Vascular anatomy of the rat liver and its implications for extended hepatectomy and the determination of the minimal liver mass

Due to increased demand for living liver donation and constant improvements in surgical methods, determination of the minimal liver mass compatible with survival is necessary for clinical as well as experimental liver surgery. A 10% remnant liver after extended hepatectomy in a rat was considered non-compatible with survival. Detailed 3-D visualization of the vascular supply and drainage of rat livers served as a basis for the development of a new surgical technique. Materials and Methods: Rat liver plastinates and vascular corrosion casts were used for visualization of the rat lobar and vascular anatomy. As a result of this detailed anatomical study, the new surgical technique consisting of a delicate stepwise piercing of the liver parenchyma at the bases of median and right superior lobes was introduced. Achieving plain cutting surface of liver lobe pedicle while skipping a Pringle maneuver or ligation of the portal vein and hepatic artery prior to resection represented key points in this "parenchyma preserving" approach. Results: The paracaval liver was identified as a separate “liver lobe” with its own multiple portal blood supply and hepatic drainage contributing to about 4% of the total liver mass. Damage of the remnant liver was clearly dependent on the surgical approach. Mass ligation procedures caused severe damage to the remnant liver, whereas the newly developed technique was preserving the remnant liver parenchyma. Timely initiation of regeneration was related to the extent of morphological damage in the small remnant liver, which was dependent on technique used. All animals subjected to 90% PH survived. Extending liver resections to 95% led to a survival rate of 66%. Further reduction of liver mass up to 97% resulted in death of all animals. Conclusion: Newly optimized "vessel oriented" surgical technique was benefitial compared to widely used "classical" methods in terms of survival and early initiation of liver regeneration after subtotal hepatectomy

Establishment of a guided, in vivo, multi-channel, abdominal, tissue imaging approach

Novel tools in humane animal research should benefit the animal as well as the experimentally obtained data. Imaging technologies have proven to be versatile and also in accordance with the demands of the 3 R principle. However, most imaging technologies are either limited by the target organs, number of repetitive imaging sessions, or the maximal resolution. We present a technique-, which enables multicolor abdominal imaging on a tissue level. It is based on a small imaging fiber endoscope, which is guided by a second commercial endoscope. The imaging fiber endoscope allows the distinction of four different fluorescence channels. It has a size of less than 1 mm and can approximately resolve single cells. The imaging fiber was successfully tested on cells in vitro, excised organ tissue, and in mice in vivo. Combined with neural networks for image restauration, high quality images from various abdominal organs of interest were realized. The second endoscope ensured a precise placement of the imaging fiber in vivo. Our approach of guided tissue imaging in vivo, combined with neuronal networks for image restauration, permits the acquisition of fluorescence-microscope like images with minimal invasive surgery in vivo. Therefore, it is possible to extend our approach to repetitive imaging sessions. The cost below 30 thousand euros allows an establishment of this approach in various scenarios. © 2020, The Author(s)

Subacute Aortic Rupture Due to Mechanical Chest Compression with Indwelling Impella

Mechanical cardiopulmonary resuscitation (CPR) devices like Lund University Cardiopulmonary Assist System (LUCAS) cause more skeletal and visceral injuries than standard CPR. A 62-year-old woman with ST-elevation myocardial infarction was resuscitated with LUCAS and Impella CP for refractory cardiogenic shock during percutaneous coronary intervention. She suffered delayed ascending aortic rupture necessitating supracommissural ascending aortic replacement plus triple bypass grafting. Prolonged mechanical CPR with concomitant Impella may lead to aortic rupture. The combined use of LUCAS and Impella may have disastrous consequences

Different acute kidney injury patterns after renal ischemia reperfusion injury and extracorporeal membrane oxygenation in mice

The use of extracorporeal membrane oxygenation (ECMO) is associated with acute kidney injury (AKI) in thoracic organ transplantation. However, multiple other factors contribute to AKI development after these procedures such as renal ischemia-reperfusion injury (IRI) due to hypo-perfusion of the kidney during surgery. In this study, we aimed to explore the kidney injury patterns in mouse models of ECMO and renal IRI. Kidneys of C57BL/6 mice were examined after moderate (35 min) and severe (45 min) unilateral transient renal pedicle clamping and 2 h of veno-venous ECMO. Renal injury markers, neutrophil infiltration, tubular transport function, pro-inflammatory cytokines, and renal heme oxygenase-1 (HO-1) expression were determined by immunofluorescence and qPCR. Both procedures caused AKI, but with different injury patterns. Severe neutrophil infiltration of the kidney was evident after renal IRI, but not following ECMO. Tubular transport function was severely impaired after renal IRI, but preserved in the ECMO group. Both procedures caused upregulation of pro-inflammatory cytokines in the renal tissue, but with different time kinetics. After ECMO, but not IRI, HO-1 was strongly induced in tubular cells indicating contact with hemolysis-derived proteins. After IRI, HO-1 was expressed on infiltrating myeloid cells in the tubulo-interstitial space. In conclusion, renal IRI and ECMO both caused AKI, but kidney damage after renal IRI was more pronounced including severe neutrophil infiltration and tubular transport impairment. Enhanced HO-1 expression in tubular cells after ECMO encourages limitation of hemolysis as a therapeutic approach to reduce ECMO-associated AKI

Benefits of intra-aortic balloon pump support in patients with postcardiotomy shock requiring venoarterial extracorporeal membrane oxygenation

Background: The benefit of the combined use of an intra-aortic balloon pump (IABP) and venoarterial extracorporeal membrane oxygenation (VA-ECMO) for postcardiotomy shock remains unclear. We aimed to analyse the potential benefits and safety of combining these two devices. Methods: We enrolled 200 patients treated with either VA-ECMO only or in combination with IABP (ECMO-I group) between January 2012 and January 2021. To adjust the patients’ backgrounds, we used propensity score matching for additional analyses, resulting in 57 pairs. The primary endpoint was 30-day survival. Secondary endpoints included successful weaning and complication rates. We also analysed hemodynamic parameters in both groups. Results: After propensity score matching, 30-day survival was better in the ECMO-I group (log-rank p = 0.004). The ECMO-I and ECMO-only groups differed regarding the secondary endpoints, including successful weaning (50.9% and 26.3%, respectively; p = 0.012) and the need for continuous renal replacement therapy (28.1% and 50.9%, p = 0.021). Complication rates were not statistically different between the two groups. Conclusion: Compared to VA-ECMO alone, the combined use of VA-ECMO and IABP is beneficial regarding 30-day survival in selected patients with postcardiotomy shock; successful ECMO weaning and freedom from renal replacement therapy is more common in patients supported with VA-ECMO plus IABP

The completeness of the left atrial appendage amputation during routine cardiac surgery

Abstract Background Left atrial appendage (LAA) is the origin of most heart thrombi which can lead to stroke or other cerebrovascular event in patients with non-valvular atrial fibrillation (AF). This study aimed to prove safety and low complication rate of surgical LAA amputation using cut and sew technique with control of its effectiveness. Methods 303 patients who have undergone selective LAA amputation were enrolled in the study in a period from 10/17 to 08/20. The LAA amputation was performed concomitant to routine cardiac surgery on cardiopulmonary bypass with cardiac arrest with or without previous history of AF. The operative and clinical data were evaluated. Extent of LAA amputation was examined intraoperatively by transoesophageal echocardiography (TEE). Six months in follow up, the patients were controlled regarding clinical status and episodes of strokes. Results Average age of study population was 69.9 ± 19.2 and 81.9% of patients were male. In only three patients was residual stump after LAA amputation larger than 1 cm with average stump size 0.28 ± 0.34 cm. 3 patients (1%) developed postoperative bleeding. Postoperatively 77 (25.4%) patients developed postoperative AF (POAF), of which 29 (9.6%) still had AF at discharge. On 6 months follow up only 5 patients had NYHA class III and 1 NYHA class IV. Seven patients reported with leg oedema and no patient experienced any cerebrovascular event in early postoperative follow up. Conclusion LAA amputation can be performed safely and completely leaving minimal to no LAA residual stump

Clinically inapparent right heart dysfunction is associated with reduced myofilament force development in coronary artery disease

Background Right ventricular dysfunction after CABG is associated with poor peri- and postoperative outcomes. We aimed to identify clinical and experimental predictors for preoperative inapparent right ventricular dysfunction and therefore hypothesized that reduced myofilament force development as well as altered levels of biomarkers might predict inapparent right ventricular dysfunction. Methods From 08/2016 to 02/2018, 218 patients scheduled for CABG were divided into two groups (TAPSE ≥ 20 mm, n = 178; TAPSE < 20 mm, n = 40). Baseline serum samples for biomarkers (Galectin, TGFß1, N Acyl-SDMA, Arginine, ADMA and Pentraxin-3), clinical laboratory and transthoracic echocardiographic parameters were evaluated. To examine the myocardial apparatus of the right ventricle intraoperative right auricular tissue was harvested for stepwise skinned fiber force measurements. Results Patients with TAPSE < 20 mm had a higher incidence of DM (55 vs. 34%, p = 0.018), preoperative AFib (43 vs. 16%, p < 0.001), reduced GFR (67 ± 18 vs. 77 ± 24 ml/min/1.73 m$^2$, p = 0.013), larger LA area (22 ± 6 vs. 20 ± 5 cm$^2$, p = 0.005) and reduced LVEF (50 vs. 55%, p = 0.008). Furthermore, higher serum ADMA (0.70 ± 0.13 vs. 0.65 ± 0.15 µmol/l, p = 0.046) and higher serum Pentraxin-3 levels (3371 ± 1068 vs. 2681 ± 1353 pg/dl, p = 0.004) were observed in these patients. Skinned fiber force measurements showed significant lower values at almost every step of calcium concentration (pCa 4.52 to pCa 5.5, p < 0.01 and pCa 5.75–6.0, p < 0.05). Multivariable analysis revealed DM (OR 2.53, CI 1.12–5.73, Euro Score II (OR 1.34, CI 1.02–1.78), preoperative AF (OR 4.86, CI 2.06–11.47), GFR (OR 7.72, CI 1.87–31.96), albumin (OR 1.56, CI 0.52–2.60), Pentraxin-3 (OR 19.68, CI 14.13–25.24), depressed LVEF (OR 8.61, CI 6.37–10.86), lower force values: (pCa 5.4; OR 2.34, CI 0.40–4.29 and pCa 5.2; OR 2.00, CI 0.39–3.60) as predictors for clinical inapparent right heart dysfunction. Conclusions These preliminary data showed that inapparent right heart dysfunction in CAD is already associated with reduced force development of the contractile apparatus

Blood cytokine expression correlates with early multi-organ damage in a mouse model of moderate hypothermia with circulatory arrest using cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) with moderate hypothermic cardiac arrest (MHCA) is essential for prolonged complex procedures in cardiac surgery and is associated with postoperative complications. Although cytokine release provoked through MHCA under CPB plays a pivotal role in postoperative organ damage, the pathomechanisms are unclear. Here, we investigated the cytokine release pattern and histological organ damage after MHCA using a recently described mouse CPB model. Eight BALB/c mice underwent 60 minutes of circulatory arrest under CPB, were successively rewarmed and reperfused. Blood cytokine concentrations and liver and kidney function parameters were measured and histological changes to these organs were compared to control animals. Our results showed a marked increase in proinflammatory cytokines and histological changes in the kidney, lung, and liver after CPB. Furthermore, clinical chemistry showed signs of hemolysis and acute kidney injury. These results suggest early onset of solid organ injury which correlates with increased leukocyte infiltration. A better understanding of the interplay between pro-inflammatory cytokine activation and solid organ injury in this model of CBP with MHCA will inform strategies to reduce organ damage during cardiac surgeries in the clinic

Multiorgan recovery in a cadaver body using mild hypothermic ECMO treatment in a murine model

Abstract Background Transplant candidates on the waiting list are increasingly challenged by the lack of organs. Most of the organs can only be kept viable within very limited timeframes (e.g., mere 4–6 h for heart and lungs exposed to refrigeration temperatures ex vivo). Donation after circulatory death (DCD) using extracorporeal membrane oxygenation (ECMO) can significantly enlarge the donor pool, organ yield per donor, and shelf life. Nevertheless, clinical attempts to recover organs for transplantation after uncontrolled DCD are extremely complex and hardly reproducible. Therefore, as a preliminary strategy to fulfill this task, experimental protocols using feasible animal models are highly warranted. The primary aim of the study was to develop a model of ECMO-based cadaver organ recovery in mice. Our model mimics uncontrolled organ donation after an “out-of-hospital” sudden unexpected death with subsequent “in-hospital” cadaver management post-mortem. The secondary aim was to assess blood gas parameters, cardiac activity as well as overall organ state. The study protocol included post-mortem heparin–streptokinase administration 10 min after confirmed death induced by cervical dislocation under full anesthesia. After cannulation, veno-arterial ECMO (V–A ECMO) was started 1 h after death and continued for 2 h under mild hypothermic conditions followed by organ harvest. Pressure- and flow-controlled oxygenated blood-based reperfusion of a cadaver body was accompanied by blood gas analysis (BGA), electrocardiography, and histological evaluation of ischemia–reperfusion injury. For the first time, we designed and implemented, a not yet reported, miniaturized murine hemodialysis circuit for the treatment of severe hyperkalemia and metabolic acidosis post-mortem. Results BGA parameters confirmed profound ischemia typical for cadavers and incompatible with normal physiology, including extremely low blood pH, profound negative base excess, and enormously high levels of lactate. Two hours after ECMO implantation, blood pH values of a cadaver body restored from  130 to 41.7 ± 10.5 mmHg, sO2, base excess, and HCO3 were all elevated from below detection thresholds to 99.5 ± 0.6%, − 4 ± 6.2 and 22.0 ± 6.0 mmol/L, respectively (Student T test, p  20 to 10.5 ± 1.7 mmol/L) and hyperkalemia (from > 9 to 6.9 ± 1.0 mmol/L) was observed when hemodialysis was implemented. On balance, the first signs of regained heart activity appeared on average 10 min after ECMO initiation without cardioplegia or any inotropic and vasopressor support. This was followed by restoration of myocardial contractility with a heart rate of up to 200 beats per minute (bpm) as detected by an electrocardiogram (ECG). Histological examinations revealed no evidence of heart injury 3 h post-mortem, whereas shock-specific morphological changes relevant to acute death and consequent cardiac/circulatory arrest were observed in the lungs, liver, and kidney of both control and ECMO-treated cadaver mice. Conclusions Thus, our model represents a promising approach to facilitate studying perspectives of cadaveric multiorgan recovery for transplantation. Moreover, it opens new possibilities for cadaver organ treatment to extend and potentiate donation and, hence, contribute to solving the organ shortage dilemma