Endothelial dysfunction following coronary artery bypass grafting : Influence of patient and procedural factors.

BACKGROUND: Angiopoietin-2 (Angpt2) mediates endothelial dysfunction (ED) following coronary artery bypass grafting (CABG). Its triggers are, however, poorly understood. METHODS: We examined the time course of ED beyond the early phase of postoperative recovery in 75 patients following CABG with a special focus on different cardiopulmonary bypass (CPB) modes as potential triggers of Angpt2 release. RESULTS: Nine patients (12.0%) underwent off-pump coronary artery bypass (OPCAB), 31 patients (41.3%) received minimized extracorporeal circulation (MECC), and 35 patients (46.6%) were operated on with (conventional) CPB. Angpt2 levels steadily increased across the observation period (1.7 [1.4-2.1] to 3.4 [2.5-6.1] ng/ml, p < 0.001). Angpt2 levels did not differ between the MECC and CPB groups (p = 0.564). There was no difference between MECC and CPB patients regarding net fluid balance (p = 0.821) and other surrogate markers of postoperative ED. The magnitude of Angpt-2 increase correlated more strongly with baseline C­reactive protein (r = 0.459, p < 0.001) than with any other parameter. Hospital length of stay correlated more strongly with baseline Angpt2 levels (r = 0.512, p = 0.005) than with follow-up Angpt2 levels and appeared not to be influenced by CPB mode (p = 0.428). CONCLUSION: CABG is associated with prolonged ED, which is determined by the patient's preoperative inflammatory state rather than by CPB modifications.

Predictive value of ScvO2 monitoring for pericardial tamponade after cardiac surgery.

BACKGROUND: We examined the predictive value of central venous oxygen saturation (ScvO2) changes regarding the occurrence of pericardial tamponade following cardiac surgery. METHODS: We retrospectively identified 66 consecutive patients in whom ScvO2 and arterial lactate levels were analyzed during an 8­h time interval preceding pericardiotomy due to pericardial tamponade (PT), and at equivalent time points in 30 control patients (C) who had an uncomplicated course. RESULTS: The median age of the patients was 74 years (interquartile range, 63-78). Three percent of procedures were re-operations. There were no differences between the baseline values of PT and C patients. Pericardiotomy was performed on average 1 day (0-3.5) after cardiac surgery. PT patients displayed a significant decline (p < 0.001) to lower ScvO2 levels (p < 0.001) and a significant increase (p = 0.005) to higher arterial lactate levels (p = 0.019) during the 8 h preceding pericardiotomy, whereas C patients did not (p = 0.440 and p = 0.279, respectively). PT was associated with a longer hospital stay (p = 0.04) and a higher in-hospital mortality (p = 0.008). An ScvO2 decline below 60% (p = 0.018), a delta ScvO2 decline greater than 5% (p = 0.001), and a delta lactate increase greater than 0.18 mmol/l (p = 0.002) during the 8 h preceding pericardiotomy were independently associated with PT. None of these parameters predicted in-hospital mortality. CONCLUSION: Deteriorations in ScvO2 might serve as an early marker of PT following cardiac surgery.

Protective regulation of the ACE2/ACE gene expression by estrogen in human atrial tissue from elderly men.

Data from animal experiments and clinical investigations suggest that components of the renin-angiotensin system are markedly affected by sex hormones. However, whether estrogen affects human atrial myocardium has not been investigated yet. In this study, we determined the effects of estrogen on key components of atrial renin-angiotensin system: angiotensin-converting enzyme, responsible for generation of angiotensin II and angiotensin-converting enzyme 2, counteracting majority of AngII effects, and different renin-angiotensin system receptors, AT1R, AT2R, and MAS. First, the expression levels of estrogen receptors mRNA were determined in right atrial appendages obtained from patients undergoing heart surgery. The amounts of estrogen receptor α and estrogen receptor ß mRNA were similar between women ( n = 14) and men ( n = 10). Atrial tissue slices (350 µm) were prepared from male donors which were exposed to estrogen (1-100 nM; n = 21) or stimulated at 4 Hz for 24 h in the presence or absence of 100 nM estrogen ( n = 16), respectively. The administration of estrogen did not change mRNA levels of estrogen receptors, but activated MAP kinases, Erk1/2. Furthermore, estrogen increased the amounts of angiotensin-converting enzyme 2-mRNA (1.89 ± 0.23; P < 0.05) but reduced that of angiotensin-converting enzyme-mRNA (0.78 ± 0.07, P < 0.05). In addition, the transcript levels of AT2R and MAS were upregulated by estrogen. Pacing of tissue slices significantly increased the angiotensin-converting enzyme/angiotensin-converting enzyme 2 ratio at both the mRNA and protein level. During pacing, administration of estrogen substantially lowered the angiotensin-converting enzyme/angiotensin-converting enzyme 2 ratio at the transcript (0.92 ± 0.21 vs. 2.12 ± 0.27 at 4 Hz) and protein level (0.94 ± 0.20 vs. 2.14 ± 0.3 at 4 Hz). Moreover, estrogen elicited anti-inflammatory and anti-oxidative effects on renin-angiotensin system-associated downstream effectors such as pro-oxidative LOX-1 and pro-inflammatory ICAM-1. An antagonist of estrogen receptor α reversed these anti-inflammatory and anti-oxidative effects of estrogen significantly. Overall, our results demonstrated that estrogen modifies the local renin-angiotensin system homeostasis and achieves protective effects in atrial myocardium from elderly men. Impact statement The present study demonstrates that estrogen affects the human atrial myocardium and mediates protective actions through estrogen receptors-(ER) dependent signaling. Estrogen substantially modulates the local RAS via downregulation of ACE and simultaneous upregulation of ACE2, AT2R and MAS expression levels. This is indicative of a shift of the classical RAS/ACE axis to the alternative, protective RAS/ACE2 axis. In support of this view, estrogen attenuated the expression of RAS-associated downstream effectors, LOX-1, and ICAM-1. A specific antagonist of ERα reversed the anti-inflammatory and anti-oxidative effects of estrogen in paced and non-paced atrial tissue slices. In summary, our data demonstrate the existence of protective effects of estrogen in atrial tissue from elderly men which are at least in part, mediated by the regulation of local RAS homeostasis.

Does pulsatile perfusion improve outcome after cardiac surgery? A propensity-matched analysis of 1959 patients.

OBJECTIVE: We analyzed the influence of pulsatile perfusion on recovery after coronary bypass grafting (CABG) or aortic valve replacement (AVR). PATIENTS AND METHODS: Between January 2008 and December 2010, 1959 consecutive patients underwent CABG, AVR, or both. The choice for pulsatile perfusion (PP, n=220) or non-pulsatile perfusion (NPP, n=1739) was made by the surgeon. Patient propensity score to receive PP or NPP was calculated according to 15 preoperative variables. Resulting propensity scores, logistic EuroSCORE, perfusion type and surgeon were analyzed to evaluate their role for mortality, length of postoperative ICU and hospital stay (LOHS), transfusion requirements and renal function. Risk stratified non-parametric univariate analyses and propensity adjusted multivariate analyses were performed. RESULTS: EuroSCORE and hospital mortality did not differ significantly between PP and NPP. EuroSCORE was the best predictive factor for all examined variables (p<0.001). PP was superior concerning LOHS (p=0.019) and this benefit increased with higher logistic EuroSCORE. The surgeon significantly influenced ventilation time, ICU stay and transfusion requirements. CONCLUSION: Pulsatile perfusion did not influence perioperative outcome parameters, renal function and mortality, but resulted in shorter hospital stay, especially in critically ill patients.

Simultaneous mitral valve replacement and liver transplantation.

We report the case of a 57-year-old man who underwent successful simultaneous surgery involving mitral valve replacement for acute endocarditis and orthotopic liver transplantation for end-stage liver disease.

Beneficial effects of modern perfusion concepts in aortic valve and aortic root surgery.

Minimized perfusion circuits (MPC) were found to reduce side effects of standard extracorporeal circulation (ECC). We evaluated the safety and efficacy of the ROCsafe MPC for aortic valve and aortic root surgery. One hundred and seventy patients were randomized for surgery using either MPC [n = 85, 30 female/55 male, mean age: 69.8 +/- 11.8 years; aortic valve replacement (AVR): n = 40; AVR + coronary artery bypass graft (CABG): n = 31; David operation: n = 3; aortic root replacement (ARR): n = 11] or ECC [n = 85, 29 female/56 male, mean age: 67.7 +/- 9.5 years; AVR: n = 39; AVR+CABG: n = 35, David operation: n = 2; ARR: n = 9]. Neurological status, length of ICU stay, C-reactive protein (CRP), blood count, transfusion requirements and bleeding volume were analyzed. The MPC system provided ultrasound-controlled de-airing. A small roller pump and a flexible reservoir were used for left ventricular venting. As a control, we used a standard ECC with cardiotomy suction and hard-shell reservoir. Cross-clamp time (MPC: 76.5 +/- 29.5; ECC: 79.0 +/- 34.0 min) and bypass time (MPC: 103.0 +/- 37.9; ECC: 106.9 +/- 44.9 min) were comparable between groups. Transfusion requirements (red blood cells: MPC: 1.5 +/- 1.5 vs. ECC: 2.2 +/- 2.1 units [p = 0.05], frozen plasma: MPC: 1.2 +/- 1.8 vs. ECC: 1.9 +/- 2.4 units [p = 0.03]), postoperative bleeding (MPC: 521 +/- 283 vs. ECC: 615 +/- 326 ml/24 h, p = 0.09) were lower using MPC. ICU stay was shorter with MPC (1.6 +/- 1.6 days) compared to ECC (2.4 +/- 2.8 days, p = 0.001). One stroke occurred in each group. The ROCsafe MPC provides safe circulatory support for a wide range of aortic valve surgeries. Transfusion requirements, postoperative bleeding and length of ICU stay were markedly reduced compared to standard extracorporeal perfusion.

[Vacuum assisted closure for the treatment of sternal wound infections -- rapid infection control and bridging to reconstructive surgery]. / Vakuumtherapie bei sternaler Wundinfektion -- Initiale Therapie zur Infektkontrolle und Uberbrückung zur plastisch chirurgischen Rekonstruktion.

Vacuum Assisted Closure (V.A.C.) is a sound strategy to control severe post-sternotomy infection. Secondary re-wiring of the sternal bone or reconstructive surgery may be required later to achieve complete wound closure. Ten patients with severe sternal bone infection underwent initial V.A.C. therapy and delayed surgery for wound closure. Complete wound healing was achieved in all cases. As a case report we describe a patient with right-sided mastectomy and irradiation for breast cancer, who developed severe post-sternotomy infection and sternal bone necrosis following CABG. A combination of V.A.C. therapy and surgical reconstruction using a pedicled latissimus dorsi musculocutaneous flap led to complete wound closure.

[Vacuum assisted closure therapy improves early postoperative lung function in patients with large sternal wounds]. / Vakuumtherapie bei sternalen Wundinfektionen - Auswirkungen auf die frühpostoperative Lungenfunktion.

Vacuum assisted closure of sternal wounds is a sound strategy for patients with severe poststernotomy mediastinitis and sternal bone necrosis. As a bridging therapy to reconstructive surgery it provides an adequate temporary stabilization of the thorax. It enhances lung function and reduces pulmonary complications.

Homocysteine--a treatable risk factor for allograft vascular disease after heart transplantation?

Growing evidence suggests that elevated total plasma homocysteine (tHCY) levels are associated with cardiac allograft vasculopathy following heart transplantation. To assess the effect of folic acid supplementation on tHCY levels, we performed a prospective study in a cohort of 69 patients (7.0 +/- 3.2 years after heart transplantation; mean age, 55.0 +/- 9.6 years; 61 male) treated with 5 mg folic acid/day (n = 34) vs no medication (n = 35). Therapy with folic acid resulted in significantly decreased tHCY levels, from 22.6 +/- 9.6 micromol/liter to 17.3 +/- 5.5 micromol/liter (p = 0.001) within 3 months, whereas values in the control group remained unchanged. We conclude that folic acid supplementation (5 mg per day) provides a simple and effective measure to lower elevated tHCY levels in heart transplant recipients.

Systemic inflammatory response in cardiac allograft vasculopathy: high-sensitive C-reactive protein is associated with progressive luminal obstruction.

BACKGROUND: Response to immunologic and nonimmunologic injury has been reported to initiate the development of cardiac allograft vasculopathy (CAVD). Although histopathologic examinations reveal signs of focal inflammation, little is known about the systemic inflammatory response in this accelerated coronary syndrome. METHODS AND RESULTS: Therefore, we investigated high-sensitive C-reactive protein (CRP) in a large cohort of heart transplant (HTX) recipients (n=102, 90 male, mean age 45.2+/-11.5 years, 6.1+/-3.3 years after HTX) in correlation with a progression of luminal obstruction as assessed by serial coronary angiography (defined as an increase of focal stenosis >/=30% or detection of a new lesion) after a mean interval of 1.8+/-1.0 years. Patients with signs of an acute rejection or infection were excluded. In the entire group, CRP levels ranged from 0.2 to 12.7 mg/L (mean 2.6+/-2.7 mg/L). Patients with progressive CAVD (n=35) presented with significantly higher levels of CRP (4.1+/-3.3 mg/L) than did those with a nonprogressive course (n=67) (1.8+/-1.9 mg/L, P:=0.001). These observations were independent of the initial indication for HTX (atherosclerotic disorder versus cardiomyopathy, P:=0.18) and the severity of CAVD at baseline examination (P:=0.12). CONCLUSIONS: Progressive cardiac allograft vasculopathy is accompanied by a systemic inflammatory reaction, which gives further insight into the pathogenesis of this coronary syndrome and may well serve as an indicator for patients at risk.

Improved right ventricular function after intracoronary administration of a C1 esterase inhibitor in a right heart transplantation model.

OBJECTIVE: Myocardial injury from ischemia can be augmented after reperfusion due to proinflammatory events including complement activation, leukocyte adhesion, and release of various chemical mediators. It has been shown that intracoronary administration of a C1 esterase inhibitor (C1 INH) significantly reduces myocardial necrosis in an experimental model of ischemia. Our study addresses the question whether the most susceptible region of the heart for ischemic injury, the right ventricle (RV), can benefit from the protective effects of C1 esterase inhibition after transplantation. METHODS: To precisely control RV volume in vivo an isovolumic model was used in which the RV volume was regulated using an intracavity high compliance balloon inserted into donor hearts of domestic pigs (34+/-4 kg). After 4 h of ischemia, donor hearts were transplanted into recipient pigs (44+/-4 kg). Treatment groups, each with six animals, consisted of C1 INH treatment or control. After opening the cross clamp, the C1 INH group animals received 20 IU/kg body weight of C1 INH intracoronary over a 5 min period. The control animals received no drug therapy. The hearts were reperfused for 60 min, and thereafter the RV balloon volume was increased in 10 ml increments until RV failure occurred. These measurements were repeated after 120 min of reperfusion. RESULTS: There was no significant difference in maximal RV developed pressure between the two groups (after 1 h, 35.7+/-5.9 vs. 40.6+/-12.7 mm Hg; after 2 h, 41.5+/-10.7 vs. 46.3+/-15.2 mm Hg; for C1 INH and control animals, respectively). However, the RV could be loaded with a significantly higher volume after both 1 h (60.0+/-20.0 ml (C1 INH) vs. 46.7+/-13.7 ml (control) balloon volume, P<0.05), and 2 h of reperfusion (70.0+/-8.9 ml vs. 60.0+/-6.3 ml; C1 INH and control animals, respectively; P<0.05). CONCLUSIONS: Intracoronary administration of a C1 INH significantly improves right ventricular function in an experimental transplant model. Thus, inhibition of the classic complement cascade may be a promising therapeutic approach for effective protection of myocardium from reperfusion injury after transplantation.

[Therapy of acute heart failure--surgical possibilities]. / Therapie des akuten Herzversagens--Chirurgische Möglichkeiten.

Acute heart failure represents a severe complication of several cardiac disorders. Coronary artery disease, acute bacterial endocarditis or acute decompensation of preexisting heart valve disease as well as endstage cardiomyopathies are the most frequent underlying causes. Because of the high mortality, surgical therapy should be always considered in addition to medical treatment. However, any therapeutical intervention must be based on an immediate diagnosis to evaluate type and severity of the disease. Surgical options comprise coronary revascularization, valve replacement or--reconstruction as well as a temporary support by means of mechanical assist devices.

Expression and activity of mitogen activated protein kinases in human colorectal carcinoma.

BACKGROUND: Mitogen activated protein kinases (MAPKs) play a central role in the regulation of both cell growth and differentiation. They are involved in signal transduction of oncogenes and growth factors. The role of MAPK in colonic carcinoma is unknown. AIMS: To establish whether the expression and activity of p42/44 MAPKs are altered in colorectal tumours as compared with normal mucosa. METHODS: The expression and activity of p42/p44 MAPK were investigated in 22 colorectal carcinomas, four adenomas, and the corresponding normal colorectal mucosa by the use of western blotting, immunoprecipitation, and in vitro kinase assays. RESULTS: After immunoprecipitation with an antibody specific for p42 MAPK, we found significant inactivation of p42 MAPK in colonic carcinomas as well as in adenomas, whereas most sample pairs showed only minor differences in p42 MAPK expression. Investigation of MAPK with an antibody capable of detecting both p42 and p44 MAPK showed a slight but significant decrease in p44 MAPK content in malignant tissues. With this antibody, only minor alterations in MAPK activity and no correlation with p42 MAPK activity were found. CONCLUSIONS: Inactivation of p42 MAPK could be associated with colonic carcinogenesis.

A new minimally invasive approach to the subclavian artery.

Aneurysms of the subclavian artery are rare. We report a case in which an aneurysm of the right subclavian artery presented as localized atrophy of the deltoid muscle. Operative repair was accomplished by a new minimally invasive surgical approach.