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Cirrhotic patients often suffer from cirrhotic cardiomyopathy (CCM). Previous animal models of CCM were inconsistent concerning the time and mechanism of injury; thus, the temporal dynamics and cardiac vulnerability were studied in more detail. Rats underwent bile duct ligation (BDL) and a second surgery 28 days later. Cardiac function was assessed by conductance catheter and echocardiography. Histology, gene expression, and serum parameters were analyzed. A chronotropic incompetence (Pd31 < 0.001) and impaired contractility at rest and a reduced contractile reserve (Pd31 = 0.03, Pdob-d31 < 0.001) were seen 31 days after BDL with increased creatine (Pd35, Pd42, and Pd56 < 0.05) and transaminases (Pd31 < 0.001). A total of 56 days after BDL, myocardial fibrosis was seen (Pd56 < 0.001) accompanied by macrophage infiltration (CD68: Pgroup < 0.001) and systemic inflammation (TNFα: Pgroup < 0.001, white blood cell count: Pgroup < 0.001). Myocardial expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC1α) was increased after 31 (Pd31 < 0.001) and decreased after 42 (Pd42 < 0.001) and 56 days (Pd56 < 0.001). Caspase-3 expression was increased 31 and 56 days after BDL (Pd31 = 0.005; Pd56 = 0.005). Structural changes in the myocardium were seen after 8 weeks. After the second surgery (second hit), transient myocardial insufficiency with secondary organ dysfunction was seen, characterized by reduced contractility and contractile reserve.

The physical fitness of patients with terminal heart failure and an implanted left ventricular assist device (LVAD) might be improved by load-adaptive control of the LVAD. In this study, three control strategies for LVAD were compared in eight pigs: (1) a constant stroke work (CSW) control strategy that ensures a constant ventricular load using ventricular stroke work as the control variable; (2) a work ratio (WR) controller that maintains a constant ratio of ventricular work to hydraulic pump work; and (3) a controller that maintains the pump pace at a constant speed (CS). Biventricular heart insufficiency was induced by increased isoflurane application, and preload, afterload, and contractility alterations were performed. LVAD speed changes were significantly more pronounced in all load interventions with the CSW control strategy (preload: P0.001 vs. CS and P = 0.004 vs. WR; afterload: P0.001 vs. CS and P0.001 vs. WR; contractility: P0.001 vs. CS and P0.001 vs. WR). However, a significant difference in systemic flow only became evident in the experiments upon afterload increase ( P0.001 vs. CS and P = 0.004 vs. WR). An implementation of an evolved version of the CSW control strategy that dispenses with invasively measured parameters might be feasible for clinical use.

The implantation of a left ventricular assist device (LVAD) is often the only therapy in terminal heart failure (HF). However, despite technical advancements, the physical fitness of the patients is still limited. One strategy to improve the benefits of ventricular assist device therapy might be the implementation of load adaptive control strategies. Two control strategies and a constant speed controller (CS) were implemented in an acute animal model where four healthy pigs received LVAD implantations. In the first strategy (preload recruitable stroke work [SW] controller, PRS), the desired pump work was computed in relation to the end-diastolic volume. In the second strategy, the controller was programmed to keep a fixed ratio of the mean hydraulic power of the assist device to the mean hydraulic power of the left ventricle (power relation controller, PR). Preload reduction, afterload increase experiments and short-term coronary artery occlusions were conducted to test the behavior of the control strategies under variable conditions. Within the experiments, the PR controller demonstrated the best preload sensitivity. The PRS controller had the best response to an increased afterload and to a reduced ventricular contractility in terms of effectively preventing ventricular overloading and increasing VAD support. No significant differences in systemic flow were observed.

The number of patients awaiting liver transplantation still widely exceeds the number of donated organs available. Patients receiving extended criteria donor (ECD) organs are especially prone to an aggravated ischemia reperfusion syndrome during liver transplantation leading to massive hemodynamic stress and possible impairment in organ function. Previous studies have demonstrated aprotinin to ameliorate reperfusion injury and early graft survival. In this single center retrospective analysis of 84 propensity score matched patients out of 274 liver transplantation patients between 2010 and 2014 (OLT), we describe the association of aprotinin with postreperfusion syndrome (PRS), early allograft dysfunction (EAD: INR 1,6, AST/ALT &gt, 2000 within 7–10 days) and recipient survival. The incidence of PRS (52.4% vs. 47.6%) and 30-day mortality did not differ (4.8 vs. 0%, p = 0.152) but patients treated with aprotinin suffered more often from EAD (64.3% vs. 40.5%, p = 0.029) compared to controls. Acceptable or poor (OR = 3.3, p = 0.035, OR = 9.5, p = 0.003) organ quality were independent predictors of EAD. Our data do not support the notion that aprotinin prevents nor attenuates PRS, EAD or mortality.

In clinical practice ventricular assist devices are generally applied with a constant rotary speed. The lack of adaptivity to changes in hemodynamic conditions might result in underpumping or suction. In this paper, a norm-optimal iterative learning control algorithm incorporating variable cycle durations is developed and tested in silico to changes in afterload, contractility, and heart rate. To simulate exercise, a fourth experiment with parallel variations of preload, afterload, contractility and heart rate is done. For this purpose, a simplified simulation model of the cardiovascular system is used. The results confirm that the algorithm is able to prevent the dilatation of the ventricle and adapt to varying cycle lengths.

Scientific reports 11, 3353 (2021). doi:10.1038/s41598-021-82791-3, Published by Macmillan Publishers Limited, part of Springer Nature, London

Journal of Clinical Medicine 10(23), 5471 (2021). doi:10.3390/jcm10235471, Published by MDPI, Basel

Background: The goal of cardiac evaluation of patients awaiting orthotopic liver transplantation (OLT) is to identify the patients at risk for cardiovascular events (CVEs) in the peri- and postoperative periods by opportunistic evaluation of coronary artery calcium (CAC) in non-gated abdominal computed tomographs (CT). Methods: We hypothesized that in patients with OLT, a combination of Lee’s revised cardiac index (RCRI) and CAC scoring would improve diagnostic accuracy and prognostic impact compared to non-invasive cardiac testing. Therefore, we retrospectively evaluated 169 patients and compared prediction of CVEs by both methods. Results: Standard workup identified 22 patients with a high risk for CVEs during the transplant period, leading to coronary interventions. Eighteen patients had a CVE after transplant and a CAC score &gt, 0. The combination of CAC and RCRI ≥ 2 had better negative (NPV) and positive predictive values (PPV) for CVEs (NPV 95.7%, PPV 81.6%) than standard non-invasive stress tests (NPV 92.0%, PPV 54.5%). Conclusion: The cutoff value of CAC &gt, 0 by non-gated CTs combined with RCRI ≥ 2 is highly sensitive for identifying patients at risk for CVEs in the OLT population.

PLOS ONE 16(8), e0256790 (2021). doi:10.1371/journal.pone.0256790, Published by PLOS, San Francisco, California, US

Background: The number of patients awaiting liver transplantation still widely exceeds the number of donated organs available. Patients receiving extended criteria donor (ECD) organs are especially prone to an aggravated ischemia reperfusion syndrome during liver transplantation leading to massive hemodynamic stress and possible impairment in organ function. Previous studies have demonstrated aprotinin to ameliorate reperfusion injury and early graft survival. Methods: In this single center retrospective analysis of 84 propensity score matched patients out of 290 liver transplantation patients between 2010 and 2014 (OLT), we describe the association of aprotinin with postreperfusion syndrome (PRS), early allograft dysfunction (EAD: INR  1,6, AST/ALT >2000 within 7-10 days) and recipient survival. Results: The Incidence of PRS (52,4% vs 47,6%) and 30-day mortality did not differ (4.8 vs 0%; p=0.152) but patients treated with aprotinin suffered more often from EAD (64,3% vs 40,5%, p=0.029) compared to controls. Acceptable or poor (OR=3.3, p=0.035; OR=9.5, p=0.003) organ quality were independent predictors of EAD. Conclusion: Our data does not support the notion that aprotinin prevents nor attenuates PRS, EAD or mortality.

Die chirurgischen Patholgien der Leber umfassen tumorartige Lasionen, benigne und primar sowie sekundar maligne Lebertumoren, das Patientengut differiert stark und die operativen Eingriffe variieren deutlich in ihrer Ausdehnung, Invasivitat und Auswirkungen auf das anasthesiologische Vorgehen. Dieses Kapitel gibt einen Uberblick uber gangige Operationsverfahren.

Intermittent hypoxia and various pharmacological compounds protect the heart from ischemia reperfusion injury in experimental approaches, but the translation into clinical trials has largely failed. One reason may lie in species differences and the lack of suitable human in vitro models to test for ischemia/reperfusion. We aimed to develop a novel hypoxia-reoxygenation model based on three-dimensional, spontaneously beating and work performing engineered heart tissue (EHT) from rat and human cardiomyocytes. Contractile force, the most important cardiac performance parameter, served as an integrated outcome measure. EHTs from neonatal rat cardiomyocytes were subjected to 90 min of hypoxia which led to cardiomyocyte apoptosis as revealed by caspase 3-staining, increased troponin I release (time control vs. 24 h after hypoxia: cTnI 2.7 vs. 6.3 ng/mL, ** p = 0.002) and decreased contractile force (64 &plusmn, 6% of baseline) in the long-term follow-up. The detrimental effects were attenuated by preceding the long-term hypoxia with three cycles of 10 min hypoxia (i.e., hypoxic preconditioning). Similarly, [d-Ala2, d-Leu5]-enkephalin (DADLE) reduced the effect of hypoxia on force (recovery to 78 &plusmn, 5% of baseline with DADLE preconditioning vs. 57 &plusmn, 5% without, p = 0.012), apoptosis and cardiomyocyte stress. Human EHTs presented a comparable hypoxia-induced reduction in force (55 &plusmn, 5% of baseline), but DADLE failed to precondition them, likely due to the absence of &delta, opioid receptors. In summary, this hypoxia-reoxygenation in vitro model displays cellular damage and the decline of contractile function after hypoxia allows the investigation of preconditioning strategies and will therefore help us to understand the discrepancy between successful conditioning in vitro experiments and its failure in clinical trials.

Speckle tracking echocardiography enables the detection of subclinical left ventricular dysfunction at rest in many heart diseases and potentially in severe liver diseases. It could also possibly serve as a predictor for survival. In this study, 117 patients evaluated for liver transplantation in a single center between May 2010 and April 2016 with normal left ventricular ejection fraction were included according to clinical characteristics of their liver disease: (1) compensated (n = 29), (2) clinically significant portal hypertension (n = 49), and (3) decompensated (n = 39). Standard echocardiography and speckle tracking echocardiography were performed at rest and during dobutamine stress. Follow-up amounted to three years to evaluate survival and major cardiac events. Altogether 67% (78/117) of the patients were transplanted and 32% (31/96 patients) died during the three-year follow-up period. Global longitudinal strain (GLS) at rest was significantly increased (became more negative) with the severity of liver disease (p &lt, 0.001), but reached comparable values in all groups during peak stress. Low (less negative) GLS values at rest (male: &gt, &minus, 17/female: &gt, 18%) could predict patient survival in a multivariate Cox regression analysis (p = 0.002). GLS proved valuable in identifying transplant candidates with latent systolic dysfunction.

Norm-optimal iterative learning control algorithms use plant models to predict the system behavior. In this paper, we focus on improving the performance in the norm-optimal iterative learning control of left ventricular assist devices. For this purpose, the previously used simple plant model is replaced by a piecewise linearized version of a nonlinear cardiovascular system model including the left ventricular assist device. Simulations are carried out to study the controller response to end-diastolic volume setpoint and preload changes. The results show minor improvements regarding the tracking performance and the rejection of disturbances but also an increase of computational effort compared to the previous algorithm.

The potential effect of graft steatosis on the postoperative liver function is discussed controversially. The present study aimed to evaluate the effect of the donor liver microvesicular steatosis on the postoperative outcome after liver transplantation.Ninety-four patients undergoing liver transplantation at the University Hospital Aachen were included in this study. The patient cohort was divided into three groups according to the grade of microvesicular steatosis (MiS): MiS30% (n=27), MiS 30%-60% (n=41) and MiS60% (n=26). The outcomes after liver transplantation were evaluated, including the 30-day and 1-year patient and graft survival rates and the incidences of early allograft dysfunction (EAD) and primary nonfunction (PNF).The incidences of EAD and PNF did not differ significantly between the groups. We observed 5 cases of PNF, one occurred in the MiS30% group and 4 in the MiS 30%-60% group. The 30-day and 1-year graft survivals did not differ significantly between groups. The 30-day patient survival rates were 100% in all groups. The 1-year patient survival rates were 94.4% in the MiS30% group, 87.9% in the MiS 30%-60% group and 90.9% in the MiS60% group.Microvesicular steatosis of donor livers has no negative effect on the postoperative outcome after liver transplantation.

Due to the lack of donor organs, the importance of left ventricular assist devices (LVADs) increases. State of the art is to operate the pumps with a constant speed (CS) leading to effects such as underpumping, ventricular suction or the backflow of blood from the aorta in the ventricle. The end-diastolic volume (EDV) is influenced by venous return, as well as diastolic function and systolic pressure development. Thus it is a good medical indicator of ventricular load. In this paper a norm-optimal iterative learning control (NOILC) algorithm is designed to shape the EDV of a pathological ventricle. In addition, further constraints such as for example a uniform filling of the ventricle and the prevention of pumping during the systole are considered. A simplified model of the systemic circulation and the pump is used to study the system response to changes in pulmonary vein pressure and to benchmark controller performance. The results show that the algorithm obtains an excellent tracking performance and prevents the dilation of the ventricle. The approach offers the physician the opportunity to control multiple physiological variables even though the optimal control output trajectory is not known. Future work will focus on the improvement of the controller performance regarding the rejection of instantaneous disturbances and the incorporation of variable cycle duration.

The first ever venous thrombotic condition associated with spaceflight, an internal jugular vein thrombus requiring anticoagulation, has recently been reported. Systematic investigation of space travel-associated thrombotic risk has not been conducted. Cellular, animal, and human studies performed in ground-based models and in actual weightlessness revealed influences of weightlessness and gravity on the blood coagulation system. However, human study populations were small and limited to highly selected participants. Evidence in individuals with medical conditions and older persons is lacking. Evidence for thrombotic risk in spaceflight is unsatisfactory. This issue deserves further study in heterogeneous, high risk populations to find prevention strategies and to enable safe governmental and touristic human spaceflight.

In clinical practice left ventricular assist devices are usually driven at constant speed and thus not adaptive to changes in hemodynamic conditions. In this paper, a norm-optimal iterative learning control algorithm with an economically motivated cost function is developed, which aims at keeping ventricular volume and pressure in a predefined valid range instead of tracking specific setpoints. The algorithm is tested in silico to changes in preload and afterload. Both experiments represent naturally occurring types of parameter variations. A comparative assessment is performed between the proposed control algorithm and a constant speed controller as well as a norm-optimal iterative learning control algorithm, which is designed to shape the end-diastolic volume. The results confirm that the algorithm is able to keep ventricular volume and pressure in predefined ranges to prevent e.g. ventricular suction and dilatation. Furthermore, it offers the physician the opportunity to implement different training protocols by adapting the economic cost function.

Objective A simple but reliable and safe anaesthetic procedure is required for surgical interventions in small rodents. Combined ketamine and xylazine injections are often used in rats for less invasive surgery, possibly with spontaneous breathing and without airway management. However, there are important pitfalls to be avoided by special precautions and monitoring, as shown subsequently. Study design Observational study. Animals Twenty-four anaesthetic procedures for bile duct ligation, sham operation or carotid artery dilatation in 20 male Sprague-Dawley rats, preoperatively weighing between 440 and 550 g. Methods Intolerable high mortality rates occurred in the first 7 postoperative days while establishing a new experimental model in rats using ketamine-xylazine anaesthesia. Rats were spontaneously breathing ambient air during the first 12 surgeries without airway management. An observed high mortality rate in these animals led to a change in the trial protocol: the insufflation of 2 litres of oxygen per minute via nose cone during the following 12 rat surgeries. Retrospective comparison of the outcome (without oxygen vs. with oxygen insufflation) was conducted. Results The perioperative mortality rate could be significantly reduced from 58% (7/12) to 17% (2/12) (p = 0.036) by oxygen insufflation via nose cone. Significantly different levels of intraoperative oxygen saturation (SpO2; 89 ± 4% [without oxygen] vs. 97 ± 0.5% [with oxygen], p < 0.0001), but no significant differences in heart rate (HR; 267 ± 7 beats minute–1 [bpm] [without oxygen] vs. 266 ± 6 bpm [with oxygen], p = 0.955) were observed. Conclusions and clinical relevance In summary, rats under ketamine-xylazine anaesthesia are susceptible to hypoxia. This may lead to increased delayed mortality related to hypoxia induced lung failure. Apparently, this is an underestimated problem. We highly recommend using additional oxygen insufflation in spontaneously breathing rats under ketamine-xylazine anaesthesia with basic monitoring such as measurement of oxygen saturation.

Background: The discrepancy between demand and supply for liver transplants (LT) has led to an increased transplantation of organs from extended criteria donors (ECD).Methods: In this single center retrospective analysis of 122 cadaveric LT recipients, we investigated predictors of postreperfusion syndrome (PRS) including transplant liver quality categorized by both histological assessment of steatosis and subjective visual assessment by the transplanting surgeon using multivariable regression analysis. Furthermore, we describe the relevance of PRS during the intraoperative and postoperative course of LT recipients.Results: 53.3% (n = 65) of the patients suffered from PRS. Risk factors for PRS were visually assessed organ quality of the liver grafts (acceptable: OR 12.2 [95% CI 2.43-61.59], P = 0.002; poor: OR 13.4 [95% CI 1.48-121.1], P = 0.02) as well as intraoperative norepinephrine dosage before reperfusion (OR 2.2 [95% CI 1.26-3.86] per 0.1 mu g kg(-1) min(-1), P = 0.01). In contrast, histological assessment of the graft was not associated with PRS. LT recipients suffering from PRS were hemodynamically more instable after reperfusion compared to recipients not suffering from PRS. They had lower mean arterial pressures until the end of surgery (P Conclusions: Patients receiving ECD liver grafts are especially prone to PRS. Anesthesiologists should keep these newly described risk factors in mind when preparing for reperfusion in patients receiving high-risk organs.

The extent of right ventricular compensation compared to the left ventricle is restricted and varies among individuals, which makes it difficult to define. While establishing a model of acute pulmonary hypertension in pigs we observed two different kinds of compensation in our animals. Looking deeper into the hemodynamic data we tried to delineate why some animals could compensate and others could not. Pulmonary hypertension (mean pressure 45 mmHg) was induced gradually by infusion of a stable thromboxane A 2 analogue U46619 in a porcine model ( n = 22). Hemodynamic data (pressure‐volume loops, strain‐analysis of echocardiographic data and coronary flow measurements) were evaluated retrospectively for the short‐term right ventricular compensatory mechanisms and limits (Roehl et al. [2012] Acta Anaesthesiol. Scand., 56:449–58) 10 animals showed stable arterial blood pressures, whereas 12 pigs exhibited a significant drop of 16.4 ± 9.9 mmHg. Cardiac output and heart rate were comparable in both groups. In contrast, right ventricular contractility and coronary flow only rose in the stable group. The unchanging values in the decrease group correlated with an increasing ST‐segment depression and a loss of ventricular synchronism and resulted in a larger septum bulging to the right ventricle. Simultaneously, a reduced left‐ventricular end‐diastolic volume and a missing improvement in contractility in the posterior septal and inferior free wall of the left ventricle have been observed. Our findings suggest that right ventricular compensation during acute pulmonary hypertension is strongly dependent on the individual capability to increase coronary flow. The cause for inter‐individual variability could be the dimension and reactivity of the coronary system.

In contrast to volatile anaesthetics, xenon acts by antagonism at N-methyl-d-aspartate receptors and antagonizes 5-hydroxytryptamine type 3 receptors that mediate nausea and vomiting. Therefore, it is unknown whether the same risk factors for postoperative nausea and vomiting (PONV) after volatile anaesthetics apply to xenon-based anaesthesia.With ethics committee approval and written informed consent, 502 consecutive patients undergoing xenon-based anaesthesia were included in a multicentre prospective observational study. Antiemetic prophylaxis was administered at the discretion of the attending anaesthetists. Postoperative nausea and vomiting and need for antiemetic rescue medication were assessed for 24 h after anaesthesia. Multivariate logistic regression analysis was performed to quantify risk factors for PONV and need for rescue medication.Four hundred and eighty-eight subjects were available for the final analysis. The incidence of PONV in subjects without prophylaxis was lower than expected according to the Apfel Score (28% observed; 42% expected, P0.001). Independent predictors for PONV were (adjusted odds ratio; 95% confidence interval) female sex (1.76; 1.08-2.89), younger patient age (0.82 per 10 yr; 0.69-0.97), and longer duration of anaesthesia (1.36 per hour; 1.17-1.59).The incidence of PONV was significantly lower than predicted by the Apfel Score. Female sex, younger age, and longer duration of anaesthesia are risk factors for PONV after xenon-based anaesthesia.German Federal Institute for Drugs and Medical Devices number AL-PMS-01/07GER.

In this paper we present a mathematical model for isovolumic left-ventricular pressure curves intended for applications in computer simulation models of the cardiovascular system. We chose a quadratic spline to individually account for the specific phases of isovolumic beats. Besides, we describe a method to identify subject specific isovolumic pressure curves based on measured physiological (non-isovolumic) pressure curves. Therefore, we used experimental data obtained from a trial on an anesthetized pig. Specifically, we investigated the effect of a preload reduction for a given contractile state on the isovolumic pressure curves. Towards validation of the proposed model we compared the predicted isovolumic pressure curve to data of real experimentally obtained isovolumic beats. Besides, a comparison to alternative isovolumic pressure curve identification approaches for a different application (estimating contractility by single-beat evaluation) is drawn.