Different treatment options in chronic coronary artery disease: when is it the time for medical treatment, percutaneous coronary intervention or aortocoronary bypass surgery?

BACKGROUND: 3% to 4% of the population suffers from chronic coronary artery disease (CAD). Primary care physicians, internists, cardiologists, and cardiac surgeons are involved in their long-term care. This article presents a complementary care pathway that integrates two apparently competing treatment options, aortocoronary bypass surgery (ACB) and percutaneous coronary intervention (PCI). Together with lifestyle changes and medical therapy, these treatments reduce morbidity and mortality and improve quality of life. METHODS: This article was written by cardiac surgeons and cardiologists on the basis of the current treatment guidelines for coronary artery disease, a selective review of the literature (randomized, controlled trials and registry data), and a process of interdisciplinary consensus building. RESULTS AND CONCLUSIONS: Lifestyle changes can reduce cardiovascular risk factors, improve quality of life, and lower cardiovascular morbidity and mortality. They provide additional benefit over and above medical therapy and/or revascularization procedures and should be strongly recommended to all patients. Revascularization is not indicated for patients who are asymptomatic on medical therapy or who have only a small area of myocardial ischemia. With either PCI or ACB, the symptoms of angina pectoris can be markedly improved, or even eliminated. Both of these revascularization procedures should be accompanied by optimized medical treatment. Revascularization is indicated when the area of myocardial ischemia is large, whether or not symptomatic angina is present. ACB is the treatment of choice for 3-vessel disease and/or left main stenosis. For all other constellations of coronary findings, ACB and PCI are equally good therapeutic options. The treating physician should take the patient's expectations into account and present the short- and long-term benefits and drawbacks of each proposed treatment to the patient so that an informed decision can be made.

"Turnover proteome" of human atrial trabeculae.

Most of the biologically relevant data on cardiomyocytes are derived from isolated cells under conditions that are, to some extent, altered compared to the natural milieu of the functional heart. The handling procedure of the dissection, isolation, and short-term culturing induces changes in the cells such that the subsequently measured parameters (among others, the protein synthesis) reflect the actual experimental conduct rather than the intrinsic properties of these terminally differentiated cells. Although it is known that the protein synthetic machinery of isolated cardiomyocytes is operational and functional, the biosynthetic yield of human cardiomyocytes in the natural milieu of the trabeculae remains to be established, with a special emphasis to clarify whether the protein synthesis includes just a limited set of polypeptides or it encompasses all cellular constituents. Knowledge on this issue is a prerequisite for achieving further advances in our understanding of heart remodeling related to hypertrophy in particular, and for attempting interventions leading to repair of damaged heart in general. The experimental system of "organ bath" enables simultaneous registration of contractile forces of portions of cardiac muscle tissue (and other myocyte-containing tissues) and biosynthetic labeling of newly synthesized cellular constituents. The organ bath methodology was adapted for this project such as enabling to measure molecular changes in response to in vitro applied stimuli. Instead of Krebs-Henseleit-solution, as used in classical protocols of organ bath studies, we utilized cell culture media suitable to experimental conditions related to metabolic labeling. Proteome patterns established by performing two-dimensional gel electrophoresis of the extracts from biosynthetically labeled trabeculae revealed that cardiomyocytes synthesize the full spectrum of cellular proteins. Proteomic silver-stain readout was used to obtain samples for spot excisions, as material suitable for mass spectrometric analysis. Protein spots were identified both from the excised spots and also by matching with the in-house- and www-databases (Swiss-Prot/High-Performance Heart). From our findings that protein synthesis in terminally differentiated cardiomyocytes is not confined just to the synthesis of those structures needed for the post-mitotic house-keeping functions, we conclude that this model might serve as a valid experimental system to study and elucidate the effects of various pharmacological compounds under conditions where physiology (contractile forces) and biochemistry (protein synthesis) of intact human heart tissue are monitored simultaneously.

Proteomic alterations in heat shock protein 27 and identification of phosphoproteins in ascending aortic aneurysm associated with bicuspid and tricuspid aortic valve.

Whether or not there are molecular differences, at the intra- and extracellular level, between aortic dilatation in patients with bicuspid (BAV) and those with a tricuspid aortic valve (TAV) has remained controversial for years. We have performed 2-dimensional gel electrophoresis and mass spectrometry coupled with dephosphorylation and phosphostaining experiments to reveal and define protein alterations and the high abundant structural phosphoproteins in BAV compared to TAV aortic aneurysm samples. 2-D gel patterns showed a high correlation in protein expression between BAV and TAV specimens (n=10). Few proteins showed significant differences, among those a phosphorylated form of heat shock protein (HSP) 27 with significantly lower expression in BAV compared to TAV aortic samples (p=0.02). The phosphoprotein tracing revealed four different phosphoproteins including Rho GDP dissociation inhibitor 1, calponin 3, myosin regulatory light chain 2 and four differentially phosphorylated forms of HSP27. Levels of total HSP27 and dually phosphorylated HSP27 (S78/S82) were investigated in an extended patient cohort (n=15) using ELISA. Total HSP27 was significantly lower in BAV compared to TAV patients (p=0.03), with no correlation in levels of phospho-HSP27 (S78/S82) (p=0.4). Western blots analysis showed a trend towards lower levels of phospho-HSP27 (S78) in BAV patients (p=0.07). Immunohistochemical analysis revealed that differences in HSP27 occur in the cytoplasma of VSMC's and not extracellularly. Alterations in HSP27 may give early evidence for intracellular differences in aortic aneurysm of patients with BAV and TAV. Whether HSP27 and the defined phosphoproteins have a specific role in BAV associated aortic dilatation remains to be elucidated.

Proteomics of ascending aortic aneurysm with bicuspid or tricuspid aortic valve.

Bicuspid aortic valve is often associated with lesions of the ascending aorta, which differ histologically from those in tricuspid valve patients. We undertook proteomic analyses to assess differences at the proteome level. Aortic samples were collected from 20 patients undergoing aortic valve and/or ascending aortic replacement; 9 had a bicuspid valve: 5 with aortic aneurysm (diameter > 50 mm) and 4 without dilation; 11 had a tricuspid valve: 6 with aortic aneurysm and 5 without dilation. Patients with histologically proven connective tissue disorders were excluded. Samples were dissected, solubilized, and subjected to 2-dimensional gel electrophoresis. Gel patterns showed an average of 580 protein spots in samples from bicuspid valve patients, and 564 spots in those with tricuspid valves. Comparative analysis revealed a correlation coefficient of 0.93 for protein expression in the bicuspid valve group compared to the tricuspid group. Three protein spots were significantly over-expressed and 4 were significantly down-regulated in the bicuspid group compared to the tricuspid group. The lowest correlation in protein expression was between non-dilated aortic tissues. These differences between aortic tissues of bicuspid and tricuspid valve patients suggest that mechanisms of aortic dilation might differ, at least in part, between such patients.

Single-center outcome analysis of 1,161 patients with St. Jude medical and ATS open pivot mechanical heart valves.

BACKGROUND AND AIM OF THE STUDY: The clinical performance of mechanical heart valves and valve-related complications are important safety endpoints in patients after heart valve replacement. In this retrospective analysis, the mid- to long-term clinical outcomes of two similar bileaflet heart valves, routinely implanted at the authors' institution over an 11-year period, were compared. METHODS: Between January 1993 and December 2003, a total of 1,161 patients (758 males, 403 females) received either a St. Jude Medical (SJM) or ATS mechanical heart valve. Follow up was obtained via an in-house Quality Management Database, ascertained by telephone questionnaire of the patients and/or family physicians. Follow up was 98.9% complete; the median follow up was 4.6 years; total follow up was 5,624 patient-years (pt-yr). RESULTS: A total of 604 SJM and 601 ATS prostheses was implanted as isolated (n = 669) or combined (n = 492) procedures. The overall 30-day mortality for SJM and ATS was 4.1% and 3.4%, respectively (p = 0.45). Cumulative survival and freedom from valve-related mortality at 10 years for SJM and ATS valves were 66 +/- 3% versus 68 +/- 5% (p = 0.84) and 96 +/- 1% versus 97 +/- 1% (p = 0.36), respectively. No structural valve failure was encountered for both valve types. Freedom from overall valve-related complications at 10 years was 79 +/- 4% for SJM and 66 +/- 6% for ATS (p = 0.08). The linearized rates for valve-related adverse events for SJM and ATS valves, respectively, were: thromboembolism 0.9 and 1.1%/pt-yr; major bleeding requiring transfusion 0.3 and 0.5%/pt-yr; prosthetic endocarditis 0.03 and 0.1%/pt-yr; paravalvular leak 0.1 and 0.6%/pt-yr. CONCLUSION: On the basis of an 11-year experience, both bileaflet valves showed very good clinical results, with low incidences of adverse events during the mid-term outcome. Gender and/or concomitant coronary artery disease were not predictors for reduced life expectancy.

Intraindividual comparison of human radial and internal thoracic arteries in vitro and the effect of preoperative calcium blocker therapy.

The patency rate of radial artery (RA) conduits is considerably lower than that of internal thoracic artery (ITA) grafts and the evidence suggests that this is due to a clinically suspected higher incidence of vasospasm. The aim of this study was, therefore, to compare intraindividually the pharmacological reactivity of RA with that of ITA. Both RA and ITA were taken from the same patients and investigated in parallel. Changes in tone were monitored isometrically on ring preparations from both arteries in organ baths with modified Krebs-Henseleit solution containing 1.25 mm calcium chloride at 1 g passive preload. In intraindividual comparisons maximal receptor-mediated contractile responses to noradrenaline and endothelin-1 and endothelium-dependent acetylcholine-induced relaxant responses revealed no differences between both arteries. By contrast, depolarization-induced contractions to potassium chloride (KCl) appeared to be significantly higher in RA than in ITA. Further analysis, however, revealed that this difference was due to preoperative calcium entry blocker (Ca(2+)eB) therapy. Compared with control tissues, maximal responses to KCl were significantly attenuated in the ITA but unchanged in RA when arteries were obtained from patients with preoperative Ca(2+)eB therapy. The present results suggested that functional responses to pharmacological stimuli of both RA and ITA were quite similar. Preoperative Ca(2+)eB therapy, however, attenuated markedly responses to KCl of the ITA leaving those of RA unchanged. These results, demonstrating a lower sensitivity to Ca(2+)eB of RA, therefore suggested that in addition to Ca(2+)eB other classes of drug may be more effective at reducing the propensity of RA conduits to vasospasm.

Cancer/testis antigen expression and specific cytotoxic T lymphocyte responses in non small cell lung cancer.

Non small cell lung cancers (NSCLC) express cancer/testis antigens (CTA) genes and MAGE-A expression correlates with poor prognosis in squamous cell carcinomas. We addressed cytotoxic T lymphocytes (CTL) responses to HLA class I restricted CTA epitopes in TIL from NSCLC in an unselected group of 33 patients consecutively undergoing surgery. Expression of MAGE-A1, -A2, -A3, -A4, -A10, -A12 and NY-ESO-1 CTA genes was tested by quantitative RT-PCR. Monoclonal antibodies (MAb) recognizing MAGE-A and NY-ESO-1 CTA were used to detect CTA by immunohistochemistry. CD8(+) TIL obtained from tumors upon culture with anti CD3 and anti CD28 mAb and IL-2 were stimulated with autologous mature DC (mDC) and HLA-A*0101 restricted MAGE-A1(161-169) or MAGE-A3(168-176) peptides or HLA-A*0201 restricted MAGE-A4(230-239), MAGE-A10(254-262), NY-ESO-1(157-165) or multi-MAGE-A (YLEYRQVPV) peptides or a recombinant vaccinia virus (rVV) encoding MAGE-A and NY-ESO-1 HLA-A*0201 restricted epitopes and CD80 co-stimulatory molecule. Specificity was assessed by (51)Cr release and multimer staining. At least one CTA gene was expressed in tumors from 15/33 patients. In 10 specimens, at least 4 CTA genes were concomitantly expressed. These data were largely confirmed by immunohistochemistry. TIL were expanded from 26/33 specimens and CTA-specific CTL activity was detectable in 7/26 TIL. In 6, however, specific cytotoxicity was weak, (<40% lysis at a 50:1 E:T ratio) and multimer staining was undetectable. In one case, high (>60% lysis at 50:1 E:T ratio) MAGE-A10(254-262) specific, HLA-A*0201 restricted response was observed. Supportive evidence was provided by corresponding multimer staining. Although CTA genes are frequently expressed in NSCLC, detection of CTL reactivity against CTA epitopes in TIL from nonimmunized NSCLC patients represents a rare event.

Eleven-year single-center experience with the ATS Open Pivot Bileaflet heart valve.

BACKGROUND: The ATS Open Pivot Heart Valve was first introduced in 1992 and has been implanted routinely at our institution since 1993. Valve selection was based on surgeon preference. The objective of this study is to retrospectively analyze our 11-year clinical results with ATS prostheses. METHODS: Between January 1993 and December 2003, 601 ATS valves (393 aortic valve replacement [AVR], 168 mitral valve replacement [MVR], 20 aortic plus mitral valve replacement [DVR]) were implanted in 581 patients (377 male, 204 female; mean age, 63.7 years; range 18 to 89). Preoperatively, 47 (8%) were New York Heart Association class I, 212 (36.5%) were class II, 267 (46%) were class III, and 55 (9.5%) were class IV. Preoperative comorbidities were coronary artery disease, 167 (29%); diabetes mellitus, 72 (12%); cerebrovascular disease, 2 (0.3%); endocarditis, 53 (9%); and atrial fibrillation, 115 (20%). RESULTS: Follow-up is 99% complete. Data represent 2,500 cumulative patient-years. Mean follow-up is 4.3 +/- 2.6 years (range, 0.1 to 11.6). Overall hospital mortality is as follows: AVR, 3.8% (15 patients); MVR, 1.8% (3 patients); DVR, 10% (2 patients). Structural valve failure was not encountered. Overall survival at 10 years is AVR, 84.7% +/- 3.1%, AVR plus coronary artery bypass, 67.5% +/- 8.2%; MVR, 59.8% +/- 7.1%, MVR plus coronary artery bypass, 39% +/- 27.8%; and DVR, 74.3% +/- 10%. Freedom from valve-related death at 10 years is AVR, 99.2%; MVR, 94.6%; and DVR, 100%. Linearized rates for postoperative complications are paravalvular leak, 0.6% per patient-year; valve thrombosis, 0.04% per patient-year; thromboembolism, 1.1% per patient-year; major bleeding, 0.5% per patient-year; and de novo prosthesis endocarditis, 0.1% per patient-year. Postoperative mortality risk was significantly elevated by diabetes (p < 0.01), but not by other comorbidities. CONCLUSIONS: Our 11-year experience demonstrates low rates of adverse events and valve-related complications with the ATS Open Pivot heart valve.

Ischemia monitoring in off-pump coronary artery bypass surgery using intravascular near-infrared spectroscopy.

BACKGROUND: In off-pump coronary artery bypass surgery, manipulations on the beating heart can lead to transient interruptions of myocardial oxygen supply, which can generate an accumulation of oxygen-dependent metabolites in coronary venous blood. The objective of this study was to evaluate the reliability of intravascular near-infrared spectroscopy as a monitoring method to detect possible ischemic events in off-pump coronary artery bypass procedures. METHODS: In 15 elective patients undergoing off-pump myocardial revascularization, intravascular near-infrared spectroscopic analysis of coronary venous blood was performed. NIR signals were transferred through a fiberoptic catheter for signal emission and collection. For data analysis and processing, a miniature spectrophotometer with multivariate statistical package was used. Signal acquisition and analysis were performed before and after revascularization. Spectroscopic data were compared with hemodynamic parameters, electrocardiogram, transesophageal echocardiography and laboratory findings. RESULTS: A conversion to extracorporeal circulation was not necessary. The mean number of grafts per patient was 3.1 +/- 0.6. An intraoperative myocardial ischemia was not evident, as indicated by electrocardiogram and transesophageal echocardiography. Continuous spectroscopic analysis showed reproducible absorption spectra of coronary sinus blood. Due to uneventful intraoperative courses, clear ischemia-related changes could be detected in none of the patients. CONCLUSION: Our initial results show that intravascular near-infrared spectroscopy can reliably be used for an online intraoperative ischemia monitoring in off-pump coronary artery bypass surgery. However, the method has to be further evaluated and standardized to determine the role of spectroscopy in off-pump coronary artery bypass surgery.

Effects of on-pump versus off-pump coronary artery bypass graft surgery on right ventricular function.

OBJECTIVES: Right ventricular dysfunction is a possible cause of cardiac failure after coronary surgery. The use of cardiopulmonary bypass is regarded as a major cause for its occurrence, and it has been postulated that performing coronary surgery without cardiopulmonary bypass might reduce ventricular dysfunction. Therefore, this prospective, randomized, controlled study tested the hypothesis that off-pump coronary surgery would better preserve right ventricular systolic and diastolic function than conventional bypass surgery. METHODS: Fifty patients scheduled for elective coronary artery bypass surgery were randomly assigned to conventional or off-pump surgery. Right ventricular function was assessed by intraoperative transesophageal echocardiography immediately before and after coronary surgery. Right ventricular ejection fraction was used as a marker of global systolic function and tricuspid early/late (atrial) ratio as a marker of the global diastolic function. Peak systolic and early diastolic velocities of the lateral tricuspid annulus were studied to assess systolic and diastolic function in the area of the right ventricular free wall. RESULTS: Surgery was completed according to randomization in 48 of 50 patients. Preoperative characteristics were similar in both groups. Intraoperative differences between the two groups included a higher volume of allogeneic blood transfusion in the conventional surgery group. At the end of surgery, global systolic right ventricular function was similarly maintained and diastolic function similarly impaired in both groups. There were no significant intergroup differences in any of the echocardiographic markers of right ventricular function. CONCLUSIONS: Off-pump surgery did not better preserve right ventricular systolic and diastolic function than did conventional coronary surgery.

OPCAB surgery after right pneumonectomy.

Coronary artery bypass grafting was performed in a 58-year-old patient 3 years after right pneumonectomy for nonsmall cell lung cancer stage IIIa. The CT scan demonstrated a marked shift of the mediastinum into the right chest, but revealed a feasible access to the left coronary artery by median sternotomy. Pulmonary function was impaired. Off-pump coronary artery bypass grafting was performed to avoid cannulation under more difficult conditions and to prevent negative side effects of cardiopulmonary bypass to the pulmonary function. The postoperative recovery was uneventful. We discuss issues related to this special subgroup of patients.

Feasibility of intravascular near-infrared spectroscopy in off-pump myocardial revascularization.

OBJECTIVES: : The intravascular application of near-infrared spectroscopy was previously evaluated in acute ischemia-reperfusion studies in animal experiments. The objective of our study was to assess the technical feasibility and clinical reliability of an online myocardial ischemia monitoring by using intravascular near-infrared spectroscopy during off-pump coronary bypass surgery. METHODS: : Intravascular near-infrared spectroscopy of coronary sinus blood was performed in 10 elective patients selected for off-pump coronary bypass surgery. Light signals were transferred through a fiberoptic catheter for emission and collection from the coronary sinus blood. Spectrometric analyses were performed before and after revascularization with internal thoracic artery and saphenous vein grafts. Changes in spectroscopic data were compared with hemodynamic parameters and electrocardiographic, transesophageal echocardiographic, and laboratory findings. RESULTS: : All of the operations were finished as off-pump procedures. No remarkable intraoperative myocardial ischemia was observed in the patient group, as indicated by electrocardiography and transesophageal echocardiography. Reproducible absorption spectra of coronary sinus blood were obtained at every defined step of the surgical procedure. Clear ischemia-related changes were detected in none of the patients. CONCLUSIONS: : Our initial results showed that intravascular near-infrared spectroscopic ischemia monitoring is technically feasible. However, the method must be further evaluated and standardized under varying conditions to determine the role of near-infrared spectroscopy as an ischemia monitoring tool in off-pump coronary bypass surgery.

Freezing without surrounding cryomedium preserves the endothelium and its function in human internal mammary arteries.

PURPOSE: Cryopreserved human blood vessels may become important tools in bypass surgery. Optimal cryopreservation of an arterial graft should, therefore, preserve both histological and physiological characteristics of smooth muscle and endothelium comparable to the unfrozen artery. METHODS: Rings from human internal mammary arteries (IMA) were investigated in vitro either unfrozen or after immersion into a cryomedium (RPMI 1640 containing 1.8M Me2SO and 0.1M sucrose) and cryostorage with and without surrounding medium. RESULTS: In unfrozen IMA, neither contractile responses to noradrenaline (NA) nor endothelium-dependent relaxant responses to acetylcholine (ACH) was modified after exposure of the IMA to cryomedium or during activation of protein kinase C by phorbol-12,13-dibutyrate (PDBu). Exposure to cryomedium with gradually increasing Me2SO content before starting the cooling process did not improve the post-thaw functional activity of the artery. Optimal post-thaw recovery of contractile responses to NA and PGF(2alpha) was observed after freezing at a speed of -1.2 and -3 degrees C/min in arteries stored with and without surrounding cryomedium. Compared to unfrozen controls, the ACH-induced endothelium-dependent relaxation during active tone induced by 3 microM PGF(2alpha) reached 16 and 56% after freezing with and without surrounding medium. All functional data were reflected by electron microscopy images showing considerably better preservation of the endothelial layer after freezing without medium. CONCLUSION: Freezing of human arteries at a mean cooling rate of -3 degrees C/min and storage without surrounding medium offers the prospect of optimal preservation of both smooth muscle and endothelial function in cryopreserved human IMA.

Cortisol response in relation to the severity of stress and illness.

BACKGROUND: The aim of the study was to compare the adrenal response, the course of the ACTH/cortisol ratio, as well as the variance and the diagnostic performance of different cutoffs after 1 and 250 microg ACTH stimulation in different stress situations. METHODS: We investigated three groups with increasing stress levels: ambulatory controls (group A; n = 20), hospitalized medical patients (group B; n = 25), and patients undergoing coronary artery bypass grafting (group C; n = 29). All subjects underwent four consecutive ACTH stimulation tests and were randomized to either a 1- or 250-microg dose. RESULTS: Stimulated cortisol levels in group A were similar to basal cortisol levels under maximal stress (C3; P = 0.8). Peak cortisol concentrations were higher after 250 microg compared with 1 microg ACTH in group B (P = 0.006) and under maximal stress after extubation (group C3; P = 0.027), whereas there were no differences in group A. The ACTH/cortisol ratio was lower in surgical patients after extubation compared with unstressed conditions (P < or = 0.03) The within-subject variance was similar in ambulatory controls and medical patients and after both ACTH doses (all 17-36% of total variance). Cutoff dependent, the diagnosis of relative adrenal insufficiency would have been made in 0-58.3%, respectively. CONCLUSION: In moderate and major stress situations, cortisol concentrations in patients without hypothalamic-pituitary-adrenal disease were higher after stimulation with 250 microg compared with 1 mug ACTH. Data from our study give insight into the physiological adaptations of the hypothalamic-pituitary-adrenal axis to stress.

Surgical trauma affects the proinflammatory status after cardiac surgery to a higher degree than cardiopulmonary bypass.

OBJECTIVES: Cytokines contribute to the development of the systemic inflammatory response syndrome or multiple-organ failure frequently observed after cardiopulmonary bypass-supported cardiac surgery. To quantify the contribution of bypass-induced versus trauma-induced inflammatory response after coronary artery bypass grafting, we examined plasma cytokine levels in 120 patients with coronary artery disease who were treated with or without cardiopulmonary bypass-assisted procedures. METHODS: Patients were treated in accordance with one of the following protocols: (1) elective percutaneous coronary intervention without cardiopulmonary bypass (n = 69), (2) cardiopulmonary bypass-supported percutaneous coronary intervention (cardiopulmonary bypass-percutaneous coronary intervention; n = 10), and (3) cardiopulmonary bypass-supported coronary artery bypass grafting (cardiopulmonary bypass-coronary artery bypass grafting; n = 41). Cytokine levels (picograms/milliliter) were measured by enzyme-linked immunosorbent assay from plasma samples obtained at various time points. RESULTS: Interleukin-6 was measured in blood samples from all 3 patient populations. The maximum interleukin-6 level was 13.6 +/- 22.3 pg/mL in the percutaneous coronary intervention group, 170.4 +/- 165.4 pg/mL in the cardiopulmonary bypass-percutaneous coronary intervention group, and 640.3 +/- 285.7 pg/mL in the cardiopulmonary bypass-coronary artery bypass grafting group. Interleukin-6 levels were significantly different, and the 95% confidence intervals did not overlap. In the cardiopulmonary bypass-percutaneous coronary intervention group, bypass duration correlated well with interleukin-6 production ( r = 0.915; P < .001), whereas these parameters did not correlate in patients who underwent cardiopulmonary bypass-coronary artery bypass grafting ( r = 0.307; P = .054). CONCLUSIONS: These findings support the suggestion that surgical trauma and cardiopulmonary bypass contribute to the inflammatory response after cardiac surgery, although trauma may contribute to a higher degree.