Results with decellularized xenografts.
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Animals↗
Biomedical subjects
Wolfgang Konertz
Publications and source records attributed to Wolfgang Konertz.
Age-dependent chronic rejection after experimental heart transplantation.
BACKGROUND: The progressive decline of allograft function is predominantly a consequence of chronic rejection, but the etiology of this process is not fully understood. To evaluate the influence of age we performed heart transplantation in an experimental model of chronic rejection using inbred rats of different age. METHODS: Lewis rats served as donors and F344 rats were used as recipients. Young rats were 4 weeks of age, whereas adult rats were 4 months of age. Transplanted animals were grouped as follows: Group I, old to old; Group II, old to young; Group III, young to old; and Group IV, young to young. Intra-abdominal heterotopic heart transplantation was performed. Thereafter, functional evaluation was performed by daily palpation and surface electrocardiogram (ECG) to calculate the functional heart rejection index (fHRI). One month after transplantation the hearts were explanted and examined pathohistologically. RESULTS: Functional deterioration was noted in all groups, but all hearts were still beating when explanted. Young recipients and young donors showed significantly better results. Transplantation of young recipients led to a better fHRI (p < 0.001) and to a less critical chronic graft vasculopathy, especially when there was a young heart transplanted (p = 0.03). Furthermore, whenever a young donor heart was used, there was a better graft performance and less severe chronic rejection (p = 0.02). CONCLUSIONS: Experimental cardiac transplantation of young hearts leads to a better graft performance as well as to a lower incidence of a severe chronic graft disease. Thus, older donor age may adversely influence long-term performance of cardiac allografts.
Age Factors↗
WITHDRAWN: Protracted intensive care unit-stay >14 days in cardiac surgery: risk factors and long-term survival.
Ahead of Print article withdrawn by publisher.
Journal Article↗
Seeding human endothelial cells on complex three-dimensional scaffolds.
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Bioreactors↗
Prolonged intensive care unit stay in cardiac surgery: risk factors and long-term-survival.
BACKGROUND: Risk factors have been found for prolonged intensive care unit (ICU) stay in cardiac surgery patients in only a few studies; conflicting results have been described. The focus of this study was twofold: first, to evaluate preoperative, intraoperative, and postoperative risk factors for ICU stay greater than 3 days in a cardiac surgery patient population; second, to evaluate long-term survival in cardiac surgery patients with prolonged ICU stay. METHODS: Records from 2,683 cardiac surgery patients were retrospectively evaluated. Univariate and multivariate analyses for risk factors were performed for an ICU stay greater than 3 days. Thereafter, 2,563 patients were enrolled in a follow-up study for an observational time of 3 years after surgery. RESULTS: Mortality was dependent on renal, respiratory, and heart failure, as well as age, elevated APACHE II scores, and reexploration. Long-term survival analyses demonstrated a significantly lower survival in patients with longer ICU stay. However, the 6-month to 3-year long-term survival was comparable with survival in patients without prolonged ICU stay. CONCLUSIONS: Because of the increasing acuity of patients needing cardiac surgery, it is important to identify those at risk for a prolonged ICU course. It is therefore of paramount interest to implement measures throughout their entire hospital stay that would maximize organ function to improve survival and resource utilization.
APACHE↗
Decellularized xenogenic heart valves reveal remodeling and growth potential in vivo.
We have developed an advanced tissue processing technique on porcine pulmonary heart valves for pulmonary valve replacement and its initial clinical application during the autograft operation according to Ross. The novel concept consists of a cell-free matrix achieved by deoxycholic acid treatment that is repopulated by host cells in vivo. Molecular biology, radioligand binding, and electron microscopy consistently showed that these valves are almost free of cellular components. Animal experiments and clinical investigations revealed excellent hemodynamic properties of the valves, no need for antithrombotic therapy, and repopulation by host cells without any signs of calcification. In juvenile sheep the internal diameter of the implanted valves significantly increased in growing animals by approximately 10 mm. The repopulation of the decellularized heart valves was found not only in sheep but also in humans, which indicates that the underlying mechanisms, presumably repair mechanisms, might be common in mammals. If these findings can be confirmed by others, they will lead to new concepts in the field of cardiovascular tissue engineering that will eliminate the need for in vitro construction of autologous heart valves.
Animals↗
Three-year survival after four major post-cardiac operative complications.
OBJECTIVE: After cardiac surgery, major morbidities known to be primary contributors to perioperative mortality are cardiac failure, respiratory failure, renal failure, and the need for mediastinal exploration. The first aim of this study was to ascertain long-term survival in cardiac surgery patients with and without the occurrence of major morbidities to investigate if long-term survival was comparable. The second aim of this study was to evaluate the prevalences and risk factors related to the four major morbidities in this patient population. DESIGN: Retrospective observational outcome study. SETTING: Cardiothoracic intensive care unit at a university hospital. PATIENTS: We included 2,683 of 3,253 consecutive cardiac surgery patients cared for in a uniform fashion. METHODS AND MAIN RESULTS: Perioperative mortality was significantly increased by the occurrence of major morbidity. In-hospital mortality was 0.7% in the absence of major morbidity compared with 72% when all major morbidities occurred. Three-year mortality for the entire study population was 15%, whereas the 3-yr long-term survival was significantly less for patients with morbidities compared with those without. Various independent perioperative risk factors were found for perioperative major morbidity and mortality. CONCLUSIONS: Successful acute treatment and measures to identify and reduce the risk of major morbidities are necessary to improve outcome. In addition, long-term follow-up and management of morbidities are necessary to possibly improve long-term survival.
Acute Kidney Injury↗
Low-prime system minimizes transfusions and hemodilution in coronary bypass.
Standard heart-lung machines lead to substantial hemodilution with associated impaired organ function and increased need for blood transfusions. The aim of this study was to evaluate the effect of the new PRECiSe low prime volume system on perioperative myocardial damage, hemodilution, and transfusions. In a case-matched prospective study, 40 patients undergoing coronary artery bypass surgery using PRECiSe were compared with 40 patients on a standard heart-lung machine. In the PRECiSe group, the prime volume was significantly reduced, resulting in less hemodilution and transfusion requirements during and after extracorporeal circulation: only 10% of patients needed transfusions vs. 35% in the control group, with an average transfusion need of 0.16 vs. 1.25 units. There were no significant differences in perioperative cardiac-specific enzymes. The PRECiSe system was considered safe and effective for coronary artery bypass surgery.
Blood Loss, Surgical↗
Continuous suture technique for freedom stentless valve: reduced crossclamp time.
The Pericarbon Freedom stentless valve has shown excellent hemodynamics. A continuous suture technique at the inflow site may reduce cardiopulmonary bypass and crossclamp times and affect postoperative hemodynamics. In a prospective case-matched study, interrupted and continuous suture line techniques were used in 68 and 71 patients, respectively. Isolated valve replacement was performed in 70.4% of the continuous suture group and 67.6% of the interrupted suture group. Hemodynamic data were obtained by echocardiography (mean and peak gradients, regurgitation) at discharge and after 1 year. Overall mortality was 5.0% and due to non-valve-related causes. Bypass and crossclamp times were shorter by 22.4 and 20.6 min, respectively, in the continuous suture group. The suture technique at the inflow site did not result in significant differences in the mean (11.8 +/- 6.3 vs. 12.5 +/- 6.2 mm Hg) or peak gradients (21.0 +/- 9.6 vs. 22.0 +/- 10.9 mm Hg), or degree of regurgitation. Follow-up showed a further decrease in the gradients.
Aged↗
Levosimendan may improve survival in patients requiring mechanical assist devices for post-cardiotomy heart failure.
INTRODUCTION: Most case series suggest that less than half of the patients receiving a mechanical cardiac assist device as a bridge to recovery due to severe post-cardiotomy heart failure survive to hospital discharge. Levosimendan is the only inotropic substance known to improve medium term survival in patients suffering from severe heart failure. METHODS: This retrospective analysis covers our single centre experience. Between July 2000 and December 2004, 41 consecutive patients were treated for this complication. Of these, 38 patients are included in this retrospective analysis as 3 patients died in the operating room. Levosimendan was added to the treatment protocol for the last nine patients. RESULTS: Of 29 patients treated without levosimendan, 20 could be weaned off the device, 9 survived to intensive care unit discharge, 7 left hospital alive and 3 survived 180 days. All 9 patients treated with levosimendan could be weaned, 8 were discharged alive from ICU and hospital, and 7 lived 180 days after surgery (p < 0.002 for 180 day survival). Plasma lactate after explantation of the device was significantly lower (p = 0.002), as were epinephrine doses. Time spent on renal replacement therapy was significantly shorter (p = 0.023). CONCLUSION: Levosimendan seems to improve medium term survival in patients failing to wean off cardiopulmonary bypass and requiring cardiac assist devices as a bridge to recovery. This retrospective analysis justifies prospective randomised investigations of levosimendan in this group of patients.
Aged↗
Small-dose epoprostenol decreases systemic oxygen consumption and splanchnic oxygen extraction during normothermic cardiopulmonary bypass.
Normothermic, nonpulsatile cardiopulmonary bypass (CPB) impairs systemic and splanchnic oxygen transport and increases gastrointestinal permeability. It is an important therapeutic goal to avoid splanchnic dysoxia during CPB. Small-dose prostacyclin therapy improves splanchnic oxygen transport and microcirculation in septic patients. In this study, we sought to determine if during cardiac surgery, the prostacyclin analog epoprostenol improves the balance of systemic and splanchnic oxygen transport. Eighteen patients undergoing cardiac valve replacement were randomized to receive either epoprostenol (3 ng x kg(-1) x min(-1)) or placebo during, and for 1 hour after, surgery. Systemic and splanchnic oxygen delivery, consumption, and extraction and arterial, mixed venous, and hepato-venous lactate concentrations were measured before, during, and after CPB. Gastrointestinal permeability was measured 1 day before and 1 day after surgery using the triple sugar permeability test. During CPB, the epoprostenol group had decreased systemic oxygen consumption and splanchnic oxygen extraction (P = 0.024). These effects were not present 1 hour after the end of epoprostenol infusion. The study was not adequately powered to determine whether epoprostenol altered the trend towards increased lactate metabolism and increased postoperative gastrointestinal permeability, nor could we demonstrate any differences between groups in clinically relevant end-points. In conclusion, these findings suggest that during normothermic CPB, small-dose epoprostenol therapy may reduce systemic oxygen consumption and splanchnic oxygen extraction.
Aged↗
Clonidine attenuated early proinflammatory response in T-cell subsets after cardiac surgery.
T-cells play a central role in the immune response to injury. Cardiac surgery is associated with significant risk of systemic inflammatory response syndrome and subsequent unbalanced induction of proinflammatory cytokines. As clonidine has immunomodulating properties via reducing sympathetic activity, this study involved the analysis of T-cell function in the early postoperative period in patients undergoing coronary artery bypass graft surgery. Forty patients undergoing cardiac surgery were randomly allocated to one of the following groups: clonidine group (n = 20) [clonidine 1 microg kg(-1) h(-1)] and placebo group (n = 20). Study medication was started after induction of anesthesia and maintained until 6 h after surgery. Blood samples to determine Th1 and Th2 cells and cytotoxic lymphocytes (Tc1 and Tc2 cells) were drawn preoperatively, on admission to the intensive care unit, 6 and 12 h postoperatively as well as on the morning of days 1 and 2 after surgery. In the clonidine group significantly lower levels of Th1/Th2 ratios as well as Tc1/Tc2 ratios were found 6 h postoperatively compared to the placebo group (P < 0.05). Clonidine changed the ratio of T-lymphocyte subpopulations in peripheral blood in favor of a proinflammatory response, which might be favorable for maintaining immune balance after surgery.
Adrenergic alpha-Agonists↗
Preoperative oral carbohydrate administration to ASA III-IV patients undergoing elective cardiac surgery.
In this study we investigated the effects of preoperative oral carbohydrate administration on postoperative insulin resistance (PIR), gastric fluid volume, preoperative discomfort, and variables of organ dysfunction in ASA physical status III-IV patients undergoing elective cardiac surgery, including those with noninsulin-dependent Type-2 diabetes mellitus. Before surgery, 188 patients were randomized to receive a clear 12.5% carbohydrate drink (CHO), flavored water (placebo), or to fast overnight (control). CHO and placebo were treated in double-blind format and received 800 mL of the corresponding beverage in the evening and 400 mL 2 h before surgery. Patients were monitored from induction of general anesthesia until 24 h postoperatively. Exogenous insulin requirements to control blood glucose levels <or=10.0 mmol/L were used as a marker for PIR. Gastric fluid volume was measured by passive gastric reflux and preoperative discomfort using visual analog scales. Postoperative clinical and surgical data were recorded. Blood glucose levels and insulin requirements did not differ between groups. Patients receiving CHO and placebo were less thirsty compared with controls (P < 0.01 and P = 0.06, respectively). Ingested liquids did not cause increased gastric fluid volume or other adverse events. The CHO group required less intraoperative inotropic support after initiation of cardiopulmonary bypass weaning (P < 0.05). In conclusion, preoperative CHO administration before cardiac surgery does not affect PIR. Clear fluids reduce thirst and may be recommended as a safe procedure in ASA III-IV patients. Further research is indicated to investigate possible cardioprotective effects of preoperative CHO intake.
Administration, Oral↗
[Customer satisfaction with a quality management system according to DIN EN ISO 9001:2000: Increase in the satisfaction of cooperating clinics].
The evaluation of customers' satisfaction is elementary for any quality management system. In our university cardiac surgery unit that has been certified according to DIN EN ISO 9001:2000 the influence of repeated evaluation of the referring physicians' satisfaction conducted in the course of three consecutive years on structures and processes in the scope of the quality management system was examined. Customers' satisfaction with the possibility of access to the department could be increased by targeted interventions. Further interventions in the field of documentation led to a measurable increase in satisfaction with postoperative communication. Repeated annual evaluation of the satisfaction of referring physicians has proved to be a valuable tool in the process of continuous quality improvement.
Germany↗
Operative technique and early hemodynamic results with the Freedom Solo valve.
BACKGROUND AND AIM OF THE STUDY: Stentless aortic valve prostheses usually require two separate suture lines. The Freedom Solo valve (Sorin Group, Saluggia, Italy), by using a minimized implantation technique, requires only a single running suture line of 4-0 polypropylene. Herein are reported the surgical experience and early hemodynamic results obtained with this new valve. METHODS: Following annular decalcification, the Freedom Solo prosthesis was implanted in the supraannular aortic position in the sinuses of Valsalva of 82 patients (52 females, 30 males; mean age 76.6 +/- 7.0 years). Echocardiography was performed to monitor gradients and regurgitation. RESULTS: The logistic EuroSCORE was 12.8 +/- 9.9. Isolated aortic valve replacement was performed in 48 patients; concomitant procedures included coronary artery bypass grafting, mitral procedures, subvalvular myectomy, and atrial ablation. The mean valve size implanted was 26.4 +/- 2.1 mm, and cross-clamp time was 39.0 +/- 7.0 min in primary isolated valve replacement. Non-valve-related 30-day mortality was 3.6%. At discharge, hemodynamic parameters were favorable, with low peak (16.2 +/- 8.0 mmHg) and mean (8.3 +/- 4.5 mmHg) gradients, and without paravalvular leakage and only minimal regurgitation (grade < I degrees) in 10 patients. CONCLUSION: Supraannular implantation of the Freedom Solo stentless valve is safe and reliable, using a single suture line. The valve provides excellent hemodynamics at hospital discharge, without paravalvular leakage. The reduced cross-clamp time represents an attractive surgical alternative in elderly patients.
Aged↗
Histological evaluation of tissue-engineered heart valves implanted in the juvenile sheep model: is there a need for in-vitro seeding?
BACKGROUND AND AIM OF THE STUDY: A new-generation heart valve was developed to improve long-term durability. The study aim was to evaluate the need for in-vitro autologous endothelial cell seeding of a decellularized valve scaffold. METHODS: A seeded (group I, n = 6) or non-seeded (group II, n=6) decellularized valve was implanted into the right ventricular outflow tract of 12 juvenile sheep. In group I, a jugular vein was harvested to characterize and expand endothelial cells (ECs). The scaffold was seeded in vitro, using a sedimentation technique. In group II, non-seeded decellularized scaffolds were implanted and explantation was performed at three and six months. Valves were evaluated by echocardiography, gross pathology, X-radiography, histology, and immunohistochemistry. RESULTS: In group I, the EC seeding density was 1.06 +/- 0.01 x 10(5) cells/cm2, with a cell viability of 95.7 +/- 1.4%. No regurgitation was visualized by echocardiography. Gross pathology showed smooth leaflets without retraction; calcification was absent at X-radiography, and this was confirmed by von Kossa staining. Histologically, group I valves showed a persistence of ECs, whereas a monolayer of host ECs was seen at six months in group II valves. Host fibroblasts were available in both groups, and numbers increased over time. Differences were identified in the recellularization density of in-vitro-seeded and non-seeded valves for up to three months, but no such difference was seen after six months. CONCLUSION: Based on results of studies in a sheep model, there appears to be no need for in-vitro cell seeding of decellularized scaffolds.
Animals↗
Immunological and echocardiographic evaluation of decellularized versus cryopreserved allografts during the Ross operation.
OBJECTIVE: Compare the immunological and echocardiographic data of decellularized versus cryopreserved allografts used for RVOT reconstruction during Ross operation. METHODS: From 16/01/03 thru 07/10/03, 20 Ross operations were performed using decellularized (n=11) or cryopreserved (n=9) allografts. Echocardiography was done at discharge, 1, 3, 6 and 12 months and annually thereafter. Samples for determination of antibodies against HLA class I and II were obtained preoperatively and at days 5, 10, 30, 90 and 180 postoperatively. These samples were tested by the ELISA method in LAT-M dishes (unspecific) for identification of circulating antibodies and the results expressed as mean sample values (Is=DO/cutoff). If positive, LAT-E (specific) was performed and PRA levels determined. RESULTS: There was no mortality. Cryopreserved allografts showed marked Is values elevations for class I and II antibodies which started at the first month and remained elevated up to 6 months. In contrast, of the patients receiving decellularized allografts, seven remained negative, two patients had only marginal elevation of class I antibodies and two patients showed abnormal elevations of PRA levels. This response happened earlier than in the cryopreserved group, starting on the 5th postoperative day and has returned to baseline levels in one case. Echocardiography showed mild, but significant, elevation of gradients in cryopreserved valves but none in the decellularized. CONCLUSIONS: Decellularized allografts had normal function up to 18 months and showed important reduction of the immunogenic response when compared to cryopreserved valves.
Adolescent↗
Increased interleukin-10 and cortisol in long-term alcoholics after cardiopulmonary bypass: a hint to the increased postoperative infection rate?
BACKGROUND: Previous studies have shown that 20% of all patients admitted to the hospital abuse alcohol and have increased morbidity after surgery. Long-term alcoholic patients are shown to suffer from immune alterations, which might be critical for adequate postoperative performance. Cardiac surgery with cardiopulmonary bypass (CPB) also leads to pronounced immune alteration, which might be linked with patients' ability to combat infections. Therefore, the aim of our study was to investigate the perioperative levels of TNF-alpha, interleukin-6, interleukin-10, and cortisol in long-term alcoholic and nonalcoholic patients undergoing cardiac surgery to elucidate a possible association with postoperative infections. METHODS: Forty-four patients undergoing elective cardiac surgery were included in this prospective study. Long-term alcoholic patients (n=10) were defined as having a daily ethanol consumption of at least 60 g and fulfilling the Diagnostic and Statistical Manual of Mental Disorders for alcohol abuse. The nonalcoholic patients (n=34) were defined as drinking less than 20 g ethanol per day. Blood samples were obtained to analyze the immune status upon admission to hospital, the morning before surgery and on admission to the ICU, the morning of days one and three after surgery. RESULTS: Basic characteristics of patients did not differ between groups. Long-term alcoholics had a fourfold increase in postsurgery infection rate and prolonged need for ICU treatment and mechanical ventilation. Postoperative levels of interleukin-10 and cortisol were significantly increased in long-term alcoholic patients compared with nonalcoholic patients. These observations were in line with postoperative interleukin-10 being predictive for postoperative infectious complications. CONCLUSIONS: The increased infection rate in long-term alcoholics strengthens the urgent need for interventional approaches providing modulation of the perioperative immune and HPA response in these high-risk patients to counteract their postoperative immune suppression.
Aged↗