Phosphorylation of transcriptional factors and cell-cycle-dependent proteins by casein kinase II.

Casein kinase II is involved in the phosphorylation of several proto-oncogenes, anti-oncogenes, and oncogenes that are nuclear transcriptional regulatory factors. The potential functions of the phosphorylations in each of these proteins are evaluated. New findings indicate that casein kinase II is a critical component of the mechanisms regulating the cell cycle.

Interactions of Cbl with Grb2 and phosphatidylinositol 3'-kinase in activated Jurkat cells.

T-cell receptor (TCR) cross-linking increases tyrosine phosphorylation of multiple proteins, only a few of which have been identified. One of the most rapidly tyrosine-phosphorylated polypeptides is the 120-kDa product of the proto-oncogene c-cbl, a cytosolic and cytoskeletal protein containing multiple proline-rich motifs that are potential binding sites for proteins containing Src homology 3 (SH3) domains. We report here that in cultured Jurkat T cells, Cbl is coprecipitated with antibody against the adapter protein Grb2. Upon activation of Jurkat T cells via the TCR-CD3 complex, we find that high-affinity binding of Cbl requires the N-terminal SH3 domain of GST-Grb2 fusion protein but after cross-linking of the TCR-CD3 and CD4 receptors, Cbl binds equally to its SH2 domain. Grb2 antisera also precipitated p85 from serum-starved cells, while TCR activation increased p85 and tyrosine-phosphorylated Cbl but not Cbl protein in Grb2 immunocomplexes. Phosphatidylinositol (PI) 3-kinase activity was immunoprecipitated from serum-starved cells with Cbl and to a lesser extent with Grb2 antisera, and TCR cross-linking increased this activity severalfold. The PI 3-kinase activity associated with Cbl amounted to 5 to 10% of the total cellular activity that could be precipitated by p85 antisera. The Ras exchange factor Son-of-sevenless 1 (Sos-1) was not found in anti-Cbl immunoprecipitates from activated cells, and Cbl was not detectable in anti-Sos-1 precipitates, supporting the likelihood that Sos-Grb2 and Cbl-Grb2 are present as distinct complexes. Taken together, these data suggest that Cbl function in Jurkat T cells involves its constitutive association with Grb2 and its recruitment of PI 3-kinase in response to TCR activation.

Interactions of Drosophila Cbl with epidermal growth factor receptors and role of Cbl in R7 photoreceptor cell development.

The human proto-oncogene product c-Cbl and a similar protein in Caenorhabditis elegans (Sli-1) contain a proline-rich COOH-terminal region that binds Src homology 3 (SH3) domains of proteins such as the adapter Grb2. Cb1-Grb2 complexes can be recruited to tyrosine-phosphorylated epidermal growth factor (EGF) receptors through the SH2 domain of Grb2. Here we identify by molecular cloning a Drosophila cDNA encoding a protein (Drosophila Cbl [D-Cbl]) that shows high sequence similarity to the N-terminal region of human c-Cbl but lacks proline-rich sequences and fails to bind Grb2. Nonetheless, in COS-1 cells, expression of hemagglutinin epitope-tagged D-Cbl results in its coimmunoprecipitation with EGF receptors in response to EGF. EGF also caused tyrosine phosphorylation of D-Cbl in such cells, but no association of phosphatidylinositol 3-kinase was detected in assays using anti-p85 antibody. A point mutation in D-Cbl (G305E) that suppresses the negative regulation of LET-23 by the Cbl homolog Sli-1 in C. elegans prevented tyrosine phosphorylation of D-Cbl as well as binding to the liganded EGF receptor in COS-1 cells. Colocalization of EGF receptors with both endogenous c-Cbl or expressed D-Cbl in endosomes of EGF-treated COS-1 cells is also demonstrated by immunofluorescence microscopy. In lysates of adult transgenic Drosophila melanogaster, GST-DCbl binds to the tyrosine-phosphorylated 150-kDa torso-DER chimeric receptor. Expression of D-Cbl directed by the sevenless enhancer in intact Drosophila compromises severely the development of the R7 photoreceptor neuron. These data suggest that despite the lack of Grb2 binding sites, D-Cbl functions as a negative regulator of receptor tyrosine kinase signaling in the Drosophila eye by a mechanism that involves its association with EGF receptors or other tyrosine kinases.

Preoperative positron emission tomographic viability assessment and perioperative and postoperative risk in patients with advanced ischemic heart disease.

OBJECTIVES: This study sought to investigate whether determination of tissue viability by means of positron emission tomography (PET) before coronary artery bypass graft surgery (CABG) affects clinical outcome with respect to both in-hospital mortality and 1-year survival rate. BACKGROUND: Patients with coronary artery disease (CAD) and severe left ventricular (LV) dysfunction are at higher risk for perioperative complications associated with CABG. Therefore, the selection of patients who will benefit from CABG is an important clinical issue. METHODS: This study retrospectively evaluated 76 patients with advanced CAD and LV dysfunction (LV ejection fraction < or = 0.35) who were considered candidates for CABG. Thirty-five patients were selected for CABG on the basis of clinical presentation and angiographic data (group A), and 34 of 41 patients were selected according to extent of viable tissue determined by PET (group B) in addition to clinical presentation and angiographic data. RESULTS: There were four in-hospital deaths (11.4%) in group A and none in group B (p = 0.04). After 12 months, the survival rate was 79% in group A and 97% in group B (p = 0.01). Postoperatively, group B patients had a less complicated recovery (p = 0.05). They required lower doses of catecholamines (p = 0.002) and demonstrated a significantly decreased incidence of low output syndrome (p = 0.05). CONCLUSIONS: This retrospective data analysis suggests that selection of patients with impaired LV function on the basis of extent of viability supplementary to clinical and angiographic data may lead to postoperative recovery with a low early mortality and promising short-term survival. Therefore, viability studies permit selection of patients who are at low risk for serious perioperative complications.

Time course and extent of improvement of dysfunctioning myocardium in patients with coronary artery disease and severely depressed left ventricular function after revascularization: correlation with positron emission tomographic findings.

OBJECTIVES: This study was performed to evaluate the prevalence, time course of recovery and extent of improvement of segments with a positron emission tomographic (PET) flow-metabolism mismatch and match pattern, as well as of PET segments with normal perfusion but with impaired myocardial function. BACKGROUND: Previous studies have shown that scintigraphic techniques evaluating myocardial viability provide predictive information about the improvement of regional wall motion. However, there are little data concerning the time course and extent of improvement of segments according to preoperative scintigraphic patterns. METHODS: Twenty-nine patients with ischemic cardiomyopathy (ejection fraction 18% to 35%) underwent preoperative PET viability assessment and were functionally assessed by two-dimensional echocardiography preoperatively and at 11 days, 14 weeks and >12 months after coronary artery bypass graft surgery. RESULTS: In 168 (70%) of 240 dysfunctional segments, a "normal" scintigraphic pattern was present, whereas a "mismatch" pattern was observed in 24% (p<0.01). Mismatch areas were associated with more severe preoperative wall motion abnormalities and incomplete postoperative recovery. After one year, 31% of normal scintigraphic segments, compared with only 18% of mismatch segments, showed complete functional restoration (p<0.05). CONCLUSIONS: These data suggest that in patients with severe left ventricular dysfunction, a scintigraphic pattern of normal perfusion and normal metabolism is more prevalent than a flow-metabolism mismatch pattern. Functional recovery is more frequent in normal scintigraphic segments, whereas in mismatch segments, postoperative recovery remains incomplete even after one year.

Acute cardiac inflammatory responses to postischemic reperfusion during cardiopulmonary bypass.

OBJECTIVES: The investigation centers on whether there is a reperfusion-induced specific cardiac inflammatory reaction after bypass surgery. BACKGROUND: Cardiopulmonary bypass (CPB) leads to systemic inflammation. Additionally, cardiac inflammation due to reperfusion could occur. Knowledge about nature and time course of this reaction might help to develop cardioprotective interventions. METHODS: In 12 patients receiving coronary bypass grafts, arterial and coronary venous blood was obtained before onset of CPB, and 1, 5, 10, 25, 35 and 75 min after cardiac reperfusion. Plasma levels of IL6 and IL8 were measured by immunoassay. CD11b, CD41, and CD62 on blood cells were quantified by flow cytometry. Measurement of CD41, a platelet marker, on neutrophils and monocytes allowed detection of leukocyte-platelet microaggregates. RESULTS: Transcardiac veno-arterial difference of IL6 rose in the 10th and 25th min of reperfusion (from 0 to 7 pg/ml; p < 0.05), and after 75 min (15 pg/ml). IL8 did not change. CD11b on neutrophils (PMN) decreased transcardially to 95, 88 and 82% of the initial level in the 5th, 10th, and 75th min, respectively, suggesting sequestration of activated neutrophils. CD62 on platelets rose about 30% in the 75th min. Initially, leukocyte-platelet microaggregates were formed during coronary passage (+31% of the arterial level for PMN, +23% for monocytes). During reperfusion, coaggregates were retained (PMN: -1% and -7% in the 5th and 10th min, monocytes: -22%, -13% and -12% in the 1st, 5th and 10th min. CONCLUSIONS: During early reperfusion after aortic declamping, the coronary bed is already a source of proinflammatory stimuli and target for activated leukocytes, partly in conjunction with platelets. Mitigation of these phenomena might help to improve cardiac function after CPB especially in patients at risk.

Changes of renal mRNA species abundance by ochratoxin A.

Ochratoxin A is a nephrotoxin produced by certain species of Aspergillus and Penicillium. We have found previously that renal but not hepatic P-enolpyruvate carboxykinase, and the mRNA for this enzyme, are rapidly decreased in rats and swine fed 0.1 to 1 mg/kg body weight for a few days. In the present study, we isolated kidney mRNA from rats fed ochratoxin A for 2-5 days. By screening a rat kidney cDNA library with [32P]RNA, we have identified several renal mRNAs whose concentration is changed within 2 days by the toxin. The transcription rate of each mRNA was measured in nuclei isolated from kidneys of rats fed ochratoxin A. The incorporation of [32P]UMP into P-enolpyruvate carboxykinase mRNA and the synthesis of other RNAs were not affected. Therefore, the toxin changes mRNA abundance at the post-transcriptional level.

Risk factors for perioperative mortality in children with anomalous origin of the left coronary artery from the pulmonary artery.

The present study was conducted on 33 children (median age at initial cardiac catheterization 0.4 years [0.1 to 11.8]) with anomalous origin of the left coronary artery from the pulmonary artery, without associated hemodynamically significant cardiovascular anomalies, who were treated throughout a period of 18 years in our hospital. A two coronary artery circulation was reestablished in 31 of 33 children. One child died before the intended operation, and in one child the left coronary artery was ligated. There were six operative deaths, five intraoperative and one 12 hours after operation. The purpose of the study was to assess which preoperative clinical and angiographic features were associated with a higher perioperative mortality. The following preoperative factors were associated with a statistically significant higher perioperative mortality: young age at operation (p less than 0.03), left and balanced type of coronary circulation (p less than 0.01), and electrocardiographic signs of extensive acute myocardial infarction, namely, marked ST elevation (greater than or equal to 0.2 mV in at least two leads) (p less than 0.03). Left axis deviation on the electrocardiogram was associated with an extreme right dominant type of coronary circulation (p less than 0.005). The latter was also linked with adequate perfusion of the posterolateral left ventricular wall (p less than 0.005). At autopsy, severe increase of heart weight to two or three times the normal heart weight was established in six of seven children. Thus the perioperative mortality was determined primarily by the extent of myocardial ischemia. This in turn is decisively influenced by the dominant type of coronary circulation and the extent of inter-arterial collateralization. Young age, in addition, proved to be a risk factor for mortality at corrective surgery.

Evidence for inflammatory responses of the lungs during coronary artery bypass grafting with cardiopulmonary bypass.

OBJECTIVE: The occurrence of a systemic inflammatory reaction during cardiac surgery with cardiopulmonary bypass (CPB) has been well established, and the heart itself has been shown to release inflammatory mediators after ischemia. The hypothesis of the present study was that the lungs are also a site of inflammatory responses during early reperfusion. METHODS: In 20 consecutive patients undergoing coronary artery bypass grafting, blood was simultaneously drawn from the right atrium (RA) and the pulmonary vein (PV) before CPB and at 1 min, 10 min, and 20 min of reperfusion. The levels of interleukin (IL)-6, IL-8, IL-10, and tumor necrosis factor (TNF)-alpha were determined, as well as the adhesion molecules CD41 and CD62 on platelets and CD11b and CD41 on leukocytes. As a measure of the pulmonary release, ratios of PV and RA levels were calculated. RESULTS: Before CPB, the concentrations of cytokines tended to be lower in the PV compared with the RA. At 1 min of reperfusion, no significant concentration increases were found in the PV. At 10 min of reperfusion, the PV/RA ratio (mean +/- SEM) for IL-6 was 2.06 +/- 0.37 and 1.24 +/- 0.15 for IL-8 (p = 0.02 and p = 0.04, respectively, compared with the pre-CPB ratios of 0.89 +/- 0.4 and 0.99 +/- 0.2). At 20 min of reperfusion, PV/RA ratios for IL-6 (1.95 +/- 0.37) and IL-10 (0.99 +/- 0.4) were higher than before CPB (0.89 +/- 0.04, p = 0.05 and 0.85 +/- 0.06, p = 0.03, respectively). Adhesion molecule counts on platelets and polymorphonuclear neutrophils (PMNs) tended to be higher in the PV than in the RA before CPB. At 1 min of reperfusion, the PV/RA ratio of CD41 on monocytes (0.89 +/- 0.04) and of CD41 on PMNs (1.05 +/- 0.05) was less than before CPB (1.24 +/- 0.08, p = 0.0002 and 1.55 +/- 0.14, p = 0.0002). At 10 min and 20 min of reperfusion, similar changes were found. CONCLUSIONS: The observed changes indicate an inflammatory response of the lungs. Proinflammatory cytokines are increased in pulmonary venous blood. At the same time, activated blood cells are retained in the pulmonary circulation. This may contribute to pulmonary dysfunction almost routinely observed after CPB.

Left ventricular function assessed with echocardiography and myocardial perfusion assessed with scintigraphy under dipyridamole stress in pediatric patients after repair for anomalous origin of the left coronary artery from the pulmonary artery.

Twenty-three patients who underwent operation for anomalous origin of the left coronary artery from the pulmonary artery were reexamined with two-dimensional echocardiography and thallium 201 perfusion imaging. Follow-up studies were performed 0.6 to 16.2 years (median 2.9 years) after operation. In 22 of 23 patients, a two coronary artery system had been established by implantation of the left coronary artery into the aorta (n = 8) or by anastomosis of the left subclavian artery with the left coronary artery (n = 14). The left coronary artery had been ligated in only one patient. For stress testing, 0.8 mg dipyridamole per kilogram body weight was infused in a 10-minute period in 20 of the 23 patients. High-dose dipyridamole infusion increased mean heart rate (98.1 +/- 27.1 to 122.3 +/- 19.2 beats/min, p < 0.001) and mean left ventricular ejection fraction (54.8% +/- 11.8% to 61.3% +/- 12.5%, p < 0.05) and decreased left ventricular end-diastolic volume index (38.8 +/- 26.7 to 29.9 +/- 8.3 ml/m2, p < 0.005). At rest, left ventricular dimensions were abnormal in only one patient, in whom the anastomosis with the left coronary artery proved to be occluded, as seen with subsequent angiography. Left ventricular function seen with two-dimensional echocardiography was normal in 19 patients and was compromised in 3 (all of whom had major structural anomalies of the left ventricle, such as left ventricular aneurysm, occlusion of the anastomosis, or mitral valve prosthesis). Patients with R-wave loss as seen with preoperative electrocardiography tended to have larger left ventricular volumes at follow-up (69.2 +/- 56.5 ml/m2 versus 32.4 +/- 9.6 ml/m2, p < 0.07). Ten of 20 patients had normal thallium 201-perfusion scans. In 9 of 20 patients defects revealed by permanent thallium 201-perfusion were observed and determined to be myocardial scars. Transient perfusion defects under dipyridamole stress with redistribution at rest occurred in three children, two of whom also had permanent thallium 201 defects. None of the three patients had angina-like symptoms or S-T segment changes during dipyridamole stress. Left ventricular ejection fraction, however, decreased severely during dipyridamole infusion in the single patient with ligature of the left coronary artery. The two remaining patients had normal echocardiographic left ventricular function under stress, and the diagnosis of myocardial ischemia as seen with scintigraphy must be questioned.(ABSTRACT TRUNCATED AT 400 WORDS)

Intracardiac thrombus formation after the Fontan operation.

OBJECTIVES: Intracardiac thrombus formation is suspected to be a specific sequela after the Fontan operation and is difficult to determine by means of routine transthoracic echocardiography. The aim of our study was to evaluate the occurrence of intracardiac thrombi in the different types of Fontan modifications and to identify predisposing risk factors. METHODS: We evaluated 52 patients who had undergone a Fontan-type operation and were free of symptoms regarding thrombosis as determined by transesophageal echocardiography. RESULTS: In 17 (33%) patients thrombus formation could be found without clinical evidence of thromboembolic complications. Neither underlying morphologic disease nor age at operation, type of Fontan operation, sex, follow-up interval, arrhythmias, or laboratory or hemodynamic findings could be identified as predisposing risk factors. CONCLUSION: In patients having had a Fontan operation with inadequate or without anticoagulation medication, we would recommend routine transesophageal echocardiography to exclude eventual thrombi. Because of the high incidence of thrombi, we suggest oral anticoagulation therapy in all patients.

Hemostatic activation during cardiopulmonary bypass with different aprotinin dosages in pediatric patients having cardiac operations.

The effect of high-dose aprotinin treatment on hemostatic activation during cardiopulmonary bypass in pediatric patients having cardiac operations was investigated. Sixty patients weighing less than 10 kg undergoing cardiac operations for different types of congenital heart diseases were studied: 20 patients were treated with aprotinin 2 x 15,000 KIU/kg, 20 patients with 2 x 30,000 KIU/kg, and 20 patients without aprotinin treatment served as the control group. Different split products of fibrinogen and/or fibrin and the fibrinolytic activity on fibrin plates were measured to assess fibrinolytic activation. F1/F2 prothrombin fragments, thrombin-antithrombin III-complex, and fibrin monomers were measured to estimate thrombin activation. There was a significant dose-dependent reduction in fibrin-fibrinogen split product formation during cardiopulmonary bypass: In the high-dose aprotinin group the concentration of the split products at the end of bypass was 1.5 +/- 0.6 micrograms/ml, compared with 3.4 +/- 3.0 micrograms/ml in the low-dose aprotinin group and 6.7 +/- 3.5 micrograms/ml in the control group (p < 00.5). Fibrinolytic activation on fibrin plates was also significantly reduced by aprotinin. Fibrin monomer formation was significantly diminished at the end of cardiopulmonary bypass in the high-dose group: 9.2 +/- 5.2 micrograms/ml compared with 21.6 +/- 14 micrograms/ml in the control group (p < 00.5). Elastase in complex with alpha 1-protease inhibitor at the end of bypass was increased to the same amount in the three groups: 784 +/- 278 ng/mL (control group), 693 +/- 189 ng/ml (low-dose aprotinin), and 719 +/- 270 ng/mL (high dose aprotinin) (no significant difference). Blood loss 6 hours postoperatively was significantly (p < 00.5) less in the high-dose group (99 +/- 32 ml/m2) than in the control group (164 +/- 87 ml/m2; low-dose group: 160 +/- 106 ml/m2). These observations suggest an attenuation of hemostatic activation during cardiopulmonary bypass with less plasmin formation and, because of inhibition of contact activation, less thrombin generation with aprotinin treatment. Thus the thrombotic-thrombolytic equilibrium is kept more balanced after cardiopulmonary bypass. High-dose aprotinin treatment is recommended for pediatric patients undergoing cardiac operations.

Sodium nitroprusside in patients with compromised left ventricular function undergoing coronary bypass: reduction of cardiac proinflammatory substances.

OBJECTIVE: The aim of the present study was to investigate whether the nitric oxide donor sodium nitroprusside can reduce the cardiac inflammatory response during coronary artery bypass grafting in patients with severely compromised left ventricular function. METHODS: Patients (n = 30) were assigned to receive placebo or sodium nitroprusside (0.5 microg. kg(-1). min(-1)) for the first 60 minutes of reperfusion. Interleukin 6, interleukin 8, and tumor necrosis factor alpha levels; platelet adhesion molecule CD41 and CD62 levels; and CD11b on leukocytes were determined in the radial artery and coronary sinus before cardiopulmonary bypass and during reperfusion (1, 5, 10, 35, and 75 minutes). RESULTS: At 1 minute of reperfusion, coronary venous levels of CD41-positive polymorphonuclear leukocytes were 8% lower than arterial levels in the placebo group and 18% higher in the sodium nitroprusside group (P =.021). At 5 minutes of reperfusion, the respective levels were 29% and 1% for interleukin 6 (P =.015), -5% and 20% for CD41-positive monocytes (P =.032), and -2% and 16% for CD11b-positive monocytes (P =.038). At 10 minutes of reperfusion, these levels were -14% and 21% for CD41-positive monocytes (P =.006). At 35 minutes of reperfusion, these levels were -13% and 7% for CD41-positive monocytes (P =.017), -41% and 23% for CD11b-positive monocytes (P =.001), and 7% and 25% for CD62-positive platelets (P =. 041). At 75 minutes of reperfusion, the levels were 15% and -7% for tumor necrosis factor alpha (P =.025) and -10% and 10% for CD62-positive platelets (P =.041). CONCLUSIONS: Transcardiac production of proinflammatory cytokines is reduced in patients undergoing coronary artery bypass grafting treated with the nitric oxide donor sodium nitroprusside. At the same time, less activated leukocytes and platelets are retained in the coronary circulation.

Acute effects of aortocoronary bypass surgery on left ventricular function and regional myocardial mechanics: a clinical study.

The acute effects of myocardial revascularization on overall left ventricular performance and on myocardial segmental wall motion were assessed intraoperatively in 22 patients who had unstable (11 patients) or stable angina pectoris (11 patients). Segmental contraction patterns were evaluated using an ultrasonic transit-time method. In 9 patients with unstable angina pectoris, notable improvement in segmental wall motion was observed as the short-term response to coronary bypass grafting. Hypokinetic patterns were rendered normal after revascularization. Despite marked changes in segmental myocardial function, overall left ventricular performance was not altered notably. In contrast, reperfusion did not lead to acute effects on either segmental wall motion or total left ventricular function in patients with stable angina pectoris. The results indicate that aortocoronary bypass grafting may improve segmental wall motion in patients with unstable angina.

Long-term survival and functional follow-up in patients after the arterial switch operation.

BACKGROUND: For many years, the arterial switch operation (ASO) has been the therapy of choice for patients with transposition of the great arteries (TGA). Although excellent short- and mid-term results were reported, long-term results are rare. METHODS: Between May 1983 and September 1997, ASO was performed on 285 patients with simple TGA (n = 171), TGA with ventricular septal defect (VSD) (n = 85), and Taussig-Bing (TB) anomaly (n = 29). This retrospective study describes long-term morbidity and mortality over a 15-year period. RESULTS: Hospital mortality was 3.5% for simple TGA, 9.4% for TGA with VSD, and 13.8% for TB anomaly. Late death occured in 2 patients, 1 with simple TGA and 1 with TGA and VSD. The cumulative survival for all patients at 5 and 10 years is 93%, and at 15 years is 86%. Reoperations were required in 31 patients and were most common for stenosis of the right ventricular outflow tract (RVOT). However, no correlation was found between technical variations on pulmonary artery reconstruction and this type of complication. Forty-six patients underwent follow-up angiography, which revealed five cases with coronary occlusion or stenosis. Follow-up is complete in 96% of the patients from 1 to 15.2 years. Sinus rhythm is present in 97%; 88% of the patients show no limitations on exertion. CONCLUSIONS: The ASO can be performed with low early mortality, almost absent late mortality, and infrequent need for reoperation. The favorable long-term results demonstrate that the ASO can be considered as the optimal approach for patients with TGA and special forms of double-outlet right ventricle.

Results after surgical repair of Ebstein's anomaly.

BACKGROUND: Ebstein's anomaly of the tricuspid valve is a complex malformation. Various operations have been undertaken with varying results. Because valve replacement yielded poor results, surgical treatment has focused on valvuloplasties. METHODS: Between April 1974 and February 1995, 60 patients with Ebstein's anomaly underwent surgical repair. Age ranged from 5 months to 54 years. In 56 patients (93.3%), tricuspid valvuloplasty was feasible, mainly by creating a monocusp valve with the single-stitch technique. The other 4 patients had valve replacement with a bioprosthesis. Six reoperations were necessary (10.0%): four valve replacements and two repeat valvuloplasties. RESULTS: There were two hospital deaths (3.3%) and a late mortality rate of 10.0% (6 patients). Forty-nine (94.2%) of 52 survivors were followed for 5 months to 18.6 years (median follow-up, 5.0 years; mean follow-up, 6.9 years). The actuarial survival rate (Kaplan-Meier) was 96.5% +/- 2.4% at 1 year and 83.3% +/- 5.6% at 18 years. At follow-up evaluation, nearly all patients showed substantial improvement (93.9% were in functional class I or II) compared with their preoperative status. Doppler echocardiographic studies demonstrated good tricuspid valve function in most patients. CONCLUSIONS: Valvuloplasty using the single-stitch technique is a rewarding operation. It yields good long-term results with substantial improvement in functional performance and clinical status.

Allograft implantation in pediatric cardiac surgery: surgical experience from 1982 to 1994.

Between July 1982 and April 1994, a total of 290 patients (median age 6.5 years, range 1 month to 32.1 years, 69 patients younger than 1 year) underwent repair of their cardiac malformation by insertion of an allograft. The diagnoses were truncus arteriosus communis (n = 78, 27.0%), tetralogy of Fallot (n = 59, 20.0%), pulmonary atresia (n = 72, 25.0%), double outlet right ventricle (n = 15, 5.0%), complex transposition of the great arteries plus pulmonary stenosis (n = 37, 13.0%), and others (n = 29, 10.0%). Either pulmonary (n = 69) or aortic (n = 221) cadaver allografts were implanted. Two hundred twenty-nine of the allografts were antibiotic preserved. Since January 1991 (n = 61), a new cryopreservation procedure was employed for standardized uniform cooling using heat sinks and defined package geometry. Follow-up was complete for 95.2% (n = 276, 1,320 patient-years). Thirty-day mortality was 9.0% (n = 26) and late mortality was 12.1% (n = 35). Kaplan-Meier analysis revealed that patient survival was determined mainly by their underlying cardiac disease. All allografts with valve sizes less than 15.0 mm had to be exchanged within 7 years as these patients had outgrown their conduits. When the allograft was larger than 15.0 mm, exchange was necessary in 20% at 10 years. ABO compatibility and aortic or pulmonary origin of the allograft were not significant influences on allograft survival.(ABSTRACT TRUNCATED AT 250 WORDS)

Bioprosthetic and mechanical valves in the elderly: benefits and risks.

There is controversy over whether elderly patients benefit from the durability of mechanical valves when balanced against the risk of anticoagulation. From 1976 to 1993, 576 patients 65 years old or older underwent isolated valve replacement with mechanical (n = 250) or bioprosthetic valves (n = 326). Total follow-up was 2,222 patient-years. Probability of survival and freedom from thromboembolism and prosthetic valve endocarditis were not different between the two groups. There was a significant difference (p = 0.015) in freedom from anticoagulant-related hemorrhage. Two patients with mechanical prostheses and 7 patients with bioprostheses were reoperated. However, actuarial freedom from reoperation was not different (p = 0.73) in both groups, with no hospital mortality, whereas mortality from thromboembolic events and anticoagulant-related hemorrhage was three times higher in patients with mechanical prostheses as compared with patients with bioprostheses (1.08% versus 0.36% per patient-year). The benefit from the durability of mechanical valves, compared with bioprostheses, is smaller than expected because of the limited number of patients exposed to the onset of bioprosthetic structural deterioration. Elderly patients without absolute indication for anticoagulation should preferentially receive bioprostheses for valvular replacement.

Drew-Anderson technique attenuates systemic inflammatory response syndrome and improves respiratory function after coronary artery bypass grafting.

BACKGROUND: Cardiopulmonary bypass causes inflammatory reactions leading to organ dysfunction postoperatively. This study was undertaken to determine whether using patients' own lungs as oxygenator in a bilateral circuit (Drew-Anderson Technique) could reduce systemic inflammatory response to cardiopulmonary bypass, improving patients clinical outcome following coronary artery bypass grafting. METHODS: A prospective randomized controlled trial involving 30 patients, divided in two groups of 15 patients each, undergoing elective coronary artery bypass grafting, was undertaken. In the Drew-group bilateral extracorporeal circulation using patient's lung as oxygenator was performed. The other patients served as control group, where standard cardiopulmonary bypass procedure was used. RESULTS: Pro-inflammatory and anti-inflammatory mediators were measured. Peak concentrations of proinflammatory interleukin-6, interleukin-8, were significantly lower in 15 patients undergoing Drew-Anderson Technique compared with the concentrations measured in 15 patients treated with standard cardiopulmonary bypass technique. Differences in patient recovery were analyzed with respect to time of intubation, blood loss, intrapulmonary shunting, oxygenation, and respiratory index. In patients undergoing uncomplicated coronary artery bypass grafting procedures bilateral extracorporeal circulation using the patients' own lung as oxygenator provided significant biochemical and clinical benefit in comparison to the standard cardiopulmonary bypass procedure. CONCLUSIONS: This prospective randomized clinical study has demonstrated that exclusion of an artificial oxygenator from cardiopulmonary bypass circuit significantly decreases the activation of inflammatory reaction, and that interventions that attenuate this response may result in more favorable clinical outcome.

Sodium nitroprusside during coronary artery bypass grafting: evidence for an antiinflammatory action.

BACKGROUND: It was the aim of the present study to investigate whether a nitric oxide donor can reduce systemic inflammation and the cardiac inflammatory response during coronary artery bypass grafting with cardiopulmonary bypass. METHODS: Patients undergoing elective coronary artery bypass grafting (n = 22) were randomly assigned to treatment with either sodium nitroprusside (0.5 microg x kg(-1) x min(-1)) or placebo (controls), both for the first 20 minutes of reperfusion. Interleukin-6 and interleukin-8 levels, the adhesion molecules CD41 and CD62 on platelets and CD41 on monocytes and PMN (as markers for coaggregate formation), CD11b on monocytes and PMN, as well as platelet and leukocyte counts were determined in radial artery and coronary sinus blood before cardiopulmonary bypass and during reperfusion (1, 5, 10, 25, and 35 minutes). RESULTS: A reduction of systemic interleukin-6 levels (15.4+/-3.5 pg/mL, 36.7+/-5.9 pg/mL, and 46.8+/-8.0 pg/mL versus 33.4+/-7.7 pg/mL, 76.7+/-13.2 pg/mL, and 106.0+/-26.5 pg/mL, respectively, at 1, 25, and 35 minutes of reperfusion) and interleukin-8 (29.6+/-4.5 pg/mL versus 54.0+/-9.4, pg/mL, resp., at 35 minutes of reperfusion) resulted from treatment with sodium nitroprusside. No intracardiac production of interleukin-8 in sodium nitroprusside-treated patients (-1.1+/-0.4 pg/mL and -2.8+/-2.2 pg/mL, resp., for the coronary sinus-radial artery difference at 5 and 25 minutes of reperfusion) was observed, whereas cardiac production of interleukin-8 was present in controls (2.5+/-1.5 pg/mL and 5.5+/-2.8 pg/mL, resp.). Retention of platelet/leukocyte coaggregates occurred during coronary passage in controls (coronary sinus-radial artery difference for CD41-positive monocytes at 1 and 10 minutes of reperfusion, -16.3%+/-8.5% and -8.8%+/-2.6%, resp.). This was reduced in sodium nitroprusside-treated patients (with 5.8%+/-5.2% and 0.0%+/-3.2%). Retention of platelets in controls (ratio of coronary sinus to radial artery platelet count at 5 and 10 minutes of reperfusion, 88%+/-6% and 91%+/-5%) was compared to washout in treated patients (108%+/-6% and 113%+/-7%). CONCLUSIONS: In patients undergoing routine coronary artery bypass grafting, administration of sodium nitroprusside during early reperfusion alleviates systemic inflammation and the cardiac inflammatory response.