OBJECTIVES:Although extracorporeal circulation (ECC) is routinely used in invasive cardiovascular medicine and can cause severe complications, the impact of ECC on arterial blood flow is not yet fully understood. This study aims to reveal actual bloodflow profiles during different ECC scenarios. METHODS:Twenty-three New Zealand White rabbits underwent ECC by ante- (n = 7) or retro-grade (n = 9) or physiological perfusion (n = 7). Arterial blood flow profiles were assessed with a focus on cerebral and visceral perfusion. Numerical simulation models were tuned and validated based on magnetic resonance imaging (MRI). RESULTS:Ante- and retrograde ECC resulted in completely divergent aortic blood flow patterns. Supraaortic and visceral perfusions were not impaired during ante- or retro grade ECC. Excellent correlation of volume flow rates was achieved between MRI and simulations (r = 0.98). Intima damage was observed in regions of high wall shear stress (WSS). CONCLUSIONS:This is the first study assessing arterial blood flow during different ECC scenarios in a living organism, and additionally validating precise blood flow simulations by in vivo measurements. Retrograde ECC does not a priori impair cerebral perfusion. Individualized simulations may guide cannulation strategies aiming at minimization of ECC-related complications.

Background The rising complexity of cardiac surgery patients, coupled with new regulations reducing working hours for surgical residents, and increased healthcare costs, has led to the growing introduction of physician assistants (PAs) into cardiacsurgery teams in German hospitals. This study aims to systematically explore the experience of introducing PAs into the cardiac surgery workforce in a tertiary university hospital in Germany, identifying what is working well and areas for improvement, as well as offering suggestions for appropriate measures. Methods The study was of an observational nature and comprised both quantitative assessments and qualitative interviews. For the quantitative component, a survey was distributed internally to employees of the cardiovascular surgery department. The survey was first distributed within 1 month of the first PAs starting in our department ("baseline") and again 1 year later ("follow-up" [FU]). Results Forty-one healthcare professionals completed the baseline, and 37 completed the FU survey. Overall satisfaction with PAs was high across all professional groups. Among residents,73.3% reported being satisfied at baseline and 70% at FU. All cardiovascular surgeons (6/6) and PAs (10/10) reported high satisfaction at both time points, and 90% of nursing staff reported being satisfied or very satisfied at baseline, with no dissatisfaction reported at baseline or FU. All PAs reported providing workload relief and feeling fully integrated into the team, while two-thirds of residents reported workload relief due to PAs assuming ward-based clinical and administrative tasks. PAs were consistently perceived as improving continuity of care as a stable point of contact for patients and nursing staff. Conclusion PAs substantially strengthen cardiac surgery teams in the German healthcare system. To successfully establish the implementation of PAs, the challenges of long-term retention incentives and clear delineation of responsibilities have to be addressed.

Endoscopic graft harvesting was first introduced clinically in the 1990s and is currently used in 80-90% of all CABG cases in the United States. Several studies have compared open and endoscopic harvesting techniques in terms of long-term clinical outcomes and major adverse events. In summary, endoscopic graft harvesting allows for reduced postoperative pain, minimization of wound infection risk and a better cosmetic result with higher patients' satisfaction. Harvester experience guarantees a graft quality that is comparable to open harvesting techniques. Thus, American as well as European guidelines recommend endoscopic harvesting - particularly in patients at high risk of wound healing disorders.

Cardiopulmonary bypass (CPB) is the standard approach for coronary artery bypass grafting (CABG) in advanced ischaemic cardiomyopathy. Microaxial pump support has been envisioned to allow for beating-heart CABG without CPB (MPCAB), thereby avoiding CPB-inherent complications. This study aims to compare the in-hospital and follow-up outcome of MPCAB versus CPB-CABG in patients with severely impaired left ventricular function. Eleven patients suffering from three-vessel coronary artery disease with median ejection fraction of 27% and deemed appropriate for CABG according to a heart team decision underwent MPCAB (support up to 5.5 L/min). Propensity score matching generated a CPB-CABG control group (n = 33). The primary endpoint was defined as death from any cause by the end of the follow-up (up to 4 years). MPCAB enabled continuous intraoperative and postoperative haemodynamic stabilization and complete myocardial revascularization. After CPB-CABG, additional mechanical circulatory support was required in 45.5% (vs. 9.1% in MPCAB; P = 0.0363). The follow-up all-cause mortality after MPCAB amounted to 0% (vs. 33.3% after CPB-CABG; P = 0.0414; NNT = 3). MPCAB patients showed a significantly decreased occurrence of major adverse cardiovascular events (MACE: 0% vs. 39.4%; P = 0.0189). MPCAB allows for complete surgical revascularization without the necessity of extracorporeal circulation in spite of severely impaired left ventricular function. This first comparative study on the outcome after MPCAB versus CPB-CABG demonstrates a significantly decreased risk of death as well as MACE in MPCAB patients. The MPCAB concept expands the spectrum of patients eligible for CABG without CPB towards patients with severely impaired left ventricular function.

Abstract Background Aortic atherosclerosis increases the risk of embolic events under extracorporeal circulation (ECC). To evaluate the hemodynamic impact of ECC on atheromatous plaques, an atherosclerosis animal model, which is also eligible for ECC, is required. Methods Twenty‐nine New Zealand White rabbits received a pro‐atherosclerotic diet (group diet, n = 10), a pro‐atherosclerotic diet and additional intraaortic balloon insufflation injury (group BI, n = 9), or served as controls (n = 10). After 3 or 6 months, aortic explants were analyzed by (immuno‐)histology and RT‐PCR. Results Blood serum analyses revealed increased cholesterol‐levels in groups diet and BI compared to controls (3 months: p = 0.03 each, 6 months: p < 0.0001 each). Aortic inflammatory infiltration was significantly enhanced in groups diet (CD3 at 3 months: p < 0.0001, 6 months: p = 0.02; CD68 at 3 months: p = 0.01) and BI (CD3 at 3 months: p < 0.0001, 6 months: p = 0.03; CD68 at 3 months: p = 0.04, 6 months: p = 0.02). Increased intima hyperplasia occurred in both groups (p < 0.0001 each). Macroscopic analyses after 3 and 6 months showed ubiquitous lumen‐narrowing aortic plaques. Calcification of the intima and media was increased in groups diet (intima: p < 0.0001 at 3 and 6 months; media at 3 months: p < 0.0001, 6 months: p = 0.01) and BI (intima: p < 0.0001 at 3 and 6 months; media at 3 months: p < 0.0001, 6 months: p = 0.02). Extensive lipid accumulation was found in the intima in both treatment groups (p < 0.0001 each). Conclusions A rabbit model with high aortic calcific plaque burden—diet‐induced with no implicit need of an additional intimal injury by an intraaortic balloon insufflation due to comparable outcome—exhibiting multiple pathophysiological aspects of human atherosclerosis has been designed and thoroughly characterized. It is suitable for use in future studies on the interaction between atherosclerotic plaques and the arterial blood flow under ECC.

While oxidative stress is known as a key element in the pathogenesis of atherosclerosis and calcific aortic valve disease, its role in the degeneration of biological cardiovascular grafts has not yet been clarified. Therefore, the present study aimed to examine the impact of oxidative stress on the degeneration of cardiovascular allografts in a standardized chronic implantation model in genetically modified rats exhibiting superoxide dismutase 3 deficiency (SOD3((-)); loss of function mutation). The SOD3((-)) rats (n = 24) underwent infrarenal implantation of cryopreserved valved aortic conduits, while SOD3-competent recipient rats served as controls (n = 28). After a follow-up observational period of 4 or 12 weeks, comparative analyses were carried out to address degenerative processes, hemodynamics and evaluation of the oxidative stress model. The SOD3((-)) rats presented decreased serum SOD activity (p = 0.0079). After 12 weeks 58% of the implanted valves in SOD3((-)) rats showed regurgitation (vs. 31% in control animals, p = 0.2377). Progressive intimal hyperplasia and chondro-osteogenic transformation contributed to a massive graft calcification (p = 0.0024). At 12 weeks, hydroxyapatite deposition (p = 0.0198) and the gene expression of runt-related transcription factor 2 (RUNX2, p = 0.0093) were significantly enhanced in the SOD3((-)) group. The results of this study provide first in vivo indications that impaired systemic antioxidant activity contributes to biological cardiovascular graft degeneration.

Während oxidativer Stress als Schlüsselelement der Pathogenese sowohl der Atherosklerose als auch der kalzifizierenden Aortenklappendegeneration identifiziert wurde, ist seine Rolle bei der Degeneration biologischer kardiovaskulärer Prothesen bislang unklar. Aus diesem Grund wurde in der vorliegenden Studie der Einfluss oxidativen Stresses auf die Degeneration kardiovaskulärer Allografts in einem standardisierten chronischen Implantationsmodell in genetisch modifizierten Ratten mit einer Superoxiddismutase-3-Defizienz (SOD3(−); Funktionsverlust-Mutation) untersucht. SOD3(−)-Ratten (n = 24) wurden einer infrarenalen Implantation eines kryopräservierten klappentragenden Aortenkonduits unterzogen, während SOD-kompetente Empfängerratten als Kontrolle dienten (n = 28). Nach einer Beobachtungszeit von 4 oder 12 Wochen erfolgten vergleichende Analysen hinsichtlich degenerativer Prozesse und Hämodynamik sowie die Evaluation des Modells des oxidativen Stresses. SOD3(−)-Ratten zeigten eine verminderte Serum-SOD-Aktivität (p = 0,0079). Nach 12 Wochen imponierten 58

Central MessageAnaortic off-pump MICS-CABG allows for minimally invasive revascularization with both internal thoracic arteries by means of double-lung ventilation even in patients with impaired lung function.See Commentary on page XXX. Anaortic off-pump MICS-CABG allows for minimally invasive revascularization with both internal thoracic arteries by means of double-lung ventilation even in patients with impaired lung function. See Commentary on page XXX. Minimally invasive coronary artery bypass grafting (MICS-CABG) is as safe as off-pump CABG (OPCAB) via sternotomy while allowing for superior cosmetics, wound healing, and recovery.1Lapierre H. Chan V. Sohmer B. Mesana T.G. Ruel M. Minimally invasive coronary artery bypass grafting via a small thoracotomy versus off-pump: a case-matched study.Eur J Cardio Thorac Surg. 2011; 40: 804-810PubMed Google Scholar,2Davierwala P.M. Verevkin A. Sgouropoulou S. Hasheminejad E. von Aspern K. Misfeld M. et al.Minimally invasive coronary bypass surgery with bilateral internal thoracic arteries: early outcomes and angiographic patency.J Thorac Cardiovasc Surg. 2021; 162: 1109-1119.e1104Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar MICS-CABG with conventional single-lung ventilation is limited by a variety of chronic lung diseases as well as technique-inherent pathomechanisms such as missing left lung ventilation that results in intrapulmonary shunting and consecutive hypoxemia, left lung hypoxic pulmonary vasoconstriction leading to pulmonary hypertension, and right lung enhanced airway pressure promoting acute lung injury. Recently, we demonstrated that patients with severely impaired lung function are eligible for MICS-CABG when using a pulmonary fan.3Assmann A.K. Lichtenberg A. Assmann A. Bilateral internal thoracic artery minimally invasive CABG management in COPD.Thorac Cardiovasc Surg Rep. 2022; 11: e14-e16Crossref Google Scholar Here, we present in detail our bilateral internal thoracic artery (BITA)-MICS-CABG technique with double-lung ventilation. BITA-MICS-CABG requires thorough planning considering several contraindications (Table 1). A computed tomography chest scan reveals the patients' intrathoracic anatomy and thus eligibility. Institutional review board approval was not required. An informed written consent for publication of study data was obtained from the patient in the video.Table 1Contraindications for bilateral internal thoracic artery minimally invasive cardiac surgery coronary artery bypass graftingEmergency operationHemodynamic instabilitySeverely impaired ventricular function/dilated ventriclesCardiac redo operationSeverely stenotic or occluded subclavian arterySevere obesity (relative contraindication)Chest deformity (relative contraindication) Open table in a new tab An anesthesiologist team with profound experience in MICS and OPCAB is mandatory. We routinely use pulmonary artery catheters to continuously monitor pulmonary arterial, central venous, and left ventricular filling pressure and cardiac output. Adequate volume management and differentiated catecholamine use are of utmost importance. Patients are placed in the supine position with the left thorax lifted up by 30°. After a submammary skin incision (5-8 cm along the fifth intercostal space) and extrathoracic preparation, the parietal pleura is widely opened to reduce the risk of costal fractures (Video 1). Double-lung ventilation is achieved by our pulmonary fan technique as previously described.3Assmann A.K. Lichtenberg A. Assmann A. Bilateral internal thoracic artery minimally invasive CABG management in COPD.Thorac Cardiovasc Surg Rep. 2022; 11: e14-e16Crossref Google Scholar In brief, the mediastinal pleura is incised 1 to 2 cm anterior of the phrenic nerve, and 6 to 12 sutures are stitched along the pericardio-pleural margin and pulled laterally through the third or fourth intercostal space. Thus, the constructed fan retracts the left lung to enable continuous double-lung ventilation (Video 1). The left ITA (LITA) is skeletonized. For right ITA (RITA) preparation, an additional subxiphoidal retractor lifts the sternum (Video 1). After LITA-RITA T-graft construction, the LITA is typically sutured to the left anterior descending artery and the RITA to coronaries of the (postero) lateral wall (Video 2). For cardiac positioning and target vessel exposure, suctioning positioner devices and stabilizers are utilized. Afterward, a transit-time-flow measurement confirms adequate blood flow to the coronary targets. So far, 16 patients have undergone BITA-MICS-CABG in our department (baseline characteristics are presented in Table E1). All patients received a LITA-to- left anterior descending artery bypass and an RITA T-graft to either a diagonal (n = 11) or an obtuse marginal branch (n = 5). During the whole operation (cut-suture time 347.3 ± 59.6 minutes), patients showed adequate pulmonary gas exchange and aerobic metabolism (Figure E1). All patients were extubated on the day of surgery and showed regular postoperative cardiac enzymes and in-hospital outcome (Table E2). BITA-MICS-CABG allows for totally arterial revascularization without aortic manipulation via anterolateral minithoracotomy. Anaortic coronary surgery decreases the risk of intraoperative stroke,4Albert A. Ennker J. Hegazy Y. Ullrich S. Petrov G. Akhyari P. et al.Implementation of the aortic no-touch technique to reduce stroke after off-pump coronary surgery.J Thorac Cardiovasc Surg. 2018; 156: 544-554.e544Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar and the long-term patency of arterial grafts should be considered superior to venous bypasses.5Taggart D.P. The role of multiple arterial grafts in CABG: all roads lead to ROMA.J Am Coll Cardiol. 2019; 74: 2249-2253Crossref PubMed Scopus (0) Google Scholar Compared with OPCAB via sternotomy, MICS-CABG results in fewer wound infections, more rapid recovery, and reduced length of hospital stay.1Lapierre H. Chan V. Sohmer B. Mesana T.G. Ruel M. Minimally invasive coronary artery bypass grafting via a small thoracotomy versus off-pump: a case-matched study.Eur J Cardio Thorac Surg. 2011; 40: 804-810PubMed Google Scholar Our pulmonary fan technique guarantees continuous double-lung ventilation and adequate gas exchange without impairing the surgeon's view and working space. Thereby, even patients with impaired lung function can benefit from MICS-CABG. Furthermore, inherent issues of single-lung ventilation (ie, hypoxemia, pulmonary hypertension, and acute lung injury) may be avoided. Left lung ventilation is all the more important for BITA-MICS-CABG because right lung extension frequently has to be partially restricted during RITA preparation. Moreover, compared with minimally invasive direct CABG with only 1 anastomosis, multivessel MICS-CABG requires substantially more time so that adverse cascades triggered by single-lung ventilation have greater influence on the patient. Thus, continuous double-lung ventilation has the potential to avoid conversions to cardiopulmonary bypass and sternotomy. Actually, the usefulness of left lung ventilation to make sternal sparing coronary surgery accessible to a larger group of coronary artery disease patients has been previously shown in the context of robotic totally endoscopic bypass grafting.6Balkhy H.H. Nisivaco S. Tung A. Torregrossa G. Mehta S. Does intolerance of single-lung ventilation preclude robotic off-pump totally endoscopic coronary bypass surgery?.Innovations. 2020; 15: 456-462Crossref Scopus (5) Google Scholar MICS-CABG is a complex microsurgical procedure, particularly when combined with BITA use. To guarantee a safe procedure and optimal long-term graft patency, an expert team is required, including trained cardioanesthetists. The specialization process of a MICS-CABG team should start from profound expertise in OPCAB, including complications management. Further learning steps comprise basic elements of MICS, adoption of minimally invasive direct CABG with a single anastomosis, evolution toward multivessel MICS, and finally integration of BITA preparation. BITA-MICS-CABG is an excellent, innovative approach that combines the advantages of off-pump surgery without aortic manipulation, totally arterial revascularization, and minimal invasiveness. Thus, multivessel arterial bypass grafting is realized in conjunction with reduction of surgical trauma and operative risk. The presented double-lung ventilation technique counteracts pathomechanisms inherent to MICS under single-lung ventilation and expands the spectrum of eligible patients toward those with concomitant lung diseases.

Um die Auswirkung von Pioglitazon, einem Peroxisom-Proliferation-aktivierter-Rezeptor(PPAR)-gamma-Agonisten, auf die Degeneration kardiovaskulärer Prothesen zu untersuchen, wurde das durch unsere Arbeitsgruppe etablierte mikrochirurgische Kleintiermodell der heterotopen Aorten-Conduit-Implantation adaptiert [1, 21]. Es konnte in einer ersten Studie mit Ratten unter Standarddiät gezeigt werden, dass die systemische Applikation von Pioglitazon zu einer signifikanten Reduktion der inflammatorischen und kalzifizierenden Degeneration der Prothesen führt [3]. Auch das funktionelle Outcome der Aortenklappenprothesen zeigte sich signifikant besser in der Pioglitazongruppe. Im Sinne eines translationalen Ansatzes mit besonderem Augenmerk auf für Menschen typische Begleiterkrankungen bei kardiovaskulären Patienten wurden in einer zweiten Studie adipöse Ratten mit einer Hypercholesterinämie untersucht. Auch hier wurde durch die Therapie mit Pioglitazon eine signifikante Reduktion der kalzifizierenden, durch eine Hyperplasie induzierten Degeneration der Implantate gezeigt [4]. Die Reduktion degenerativer Prozesse und die daraus resultierende Verlängerung der Haltbarkeit kardiovaskulärer Prothesen spielen insbesondere in unserer alternden Gesellschaft eine zunehmende Rolle. Die Vermeidung rezidivierender Operationen infolge einer Implantatdegeneration ist ein unumstrittenes Ziel kardiovaskulärer Forschung und klinischer Therapie. In diesem Kontext vergegenwärtigen die Resultate unserer Arbeiten das Potenzial einer antidegenerativen Therapie mit PPAR-gamma-Agonisten.

OBJECTIVES: To achieve a beneficial impact on long-term outcome after coronary artery bypass grafting (CABG), the goal of the present study was the early identification of patients at risk of impaired postoperative health-related quality of life (HRQoL), particularly evaluating the significance of socio-demographic variables. METHODS: In this prospective, single-centre cohort study of patients having an isolated CABG (January 2004-December 2014), preoperative socio-demographic (preSOC) and preoperative medical variables as well as 6-month follow-up data including the Nottingham Health Profile were analysed in 3,237 patients. RESULTS: All preSOC (gender, age, marriage and employment) and follow-up (chest pain, dyspnoea) variables proved to have significant influence on HRQoL (P < 0.001), male patients below 60 years being particularly impaired. The effects of marriage and employment on HRQoL are modulated by age and gender. The significance of the predictors of reduced HRQoL differs between the 6 Nottingham Health Profile domains. Multivariable regression analyses revealed explained proportions of variance amounting to 7% for preSOC and 4% for preoperative medical variables. CONCLUSIONS: The identification of patients at risk of impaired postoperative HRQoL is decisive for providing additional support. This study reveals that the assessment of 4 preoperative socio-demographic characteristics (age, gender, marriage, employment) is more predictive of HRQoL after CABG than are multiple medical variables.

Aortic valve replacement for severe stenosis is a standard procedure in cardiovascular medicine. However, the use of biological prostheses has limitations especially in young patients because of calcifying degeneration, resulting in implant failure. Pioglitazone, a peroxisome proliferator-activated receptor gamma (PPAR-gamma) agonist, was shown to decrease the degeneration of native aortic valves. In this study, we aim to examine the impact of pioglitazone on inflammation and calcification of aortic valve conduits (AoC) in a rat model. Cryopreserved AoC (n = 40) were infrarenally implanted into Wistar rats treated with pioglitazone (75 mg/kg chow; n = 20, PIO) or untreated (n = 20, controls). After 4 or 12 weeks, AoC were explanted and analyzed by histology, immunohistology, and polymerase chain reaction. Pioglitazone significantly decreased the expression of inflammatory markers and reduced the macrophage-mediated inflammation in PIO compared with controls after 4 (P = 0.03) and 12 weeks (P = 0.012). Chondrogenic transformation was significantly decreased in PIO after 12 weeks (P = 0.001). Calcification of the intima and media was significantly reduced after 12 weeks in PIO versus controls (intima: P = 0.008; media: P = 0.025). Moreover, echocardiography revealed significantly better functional outcome of the AoC in PIO after 12 weeks compared with control. Interestingly, significantly increased intima hyperplasia could be observed in PIO compared with controls after 12 weeks (P = 0.017). Systemic PPAR-gamma activation prevents inflammation as well as intima and media calcification in AoC and seems to inhibit functional impairment of the implanted aortic valve. To further elucidate the therapeutic role of PPAR-gamma regulation for graft durability, translational studies and long-term follow-up data should be striven for.

Background  Off-pump multi-arterial minimally invasive coronary surgery via anterolateral mini-thoracotomy has become a feasible and safe procedure. Case Description  We report on a 61-year-old patient with a coronary one-vessel disease with severely stenotic left anterior descending artery and diagonal branch, additionally suffering from chronic obstructive pulmonary disease with severely impaired lung function. Using a fan technique allowing for double lung ventilation, the patient was successfully operated grafting both internal thoracic arteries via a left anterolateral mini-thoracotomy. Conclusion  Anaortic, minimally invasive off-pump coronary artery bypass grafting is an excellent technique to achieve myocardial revascularization with both internal thoracic arteries even in patients with impaired lung function.

OBJECTIVES:Hypercholesterolaemia and obesity are risk factors for the development of calcified aortic valve disease and common comorbidities in respective patients. Peroxisome proliferator-activated receptor gamma activation has been shown to reduce the progression of native aortic valve sclerosis, while its effect on bioprosthetic valve degeneration is yet unknown. This project aims to analyse the impact of pioglitazone, a peroxisome proliferator-activated receptor gamma agonist, on the degeneration of biological aortic valve conduits in an implantation model in obese and hypercholesterolaemic rats. METHODS:Cryopreserved allogenic rat aortic valve conduits (n = 40) were infrarenally implanted into Wistar rats on high-fat (34.6%) diet. One cohort was treated with pioglitazone (75 mg/kg chow; n = 20, group PIO) and compared to untreated rats (n = 20, group control). After 4 or 12 weeks, conduits were explanted and analysed by (immuno-)histology and real-time polymerase chain reaction. RESULTS:A significantly decreased intima hyperplasia occurred in group PIO compared to control after 4 (P = 0.014) and 12 weeks (P = 0.045). Calcification of the intima was significantly decreased in PIO versus control at 12 weeks (P = 0.0001). No significant inter-group differences were shown for media calcification after 4 and 12 weeks. Echocardiographically, significantly lower regurgitation through the implanted aortic valve conduit was observed in PIO compared to control after 4 (P = 0.018) and 12 weeks (P = 0.0004). Inflammatory activity was comparable between both groups. CONCLUSIONS:Systemic peroxisome proliferator-activated receptor gamma activation decreases intima hyperplasia and subsequent intima calcification of cryopreserved allografts in obese, hypercholesterolaemic recipients. Additionally, it seems to inhibit functional impairment of the implanted aortic valve. Further preclinical studies are required to determine the long-term impact of peroxisome proliferator-activated receptor gamma agonists on graft durability.

While oxidative stress is known as key element in the pathogenesis of atherosclerosis and calcific aortic valve disease, its role in the degeneration of biological cardiovascular grafts has not been clarified yet. Therefore, the present study aimed to examine the impact of oxidative stress on the degeneration of biological cardiovascular allografts in a standardized chronic implantation model realized in rats exhibiting superoxide dismutase 3 deficiency (SOD3(−)). Rats with SOD3 loss‐of‐function mutation (n = 24) underwent infrarenal implantation of cryopreserved valved aortic conduits, while SOD3‐competent recipients served as controls (n = 28). After a follow‐up period of 4 or 12 weeks, comparative analyses addressed degenerative processes, hemodynamics, and evaluation of the oxidative stress model. SOD3(−) rats presented decreased circulating SOD activity (p = .0079). After 12 weeks, 58% of the implant valves in SOD3(−) rats showed regurgitation (vs. 31% in controls, p = .2377). Intima hyperplasia and chondro‐osteogenic transformation contributed to progressive graft calcification (p = .0024). At 12 weeks, hydroxyapatite deposition (p = .0198) and the gene expression of runt‐related transcription factor‐2 (Runx2) (p = .0093) were significantly enhanced in group SOD3(−). This study provides the first in vivo evidence that impaired systemic antioxidant activity contributes to biological cardiovascular graft degeneration.

OBJECTIVES:Intima hyperplasia is a major issue of biological cardiovascular grafts resulting in progressive in vivo degeneration that particularly decreases the durability of coronary and peripheral vascular bypasses. Previously, dichloroacetate (DCA) has been reported to prevent the formation of hyperplastic intima in injured arteries. In this study, the effect of DCA on the neointima formation and degeneration of decellularized small-caliber implants was investigated in a rat model. METHODS:Donor rat aortic grafts (n = 22) were decellularized by a detergent-based technique, surface-coated with fibronectin (50 µl ml-1, 24 h incubation) and implanted via anastomoses to the infrarenal aorta of the recipients. Rats in the DCA group (n = 12) received DCA via drinking water during the whole follow-up period (0.75 g l-1), while rats without DCA treatment served as controls (n = 10). At 2 (n = 6 + 5) and 8 (n = 6 + 5) weeks, the grafts were explanted and examined by histology and immunofluorescence. RESULTS:Systemic DCA treatment inhibited neointima hyperplasia, resulting in a significantly reduced intima-to-media ratio (median 0.78 [interquartile range, 0.51-1.27] vs 1.49 [0.67-2.39] without DCA, P < 0.001). At 8 weeks, neointima calcification, as assessed by an established von Kossa staining-based score, was significantly decreased in the DCA group (0 [0-0.25] vs 0.63 [0.06-1.44] without DCA, P < 0.001). At 8 weeks, explanted grafts in both groups were luminally completely covered by an endothelial cell layer. In both groups, inflammatory cell markers (CD3, CD68) proved negative. CONCLUSIONS:Systemic DCA treatment reduces adverse neointima hyperplasia in decellularized small-caliber arterial grafts, while allowing for rapid re-endothelialization. Furthermore, DCA inhibits calcification of the implants.

The impact of different extracorporeal circulation (ECC) scenarios on arterial blood flow profiles has not yet been revealed. To allow for exact measurements, magnetic resonance imaging (MRI) during ECC is required. Therefore, the present study addressed the feasibility of a high-resolution MRI-compatible animal model of ECC. For usage in New Zealand White rabbits, we developed an ECC device, the tubes of which were long enough to eliminate impacts of the magnetic field on the blood pump and heart-lung control machine. The miniaturized ECC system via thoracic access comprised an infant oxygenator, a pulsatile centrifugal pump, 1/8″ tubes, a 10-Fr aortic cannula and a 12-Fr venous cannula for vacuum-assisted drainage. This miniaturized ECC system has very low priming volume (230-255 ml) to reduce the system-inherent haemodilution to 50%. Consequently, haemoglobin rates remained high enough to guarantee adequate oxygenation (arterial pressure of oxygen >200 mmHg). Optimized venous drainage by an additionally inserted pulmonary artery vent catheter resulted in sufficient blood flow (31.6-65.8 ml/min/kg) that was maintained for 60 min with pulsatility. The current study demonstrates the feasibility of MRI-compatible ECC in rabbits, and this model allows for real-time blood flow profile measurements during different ECC scenarios in future projects.

Optimized biocompatibility is crucial for the durability of cardiovascular implants. Previously, a combined coating with fibronectin (FN) and stromal cell-derived factor 1α (SDF1α) has been shown to accelerate the in vivo cellularization of synthetic vascular grafts and to reduce the calcification of biological pulmonary root grafts. In this study, we evaluate the effect of side-specific luminal SDF1α coating and adventitial FN coating on the in vivo cellularization and degeneration of decellularized rat aortic implants. Aortic arch vascular donor grafts were detergent-decellularized. The luminal graft surface was coated with SDF1α, while the adventitial surface was coated with FN. SDF1α-coated and uncoated grafts were infrarenally implanted (n = 20) in rats and followed up for up to eight weeks. Cellular intima population was accelerated by luminal SDF1α coating at two weeks (92.4 ± 2.95% versus 61.1 ± 6.51% in controls, p < 0.001). SDF1α coating inhibited neo-intimal hyperplasia, resulting in a significantly decreased intima-to-media ratio after eight weeks (0.62 ± 0.15 versus 1.35 ± 0.26 in controls, p < 0.05). Furthermore, at eight weeks, media calcification was significantly decreased in the SDF1α group as compared to the control group (area of calcification in proximal arch region 1092 ± 517 μm2 versus 11 814 ± 1883 μm2, p < 0.01). Luminal coating with SDF1α promotes early autologous intima recellularization in vivo and attenuates neo-intima hyperplasia as well as calcification of decellularized vascular grafts.