Performance of allografts and xenografts for right ventricular outflow tract reconstruction.

BACKGROUND: We compared the long-term durability of allografts and xenografts implanted for reconstruction of the right ventricular outflow tract. METHODS: A total of 401 patients were studied from January 1974 to June 2000 (145 xeno- and 256 allografts), follow-up being 98% complete. We analyzed freedom from reoperation and allograft specific factors that may indicate degeneration. RESULTS: The age at implantation was 2 days to 31 years (median 4.0 years). Conduit exchange rate was similar (p = 0.2) for conduit diameters less than 15 mm (41%+/-9% for allografts, 30%+/-6% for xenografts), but significantly different (p = 0.02) for diameters of 15 mm or larger (60%+/-8% for allografts, 30%+/-10% for xenografts). Diagnosis-related 20-year survival analysis showed a significantly (p = 0.01) better survival of patients with tetralogy of Fallot/pulmonary atresia (83%+/-5%) and Rastelli-type surgery (81%+/-8%) compared with patients with truncus arteriosus communis (69%+/-8%). ABO-compatibility, preservation method, and aortic or pulmonary allograft could not be identified as risk factors for allograft longevity. CONCLUSIONS: For smaller diameters (less than 15 mm), allografts exhibit no advantage over xenografts, whereas in larger diameters (15 mm or larger) allografts are the conduit of choice for the right ventricular outflow tract.

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.

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.

Effect of cardiopulmonary bypass and hemofiltration on plasma cytokines and protein leakage in pigs.

BACKGROUND: The hypothesis that an inflammatory process during and after cardiopulmonary bypass (CPB) impairs hemodynamics and causes increased capillary protein leakage and that this is possibly ameliorated by hemofiltration (HF) was tested. METHOD: 26 anesthetized pigs were subjected to 120 min CPB (90 min cardioplegia followed by 30 min reperfusion, combined with conventional and modified HF in 13 animals). Hemodynamics, leukocytes, cytokines (IL-1ra, IL-8, IL-10, TNF-alpha), LNPI, plasma protein, and the half-life of i.v. injected Evans Blue (t/2) were assessed before and after CPB. RESULTS: CPB was followed by depression of left ventricular function and activation of inflammatory mediators. Although a slight elimination of some inflammatory mediators occurred, HF did neither improve cardiac function nor reduce the inflammatory process. Plasma protein was lost during CPB and hemofiltration by protein trapping to the surfaces of the CPB system, by filtration across the hemofilter, and by increased microvascular filtration (solvent drag). The latter was probably due to an increased filtration pressure in consequence of the reduction of plasma colloid osmotic pressure by the crystalloid primed CPB. t/2 did not indicate an increased microvascular protein leakage after CPB. CONCLUSION: Hemofiltration is ineffective in improving cardiac function or reducing the inflammatory response of CPB in the pig model.

Reconstruction of the RVOT with valved biological conduits: 25 years experience with allografts and xenografts.

OBJECTIVE: The reconstruction of the RVOT in congenital heart disease often requires the implantation of a valved conduit. Although allografts are considered the conduit of choice their availability is limited and therefore xenografts are implanted as well. We compared the long-term durability of both grafts in the RVOT over a 25-year period. METHODS: Between January 1974 and August 1999, 505 patients (median age 4.0 years, range 2 days-31 years; median weight 14.5 kg, range 2.2-76.6 kg; median body length 103 cm, range 48-183 cm) with congenital malformations (PA 25.3%, TOF 14.5%, TOF+PA 2.4%, DORV 4.2%, TGA+PS 8.7%, TAC 24.8%, and other 20.2%) received their first valved conduit (174 xenografts: median diameter 14 mm, range 8-27 mm; 331 allografts: median diameter 19 mm, range 8-30 mm). RESULTS: Follow-up is 3017 patient-years. The 10-year survival-probability for all patients. was 66% with a mean reoperation-free interval for conduit-exchange of 13.3 years (mean reoperation-free interval for allografts, 16.0 years; mean reoperation-free interval for xenograft, 10.3 years). One hundred and thirteen patients underwent a conduit-exchange, mostly due to conduit stenosis. Fourteen patients had a second exchange and three patients a third exchange. For patients with conduit diameters <18 mm (n=235: allograft n=116, xenograft n=119; median age 9 months, range 0-27.3 years), the mean reoperation-free interval was 11.2 years (mean interval allograft, 13.1 years; mean interval xenograft, 8.6 years, P=0.03). For conduit diameters >/=18 mm (n=270: allograft n=215, xenograft n=55, median age 7.4 years, range 0-34.3 years) the mean interval from freedom of conduit exchange was 15.1 years (for allografts 14.1 years, for xenografts 12.5 years, P<0.01). Comparing xenografts to allografts, we found no difference in patient survival probability (P=0.62). There was no significant difference between antibiotic (n=198) preserved vs. cryopreserved (n=133) allografts (P=0.06). Blood group compatibility of allografts to recipients had no significant influence on allograft function (P=0.42). The donors allograft origin, whether aortic or pulmonary valve, had also no significant influence on allograft long-term function (P=0.15). CONCLUSION: For the reconstruction of the right ventricular outflow tract (RVOT) allografts show significantly better long-term durability than xenografts regardless of the age at implantation and the diameter.

Reduction of pro-inflammatory cytokine levels and cellular adhesion in CABG procedures with separated pulmonary and systemic extracorporeal circulation without an oxygenator.

OBJECTIVE: We have recently shown that a considerable amount of pro-inflammatory cytokines is released during pulmonary passage after aortic declamping in patients undergoing coronary artery bypass grafting. The present study was performed to investigate whether bilateral extracorporeal circulation with the lungs as oxygenators can reduce the inflammatory responses of the lungs. METHODS: Eighteen consecutive patients undergoing coronary artery bypass grafting were randomly assigned to routine extracorporeal circulation with cannulation of right atrium and aorta (routine circulation, ten patients) or to a bilateral extracorporeal circulation with additional cannulation of left atrium and pulmonary artery (bilateral circulation, eight patients). Blood was simultaneously drawn from right atrium and pulmonary vein at 1, 10 and 20 min reperfusion. The levels of interleukin (IL)-6 and IL-8 and the adhesion molecules CD41 and CD62 on platelets and CD11b and CD41 on leukocytes were determined. Because of considerable interindividual scatter, the pulmonary venous levels are normalized to percent of the respective right atrial value at each time point. RESULTS: At 1 min reperfusion pulmonary venous levels of IL-6 and IL-8 in routine circulation were +44+/-15% and +43+/-28% of the respective right atrial values. The respective values in bilateral circulation were -3+/-4% and -6+/-7% (P=0.02 and P=0.05 vs. respective right atrium). Similar increments were found after 10 and 20 min. Platelet-monocyte coaggregates were retained during pulmonary passage at 1 min reperfusion in routine circulation (-21+/-6%), but washed out in bilateral circulation (+5+/-8%, P=0. 007). At 20 min reperfusion, activated polymorphonuclear neutrophils (PMN) were retained in routine circulation (-16+/-9%) but washed out in bilateral circulation (+19+/-29%, P=0.05; all data given as mean+/-SEM). CONCLUSIONS: Bilateral extracorporeal circulation without an artificial oxygenator significantly reduces the inflammatory responses during pulmonary passage after aortic declamping.

Single centre experience on primary correction of common arterial trunk: overall survival and freedom from reoperation after more than 15 years.

OBJECTIVE: To identify predictors of early and late outcomes of common arterial trunk (CAT) after primary surgical correction, such as clinical state prior to surgery, age and weight at presentation, implications of truncal valve abnormalities and associated anomalies of this complex congenital malformation. METHODS: A consecutive series of 106 patients, operated between 1976 and 1998, were reviewed retrospectively. Using the 'Van Praagh' classification, 59 patients presented as A1, 33 as A2, six as A3, and eight as A4. The mean age at operation was 8.6 months (range, 14 days-8.9 years; median, 4.4 months), and the mean weight was 5.2 kg (range, 2.5-30.8 kg; median, 4.4 kg). At the time of operation, 32 patients had congestive heart failure, five were on ventilator support for less than 1 week, and 21 for more than 1 week. RESULTS: Between 1976 and 1989, the early mortality was 21%, and between 1990 and 1998, it dropped to 13%. After 1, 10 and 15 years, the overall survival was 66, 61 and 59%. The 1, 5, 10 and 15 year freedom from reoperation was 82, 60, 22 and 10%, respectively. Clinical condition prior to intervention, truncal valvar dysfunction, and coronary anomalies were significantly associated with poor surgical outcome, whereas weight and age at presentation in our series were not. CONCLUSIONS: In the current era of paediatric cardiac surgery, primary surgical repair of CAT can be carried out with reasonable early and late mortality. However, our data suggest that a high incidence of reoperation, mainly due to the outgrowth and failure of the conduit, has to be expected. The patient's clinical state after diagnosis is decisive for the timing of intervention.

Mitral-valve replacement in children under 6 years of age.

OBJECTIVE: In patients with congenital mitral-valve disease, reconstructive surgery is the primary goal. However, in cases with severely dysplastic valves or failed repair, mitral-valve replacement (MVR) is the only option. We analyzed, retrospectively, data of 35 patients younger than 6 years of age, who underwent MVR at our institution. METHODS: Between 1974 and 1997, 35 children underwent MVR. The ages ranged from 2.7 months to 5.5 years (mean=1. 9+/-1.7 years) and body weight varied between 3.2 and 16.7 kg (mean=8.2+/-4 kg). The main indication (57%) for valve replacement was severe mitral-valve insufficiency. Eighteen patients (51%) had undergone at least one previous reconstructive operation (mean=1. 46+/-1.86 years) before the MVR. In 29 cases (83%), mechanical prostheses were implanted. Six patients received a bioprosthesis. The size of the prostheses ranged between 14 and 27 mm. RESULTS: The overall hospital mortality was 17.1% (6/35), and decreased from 33 (1974-1985) to 11.5% (1986-1997). Seven children died late. The actuarial survival after 20 years was 51.2+/-13.3%. Eight patients (23%) required 10 reoperations (8.2%/100 patient-years). Freedom from reoperation at 10 years was 50+/-22%. Valve-related complications were thrombo-embolism (n=2; 1.6%/100 patient-years), hemorrhage (n=1; 0.8%/100 patient-years), structural deterioration (n=3; 2.5%/100 patient-years) and non-structural dysfunction (n=3; 2. 5%/100 patient-years). Follow-up is 96% complete, with a total of 122 patient-years (mean=4.2+/-4.7 years). Eighty six percent of the patients are in New York Heart Association (NYHA) class I, 95% have sinus rhythm and 59% do not need medication. All survivors, except for those who received a bioprosthesis, were placed on a regimen of Phenprocoumon (Marcumar((R))), aiming to maintain the International Normalized Ratio (INR) between 2.5 and 3.5. In one third of these children, self-management of oral anticoagulation was performed either by the patients or their parents. CONCLUSIONS: MVR in small children still carries a high risk. In our experience, the long-term results are satisfying. After failed reconstructive surgery, or as a primary procedure, we prefer mechanical prostheses. They are well tolerated and the incidence of anticoagulation-related complications is low.

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.

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.

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.

Repair of interrupted aortic arch: results after more than 20 years.

BACKGROUND: This study focused on the influence of concomitant anomalies, the individual surgical approach, and the probability for reinterventions. METHODS: Between 1975 and 1999, 94 patients with interrupted aortic arch were evaluated for short- and long-term results after surgical treatment. RESULTS: Interrupted aortic arch was associated mainly with a ventricular septal defect (85%) and left ventricular outflow tract obstruction (LVOTO, 13%). Mean follow-up was 6.7 years (median 6.9 years, 628.4 patient years). A single-stage operation was performed in 76 cases. Early mortality for two-stage procedures was 37% and late mortality was 26%, compared with single-stage procedures, with an early mortality of 12% and a late mortality of 20%, respectively. Early mortality in patients with additional LVOTO was 42% and late mortality was 50%. Freedom from reoperation at 5 years was 62%, and at 10 years was 49%. Reinterventions were performed mainly for residual arch stenosis, also with bronchus or tracheal compression, or LVOTO. CONCLUSIONS: Arch continuity and repair of associated anomalies can be achieved with an acceptable overall risk in this often complex entity. Associated anomalies play an important role in the outcome. Single-stage repair with primary anastomosis of the arch should be the surgical goal. The long-term probability for reoperation is high.

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.

Effect on coronary artery flow reserve and resistance in the remote area after acute coronary artery occlusion in the pig model.

BACKGROUND: It has been reported that vasodilator function in remote myocardial regions supplied by "angiographically normal" coronary arteries is impaired in patients after acute myocardial infarction (MI). The aim of this study was to determine whether coronary artery flow reserve and coronary artery resistance in remote, nonischemic areas are also altered in experimental MI. METHODS: Experiments were performed in anesthetized pigs. In group 1 infarction was induced by ligation of the left-anterior descending artery (LAD); group 2 consisted of sham-operated animals. Hemodynamic parameters, coronary artery resistance, and myocardial blood flow (MBF) were measured before and 4 hours after MI under rest and during infusion of adenosine. RESULTS: Coronary artery dilation by adenosine caused a similar increase in MBF before and 4 hours after coronary artery occlusion. Resting MBF after acute MI was not altered, although a significant reduction (15%; P < .04) in mean aortic pressure was observed compared with baseline. Coronary artery resistance was significantly reduced by adenosine (P < .04) before MI, as well as at 4 hours after MI (P < .03). Coronary artery flow reserve was not adversely affected. The sham-operated animals showed similar results without any significant differences between the two study groups. CONCLUSION: This study indicates that an acute MI in pigs did not increase coronary artery resistance in the remote area after MI and therefore did not adversely affect coronary artery flow reserve in the nonischemic vascular bed. Further studies are necessary to fully understand the exact mechanism of the alterations in remote flow reserve of patients after MI.

Prevalence and clinical outcome of hepatitis C infection in children who underwent cardiac surgery before the implementation of blood-donor screening.

BACKGROUND AND METHODS: There are few data on the prevalence and clinical outcome of hepatitis C infection in children. We studied 458 children who underwent cardiac surgery in Munich, Germany, before 1991, when blood-donor screening for hepatitis C was introduced in Germany. Their mean age at first operation was 2.8 years; none of the children had received blood transfusions before or 'after cardiac surgery, and none of their mothers had antibodies to the hepatitis C virus (anti-HCV). We compared these patients with 458 control subjects matched for age and sex. RESULTS: Sixty-seven (14.6 percent) of the 458 patients who had undergone cardiac surgery had anti-HCV, as compared with 3 (0.7 percent) of the control subjects (P<0.001). At a mean interval of 19.8 years after the first operation, 37 (55 percent) of the 67 patients who were positive for anti-HCV had detectable HCV RNA in their blood. The infection had cleared in the other 30 patients, as evidenced by negative results on three polymerase-chain-reaction analyses performed at six-month intervals. Only 1 of the 37 patients who were positive for HCV RNA had elevated levels of liver enzymes; that patient had severe right-sided congestive heart failure. Of the 17 patients who underwent liver biopsies, only 3 had histologic signs of progressive liver damage. These three patients had additional risk factors: two had congestive heart failure, and the third had also been infected with hepatitis B virus. CONCLUSIONS: Children who had undergone cardiac surgery in Germany before the implementation of blood-donor screening for hepatitis C had a substantial risk of acquiring the infection. However, after about 20 years, the virus had spontaneously cleared in many patients. The clinical course in those still infected seems more benign than would be expected in people infected as adults.

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.

Influence of combined zero-balanced and modified ultrafiltration on the systemic inflammatory response during coronary artery bypass grafting.

OBJECTIVE: To evaluate whether combined zero-balanced and modified ultrafiltration affects the systemic inflammatory response in coronary artery bypass graft (CABG) patients. DESIGN: Randomized and controlled. SETTING: University-affiliated heart center. PARTICIPANTS: Forty-three patients scheduled for elective CABG. INTERVENTIONS: In the ultrafiltration group (UF group; n = 21), zero-balanced ultrafiltration was performed during rewarming and modified ultrafiltration immediately after the end of cardiopulmonary bypass (CPB). A control group of patients (n = 22) was treated identically to the treatment group except no ultrafiltration process was performed. MEASUREMENTS AND MAIN RESULTS: Immediately after CPB (ie, after zero-balanced ultrafiltration), and again after the modified ultrafiltration, the concentrations of interleukin-6 and interleukin-8 were significantly less (p < 0.05) in the UF group compared with the control group. Both proinflammatory cytokine levels peaked at 2 and 4 hours after CPB, at which time no difference between the two groups could be observed. The levels of measured anti-inflammatory mediators (interleukin-10 and interleukin-1 receptor antagonist) did not show any difference between the two groups. Intrapulmonary shunt fraction decreased in the course of the modified ultrafiltration from 31% +/- 1.2% to 25% +/- 1.3% (p < 0.01), whereas mean arterial pressure increased (69 +/- 1.8 to 80 +/- 2.8 mmHg; p < 0.01); neither parameter changed in the control group. Time to extubation was shorter in the UF group (6.1 +/- 0.5 v 8.6 +/- 0.7 hours; p < 0.05). CONCLUSION: It was concluded that the use of ultrafiltration diminished inflammatory response in a very limited time period immediately after CPB and, probably as a consequence, slightly improved clinical parameters.

Role of protein kinase C in signal attenuation following T cell receptor engagement.

T lymphocyte activation through stimulation of the T cell receptor complex and co-stimulatory receptors is associated with acute tyrosine phosphorylation of intracellular proteins, which in turn mediate downstream signaling events that regulate interleukin-2 expression and cell proliferation. The extent of protein tyrosine phosphorylation is rapidly attenuated after only 1-2 min of stimulation as a means of tightly controlling the initial signaling response. Here we show that this attenuation of tyrosine phosphorylation of Shc, CrkL, and the proto-oncogene Cbl is mimicked by treatment of mouse T lymphocytes or cultured Jurkat cells with phorbol 12-myristate 13-acetate. This effect is blocked by the specific protein kinase C inhibitor GF109203X, but not by PD98059, an inhibitor of MEK1/2 kinase. Activation of protein kinase C by phorbol ester also causes rapid (t(1)/(2) = 2 min) dissociation of both CrkL and p85/phosphoinositide 3-kinase from Cbl concomitant with Cbl tyrosine dephosphorylation. More important, GF109203X treatment of Jurkat cells prior to T cell receptor stimulation by anti-CD3/CD4 antibodies results in an enhanced (2-fold) peak of Cbl phosphorylation compared with that observed in control cells. Furthermore, the rate of attenuation of both Cbl tyrosine phosphorylation and its association with CrkL following stimulation with anti-CD3/CD4 antibodies is much slower in Jurkat cells treated with GF109203X. Taken together, these data provide strong evidence that one or more isoforms of phorbol ester-responsive protein kinase C play a key role in a feedback mechanism that attenuates tyrosine phosphorylation of proteins and reverses formation of signaling complexes in response to T cell receptor activation.