Generation of microbubbles in extracorporeal life support and assessment of new elimination strategies

Occurrence of microbubbles (MB) is a major problem during venoarterial extracorporeal life support (ECLS) with partially severe clinical complications. The aim of this study was to establish an in vitro ECLS setup for the generation and detection of MB. Furthermore, we assessed different MB elimination strategies. Patient and ECLS circuit were simulated using reservoirs, a centrifugal pump, a membrane oxygenator, and an occluder (modified roller pump). The system was primed with a glycerin solution of 44%. Three different revolution speeds (2500, 3000, and 3400 rpm) were applied. For MB generation, the inflow line of the pump was either statically or dynamically (15 rpm) occluded. A bubble counter was used for MB detection. The effectiveness of the oxygenator and dynamic bubble traps (DBTs) was evaluated in regard to MB elimination capacities. MB generation was highly dependent on negative pressure at the inflow line. Increasing revolution speeds and restriction of the inflow led to increased MB activity. The significant difference between inflow and outflow MB volume identified the centrifugal pump as a main source. We could show that the oxygenator’s ability to withhold larger MB is limited. The application of one or multiple DBTs leads to a significant reduction in MB count and overall gas volume. The application of DBT can significantly reduce the overall gas volume, especially at high flow rates. Moreover, large MB can effectively be broken down for faster absorption. In general, the incidence of MBs is significantly dependent on pump speed and restriction of the inflow. The centrifugal pump was identified as a major source of MB generation

Thrombocytopenia and end stage renal disease are key predictors of survival in patients with cardiac implantable electronic device infections

Introduction Cardiac implantable electronic device (CIED) infections are associated with a high mortality. Our aim was to identify key predictors of survival in patients with CIED infections as to be able to detect high‐risk patients and possibly affect modifiable factors. Methods and Results In this observational study, we collected data from 277 patients with CIED infections treated in our department between 2001 and 2017; predictors of survival were evaluated. The median time since the last CIED procedure was 0.83 years (interquartile range [IQR]: 0.25‐3.01), median time since initial CIED implant was 4.79 years (IQR: 0.90‐11.0 years). Survival at 30 days was 94.9% (95% confidence interval [CI]: 92.3‐97.5) and survival at 1 year was 80.9% (CI: 76.4‐85.7). Age (odds ratio [OR]: 1.05, CI: 1.01‐1.09; P = .009), end stage renal disease (ESRD) with dialysis (OR: 5.14, CI: 1.87‐14.11; P = .001), positive blood cultures (OR: 2.19, CI: 1.08‐4.45; P = .030), and thrombocytopenia (OR: 2.3, CI, 1.03‐5.15; P = .042) were identified as predictors of death within 1 year of treatment of CIED infection. Conclusion Patients with CIED infection with prior ESRD with dialysis or preoperative thrombocytopenia are at an increased risk of 1‐year mortality. We suggest that these patients be evaluated critically and resources be allocated to these patients more liberally. A greater understanding of the role of platelets in immunity may improve treatment of advanced infection in the future

Simultaneous LC-ESI-MS/MS Quantification of Levosimendan and Its Metabolites for Therapeutic Drug Monitoring of Cardiac Surgery Patients

Levosimendan is used in severe chronic cardiac insufficiency, also within the peri-operative setting. Real-life pharmacokinetic data in surgical patients is lacking, making therapeutic drug monitoring (TDM) of levosimendan, its pharmacologically active metabolite OR-1896, and its intermediate OR-1855 important. A simultaneous highly sensitive quantification of levosimendan and its metabolites in small-volume samples has not yet been described. Here, levosimendan (LLOQ 0.450 nM), OR-1896, and OR-1855 (LLOQ both 1.0 nM) were successfully quantified by LC-ESI-MS/MS after liquid-liquid extraction in 300 mu L of blood. A short C8 column under reversed-phase conditions enabled simultaneous and fast quantification of levosimendan in the negative and the metabolites in the positive ionization mode in a single run within 2 min. Interestingly and unexpectedly, constitutional isomers of levosimendan metabolites with identical mass transitions and similar retention times were observed in surgical patients' samples, which we identified as the metamizole metabolites 4-aminoantipyrine and 4-acetamidoantipyrine. A longer C8 column and a modified mobile phase enabled selective quantification of all analytes in a single run within 7 min. We developed, validated, and applied highly sensitive LC-ESI-MS/MS methods for simultaneous quantification of levosimendan and its metabolites, enabling efficient TDM of cardiac surgery patients even with additional metamizole administration

The safety of moderate hypothermic lower body circulatory arrest with selective cerebral perfusion: A propensity score analysis

ObjectiveThere is no common guideline on what temperature should be achieved at the lower body circulatory arrest followed by the initiation of selective cerebral perfusion.MethodsBetween October 1999 and August 2005, a total of 377 patients underwent repair of the aortic arch with selective cerebral perfusion and hypothermic circulatory arrest at 20°C to 28°C and were divided into two groups: (1) 125 patients with deep lower body circulatory arrest at 20°C to 24.9°C (deep lower body circulatory arrest group) and (2) 252 patients with moderate lower body circulatory arrest at 25°C to 28°C (moderate lower body circulatory arrest group). To compensate for the differences in patient characteristics, we used a propensity score matching analysis, and comparable patients, 92 patients from each group, were identified for final analysis.ResultsThere were no significant differences in mortality or morbidity between deep and moderate lower body circulatory arrest, in either the entire study cohort or the propensity-matched cohort. C-reactive protein level 1 day after the operation approached but fell short of significance (108.4 ± 47.7 mg/L in deep lower body circulatory arrest group and 95.8 ± 44.2 mg/L in moderate lower body circulatory arrest group, P = .07). The mean temperatures at the initiation of lower body circulatory arrest were 24.1°C ± 2.2°C in patients who underwent reexploration for bleeding and 24.9°C ± 1.8°C in patients who did not (P = .025); the difference also reached statistical significance in multivariate analysis (P = .046, odds ratio 0.796).ConclusionsOur results suggest that moderate lower body circulatory arrest can be safely performed for aortic arch repair. In fact, postoperative inflammatory response tended to be lower in patients with moderate lower body circulatory arrest than those with deep lower body circulatory arrest, and deep lower body circulatory arrest was a strong risk factor for reexploration for bleeding

The Coronary Microcirculation in Hamster-to-Rat Cardiac Xenografts

BACKGROUND The aim of this study was to establish a new experimental model to directly analyse the coronary microcirculation in cardiac xenografts. METHODS Intravital fluorescence microscopy (IVM) of the subepicardial microcirculation in heterotopically transplanted hamster-to-rat cardiac xenografts was performed at 30 and 90 min of reperfusion. We quantitatively assessed the microcirculatory perfusion characteristics as well as the interactions of leukocytes and platelets with the endothelium of postcapillary coronary venules in non-sensitised as well as sensitised recipients. RESULTS In this first experimental IVM study of cardiac xenografts, we successfully visualised the subepicardial microcirculation, i.e. feeding arterioles, nutritive capillaries and draining postcapillary venules, during reperfusion. Leukocyte-endothelial and platelet-endothelial cell interactions could be quantified. In the non-sensitised group, the myocardial microcirculation remained stable during the observation period of 90 min, whereas in the sensitised group, xenografts were rejected immediately. CONCLUSIONS We established a model for the assessment of the microcirculatory dysfunction and inflammation during ischaemia/reperfusion injury in hamster-to-rat cardiac xenografts

A Novel Seeding and Conditioning Bioreactor for Vascular Tissue Engineering

Multiple efforts have been made to develop small-diameter tissue engineered vascular grafts using a great variety of bioreactor systems at different steps of processing. Nevertheless, there is still an extensive need for a compact all-in-one system providing multiple and simultaneous processing. The aim of this project was to develop a new device to fulfill the major requirements of an ideal system that allows simultaneous seeding, conditioning, and perfusion. The newly developed system can be actuated in a common incubator and consists of six components: a rotating cylinder, a pump, a pulse generator, a control unit, a mixer, and a reservoir. Components that are in direct contact with cell media, cells, and/or tissue allow sterile processing. Proof-of-concept experiments were performed with polyurethane tubes and collagen tubes. The scaffolds were seeded with fibroblasts and endothelial cells that were isolated from human saphenous vein segments. Scanning electron microscopy and immunohistochemistry showed better seeding success of polyurethane scaffolds in comparison to collagen. Conditioning of polyurethane tubes with 100 dyn/cm2 resulted in cell detachments, whereas a moderate conditioning program with stepwise increase of shear stress from 10 to 40 dyn/cm2 induced a stable and confluent cell layer. The new bioreactor is a powerful tool for quick and easy testing of various scaffold materials for the development of tissue engineered vascular grafts. The combination of this bioreactor with native tissue allows testing of medical devices and medicinal substances under physiological conditions that is a good step towards reduction of animal testing. In the long run, the bioreactor could turn out to produce tissue engineered vascular grafts for human applications “at the bedside”

Ten-Year Results of a Randomized Trial Comparing Tacrolimus Versus Cyclosporine A in Combination With Mycophenolate Mofetil After Heart Transplantation

Background. Long-term results of prospective randomized trials comparing triple immunosuppressive strategies combining tacrolimus (TAC) or cyclosporine A (CsA) with mycophenolate mofetil (MMF) and steroids after heart transplantation (HTX) are rarely published. Therefore, we collected long-term follow-up data of an intervention cohort 10 years after randomization. Methods. Ten-year follow-up data of 60 patients included in a prospective, randomized trial between 1998 and 2000 were analyzed as intention-to-treat (TAC-MMF n=30; CsA-MMF n=30). Baseline characteristics were well balanced. Cardiac allograft vasculopathy (CAV) was graduated in accordance with the new ISHLT classification. Results. Survival at 1, 5, and 10 years was 96.7%, 80.0%, and 66.7% for TAC-MMF and 90.0%, 83.3%, and 80.0% for CsA-MMF (P=ns). Freedom from acute rejection (AR) was significantly higher in TAC-MMF versus CsA-MMF (65.5% vs. 21.7%, log-rank 8.3, P=0.004). Freedom from ISHLT >= CAV(1) after 5 and 10 years was in TAC-MMF 64.0% and 45.8%, and in CsA-MMF 36.0% (log-rank 3.0, P=0.085) and 8.0% (log-rank 9.0, P=0.003). No difference in long-term results for freedom from coronary angioplasty or stenting, renal dysfunction, diabetes mellitus, CMV infection, or malignancy was detected. Conclusion. Cross-over effects because of treatment switch may result in impairment of significance between the groups. The long-term analysis resulted in a significant difference in manifestation of CAV between the groups after 10 years. Less rejection in the TAC-group might have contributed to the lower incidence of CAV. Superior freedom from AR and CAV in the TAC-MMF group did not result in better long-term survival

Immediate surgical coronary revascularisation in patients presenting with acute myocardial infarction

Background: The number of patients presenting with acute myocardial infarction (AMI) and being untreatable by interventional cardiologists increased during the last years. Previous experience in emergency coronary artery bypass grafting (CABG) in these patients spurred us towards a more liberal acceptance for surgery. Following a prospective protocol, patients were operated on and further analysed. Methods: Within a two year interval, 127 patients (38 female, age 68 +/- 12 years, EuroScore (ES) II 6.7 +/- 7.2\%) presenting with AMI (86 non-ST-elevated myocardial infarction (NSTEMI), 41 STEMI) were immediately accepted for emergency CABG and operated on within six hours after cardiac catheterisation (77\% three-vessel-disease, 47\% left main stem stenosis, 11\% cardiogenic shock, 21\% preoperative intraaortic balloon pump (IABP), left ventricular ejection fraction 48 +/- 15\%). Results: 30-day-mortality was 6\% (8 patients, 2 NSTEMI (2\%) 6 STEMI (15\%), p=0.014). Complete revascularisation could be achieved in 80\% of the patients using 2 +/- 1 grafts and 3 +/- 1 distal anastomoses. In total, 66\% were supported by IABP, extracorporal life support (ECLS) systems were implanted in two patients. Logistic regression analysis revealed the ES II as an independent risk factor for mortality (p<0.001, HR 1.216, 95\%-CI-Intervall 1.082-1.366). Conclusions: Quo ad vitam, results of emergency CABG for patients presenting with NSTEMI can be compared with those of elective revascularisation. Complete revascularisation obviously offers a clear benefit for the patients. Mortality in patients presenting with STEMI and cardiogenic shock is substantially high. For these patients, other concepts regarding timing of surgical revascularisation and bridging until surgery need to be taken into consideration

Hybrid Surgery for Severe Mitral Valve Calcification: Limitations and Caveats for an Open Transcatheter Approach

Background and Objectives: Mitral stenosis with extensive mitral annular calcification (MAC) remains surgically challenging in respect to clinical outcome. Prolonged surgery time with imminent ventricular rupture and systolic anterior motion can be considered as a complex of causal factors. The aim of our alternative hybrid approach was to reduce the risk of annual rupture and paravalvular leaks and to avoid obstruction of the outflow tract. A review of the current literature was also carried out. Materials and Methods: Six female patients (mean age 76 9 years) with severe mitral valve stenosis and severely calcified annulus underwent an open implantation of an Edwards Sapien 3 prosthesis on cardiopulmonary bypass. Our hybrid approach involved resection of the anterior mitral leaflet, placement of anchor sutures and the deployment of a balloon expanded prosthesis under visual control. Concomitant procedures were carried out in three patients. Results: The mean duration of cross-clamping was 95 31 min and cardiopulmonary bypass was 137 60 min. The perioperative TEE showed in three patients an inconspicuous, heart valve-typical gradient on all implanted prostheses and a clinically irrelevant paravalvular leakage occurred in the anterior annulus. In the left ventricular outflow tract, mild to moderately elevated gradients were recorded. No adverse cerebrovascular events and pacemaker implantations were observed. All but one patient survived to discharge. Survival at one year was 83.3%. Conclusions: This “off label” implantation of the Edwards Sapien 3 prosthesis may be considered as a suitable bail-out approach for patients at high-risk for mitral valve surgery or deemed inoperable due to extensive MAC