The Extracellular Matrix Signature in Vein Graft Disease.

BACKGROUND: Vein graft disease is a major and yet unsolved problem in cardiac revascularization surgery. Although accumulation of extracellular matrix is characteristic for vein graft disease, detailed analysis of the fibrotic material is lacking. Because alterations of collagen cross-links are typical for organ fibrosis, we performed a comprehensive analysis of collagen and elastin in vein graft disease. METHODS: Collagen, elastin, and their respective cross-links were analyzed using histology and amino acid analysis. The expression of collagen-modifying enzymes was analyzed using SYBR Green quantitative real-time polymerase chain reaction. Fibrillin expression was analyzed by immunohistochemistry and quantitative real-time polymerase chain reaction. RESULTS: Diseased vein grafts showed a marked increase of collagen and of intermediate collagen cross-links, which are markers for newly synthesized collagen. Furthermore, we identified in vein graft disease increased levels of mature hydroxylysine aldehyde-derived cross-links typical for skeletal tissues. This was accompanied by upregulation of lysyl hydroxylase 2 and lysyl oxidase expression. Furthermore, vein graft disease showed a reduction of the elastin/collagen ratio, using elastin cross-links as a marker of elastin content, which was accompanied by an increase of fibrillin-1. CONCLUSIONS: Vein graft disease was accompanied by marked alterations in the composition of the extracellular matrix. The altered collagen cross-link pattern and the reduced elastin/collagen ratio might synergistically increase the stiffness in diseased vein grafts. Furthermore, hydroxylysine aldehyde-derived cross-links can cause a decreased degradability of collagens by matrix-metalloproteinases. Our data suggest collagen cross-links as a therapeutic target in vein graft disease.

Sodium-hydrogen exchange inhibition by cariporide to reduce the risk of ischemic cardiac events in patients undergoing coronary artery bypass grafting: results of the EXPEDITION study.

BACKGROUND: The EXPEDITION study addressed the efficacy and safety of inhibiting the sodium hydrogen exchanger isoform-1 (NHE-1) by cariporide in the prevention of death or myocardial infarction (MI) in patients undergoing coronary artery bypass graft surgery. The premise was that inhibition of NHE-1 limits intracellcular Na accumulation and thereby limits Na/Ca-exchanger-mediated calcium overload to reduce infarct size. METHODS: High-risk coronary artery bypass graft surgery patients (n = 5,761) were randomly allocated to receive either intravenous cariporide (180 mg in a 1-hour preoperative loading dose, then 40 mg per hour over 24 hours and 20 mg per hour over the subsequent 24 hours) or placebo. The primary composite endpoint of death or MI was assessed at 5 days, and patients were followed for as long as 6 months. RESULTS: At 5 days, the incidence of death or MI was reduced from 20.3% in the placebo group to 16.6% in the treatment group (p = 0.0002). Paradoxically, MI alone declined from 18.9% in the placebo group to 14.4% in the treatment group (p = 0.000005), while mortality alone increased from 1.5% in the placebo group to 2.2% with cariporide (p = 0.02). The increase in mortality was associated with an increase in cerebrovascular events. Unlike the salutary effects that were maintained at 6 months, the difference in mortality at 6 months was not significant. CONCLUSIONS: The EXPEDITION study is the first phase III myocardial protection trial in which the primary endpoint was achieved and proof of concept demonstrated. As a result of increased mortality associated with an increase in cerebrovascular events, it is unlikely that cariporide will be used clinically. The findings suggest that sodium hydrogen exchanger isoform-1 inhibition holds promise for a new class of drugs that could significantly reduce myocardial injury associated with ischemia-reperfusion injury.

Posttraumatic and postoperative cardiac luxation: computed tomography findings in nine patients.

BACKGROUND: Posttraumatic and postoperative cardiac luxation represents a serious complication of pericardial rupture, and early diagnosis is important. The purpose of this study is to determine signs of left cardiac luxation on computed tomography (CT). METHODS: CT scans in nine patients with pericardial rupture and cardiac luxation after blunt chest trauma (n = 7) and postoperatively after extended left pneumectomy (n = 2) were reviewed for abnormalities. We analyzed the clinical history, clinical findings, and the imaging findings. RESULTS: Dislocation of the heart to the left and pneumopericardium were seen in nine patients. Five of these nine patients revealed "entrapment" of the left heart between the proximal ascending aorta and the descending aorta. All patients underwent a pneumopericardium. All patients with a history of trauma showed a left-sided pneumothorax but no pericardial effusion. CONCLUSIONS: CT plays a key role for early diagnosis of cardiac luxation. Dislodgment of the heart, entrapment of the left atrium and ventricle, and pneumopericardium associated with pneumothorax are the most important CT findings.

Cardiac surgery in patients on dialysis: decreased 30-day mortality, unchanged overall survival.

BACKGROUND: The risk of cardiac surgery in dialysis-dependent patients is high, but little is known about the determinants of survival. We initiated a retrospective multicenter study to overcome this limitation. METHODS: Nine centers provided data on 522 patients (70% male, aged 61 +/- 11 years) who had chronic dialysis-dependent renal failure. A 14-year period was covered. Most patients had coronary artery bypass grafting, either with (n = 103) or without (n = 326) valve surgery. Multivariable analysis of survival was explored using Cox models. RESULTS: The proportion of patients with diabetes mellitus increased significantly (from 17%, 1989 to 1993, to 32%, 2000 to 2003; p = 0.021) and was independently associated with 30-day mortality (odds ratio = 3.30, p = 0.001) The mean 30-day mortality was 12% (n = 60), but declined significantly during the study period (from 28%, 1989 to 1993, to 7%, 2000 to 2003; p = 0.003). The 5-year survival probability was 42% (95% confidence interval: 36% to 47%). Patients who had renal transplantation during follow-up (n = 17) had the best survival probability (hazard ratio [HR] = 0.14, p = 0.007). Sinus rhythm (HR = 0.48, p < 0.001) and use of internal thoracic artery grafts (HR = 0.67, p = 0.006) proved beneficial for long-term survival. Predictors of death during long-term follow-up were emergency surgery (HR = 2.25, p = 0.001), diabetes mellitus (HR = 1.46, p = 0.020), number of allogenic transfusions (HR = 1.03/unit, p = 0.015), and age (HR = 1.04/year, p < 0.001). CONCLUSIONS: In dialysis-dependent patients, cardiac surgery has become significantly safer in recent years, but the overall prognosis of the patients remains poor. The observed improvements in the perioperative survival do not necessarily translate into an improved long-term prognosis. Diabetes mellitus is an important independent risk factor for perioperative mortality and death during follow-up.

[Extraction of management information from the national quality assurance program]. / Gewinnung von Managementinformationen aus der externen vergleichenden Qualitätssicherung.

BACKGROUND: Starting with clinically motivated projects, the national quality assurance program has established a legislative obligatory framework. Annual feedback of results is an important means of quality control. MATERIAL AND METHODS: The annual reports cover quality-related information with high granularity. A synopsis for corporate management is missing, however. Therefore, the results of the University Clinics in Greifswald, Germany, have been analyzed and aggregated to support hospital management. RESULTS: Strengths were identified by the ranking of results within the state for each quality indicator, weaknesses by the comparison with national reference values. The assessment was aggregated per clinical discipline and per category (indication, process, and outcome). CONCLUSION: A composition of quality indicators was claimed multiple times. A coherent concept is still missing. The method presented establishes a plausible summary of strengths and weaknesses of a hospital from the point of view of the national quality assurance program. Nevertheless, further adaptation of the program is needed to better assist corporate management.

Significant damage of the conduction system during cardioplegic arrest is due to necrosis not apoptosis.

OBJECTIVES: Ventricular conduction disturbances following cardioplegic arrest remains a serious, yet unsolved problem. In the present study we examined whether myocardial conduction cells (MCC, Purkinje fibers) are more vulnerable to ischemia/reperfusion injury than working myocardial cells and whether the damage is due to necrosis or apoptosis. METHODS: Mini-pigs were subjected to 60 min of crystalloid (St Thomas; n = 15 group I) or blood (Buckberg; n = 6 group II) cardioplegic arrest followed by 3 h of reperfusion. Animals not subjected to either procedures served as controls (n = 5). Ventricular myocardial specimens were investigated by hematoxylin and eosin (HE) and periodic acid Schiff (PAS) staining and immunohistochemical labeling of apoptosis-associated proteins (Bax, Bcl-2, Caspase-3). DNA-breaks were visualized by in situ end labeling (terminal deoxynucleotidyl transferase dUTP-biotin nick-end labeling, TUNEL). Electron microscopy confirmed apoptosis or necrosis. RESULTS: MCC of control hearts intrinsically expressed Bax, Bcl-2, and Caspase-3 without signs of either apoptotic or necrotic damage. Subendocardial Purkinje fibers of groups I and II hearts exhibited focal damage, with reduced labeling of apoptosis-associated proteins, glycogen loss, karyopycnosis and increased eosinophilia (15/21 hearts). The majority of damaged MCC displayed nuclear TUNEL-positivity (2.8+/-2.5% of MCC), whereas the average TUNEL-rate of the adjacent working myocardium was low (<0.1%). Electron microscopy demonstrated ischemic changes in MCC consistent with cellular necrosis. CONCLUSIONS: Ischemia/reperfusion injury due to cardioplegic arrest inflicts significant damage on subendocardial MCC, but not on working myocardium. Ultrastructural and light-microscopic findings are consistent with coagulation necrosis, rather than apoptosis.

High incidence of sudden death late after anterior LV-aneurysm repair.

OBJECTIVES: Sudden death due to ventricular arrhythmias occurs frequently among patients with dilated cardiomyopathy and congestive heart failure (CHF). In patients with left ventricular (LV) aneurysms, LV-aneurysm repair (LVAR) reduces LV-size and ameliorates symptoms of CHF, but the incidence of late sudden death is unknown, especially after LVAR without concomitant anti-arrhythmic therapy. METHODS: Between June 1993 and June 1999, 147 patients (70% males; 62+/-9 years) with CHF (median: NYHA III) due to anterior LV-aneurysms underwent LVAR. None of the patients underwent anti-arrhythmic surgical procedures concomitant to LVAR. Ninety percent of the patients had additional myocardial revascularization. Hospital records and laevocardiograms were reviewed, and follow-up information was obtained. RESULTS: In-hospital mortality was 4.1% (n=6). The median follow-up was 3.7 years (0.1-73.4 months; overall 462 patient-years). At follow-up, the patients had significantly less symptoms than preoperatively (median: NYHA II, P<0.001). Nineteen patients had died (5-year survival rate 78%). Of these late deaths, 84% (n=16) were cardiac-related, among which sudden death was most frequent (n=7). Predictors of sudden death were a bypass graft to the right coronary artery (P=0.0100), ventricular tachyarrhythmias early postoperatively (P=0.0315), and cross-clamp time (P=0.0496). CONCLUSIONS: Although the survival and functional state of most patients were good after LVAR without concomitant anti-arrhythmic surgery, we observed a high incidence of late sudden death, which was-among others-significantly associated with postoperative ventricular tachyarrhythmias. To further improve outcomes, intra- and postoperative anti-arrhythmic therapy is advisable in patients undergoing LVAR.

Na /H+ exchange inhibitor cariporide: effects on respiratory dysfunction after cardiopulmonary bypass.

The purpose of the present study was to evaluate the potential of the Na+/H+ exchange inhibitor cariporide to protect the lung from injury after cardiopulmonary bypass (CPB). In a randomized placebo-controlled study, 16 pigs were subjected to CPB for 75 min. Administration of vehicle or cariporide (bolus 180 mg, 40 mg/hour) began 30 min pre-CPB and was continued throughout the protocol. The alveolo-arterial O2-gradient (AaDO2), the pulmonary shunt (Qs/Qt), the compliance (Cpl), haemodynamic variables and glycerol and water content in lung tissue were measured 10 min before and up to 180 min post-CPB. All animals in the control versus 75% in the cariporide group survived the experiment. At 5 and 60 min post-CPB, the mean AaDO2 and at 5, 60 and 180 min post-CPB, the mean pulmonary vascular resistance index were higher in the cariporide group (p < 0.05), respectively. More lung water accumulation was found in the cariporide group (p < 0.05). Mean Cpl decreased; the Qs/ Qt and glycerol in lung tissue increased without significant intergroup difference. In this model, the inhibitor of the Na+/H+ antiporter showed no protective effect on lung injury after CPB and might even have harmful effects on pulmonary vascular tone and function.

Diseased vein grafts express elevated inflammatory cytokine levels compared with atherosclerotic coronary arteries.

BACKGROUND: The pathologic modifications characterizing vein graft disease resemble those observed in native arteriosclerosis, but in accelerated form. Although both disorders are considered to be inflammatory diseases, it remains to be determined whether diseased vein grafts and atherosclerotic coronary arteries differentially express inflammatory mediators. Therefore, we examined whether differences in the expression of proinflammatory cytokines by these two distinct vascular pathologies favor the accelerated inflammation within diseased vein grafts. METHODS: The messengerRNA expression of various cytokines (interleukin-1 beta [IL-1 beta], IL-6, IL-8, tumor necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma]) was quantified using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in tissue samples of native saphenous veins (NSV, n = 5), diseased coronary arteries (CAD, n = 25), and diseased vein grafts (VG, n = 13). RESULTS: Native saphenous veins did not contain any detectable transcripts except for IFN-gamma. As expected, CAD was characterized by the expression of IL-1 beta, IL-6, IL-8, IFN-gamma, and TNF-alpha mRNA. Interestingly VG also expressed these mediators, but at markedly higher levels. Quantification by RT-PCR revealed that, compared with specimens from the CAD group, VG specimens contained 5.8 +/- 1.2 times, 286 +/- 22 times, and 29 +/- 7.3 times as many transcripts for the cytokines IL-1 beta, IL-6 and TNF-alpha, respectively, as well as 25 +/- 8.3 times more transcripts for the chemokine IL-8. In contrast, the expression of IFN-gamma transcripts did not differ among the groups. CONCLUSIONS: The elevated expression of proinflammatory cytokine transcripts supports the hypothesis that diseased vein grafts, compared with atherosclerotic coronary arteries, are characterized by enhanced inflammatory activity that might accelerate atherosclerotic modifications. This may implicate new therapeutic strategies for the prevention of vein graft disease.

Results of endoaneurysmorrhaphy: does the location of the aneurysm matter?

Endoaneurysmorrhaphy is mostly performed on anterior-septal left ventricular (LV) aneurysms. It may also be applied to posterior aneurysms, which is technically more challenging. Whether the surgical risk is the same, irrespective of the location of the aneurysm, has not been studied before. We reviewed our experience with 158 patients (62+/-9 years, 72% male) undergoing endoaneurysmorrhaphy. Eleven patients (7%) had posterior LV aneurysms. Perioperative mortality was 5.7%. Of all preoperative and surgical variables tested, the presence of a posterior LV aneurysm (p=0.017), concomitant mitral valve surgery (p=0.008) and duration of extracorporal circulation (p=0.001) were significantly associated with higher perioperative mortality. However, patients with posterior LV aneurysms had more severe heart failure (p=0.0061) and a higher LV end diastolic volume index (138+/-38 vs. 102+/-41 ml/kg body weight; p=0.040) than patients with antero-septal LV aneurysms. Further studies are needed to determine whether the location of the aneurysm is a risk factor for mortality irrespective of the clinical presentation.

Local generation of C-reactive protein in diseased coronary artery venous bypass grafts and normal vascular tissue.

BACKGROUND: Venous coronary artery bypass grafts (CABGs) are prone to accelerated atherosclerosis. In atherosclerotic diseases, serum C-reactive protein (CRP) levels have become an important diagnostic and prognostic marker. The origin of CRP in this setting remains to be elucidated. METHODS AND RESULTS: Monoclonal anti-CRP identified CRP expression in medial and intimal alpha-actin-positive smooth muscle cells (SMCs) of diseased CABGs with type V and VI lesions and also of native saphenous veins of atherosclerotic individuals. In addition, patent coronary arteries with type IV and V but not with type I through III lesions exhibited intense SMC staining for CRP. Calcified desobliterates of occluded coronary arteries with end-stage disease did not show SMC staining for CRP and were consistently negative for CRP mRNA, as detected by means of real-time polymerase chain reaction. However, CRP mRNA was expressed in 11 of 15 diseased CABGs and also in 10 of 15 native veins. By contrast, only 3 of 18 internal mammary and 4 of 12 radial arteries with virtually no atherosclerosis were positive for CRP mRNA. CONCLUSIONS: CRP is produced by SMCs of atherosclerotic lesions with active disease but not in end-stage plaques. The role of CRP constitutively expressed by normal vascular tissue in vein graft disease has yet to be elucidated.

Impact of sodium-hydrogen exchange inhibition by cariporide on death or myocardial infarction in high-risk CABG surgery patients: results of the CABG surgery cohort of the GUARDIAN study.

OBJECTIVES: To evaluate the effects of cariporide on all-cause mortality or myocardial infarction at 36 days in patients at risk of myocardial necrosis after coronary artery bypass graft surgery. METHODS: In the coronary artery bypass graft cohort of the GUARD During Ischemia Against Necrosis trial, patients > or =18 years who required urgent coronary artery bypass graft, repeat coronary artery bypass graft, or had a history of unstable angina and > or =2 risk factors (age >65 years, female gender, diabetes mellitus, ejection fraction <35%, or left main or 3-vessel disease) were randomized to placebo (n = 743) or cariporide 20 mg (n = 736), 80 mg (n = 705), or 120 mg (n = 734). A 1-hour intravenous infusion was initiated shortly before surgery and administered every 8 hours for 2 to 7 days. Patients were followed up for 6 months. A nonparametric covariance analysis was used to calculate the primary efficacy endpoint. RESULTS: Baseline characteristics were similar between treatment groups. The cariporide 20- and 80-mg groups had event rates similar to placebo. The endpoint of all-cause mortality or myocardial infarction at day 36 was significant with cariporide 120 mg versus placebo (event rate 12.2% vs 16.2%; P =.027). The risk reduction was evident on postoperative day 1 (3.3% vs 6.5%; P =.005) and was maintained at 6 months (event rate 15.0% vs 18.6%; P =.033). Cariporide was well tolerated, and most adverse events were mild and transient in this high-risk population. CONCLUSIONS: Clinical benefit with cariporide 120 mg was observed early after treatment initiation and continued for 6 months postsurgery, suggesting that sodium-hydrogen exchange inhibition with cariporide is cardioprotective in patients undergoing high-risk coronary artery bypass graft surgery.

Prophylactic gamma radiation of unaffected vein grafts failed to prevent vein graft disease in a chronic hypercholesterolemic porcine model.

OBJECTIVE: The value of prophylactic brachytherapy on vein graft disease is unknown. METHODS AND RESULTS: Vein bypass grafts in 23 hypercholesterolemic pigs after ex vivo gamma irradiation of the vein grafts (10, 20, and 40Gy) and 16 control veins were analyzed regarding: (1) expression of platelet-derived growth factor (PDGF-AA and -BB, ELISA); (2) smooth muscle cell (SMC) proliferation/cell death (double-immunohistochemistry Mib-1/TUNEL/SMC alpha-actin); and (3) vessel wall dimensions. Planimetric data on vessel wall dimensions revealed no positive effect of gamma radiation on neointima formation and inner lumen diameter. On the contrary, vein grafts subjected to 40Gy were significantly more likely to be occluded and to have reduced inner lumen and increased neointima formation. Radiation therapy had no effect on PDGF expression and SMC proliferation/cell death. The mean inner lumen diameter decreased as PDGF-AA expression increased. CONCLUSIONS: Prophylactic gamma radiation of unaffected vein grafts failed to prevent vein graft disease in a hypercholesterolemic porcine model. High-dose radiation (40Gy) resulted in more frequent graft occlusion and vein sclerosis.

A rise of MMP-2 and MMP-9 in bronchoalveolar lavage fluid is associated with acute lung injury after cardiopulmonary bypass in a swine model.

Postoperative acute lung injury (ALI) contributes to the morbidity and mortality following cardiopulmonary bypass (CPB). To determine whether the presence of matrix metalloproteinases (MMPs) is associated with ALI after CPB, MMP-2 and MMP-9 activities in bronchoalveolar lavage fluid (BALF) were compared with parameters indicating impaired gas exchange. In a prospective study, 17 minipigs were subjected to CPB for 60 min. Before and at five and 180 min after CPB, MMP-2 and MMP-9 were assayed in BALF and the arterial-alveolar gradient of oxygen tension (AaDO2), the pulmonary capillary wedge pressure (PCWP) and the water content of lung tissue samples (Wt) were evaluated and compared with baseline values. MMP-2 and MMP-9 increased significantly 5 minutes (2.1- and 6.2-fold, respectively) and 180 minutes (3.4- and 14.3-fold, respectively) post-CPB. AaDO2 and Wt, but not PCWP, increased significantly 180 minutes after CPB and only AaDO2, but not PCWP or Wt, was significantly correlated with MMP-2 (r = 0.66, p = 0.006) and MMP-9 (r = 0.62, p = 0.01). In conclusion, high levels of MMP-2 and MMP-9 in the pulmonary compartment are associated with ALI after CPB.

Low-energy cardioversion versus medical treatment for the termination of atrial fibrillation after CABG.

BACKGROUND: Atrial fibrillation (AF) is the most frequent complication after cardiac surgery and can cause considerable morbidity. Low-energy cardioversion (LEC) using biatrial epicardial wires implanted during surgery has been shown to be effective and safe in conscious patients, but has not been directly compared with medical treatment so far. We therefore prospectively studied the efficacy of LEC in men 60 years of age and older. METHODS: Sixteen patients (mean +/- SD, 66.4 +/- 5.4 years) were randomized to LEC and 32 patients (66.3 +/- 5.0 years) to standarized medical treatment in the event of postoperative AF. Age, comorbidity, and surgical variables did not differ significantly between the groups. RESULTS: After cardiac surgery, AF occurred in 6 patients (38%) assigned to LEC and in 11 patients assigned to medical treatment (34%; p = NS). Low-energy cardioversion restored sinus rhythm in all but 1 patient, and 1 patient in the LEC group had early recurrence of AF. All other patients in the LEC group had prompt and stable restoration of sinus rhythm. Medical treatment was associated with the restoration of sinus rhythm in all patients. Although the total time in AF was decreased significantly by LEC (median 5 minutes versus 22 hours; p = 0.037), the length of postoperative hospitalization was not (5.1 +/- 1.4 days for the LEC group compared with 5.3 +/- 1.6 days for controls). CONCLUSIONS: Low-energy cardioversion significantly decreased the amount of time cardiac surgery patients spent in AF after the operation. Larger studies are needed to determine whether this new treatment modality has the ability to decrease morbidity associated with postoperative AF and is cost-effective.

Histopathological grading of ascending aortic aneurysm: comparison of patients with bicuspid versus tricuspid aortic valve.

BACKGROUND AND AIMS OF THE STUDY: Bicuspid aortic valve (BAV) is a common inherited condition that is often accompanied by ascending aortic aneurysm. A high level of histological wall abnormalities was reported to be present in non-dilated aortas of patients with BAV. In patients with tricuspid aortic valve, there appears to exist a direct relationship between the diameter of the ascending aorta and degree of histopathological aortic wall abnormalities. Whether this situation exists in patients with BAV has not yet been investigated. METHODS: Surgical and medical records of all patients undergoing surgery of the ascending aorta were reviewed. A total of 65 patients was identified in whom an aortic wall specimen was obtained intraoperatively. These specimens were systematically re-evaluated, and graded according to the severity of seven histopathological conditions: fibrosis, atherosclerosis, medionecrosis, cystic medial necrosis, smooth muscle cell orientation, elastic fiber fragmentation, and inflammation. RESULTS: BAVs were present in 26 patients (40%). Patients with BAV had significantly less aortic wall alterations than patients with tricuspid aortic valves (p < 0.001) in all variables examined. The severity of aortic wall abnormalities was significantly dependent on aortic diameter in patients with BAV as well as tricuspid aortic valve (p = 0.036 and 0.019), but dependent on age (p = 0.009) only in patients with tricuspid aortic valve. CONCLUSION: The study results provide evidence that ascending aortic aneurysm in patients with BAV differs clinically and histologically from that in patients with tricuspid aortic valve. Further studies are needed to elucidate the impact of inherited and acquired aortic wall abnormalities on the development of aneurysms.

Is the kaolin or celite activated clotting time affected by tranexamic acid?

BACKGROUND: During cardiopulmonary bypass, the activated clotting time is frequently used for determination of anticoagulation, and either Celite or kaolin are used as activators. If aprotinin is administered concomitantly, the Celite activated clotting time (C-ACT) becomes significantly higher than the kaolin activated clotting time (K-ACT). Therefore, insufficient anticoagulation using C-ACT in the presence of aprotinin is a major concern. Whether the application of tranexamic acid (TA), a pharmacologic alternative to aprotinin, has similar effects has not been studied before. METHODS: An in vitro study using the blood of healthy volunteers was performed. Both C-ACT and K-ACT were measured at baseline, after adding TA, and after adding TA and heparin. In addition, 30 patients undergoing primary cardiac operations had simultaneous measurements of C-ACT and K-ACT after skin-incision, 5 minutes after the application of heparin and TA, every 30 minutes during cardiopulmonary bypass, and 10 minutes after the application of protamine. RESULTS: In vitro, C-ACT and K-ACT correlated significantly at each measurement. Tranexamic acid had no influence on the activated clotting time. In vivo, C-ACT and K-ACT did not differ significantly, but at each time C-ACT tended to be greater than K-ACT (p = 0.086). The average difference between K-ACT and C-ACT was stable before and after the application of TA (p = 0.85) but the variability of the differences significantly increased during cardiopulmonary bypass (p < 0.001). CONCLUSIONS: Application of TA does not seem to differentially affect the mean C-ACT and K-ACT. No recommendation seems warranted to prefer one activator over the other in patients receiving TA.

Cardiopulmonary bypass: Evidence or experience based?

OBJECTIVE: Evidence-based medicine is emerging as a new paradigm for medical practice. The purpose of this study was to evaluate the amount and quality of scientific evidence supporting principles that are currently applied for cardiopulmonary bypass performance. METHODS: A survey of all German departments of cardiac surgery regarding cardiopulmonary bypass performance disclosed major differences. Consequently, for 48 major principles of cardiopulmonary bypass performance, relevant Medical Subject Headings were identified, and a literature search of the Medline database was performed. Two sequentially applied sets of inclusion-exclusion criteria were selected to assess the best available evidence. RESULTS: Thirty-three thousand articles relating to the subject were identified. Among these, 1500 fulfilled the first set of inclusion criteria: meta-analysis of (randomized) controlled clinical trials and in vitro and animal studies. Rigorous methodological criteria were then applied to further select remaining publications. Ultimately, 225 articles referring to major cardiopulmonary bypass principles were identified as providing the best available evidence. These were graded according to their methodological rigor (susceptibility to bias). The scientific evidence on the investigated cardiopulmonary bypass principles did not prove to be of a high enough level to allow general recommendations to be made. CONCLUSIONS: The scientific data concerning the effectiveness and safety of key principles of cardiopulmonary bypass are insufficient in both amount and quality of scientific evidence to serve as a basis for practical, evidence-based guidelines.