Jens Wippermann

Preliminary results of small arterial substitute performed with a new cylindrical biomaterial composed of bacterial cellulose.

OBJECTIVE Tissue-engineered blood vessels (TEBVs) represent an innovative approach for overcoming reconstructive problems associated with extended vascular diseases by providing small-calibre vascular grafts. This study aimed to evaluate a novel biomaterial of bacterially synthesised cellulose (BC) as a potential scaffold for TEBV. METHODS Highly crystalline cellulose was produced by a bacterium (Acetobacter xylinum) using glucose as a source of carbon. Using a patented process, hollow-shaped segments of BC were created with a length of 10mm, an inner diameter of 3.0-3.7mm and a wall thickness of 0.6-1.0mm. These grafts were used to replace the carotid arteries of eight pigs, and after a follow-up period of 3 months, the grafts were removed and analysed, both macro- and microscopically. RESULTS Seven grafts (87.5%) remained patent, whereas one graft was found to be occluded. Scanning electron microscopic examination revealed rapid re-cellularisation by recipient endothelial cells. Light microscopic examination showed a three-layered wall structure of the BC segments, with cellulose still being present in the media. CONCLUSION These data indicate that the innovative BC-engineering technique results in the production of stable vascular conduits, which exhibit attractive properties for their use in future TEBV programmes for vascular surgery.

Application of ECMO in Multitrauma Patients With ARDS as Rescue Therapy

Abstract  Background: Despite recent advances in critical care management, the mortality of acute respiratory distress syndrome (ARDS) remains high. The final rescue therapy for patients with severe hypoxia refractory to conventional therapy modalities is the extracorporeal gas exchange. Methods: We report the management of three polytraumatized patients with life‐threatening injuries, severe blunt thoracic trauma, and consecutive ARDS treating by extracorporeal membrane oxygenation (ECMO). Two patients suffered a car accident with severe lung contusion and parenychmal bleeding. Bronchial rupture and mediastinal emphysema was found in one of them. Another patient developed ARDS after attempted suicide with multiple fractures together with blunt abdominal and thoracic trauma. Results: All patients were placed on ECMO and could be rapidly stabilized. They were weaned from ECMO after a mean of 114 ± 27 hours of support without complications, respectively. Mean duration of ICU stay was 37 ± 23 days. Conclusions: Quick encouragement of ECMO for the temporary management of gas exchange may increase survival rates in trauma patients with ARDS.

Minimally invasive transapical aortic valve implantation and the risk of acute kidney injury.

BACKGROUND The new technique of minimally invasive transapical aortic valve implantation (TAP-AVI) deals with high-risk patients and despite the absence of cardiopulmonary bypass it might lead to renal impairment. The aim of this study was to estimate the risk of the development of acute kidney injury (AKI) after TAP-AVI and to identify possible risk factors with regard to the morbidity and mortality of the patients. METHODS Data of 30 consecutive patients undergoing TAP-AVI were recorded and followed up for 8 weeks. Postoperative AKI has been defined according to RIFLE criteria. Two patients on chronic hemodialysis have been followed up. RESULTS Of 28 patients, AKI occurred in 16 patients (57%). Statistical analysis revealed no influence on the risk of developing AKI caused by the dose of applicated contrast medium (p = 0.09), the patients age (p = 0.5), or the existence of diabetes (p = 0. 16). Analysis concerning the relationship between a preexisting coronary heart disease and AKI showed a tendency to be associated with a higher risk of the development of AKI (70% preexisting congenital heart disease in the AKI group versus 50%; p = 0.28). Only a preoperative serum creatinine greater than 1.1 mg/dL was a strong predictor for developing AKI (p < 0.01). Length of stay in the intensive care unit and the complete length of hospital stay revealed no difference with regard to postoperative development of AKI though statistical analysis showed a trend to a higher mortality in the AKI group (27% vs 6%); univariate analysis did not reach statistical significance (p = 0.13). CONCLUSIONS The TAP-AVI seems to be a feasible procedure for high-risk patients with a clear risk of developing AKI. Patients at risk should be identified and, if indicated, already preoperatively treated in collaboration with the attending nephrologists.

In vivo application of tissue-engineered blood vessels of bacterial cellulose as small arterial substitutes: proof of concept?

BACKGROUND Tissue-engineered blood vessels (TEBVs) represent an innovative approach for overcoming reconstructive problems associated with vascular diseases by providing small-caliber vascular grafts. This study aimed to evaluate a novel biomaterial of bacterially synthesized cellulose (BC) as a potential scaffold for small-diameter TEBV. METHODS Small-diameter blood vessels with a supramolecular fiber network structure consisting of tubular hydrogels from biodesigned cellulose were created using Gluconacetobacter strains and Matrix reservoir technology. BC tubes (length: 100 mm, inner diameter: 4.0-5.0 mm) were applied to replace the carotid arteries of 10 sheep for a period of 3 mo to gain further insights into (a) functional (in vivo) performance, (b) ability of providing a scaffold for the neoformation of a vascular wall and (c) their proinflammatory potential, and the (d) technical feasibility of the procedure. RESULTS Preoperative analysis revealed a bursting strength of the grafts of approximately 800 mm Hg and suture retention strength of 4-5 N. Postexplantation analysis showed a patency rate of 50% (n = 5) and physiological performance of the patent grafts at 4, 8, and 12 wk postoperatively, compared with native arteries. Histologic analysis revealed a neoformation of a vascular wall-like structure along the BC scaffold consisting of immigrated vascular smooth muscle cells and a homogeneous endothelialization of the inner graft surface without signs of prothrombogenic or inflammatory potential. Scanning electron microscopy revealed a confluent luminal endothelial cell layer and the immigration of vascular smooth muscle cells into the BC matrix. CONCLUSIONS BC grafts provide a scaffold for the neoformation of a three-layered vascular wall exhibit attractive properties for their use in future TEBV programs for cardiovascular surgery.

Direct evidence for calcium conductance of hyperpolarization-activated cyclic nucleotide-gated channels and human native If at physiological calcium concentrations

AIMS The hyperpolarization-activated cyclic nucleotide-gated (HCN) current I(f)/I(HCN) is generally thought to be carried by Na(+) and K(+) under physiological conditions. Recently, Ca(2+) influx through HCN channels has indirectly been postulated. However, direct functional evidence of Ca(2+) permeation through I(f)/I(HCN) is still lacking. METHODS AND RESULTS To possibly provide direct evidence of Ca(2+) influx through I(HCN)/I(f), we performed inside-out and cell-attached single-channel recordings of heterologously expressed HCN channels and native rat and human I(f), since Ca(2+)-mediated I(f)/I(HCN) currents may not readily be recorded using the whole-cell technique. Original current traces demonstrated HCN2 Ca(2+) inward currents upon hyperpolarization with a single-channel amplitude of -0.87+/-0.06 pA, a low open probability of 3.02+/-0.48% (at -110 mV, n=6, Ca(2+) 2 mmol/L), and a Ca(2+) conductance of 8.9+/-1.2 pS. I(HCN2-Ca2+) was significantly activated by the addition of cAMP with an increase in the open probability and suppressed by the specific I(f) inhibitor ivabradine, clearly confirming that Ca(2+) influx indeed was conducted by HCN2 channels. Changing [Na(+)] (10 vs. 100 mmol/L) in the presence or absence of 2 mmol/L Ca(2+) caused a simple shift of the reversal potential along the voltage axis without significantly affecting Na(+)/Ca(2+) conductance, whereas the K(+) conductance of HCN2 increased significantly in the absence of external Ca(2+) with increasing K(+) concentrations. The mixed K(+)-Ca(2+) conductance, however, was unaffected by the external K(+) concentration. Notably, we could also record hyperpolarization-activated Ca(2+) permeation of single native I(f) channels in neonatal rat ventriculocytes and human atrial myocytes in the presence of blockers for all known cardiac calcium conduction pores (Ca(2+) conductance of human I(f), 9.19+/-0.34 pS; amplitude, -0.81+/-0.01 pA; open probability, 1.05+/-0.61% at -90 mV). CONCLUSION We directly show Ca(2+) permeability of native rat and, more importantly, human I(f) at physiological extracellular Ca(2+) concentrations at the physiological resting membrane potential. This might have particular implications in diseased states with increased I(f) density and HCN expression.

The Impact of Intraaortic Balloon Counterpulsation on Bypass Graft Flow in Patients with Peripheral ECMO

Abstract  Objective: Numerous reports have been performed to investigate the hemodynamic effects of intraaortic balloon pumping (IABP) and nonpulsatile circulatory extracorporeal membrane oxygenation (ECMO), but studies on its impact on coronary artery bypass graft flow during concomitant use of IABP and ECMO are lacking. The aim of this study was to assess the impact of additional IABP support on the degree of blood flow increase in bypass grafts in high‐risk patients with nonpulsatile femoral venoarterial ECMO. Methods: In six emergency coronary artery bypass graft patients (mean age = 66.3 ± 2.1 years, gender = five males and one female, ejection fraction = 25.0 ± 3.0%) requiring mechanical circulatory support with ECMO hemodynamic parameters and bypass graft flows were measured with and without IABP counterpulsation. A transit time flowmeter was used for intraoperative graft flow and pulsatility index (PI) measurements. Patients provided their control values. Results: The average value of the mean arterial pressure recorded prior to IABP was 63.6 + 2.9 mmHg and during IABP support 67.8 + 2.9 mmHg (p < 0.0001). IABP augmented the mean bypass graft flow from 46.8 ± 9.6 mL/min to 56.4 ± 12.1 mL/min (p < 0.005), resulting in a 17% increase. The difference in the PI was not statistically significant (2.6 ± 0.2 with IABP, 2.6 ± 0.3 without IABP). Conclusions: We conclude that IABP‐induced pulsatility significantly improves coronary bypass graft flows during nonpulsatile peripheral ECMO.

Impact of major non-cardiac complications on outcome following cardiac surgery procedures: logistic regression analysis in a very recent patient cohort

OBJECTIVES In this study, we sought to analyse the incidence of major non-cardiac complications and their impact on survival following cardiac surgery procedures in a contemporary patient cohort. We further determined independent predictors of perioperative mortality and created a logistic regression model for prediction of outcome after the occurrence of these complications. METHODS Prospectively collected data of 5318 consecutive adult patients (mean age 68.9±11.0 years; 29.3% [n=1559] female) undergoing cardiac surgery from January 2009 to May 2012 were retrospectively analysed. Outcome measures were six major non-cardiac complications including respiratory failure, dialysis-dependent renal failure, deep sternal wound infection (DSWI), cerebrovascular accident (CVA), gastrointestinal complications (GIC) and sepsis and their impact on perioperative mortality and hospital length of stay using multivariate regression models. The discriminatory power was evaluated by calculating the area under the receiver operating characteristic curves (C statistic). RESULTS A total of 1321 complications were observed in 846 (15.9%) patients: respiratory failure (n=432; 8.1%), dialysis-dependent renal failure (n=295; 5.5%), GIC (n=154; 2.9%), CVA (n=151; 2.8%), DSWI (n=146; 2.7%) and sepsis (n=143; 2.7%). Perioperative mortality was 17.0% in patients with at least one major non-cardiac complication and correlated with the number of complications (single, 9.7%; n=53/549; double, 24.0%; n=44/183; ≥3, 41.2%; n=47/114, P<0.001). Six preoperative and four postoperative independent predictors of operative mortality were identified (age (odds ratio [OR] 1.8; 95% confidence interval [CI] 1.3-2.4), peripheral vascular disease (OR 2.6; 95% CI 1.6-4.2), pulmonary hypertension (OR 2.7; 95% CI 1.5-4.9), atrial fibrillation (OR 1.5; 95% CI 1.0-2.3), emergency (OR 5.0; 95% CI 3.4-7.2), other procedures than CABG (OR 1.5; 95% CI 1.0-2.1), postoperative dialysis (OR 4.0; 95% CI 2.6-6.1), sepsis (OR 3.4; 95% CI 2.0-5.6), respiratory failure (OR 3.2; 95% CI 2.2-4.9), GIC (OR 3.2; 95% CI 1.9-5.3)) and included in the logistic model, which accurately predicted outcome (C statistic, 0.892; 95% CI 0.868-0.916). Length of hospital stay was significantly increased according to the number of complications (single: median 15 (IQR 10-24) days, double: 16 (IQR 8-28) days, ≥3: 20 (IQR 13-39) days, P<0.001). CONCLUSIONS With a worsening in the risk profile of patients undergoing cardiac surgery, an increasing number of patients develop major complications leading to increased length of stay and mortality, which is correlated to the number and severity of these complications. Our predictive model based on preoperative and postoperative variables allowed us to determine with accuracy the perioperative mortality in critically ill patients after cardiac surgery.

Sarcoplasmic Ca2+ release is prolonged in nonfailing myocardium of diabetic patients

Background Asymptomatic diabetic patients have a high incidence of clinically unrecognized left ventricular dysfunction with an abnormal cardiac response to exercise. We, therefore, examined subclinical defects in the contraction–relaxation cycle and intracellular Ca2+ regulation in myocardium of asymptomatic type 2 diabetic patients. Methods Alterations in the dynamics of the intracellular Ca2+ transient and contractility were recorded in right atrial myocardium of type 2 diabetic patients and non-diabetic control tissue loaded with fura-2. In order to gain an insight into mechanisms underlying the altered Ca2+ handling in diabetic myocardium levels of mRNA, protein expression and phosphorylation of key proteins in sarcoplasmic Ca2+ handling were determined. Results In isolated atrial trabeculae of diabetic myocardium the rise of systolic Ca2+ was significantly prolonged, but relaxation of the Ca2+ transient was unaltered compared to control tissue. Accordingly, the levels of expression of mRNA and protein of the Ca2+ release channel (RyR2) of the sarcoplasmic reticulum were reduced by 68 and 22%, respectively. Endogenous phosphorylation of RyR2 by protein kinases C, however, was increased by 31% in diabetic myocardium, as assessed by the back-phosphorylation technique. Levels of expression of SERCA2 and phospholamban were unaltered between both groups. Conclusions Intracellular Ca2+ release is prolonged in non-failing myocardium of type 2 diabetic patients and this may be primarily due to a decreased expression of RyR2. This defective Ca2+ release may represent an early stage of ventricular dysfunction in type 2 diabetes and would favor the abnormal response to exercise frequently observed in asymptomatic diabetic patients.

Long-term results after lung transplantation using organs from circulatory death donors: a propensity score-matched analysis †

OBJECTIVES Due to organ shortage in lung transplantation (LTx), donation after circulatory death (DCD) has been implemented in several countries, contributing to an increasing number of organs transplanted. We sought to assess long-term outcomes after LTx with organs procured following circulatory death in comparison with those obtained from donors after brain death (DBD). METHODS Between January 2007 and November 2013, 302 LTxs were performed in our institution, whereby 60 (19.9%) organs were retrieved from DCD donors. We performed propensity score matching (DCD:DBD = 1:2) based on preoperative donor and recipient factors that were significantly different in univariate analysis. RESULTS After propensity matching, there were no statistically significant differences between the groups in terms of demographics and preoperative donor and recipient characteristics. There were no significant differences regarding intraoperative variables and total ischaemic time. Patients from the DCD group had significantly higher incidence of primary graft dysfunction grade 3 at the end of the procedure (P = 0.014), and significantly lower pO2/FiO2 ratio during the first 24 h after the procedure (P = 0.018). There was a trend towards higher incidence of the need for postoperative extracorporeal life support in the DCD group. Other postoperative characteristics were comparable. While the overall cumulative survival was not significantly different, the DCD group had significantly poorer results in terms of bronchiolitis obliterans syndrome (BOS)-free survival in the long-term follow-up. CONCLUSIONS Long-term results after LTx with organs procured following DCD are in general comparable with those obtained after DBD LTx. However, patients transplanted using organs from DCD donors have a predisposition for development of BOS in the longer follow-up.

Unilateral Re-Expansion Pulmonary Edema: A Rare Complication Following One-Lung Ventilation for Minimal Invasive Mitral Valve Reconstruction

Abstract  A rare case of a unilateral re‐expansion pulmonary edema following one‐lung ventilation for minimally invasive mitral valve reconstruction in cardiopulmonary bypass is described.