U. Boeken

Acceleration of autologous in vivo recellularization of decellularized aortic conduits by fibronectin surface coating

Decellularization is a promising option to diminish immune and inflammatory response against donor grafts. In order to accelerate the autologous in vivo recellularization of aortic conduits for an enhanced biocompatibility, we tested fibronectin surface coating in a standardized rat implantation model. Detergent-decellularized rat aortic conduits (n = 36) were surface-coated with covalently Alexa488-labeled fibronectin (50 μg/ml, 24 h) and implanted into the systemic circulation of Wistar rats for up to 8 weeks (group FN; n = 18). Uncoated implants served as controls (group C; n = 18). Fibronectin-bound fluorescence on both surfaces of the aortic conduits was persistent for at least 8 weeks. Cellular repopulation was examined by histology and immunofluorescence (n = 24). Luminal endothelialization was significantly accelerated in group FN (p = 0.006 after 8 weeks), however, local myofibroblast hyperplasia with significantly increased ratio of intima-to-media thickness occurred (p = 0.0002 after 8 weeks). Originating from the adventitial surface, alpha-smooth muscle actin and desmin positive cell invasion into the media of fibronectin-coated conduits was significantly increased as compared to group C (p < 0.0001). In these medial areas, in situ zymography revealed enhanced matrix metalloproteinase activity. In both groups, inflammatory cell markers (CD3 and CD68) and signs of thrombosis proved negative. With regard to several markers of cell adhesion, inflammation and calcification, quantitative real-time PCR (n = 12) revealed no significant inter-group differences. Fibronectin surface coating of decellularized cardiovascular implants proved feasible and persistent for at least 8 weeks in the systemic circulation. Biofunctional protein coating accelerated the autologous in vivo endothelialization and induced a significantly increased medial recellularization. Therefore, this strategy may contribute to the improvement of current clinically applied bioprostheses.

Procalcitonin (PCT) in cardiac surgery: diagnostic value in systemic inflammatory response syndrome (SIRS), sepsis and after heart transplantation (HTX).

PURPOSE Since it is of great importance to distinguish between a systemic inflammatory response syndrome (SIRS) and an infection caused by microbes especially after heart transplantation (HTX), we examined patients following heart surgery by determining procalcitonin (PCT), because PCT is said to be secreted only in patients with microbial infections. METHODS Sixty patients undergoing coronary artery bypass grafting (CABG) and 14 patients after heart transplantation were included in this prospective study. In the CABG group we had 30 patients without any postoperative complications (group A). Furthermore we took samples of 30 patients who suffered postoperatively from a sepsis (group B, n=15) or a systemic inflammatory response syndrome (C, n=15). In addition we measured the PCT-levels in 65 blood samples of 14 patients after heart transplantation (Group I: rejection > IIa, II: viral infection (CMV), III: bacterial/fungal infection, IV: controls). RESULTS In all patients of group A the pre- and intraoperative PCT-values and the measurement at arrival on intensive care unit (ICU) were less than 0.2 ng/ml. On the second postoperative day the PCT-value was 0.33+/-0.15 ng/ml in the control group. At the same time it was 19.6+/-6.2 ng/ml in sepsis and 0.7+/-0.4 ng/ml in systemic inflammatory response syndrome patients (P<0.05). In transplanted patients we could find the following PCT-values: Gr.I: 0.18+/-0.06 II: 0.30+/-0.09 III: 1.63+/-1.16 IV: 0.21+/-0.09 ng/ml (P<0.05 comparing group III with I, II and IV). CONCLUSIONS These results show that extracorporeal circulation (ECC) and systemic inflammatory response syndrome do not initiate a PCT-secretion. Septic conditions cause a significant increase of PCT. In addition, PCT is a reliable indicator concerning the essential differentiation of bacterial or fungal--not viral--infection and rejection after heart transplantation.

Predictors and outcome of ICU readmission after cardiac surgery.

OBJECTIVE Readmission to the intensive care unit (ICU) after cardiac surgery is associated with higher costs and may be correlated with an increased mortality. We wanted to evaluate predictors of ICU readmission and to analyze the outcome of those patients. METHODS 3523 patients who underwent CABG and/or valve surgery between 2004 and 2007 were reviewed retrospectively. The reasons for readmission and the postoperative course were analyzed. Furthermore, perioperative risk factors for readmission were determined by multivariate regression analysis. RESULTS Of the 3374 patients discharged from the ICU, 5.9 % (198) of patients required a second stay in the intensive care (group r). The readmission rate was 4.8 % following CABG and 8.9 % following valve +/- CABG ( P < 0.05). The mean interval from ICU discharge to readmission was 3.3 +/- 6.2 days. Of the patients who were not readmitted, 1.3 % died in hospital, compared to 14.4 % in group r ( P < 0.05). After readmission, the mean length of stay in the ICU and in hospital was 7.1 +/- 5.9 and 21.3 +/- 11.1 days (3.1 +/- 1.2 and 13.1 +/- 5.1 days for all other patients [ P < 0.05]). Main reasons for readmission were respiratory failure (59 %), cardiovascular instability (25 %), renal failure (6.5 %), cardiac tamponade/bleeding (6 %), gastrointestinal complications (2 %) and sepsis (1.5 %). Multivariate logistic regression analysis revealed that preoperative renal failure, mechanical ventilation > 24 h, reexploration for bleeding and low cardiac output state were independent predictors for readmission. CONCLUSIONS Patients after valve/combined surgery are more likely to require readmission to the ICU. Respiratory complications were the most common reasons for readmission. To reduce the readmission rate, it is necessary to treat cardio-respiratory problems early, particularly in patients showing predictive risk factors.

Increased preoperative C-reactive protein (CRP)-values without signs of an infection and complicated course after cardiopulmonary bypass (CPB) – operations

OBJECTIVE C-Reactive protein (CRP) is known to be a sensitive indicator of infection. Since it is also involved in the acute phase reaction, it is of great interest, whether an isolated preoperative increase of CRP without further signs of infection is of any prognostic value for postoperative outcome after cardiac surgery with cardiopulmonary bypass (CPB), which itself is possibly causing a systemic inflammatory response syndrome (SIRS). METHODS Fifty patients with an isolated CRP-elevation (>5 mg/l) (from 6.2 to 93.3 mg/l) were operated using CPB (group A). A control group (group B) consisted of 50 cardiac surgery patients, matched in the patterns of age, gender and kind of disease. No preoperative CRP-elevation (from 0 to 4.8 mg/l) occurred in this group. RESULTS The postoperative course of both groups showed significant differences. Septic complications were seen more often in group A (20%) than in the controls (2%) (P < 0.01). Microbiology (blood culture, cultures from nose, tracheal aspirate and urine) was positive only in 10% of these patients. Catecholamine support (epinephrine, norepinephrine and/or doses of dopamine or dobutamine of more than 3 microg/kg per min) was needed in 26% of group A cases, whereas it was only needed in 10% of group B (P < 0.05). A significantly longer respiratory support was also necessary in patients with elevated CRP (25.2 +/- 6.4 h vs. 6.6 +/- 0.8 h) (P < 0.01). Furthermore there was a significant difference in the duration of intensive care (4.6 +/- 0.8 days vs. 2.6 +/- 0.3 days) (P < 0.05). CONCLUSIONS These data show that patients without apparent infection or inflammation, who had elevated CRP-values preoperatively, face an increased risk of septic complications after extracorporeal circulation. As microbiology tests are negative in most cases, it may be speculated that the majority of septic complications are due to a SIRS.

Heart-type fatty acid binding protein (hFABP) in the diagnosis of myocardial damage in coronary artery bypass grafting

OBJECTIVES Heart-type fatty acid binding protein (hFABP) is an intracellular molecule engaged in the transport of fatty acids through myocardial cytoplasm and has been used as a rapid marker of myocardial infarction. However, its value in the evaluation of perioperative myocardial injury has not yet been assessed. METHODS 32 consecutive patients undergoing coronary artery bypass grafting were included in a prospective, randomized study using standardized operative procedures and myocardial protection. Three patients with perioperative myocardial infarction were added. Serial blood samples were taken preoperatively, before ischemia, 5 and 60 min after declamping, 1 and 6 h postoperatively and on postoperative days 1, 2 and 10 and were tested for hFABP, creatine kinase isoenzyme MB (CKMB) and troponin I (TnI). RESULTS Hospital mortality was zero. The kinetics of the biochemical parameters revealed a typical pattern for each marker. In routine patients, hFABP levels peaked as early as 1 h after declamping, whereas CKMB and TnI peaked only 1 h after arrival in the intensive care unit. Patients with perioperative infarction displayed peak levels some hours later in all marker proteins. Peak serum levels of hFABP correlated significantly with peak levels of CKMB (r=0.436, P=0.011) and TnI (r=0.548, P=0.001), indicating the degree of myocardial damage. CONCLUSIONS hFABP is a rapid marker of perioperative myocardial damage and peaks earlier than CKMB or TnI. The kinetics of marker proteins in serial samples immediately after reperfusion is more suitable for the detection of perioperative myocardial infarction than a fixed cut-off level.

Intraaortic balloon pumping in patients with right ventricular insufficiency after cardiac surgery: parameters to predict failure of IABP Support.

BACKGROUND The indications for intra-aortic balloon pump (IABP) in the case of a failing right ventricle after operations with extracorporeal circulation (ECC) are still discussed controversially. We investigated the benefit of IABP in patients with a predominantly right ventricular dysfunction after ECC. Additionally, we wanted to identify early and easily available prognostic markers for outcome in all patients receiving IABP support. PATIENTS AND METHODS Between 1/2004 and 1/2008, 4550 patients underwent cardiac surgical procedures with ECC, 223 of whom (4.9 %) had an IABP inserted intra- or postoperatively (group 1). 79 of these patients were treated intraoperatively with IABP for early postoperative low cardiac output syndrome (LCOS) characterized by predominantly right ventricular failure (RV group). Clinical data and hemodynamic variables were recorded perioperatively. Multiple potential markers of mortality and postoperative complications were analyzed statistically, especially with regard to their predictive ability. RESULTS 68 % of all IABP patients were successfully weaned from IABP support and 63 % survived to hospital discharge. In the RV group, cardiac index (CI) and mean arterial pressure (MAP) increased (CI 1.8 +/- 0.2 to 2.8 +/- 0.2, MAP 53 +/- 10 to 73 +/- 8, P < 0.05) within 1 hour after IABP, whereas central venous pressure (CVP) and pulmonary artery wedge pressure (PAWP) decreased ( P < 0.05). 59 patients in the RV group (75 %) could be weaned from IABP successfully and 69 % survived to hospital discharge. Serum lactate of more than 11 mmol/L in the first 10 hours of IABP support predicted a 100 % mortality. A base deficit of more than 12 mmol/L, mean arterial pressure less than 55 mmHg, urine output of less than 50 ml/h for 2 hours, and dose of epinephrine or norepinephrine of more than 0.4 mg/kg/min were other highly predictive prognostic markers. Furthermore, multivariate analysis showed that patients with a left atrial pressure > 17 mmHg or a mixed venous saturation (SVO (2)) < 65 % had poor outcomes. CONCLUSIONS In patients with IABP support for postcardiotomy cardiogenic shock, elevated serum lactate, elevated base deficit, hypotension, oliguria and large vasopressor doses are all predictors of mortality. In these patients, the use of another mechanical assist device should be considered in good time. Our study additionally shows that LCOS caused by predominantly right ventricular failure - particularly after CABG - may be an additional indication for IABP.

Macrovascular and microvascular function after implantation of left ventricular assist devices in end-stage heart failure: Role of microparticles

BACKGROUND The hemodynamic vascular consequences of implanting left ventricular assist devices (LVADs) have not been studied in detail. We investigated the effect of LVAD implantation compared with heart transplant (HTx) on microvascular and macrovascular function in patients with end-stage heart failure and evaluated whether microparticles may play a role in LVAD-related endothelial dysfunction. METHODS Vascular function was assessed in patients with end-stage heart failure awaiting HTx, patients who had undergone implantation of a continuous-flow centrifugal LVAD, and patients who had already received a HTx. Macrovascular function was measured by flow-mediated vasodilation (FMD) using high-resolution ultrasound of the brachial artery. Microvascular function was assessed in the forearm during reactive hyperemia using laser Doppler perfusion imaging and pulsed wave Doppler. Age-matched patients without heart failure and without coronary artery disease (CAD) (healthy control subjects) and patients with stable CAD served as control subjects. Circulating red blood cell (CD253(+)), leukocyte (CD45(+)), platelet (CD31(+)/CD41(+)), and endothelial cell (CD31(+)/CD41(-), CD62e(+), CD144(+)) microparticles were determined by flow cytometry and free hemoglobin by enzyme-linked immunosorbent assay. RESULTS FMD and microvascular function were significantly impaired in patients with end-stage heart failure compared with healthy control subjects and patients with stable CAD. LVAD implantation led to recovery of microvascular function, but not FMD. In parallel, increased free hemoglobin was observed along with red and white cell microparticles and endothelial and platelet microparticles. This finding indicates destruction of blood cells with release of hemoglobin and activation of endothelial cells. HTx and LVAD implantation led to similar improvements in microvascular function. FMD increased and microparticle levels decreased in patients with HTx, whereas shear stress during reactive hyperemia was similar in patients with LVADs and patients with HTx. CONCLUSIONS Our data suggest that LVAD support leads to significant improvements in microvascular perfusion and hemodynamics. However, destruction of blood cells may contribute to residual endothelial dysfunction potentially by increasing nitric oxide scavenging capacity.

The Impact of Pre- and Postoperative Renal Dysfunction on Outcome of Patients Undergoing Coronary Artery Bypass Grafting (CABG)*

OBJECTIVE Acute changes in renal function after elective coronary bypass surgery represent a challenging clinical problem. In this study, we evaluated perioperative risk factors for the development of postoperative renal dysfunction (PRD), and the impact of such an event on the perioperative course. Additionally, we investigated the influence of preoperatively mildly increased serum creatinine on perioperative mortality and morbidity. METHODS We retrospectively analyzed data of 2511 patients undergoing isolated CABG between 2004 and 2007 with a preoperative serum creatinine < or = 2.2 mg/dL. There were 592 patients with a preoperative serum creatinine of between 1.4 and 2.2 mg/dl (mild renal dysfunction group) and 1919 patients with a serum creatinine < 1.4 mg/dl. Perioperative risk factors for PRD were analyzed by multivariate regression analysis. RESULTS Global in-hospital mortality was 3.1 %.The incidence of PRD was 6.2 %. Mortality for patients who had PRD was 7.8 vs. 2.9 % for patients who did not ( P < 0.05). PRD increased the length of hospital stay by 3.7 days (12.2 vs. 15.9; P < 0.05). Multivariate logistic regression identified the following variables as independent predictors of PRD: age, angina class III/IV, diabetes mellitus, prolonged cardiopulmonary bypass time, and preoperative serum creatinine. With regard to preoperative renal function, we found that operative mortality was higher in the mild renal dysfunction group (5.7 % vs. 2.5 %; P < 0.05). New dialysis/hemofiltration (5.1 % vs. 1.2 %; P < 0.05) and postoperative stroke (5.1 % vs. 1.6 %; P < 0.05) were also more common in these patients. CONCLUSIONS Mild renal dysfunction preoperatively is an important predictor of outcome after CABG. In these patients, PRD dramatically increases mortality, morbidity and length of hospital stay.

Vacuum-assisted wound closure is superior to primary rewiring in patients with deep sternal wound infection.

OBJECTIVE Deep sternal wound infections are serious complications after cardiac surgery. The aim of the present study is to compare the outcome after vacuum-assisted wound closure to that after primary rewiring with disinfectant irrigation. The study additionally focuses on defining predictors for the failure of primary rewiring and its impact on postoperative outcome. METHODS Retrospective analysis was performed in 5232 patients who underwent cardiac surgery with a median sternotomy. 192 patients postoperatively developed deep sternal wound infections and were distributed into 2 therapy groups: a vacuum-assisted wound closure (= VAC) group and a primary rewiring (= RW) group, which was subdivided into healing after rewiring (= RW-h) and failure of rewiring (= RW-f). These groups were compared statistically to reveal coincidental pre-, intra- and postoperative parameters. RESULTS Compared to the VAC group, the RW group showed a poorer outcome, although RW baseline characteristics were apparently beneficial. Primary rewiring failed in 45.8 % of all cases, which led to even worse outcomes. Important predictors for failure of primary rewiring were morbid obesity, diabetes mellitus type II, chronic obstructive pulmonary disease, preoperatively impaired left ventricular function, postoperatively positive blood and wound cultures, bilateral harvesting of internal thoracic arteries and the need for surgical reexploration. CONCLUSIONS In spite of patients being in a worse condition, vacuum-assisted wound closure therapy resulted in improved outcomes and thus should be preferred to primary rewiring. Moreover we report on predictors which may indicate whether there is a high risk of rewiring failure.

Early reintubation after cardiac operations: impact of nasal continuous positive airway pressure (nCPAP) and noninvasive positive pressure ventilation (NPPV).

BACKGROUND Due to an increasing number of comorbidities there is still a significant incidence of respiratory failure after primary postoperative extubation in patients who undergo cardiosurgery. We wanted to study whether nCPAP could improve pulmonary oxygen transfer and avoid the necessity for reintubation after cardiac surgery. Additionally, we compared this protocol to noninvasive positive pressure ventilation (NPPV). PATIENTS AND METHODS Over a period of 3 years we analyzed all patients who were extubated within 12 hours after cardiac surgery, and in whom pulmonary oxygen transfer (PaO₂/FIO₂) deteriorated without hypercapnia so that all these patients met predefined criteria for reintubation. There were three groups of patients: A = patients required immediate reintubation (n = 125); B = patients had nCPAP with intermittent mask CPAP (n = 264); and C = patients had NPPV (n = 36). RESULTS 25.8 % of patients in Group B and 22.2 % of patients in Group C were also intubated after a period of CPAP or NPPV. All other patients of Groups B and C could be weaned from these devices (B: 33.4 ± 5.8 hours, C: 26.2 ± 4.2 h; P < 0.05) and were well oxygenated using a face mask at ambient pressures (PaO₂/FIO₂: B: 136 ± 12, C: 141 ± 12). In Group A, we found a higher mortality (8.8 %) than in Group B (4.2 %) and Group C (5.6 %). The ICU stay and in-hospital stay were significantly prolonged in Group A. The incidence of pulmonary infections (A: 24 %, B: 10.6 %, C: 13.8 %; P < 0.05) and the need for catecholamines were significantly increased in Group A, whereas nCPAP patients suffered significantly more often from impaired sternal wound healing (A: 4.8 %, B: 8.3 %; P < 0.05). CONCLUSIONS We conclude that reintubation after cardiac operations should be avoided since nCPAP and NPPV are safe and effectively improve arterial oxygenation in the majority of patients with nonhypercapnic oxygenation failure. However, it is of great importance to pay special care to sternal wound complications in these patients.