femoral cannulation underwent cardiopulmonary bypass through axillary artery and axillary vein cannulation, approached through a small single subclavicular incision. RESULTS: All patients were successfully cannulated and axilloaxillary cardiopulmonary bypass was possible without the need for additional cannulas. All axillary vessels were closed primarily without complication. CONCLUSION: For an expanding population of patients with peripheral vascular and aortic disease, axilloaxillary bypass is a safe and practical alternative to aortic or femoral cannulation.  相似文献   

6.
OBJECTIVES: The purpose of this study was to determine risk factors for adverse events following protamine administration after cardiopulmonary bypass. BACKGROUND: Intravenous protamine administration is associated with a risk of severe systemic reactions. However, risk factors for these events have not been well delineated, thus hampering development of preventive strategies. METHODS: A case-control study nested within a cohort of consecutive patients undergoing surgery requiring cardiopulmonary bypass was performed. The primary case definition included those events (pulmonary hypertensive and systemic hypotensive) occurring within 10 min of protamine administration in the absence of other measurable causes of hemodynamic compromise. RESULTS: Comparing the 53 cases to the 223 control subjects, three risk factors were independently associated with events (multivariable odds ratio [95% confidence interval]): neutral protamine Hagedorn insulin use (8.18 [2.08, 32.2]); fish allergy (24.5 [1.24, 482.3]), and a history of nonprotamine medication allergy (2.97 [1.25, 7.07]). These risk factors demonstrated an increasingly strong association with progressively more specific case definitions. An estimated 39% of cardiopulmonary bypass patients had one or more of these risk factors. Prior intravenous protamine, central venous pressure prior to protamine, preoperative ejection fraction and the need for inotropes when coming off bypass did not exhibit statistically significant associations with events (all p > 0.15). Prior protamine allergy was associated specifically with an increased risk of pulmonary hypertension (multivariable odds ratio 189; 95% confidence interval 13, 2,856). CONCLUSIONS: Immunologic factors are important in predisposing individuals to protamine reactions, and a substantial proportion of patients are at considerably increased risk Strategies to reduce the risk of protamine-associated events are needed.  相似文献   

7.
8.
The hypothesis that heparin-coated perfusion circuits reduce thrombin formation and activity; fibrinolysis; and platelet, complement, and neutrophil activation was tested in 20 consecutive, randomized adults who had cardiopulmonary bypass. Twenty identical perfusion systems were used; in 10, all blood-contacting surfaces were coated with partially degraded heparin (Carmeda process; Medtronic Cardiopulmonary, Anaheim, Calif.). All patients received a 300 U/kg dose of heparin. Activated clotting times were maintained longer than 400 seconds. Cardiopulmonary bypass lasted 36 to 244 minutes. Blood samples for platelet count, platelet response to adenosine diphosphate, plasma beta-thromboglobulin, inactivated complement 3b, neutrophil elastase, fibrinopeptide A, prothrombin fragment F1.2, thrombin-antithrombin complex, tissue plasminogen activator, plasminogen activator inhibitor-1, plasmin alpha 2-antiplasmin complex, and D-dimer were obtained at these times: after heparin was given, 5 and 30 minutes after cardiopulmonary bypass was started, within 5 minutes after bypass was stopped, and 15 minutes after protamine was given. After cardiopulmonary bypass, tubing segments were analyzed for surface-adsorbed anti-thrombin, fibrinogen, factor XII, and von Willebrand factor by radioimmunoassay. Heparin-coated circuits significantly (p < 0.001) reduced platelet adhesion and maintained platelet sensitivity to adenosine diphosphate (p = 0.015), but did not reduce release of beta-thromboglobulin. There were no significant differences between groups at any time for fibrinopeptide A, prothrombin fragment F1.2, or thrombin-antithrombin complex or in the markers for fibrinolysis: D-dimer, tissue plasminogen activator, plasminogen activator inhibitor-1, and alpha 2-antiplasmin complex. In both groups, concentrations of prothrombin fragment F1.2 and thrombin-antithrombin complex increased progressively and significantly during cardiopulmonary bypass and after protamine was given. Concentrations of D-dimer, alpha 2-antiplasmin complex, and plasminogen activator inhibitor-1 also increased significantly during bypass in both groups. Fibrinopeptide A levels did not increase during bypass but in both groups increased significantly after protamine was given. No significant differences were observed between groups for levels of inactivated complement 3b or neutrophil elastase. Radioimmunoassay showed a significant increase in surface-adsorbed antithrombin on coated circuits but no significant differences between groups for other proteins. We conclude that heparin-coated circuits used with standard doses of systemic heparin reduce platelet adhesion and improve platelet function but do not produce a meaningful anticoagulant effect during clinical cardiopulmonary bypass. The data do not support the practice of reducing systemic heparin doses during cardiac operations with heparin-coated extracorporeal perfusion circuitry.  相似文献   

9.
OBJECTIVE: To determine if lactic acidosis occurring after cardiopulmonary bypass could be attributed to the metabolic or other effects of epinephrine administration. DESIGN: Prospective, randomized study. SETTING: Postsurgical cardiothoracic intensive therapy unit. PATIENTS: Thirty-six adult patients, without acidosis, requiring vasoconstrictors for the management of hypotension after cardiopulmonary bypass. INTERVENTIONS: Randomized administration of either epinephrine or norepinephrine by infusion. MEASUREMENTS AND MAIN RESULTS: Hemodynamic and metabolic data were collected before commencement of vasoconstrictor therapy (time 0) and then 1 hr (time 1), 6 to 10 hrs (time 2), and 22 to 30 hrs (time 3) later. Six of the 19 patients who received epinephrine developed lactic acidosis. None of the 17 patients receiving norepinephrine developed lactic acidosis. In the epinephrine group, but not in the norepinephrine group, lactate concentration increased significantly at times 1 and 2 (p = .01), while pH and base excess decreased (p < or = .01). Blood glucose concentration was higher in the epinephrine group at time 2 (p = .02), while the cardiac index (p < .03) and the mixed venous Po2 (p = .04) were higher at time 1. compared with the norepinephrine group, the patients receiving epinephrine had higher femoral venous lactate concentrations (p = .03), increased lower limb blood flow (p = .05), and increased femoral venous oxygen saturations (p = .04). CONCLUSIONS: The use of epinephrine after cardiopulmonary bypass precipitates the development of lactic acidosis in some patients. This phenomenon is presumably a beta-mediated effect, and is associated with an increase in whole-body and lower limb blood flow and a decrease in whole-body and transfemoral oxygen extraction. The phenomenon does not appear to be related to reduced tissue perfusion and does not have the poor outlook of lactic acidosis associated with shock.  相似文献   

10.
Over a 5-year period, 9 patients (0.85 per cent) developed a major acute abdominal complication after cardiopulmonary bypass surgery. Difficulties in the initial recognition and diagnosis of these complications in sedated, ill patients are highlighted. A high index of suspicion is important in the early diagnosis of these complications. The numbers are too small for statistical analysis, but experience suggests that each case should be dealt with on its merits in accordance with common surgical practice and that operative management should not be rejected because the patient has recently undergone a major cardiac operation.  相似文献   

11.
Thromboelastography (TEG) has been used after cardiopulmonary bypass (CPB) to diagnose excessive postoperative hemorrhage. Conventional TEG during CPB is not possible due to the sensitivity of the TEG to even small amounts of heparin, which produces a nondiagnostic tracing. The purpose of this study was to compare heparin neutralization using heparinase or protamine in TEG blood samples obtained during CPB. TEG testing was performed on 48 patients before, during and after CPB. Tissue plasminogen activator activity and antigen were measured on a subset of 32 patients. We found: 1) heparinase neutralized at least 10 IU/ml heparin while 1.6 ug/ml protamine neutralized up to 7 IU/ml heparin, 2) in samples with complete heparin neutralization by both methods, there was no significant difference in the R values, 3) while there was good correlation for other TEG parameters between heparinase and protamine treated samples, heparinase treatment produced shorter K values and higher angle, MA and A60, 4) while fibrinolysis was detected using both methods, heparinase treatment suppressed fibrinolysis in the TEG in both samples from patients and after in vitro addition of tissue plasminogen activator, 5) TEG was not a sensitive indicator of t-PA activity, detecting only 21% of samples with increased t-PA activity during bypass, and 5) heparinase was at least 100 times more expensive than protamine. We conclude that while both heparinase and protamine can be used to neutralize heparin in TEG samples obtained during CPB, protamine neutralization is more sensitive to fibrinolysis and less expensive, but the protamine dose must be carefully selected to match the heparin level used at individual institutions.  相似文献   

12.
The authors previously reported the development of a blood filter device containing immobilized protamine (termed "protamine filter") that could be used at the conclusion of an extracorporeal blood procedure to prevent heparin and protamine induced complications. In vitro and in vivo experiments have fully demonstrated the feasibility and utility of the approach. The bottleneck limitations of this approach, however, lie in the lack of efficacy and capacity of the filter device. In this article, the authors describe a method to improve the efficacy in heparin adsorption, by incorporating a poly(ethylene glycol) spacer arm between the immobilized protamine and the fiber surface to enhance its freedom to dynamic motion. The authors also describe a method to increase the capacity of the filter, by using a poly-L-lysine based amplification method to augment protamine loading on the fiber, and to create multiple layers of immobilized protamine for heparin adsorption. Results show that with a poly(ethylene glycol) spacer arm of 3,400 Da, heparin adsorption on the protamine-poly(ethylene glycol) fibers was increased dramatically from a value of 9.1 mg heparin per gram of fibers in the control (i.e., without the poly[ethylene glycol] spacer) to 60 mg heparin/g fiber. The use of the amplification method with 110 kDa poly-L-lysine also yielded a threefold increase in protamine loading, and, consequently, an approximately fourfold enhancement in heparin adsorption (from 9.1 to 38.0 mg heparin/g fiber). A combination of these two methods would yield an optimized protamine filter that could meet all types of clinical needs in heparin removal. As assessed from the in vivo theoretical model reported previously for the protamine filter, a 95% heparin removal under cardiopulmonary bypass conditions could be achieved with a single optimized protamine filter with a size smaller than a hemodialyzer cartridge.  相似文献   

13.
Complement activation has been deemed responsible for the damaging effects of cardiopulmonary bypass (CPB) in patients undergoing open heart surgery. We studied C3, C4 and C-reactive protein (CRP) in 22 patients undergoing CPB. In Group 1 (11 patients), protamine was given intravenously and in Group 2 (11 patients), via the aortic root after CPB. Significant decreases were observed in C3 and C4 during CPB in both groups indicating complement activation primarily by the classic pathway. Protamine did not lead to further activation of the complement system. In both groups, C3 levels gradually returned toward baseline within 24 hours but C4 levels were still lower than baseline 24 hours postoperatively. CPB and protamine administration did not cause any significant changes in CRP levels, but CRP increased abruptly 24 hours after operation. Although activation of complement system during CPB is expected to invoke an acute phase response, we conclude that this period is not long enough to induce an increased production of CRP in response to tissue injury or inflammation.  相似文献   

14.
BACKGROUND: Cardiopulmonary bypass (CPB) and hypothermic circulatory arrest (HCA) are important components of congenital cardiac surgery. Ischemia/reperfusion injury and inflammatory cascade activation result in endothelial damage and vascular leak which are clinically manifested as pulmonary edema and low cardiac output postoperatively. Newborns are particularly susceptible. Subtraction cloning is a useful method of isolating induced genes and can be applied to CPB/HCA. MATERIALS AND METHODS: We used a newborn lamb model replicating infant CPB with HCA to obtain tissues during various periods of reperfusion. We utilized subtraction cloning to identify mRNA induced in lung following CPB/HCA and reperfusion. Ribonuclease protection was used to quantify mRNA levels. RESULTS: We isolated a cDNA encoding ovine aquaporin-1 in a subtracted cDNA screen comparing control lung with lung exposed to CPB/HCA and reperfusion. Aquaporin-1 mRNA levels increased 3-fold in lung (p = .006) exposed to CPB/HCA and 6 hr of reperfusion. No induction was observed immediately following bypass or after 3 hr of reperfusion. We found no significant induction of aquaporin-1 mRNA following bypass, arrest, and reperfusion in other tissues surveyed, including ventricle, atrium, skeletal muscle, kidney, brain, and liver. CONCLUSIONS: Our finding that aquaporin-1 mRNA is reproducibly induced in lung following CPB/HCA with 6 hr of reperfusion suggests an important role for the water channel in the setting of pulmonary edema. Induction of Aquaporin-1 is late compared with other inflammatory mediators (ICAM-1, E-selectin, IL-8). Further studies are needed to determine if aquaporin-1 contributes to the disease process or if it is part of the recovery phase.  相似文献   

15.
K Furukawa  H Ohteki  M Sakai  K Doi  Y Narita 《Canadian Metallurgical Quarterly》1998,51(12):981-5; discussion 985-8
A percutaneous cardiopulmonary support system (PCPS) was used in 12 patients (mean age 68 years) between March 1991 and June 1996 for difficulties weaning from ordinary cardiopulmonary bypass. Cardiac procedures preceding the placement of the PCPS were coronary artery bypass grafting in 8 patients, aortic valve replacement in 1, double valve replacement in 1, and ascending aortic replacement for acute aortic dissection in 1. These procedures were elective in 6 patients and emergent in 6. Intraaortic balloon pumps were used in all cases except in two cases with atherosclerotic occlusive disease. Nine (75%) of the patients were weaned from PCPS, and seven (58%) were discharged. There were no complications due to the placement of PCPS except for three episodes of lower leg ischemia. We conclude that PCPS is useful in addressing difficulties in weaning from ordinary cardiopulmonary bypass and there should be further discussion about the limitations of PCPS in cases of severe circulatory failure.  相似文献   

16.
The effect of changes in medullary extracellular tonicity on mRNA expression for aldose reductase (AR), sorbitol dehydrogenase (SDH), Na+/Cl-/betaine (BGT) and Na+/myo-inositol (SMIT) cotransporter in different kidney zones was studied using Northern blot analysis and non-radioactive in situ hybridization in four groups of rats: controls, acute diuresis (the loop diuretic furosemide was administered), chronic diuresis (5 days of diuresis), and antidiuresis [5 days of diuresis followed by 24 h deamino-Cys1, d-Arg8 vasopressin (dDAVP)]. Acute administration of the loop diuretic furosemide significantly reduced AR, SMIT and BGT gene expression in the inner and outer medulla compared with controls. Administration of dDAVP to chronically diuretic rats raised the expression of these three mRNAs in the inner but not the outer medulla compared with the chronically diuretic rats. None of these alterations in medullary tonicity significantly changed SDH expression. The in situ hybridization studies showed AR, BGT and SMIT mRNAs to be expressed in both epithelial and non-epithelial cells of the outer and inner medulla. The various cell types (epithelial, endothelial and interstitial cells) differed in their expression pattern and intensity of AR, SDH, BGT and SMIT mRNA, but the inner medullary cells responded uniformly to a decrease in extracellular tonicity with a reduction, and to an increase with enhancement of their AR, BGT and SMIT expression.  相似文献   

17.
Two hundred twenty-eight patients with successful coronary stent implantation were randomized either to protamine administration and femoral sheath removal (group I, n = 117) or no heparin neutralization and delayed sheath removal (group II, n = 111). The hospital stay after treatment was shorter in patients receiving protamine; therefore, protamine use for neutralizing circulating heparin may be safely administered immediately after stent implantation.  相似文献   

18.
Recently, use of heparin-coated circuits during normothermic cardiopulmonary bypass has become a trend in cardiovascular surgery. In light of this, heparin administration protocols during bypass should be reevaluated. In twenty patients who underwent cardiac surgery using a heparin-coated circuit under normothermia, heparin concentration was measured with Hepcon/HMS. Before initiating bypass, 300 IU/kg of heparin was administered with additional heparin to maintain activated clotting time (ACT) at more than 400 seconds. The heparin dose response (HDR) was measured before heparin administration. HDR is a heparin concentration calculated to correspond to an ACT of 480 seconds. As an index of heparin control during bypass, average heparin concentration/HDR (HC/HDR) was calculated. HC/HDR was correlated with Fibrinogen degradation products E (R = -0.52). D dimer (R = -0.45). Thrombin antithrombin complex (R = -0.54). Antithrombin III (R = 0.50) and platelet number (R = 0.44), but not with 24-hour postoperative blood loss. In conclusion, even when using a heparin-coated circuit plasma coagulation activity was not sufficiently suppressed by use of a conventional ACT monitoring protocol during normothermic bypass. Therefore, the maintenance of HC/HDR at a higher level may be indicated.  相似文献   

19.
BACKGROUND: The danger of coronary reoperations is mainly hidden in the reopening of the sternum and in the manipulation of the heart and the old grafts. Therefore, the minimally invasive direct coronary artery bypass procedure seems an ideal technique for coronary reoperations if only the left anterior descending coronary artery needs to be revascularized and the left internal mammary artery has not been used previously. METHOD: From January 1995 until May 1996 we performed 81 minimally invasive direct coronary artery bypass procedures through a small anterolateral thoracotomy in the fifth intercostal space, anastomosing the left internal mammary artery to the left anterior descending coronary artery. Six of these 81 were reoperative minimally invasive direct coronary artery bypass procedures on patients who had previously undergone coronary grafting through a median sternotomy with a vein graft to the left anterior descending coronary artery. RESULTS: Mean operation time was 85.8 +/- 22.2 minutes. Mean length of the mammary pedicles was 13 +/- 2 cm. Mean coronary occlusion time was 9.2 +/- 3.2 minutes. Mean postoperative hospital stay was 5.7 +/- 1.2 days (range, 5 to 8 days). No mortality and no cardiac-related morbidity were recorded. CONCLUSIONS: These results suggest that the technique is safe and promising in selected cases of reoperative coronary operation.  相似文献   

20.
BACKGROUND: The need for cardiopulmonary bypass in the treatment of penetrating heart injuries is debated. OBJECTIVES: To review our experience with penetrating heart injuries and determine the indications and outcome for cardiopulmonary bypass. DESIGN: Retrospective review. SETTING: A university-based, level I trauma center. PATIENTS: All victims of penetrating heart injury presenting between July 1, 1989, and December 31, 1995. METHODS: Medical records were reviewed for demographic and physiological data, operative findings, and outcome. RESULTS: Overall survival for 106 patients with penetrating heart injury was 55%. In an effort to resuscitate the heart, 4 patients with unresponsive cardiogenic shock were placed on cardiopulmonary bypass; none survived. Of 30 patients with multiple-chamber injuries, 11 presented with signs of life and 7 survived. Cardiopulmonary bypass was essential to repair complex injuries in 2 of the 7 survivors. CONCLUSION: Cardiopulmonary bypass was ineffective in salvaging patients with cardiogenic shock but was essential in some patients with complex multiple-chamber cardiac injuries that could not be exposed and repaired by other means.  相似文献   

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