Andreas Keyser

Ascending aortic aneurysm associated with bicuspid and tricuspid aortic valve: involvement and clinical relevance of smooth muscle cell apoptosis and expression of cell death-initiating proteins

OBJECTIVE There is relationship between a dilated ascending aorta and a bicuspid aortic valve. Controversy exists concerning techniques available for surgical restoration of the functional and anatomical integrity of the aortic root. The present study was undertaken to define the histopathologic and molecular biologic condition of ascending aortic aneurysms associated with bicuspid (BAV) or tricuspid aortic valve (TAV) and the relationship to valve sparing or pulmonary autograft procedures. METHODS Aortic aneurysm wall specimens from 20 patients (10 BAV; 10 TAV) undergoing elective repair and normal aortic tissues from organ donors (n=5) were analysed for patterns of smooth muscle cells (SMCs) and infiltrating leukocytes (immunohistochemistry), apoptosis (in situ end-labelling of DNA-fragments (TUNEL)), and expression of the death-promoting proteins perforin, Fas, and FasLigand (Immunoblotting). RESULTS Segments from aneurysms exhibited a distinct pattern of medial destruction, elastic fragmentation, and disorientation with rarefication of SMCs. BAV wall segments contained more cells bearing markers of apoptosis than TAV specimens whereas normal aorta displayed only few apoptotic cells (P<0.05). TUNEL showed higher levels of DNA fragmentation in BAV than in TAV, and double immunostaining identified SMCs as the principal cell type displaying fragmented DNA. Immunohistochemistry confirmed expression of death-promoting mediators by infiltrating lymphocytes, and Western blotting documented their presence in BAV and TAV aneurysmal tissue, with the greatest increases seen in specimens from aneurysms associated with BAV. CONCLUSIONS There is evidence for a molecular link between SMC apoptosis initiated by infiltration and local signal expression of immune cells and weakening of the aortic wall being more prevalent in patients with BAV. Our findings may suggest a mechanism responsible for aneurysm formation of the aorta and aortic dilatation after autograft root or sinus remodelling procedures.

Pumpless Extracorporeal Lung Assist: A 10-Year Institutional Experience

BACKGROUND Pumpless extracorporeal lung assist (PECLA) was developed to support pulmonary function in patients with severe respiratory insufficiency. METHODS Since 1996, 159 patients with an age ranging from 7 to 78 years were provided with a PECLA system. Fifteen patients were referred to us by air or ground transport after insertion of the system in a peripheral hospital. RESULTS Main underlying lung diseases were acute respiratory distress syndrome (70.4%) and pneumonia (28.3%). Pumpless extracorporeal lung assist lasted for 0.1 to 33 days, mean 7.0 +/- 6.2 days; cumulative experience was greater than 1,300 days. Successful weaning and survival to hospital discharge was achieved in 33.1% of patients after a mean PECLA support of 8.5 +/- 6.3 days. During PECLA therapy, 48.7% of patients died, mainly as a result of multiorgan failure after a mean interval of 4.8 +/- 5.1 days. Inability to stabilize pulmonary function was noted in 3% of patients only. After PECLA, 30-day mortality was 13.6%. In a subgroup analysis, best outcome was obtained in patients after trauma. CONCLUSIONS Pumpless extracorporeal lung assist is a simple and efficient method to support patients with deteriorating gas exchange for prolonged periods to allow the lung protective ventilation and transportation. Best indication for use of PECLA is severe hypercapnia and moderate hypoxia.

Venovenous extracorporeal membrane oxygenation for acute lung failure in adults

BACKGROUND Acute lung failure (ALF) is an increasing problem that can be treated with venovenous extracorporeal membrane oxygenation (vv-ECMO). This report summarizes prospectively collected data of an institutional experience with vv-ECMO. METHODS From January 2007 to December 2010, 176 patients (mean age, 48 ± 16; range, 14-78 years) with ALF refractory to conventional therapy were supported with vv-ECMO. The general indication for vv-ECMO was a partial oxygen pressure/fraction of inspired oxygen (Fio(2)) < 80 mm Hg under a Fio(2) of 1.0, a positive end-expiratory pressure of 18 cm H(2)O, and refractory respiratory acidosis (pH < 7.25), despite optimization of conservative therapy. RESULTS All patients underwent peripheral cannulation. In 59 cases, vv-ECMO was placed in another facility with ECMO transport by helicopter or ambulance. The mean vv-ECMO support interval was 12 ± 9.0 days (range, 1-67 days). During ECMO, 12 patients (7%) could be extubated and stepwise mobilized. Cannula-related complications during long-term support occurred in 14%, which was mostly minor bleeding. Overall survival was 56%: 58 patients (33%) died during mechanical support, and 20 (11%) died after weaning from the system. The best outcome was noted in trauma patients. Risk factors were mainly advanced age and multiorgan failure. CONCLUSION Modern vv-ECMO is an excellent treatment in patients with severe ALF and should be more liberally used.

Endothelial apoptosis is induced by serum of patients after cardiopulmonary bypass.

OBJECTIVE Increased serum levels of a multitude of mediators like interleukins, tumor necrosis factor, elastase, adhesion molecules, and endotoxin have been described following cardiopulmonary bypass (CPB). The biological consequences of this complex response are unclear. METHODS Serum samples of nine patients scheduled for elective coronary artery bypass grafting were obtained preoperatively and 1, 6, and 12 h after weaning from CPB. Additional serum samples were obtained perioperatively from four patients undergoing major lung resection and from four healthy volunteers. The apoptosis-inducing activity of serum samples on endothelial cells was examined using a tissue culture assay system. Endothelial cells were derived from human umbilical cords and incubated for 48 h with serum samples in various dilutions during their second passage. The culture plates were fixed with methanol/acetone and stained with the DNA dye diamidinophenylindole. Apoptotic and normal cells were identified and counted using phase contrast and fluorescence microscopy. RESULTS The proportion of apoptotic endothelial cells was 5.6-fold higher in culture plates incubated with diluted (30%) serum samples obtained at 6 h after weaning from CPB when compared to plates incubated with preoperative samples (P=0.0077). A smaller effect occurred already at 1 h in some patients, whereas at 12 h after weaning from CPB no increased endothelial apoptosis was observed. No proapoptotic activity was found in preoperative as well as in control samples from patients undergoing lung resection or from healthy volunteers. CONCLUSIONS Serum of patients after CPB exerts a strong apoptosis inducing activity on human endothelial cells. Apoptotic death of endothelial cells following CPB may be responsible for postoperative vascular and bypass dysfunction including phenomena like increased capillary permeability.

Minimal Extracorporeal Circulation : An Alternative for On-Pump and Off-Pump Coronary Revascularization

BACKGROUND Coronary artery bypass surgery employing minimal extracorporeal circulation (MECC) was compared with standard extracorporeal circulation (ECC) and off-pump coronary artery bypass graft surgery (OPCABG) with regard to the perioperative course. METHODS From January 2004 to December 2007, 1,674 patients (n = 558 MECC, n = 558 ECC, n = 558 OPCABG) who underwent coronary bypass surgery were studied. The primary end point was in-hospital mortality; secondary end points were perioperative variables, intensive care, and in-hospital course. RESULTS Demographic data, comorbidity, and the European System for Cardiac Operative Risk Evaluation score (MECC 3.0%, ECC 3.5%, OPCABG 3.2%) were similar among the groups, but in-hospital mortality for elective and urgent/emergent patients was lower in the MECC and OPCABG groups (MECC 3.2%, OPCABG 3.7%, ECC 6.9%; p < 0.05). The number of distal anastomoses was lowest in the OPCABG group, but comparable for MECC and ECC patients. Postoperative ventilation time, release of creatinine kinase, catecholamine therapy, drainage loss, and transfusion requirements were lower in the MECC and OPCABG groups, whereas stay in the intensive care unit was shorter only in the latter (p < 0.05). CONCLUSIONS Minimal extracorporeal circulation is an easy and safe procedure for coronary artery bypass graft surgery. In selected patients, the advantages of MECC equal those of OPCABG. MECC should be considered as an alternative to OPCABG and standard ECC procedures.

Continuously assessed right ventricular end-diastolic volume as a marker of cardiac preload and fluid responsiveness in mechanically ventilated cardiac surgical patients

IntroductionAssessing cardiac preload and fluid responsiveness accurately is important when attempting to avoid unnecessary volume replacement in the critically ill patient, which is associated with increased morbidity and mortality. The present clinical trial was designed to compare the reliability of continuous right ventricular end-diastolic volume (CEDV) index assessment based on rapid response thermistor technique, cardiac filling pressures (central venous pressure [CVP] and pulmonary capillary wedge pressure [PCWP]), and transesophageal echocardiographically derived evaluation of left ventricular end-diastolic area (LVEDA) index in predicting the hemodynamic response to volume replacement.MethodsWe studied 21 patients undergoing elective coronary artery bypass grafting. After induction of anesthesia, hemodynamic parameters were measured simultaneously before (T1) and 12 min after volume replacement (T2) by infusion of 6% hydroxyethyl starch 200/0.5 (7 ml/kg) at a rate of 1 ml/kg per min.ResultsThe volume-induced increase in thermodilution-derived stroke volume index (SVITD) was 10% or greater in 19 patients and under 10% in two. There was a significant correlation between changes in CEDV index and changes in SVITD (r2 = 0.55; P < 0.01), but there were no significant correlations between changes in CVP, PCWP and LVEDA index, and changes in SVITD. The only variable apparently indicating fluid responsiveness was LVEDA index, the baseline value of which was weakly correlated with percentage change in SVITD (r2 = 0.38; P < 0.01).ConclusionAn increased cardiac preload is more reliably reflected by CEDV index than by CVP, PCWP, or LVEDA index in this setting of preoperative cardiac surgery, but CEDV index did not reflect fluid responsiveness. The response of SVITD following fluid administration was better predicted by LVEDA index than by CEDV index, CVP, or PCWP.

Late reoperations after repaired acute type A aortic dissection

OBJECTIVE Late complications can develop in patients after surgery for aortic type A dissection, mandating redo surgery on the ascending aorta and arch. METHODS From 2006 to 2010, 23 patients (aged 41-69 years) who had late complications related to previous aortic surgery for acute type A dissection underwent redo surgery. Initial surgery included ascending aorta replacement in all cases. RESULTS The main indications for reoperation were progressive enlargement of the false lumen of the aortic arch or descending aorta and suture line dehiscence in 10 patients each. All patients with progressive aneurysm formation in nonresected aortic segments had persistent dissection within the aortic arch since initial surgery. Suture line dehiscence led to a localized hematoma in most cases. Three patients presented with graft infection and extensive perigraft hematoma. The average time interval from the initial repair to the redo procedure was 71±56 months. Exchange of the formerly implanted Dacron graft in the ascending aorta was the most frequently used surgical procedure. Implantation of a valved conduit was deemed necessary in 4 cases, and isolated aortic valve replacement was necessary in 2 cases. A hybrid stent graft was used in 6 patients. All patients survived surgery, and 1 patient died of postoperative low output cardiac failure in hospital. Only 1 major stroke was noted. CONCLUSIONS Complex reoperations for repaired acute type A dissection can be performed safely. The concern for the reoperative risk should not dictate the operative strategy during the initial procedure in acute type A dissection.

Disseminated Cladophialophora bantiana infection in a heart transplant recipient

Cerebral phaeohyphomycosis caused by Cladophialophora bantiana, a dematiaceous fungus, is a rare disease. The majority of cases have been reported among immunocompetent patients; only 4 cases have been published that describe transplantation patients. The overall prognosis is poor. Surgical therapy in combination with chemotherapy with itraconazole is recommended. We report the case of a heart transplant recipient with cutaneous, cerebral, and lung manifestation of Cladophialophora bantiana who died despite surgical and systemic, high-dosage itraconazole treatment.

Giant coronary aneurysms exceeding 5 cm in size

Giant coronary artery aneurysms (gCAAs) with a diameter exceeding 5 cm are extremely rare. The pathomechanisms and therapeutical measures in such cases have been controversial topics of discussion. Twenty-seven patients with gCAAs exceeding 5 cm in size described in the literature were evaluated. A case with multiple gCAAs at our department was included in the analysis. Apart from atherosclerosis of all coronary arteries, a large (1.5 2.5 cm) left anterior descending coronary artery aneurysm (CAA) and a gCAA (10.6 9.2 cm) originating from the right coronary artery, the latter causing recurrent myocardial ischaemia with the occlusion of the peripheral right coronary artery and compressing the right cardiac cavities, were the pathological findings in our 43-year old male patient. gCAAs predominantly develop at the proximal right coronary artery. The majority of these aneurysms develop secondary to atherosclerotic lesions in young patients. We performed a successful surgical excision of the right gCAA, tightening of the left anterior descending artery aneurysm and concomitant coronary artery bypass grafting. A pathological examination confirmed advanced atherosclerosis. Microbiological examinations could find no signs of infectious causes. CAAs bear a significant risk of severe complications and have a high risk of mortality. A more aggressive surgical approach should be recommended.

Minimizing the risk of perioperative stroke by clampless off-pump bypass surgery: a retrospective observational analysis

ObjectivesStroke is a devastating complication after coronary artery bypass grafting, occurring in 1.4% to 4.3% of patients. A major cause of stroke is cerebral embolization of aortic atheromatous debris or calcified plaques. This report analyzes the incidence of stroke in patients treated according to the clampless concept, i.e. avoiding side-clamping of the aorta, by means of off-pump coronary artery bypass surgery (OPCAB) in combination with the HEARTSTRING device.MethodsDuring a period of 43 months (2005-2008), 412 consecutive patients were treated with the above-mentioned method by one single surgeon. A minimum of one proximal aortal anastomosis was performed in each patient. Altogether, 542 proximal anastomosis were applied, each created by means of the HEARTSTRING device.ResultsThe mean age of patients was 67+9.7 years, the predicted mortality 5.2% (logistic EuroSCORE) and the observed mortality 1.9%. Histories of preoperative neurological disorders or cerebrovascular diseases were documented in 15% of patients. The overall incidence of postoperative stroke was 0.48% in contrast to 1.3% according to the stroke risk score.ConclusionsIn accordance to previously published data, our results show that avoiding aortic side-clamping during OPCAB reduces postoperative stroke rates. The HEARTSTRING device is a safe option for creating proximal aortic anastomosis.