Signaling mechanisms inducing hyporesponsiveness of phagocytes during systemic inflammation.

The inflammatory responsiveness of phagocytes to exogenous and endogenous stimuli is tightly regulated. This regulation plays an important role in systemic inflammatory response syndromes (SIRSs). In SIRSs, phagocytes initially develop a hyperinflammatory response, followed by a secondary state of hyporesponsiveness, a so-called "tolerance." This hyporesponsiveness can be induced by endotoxin stimulation of Toll-like receptor 4 (TLR4), resulting in an ameliorated response after subsequent restimulation. This modification of inflammatory response patterns has been described as innate immune memory. Interestingly, tolerance can also be triggered by endogenous TLR4 ligands, such as the alarmins myeloid-related protein 8 (MRP8, S100A8) and MRP14 (S100A9), under sterile conditions. However, signaling pathways that trigger hyporesponsiveness of phagocytes in clinically relevant diseases are only barely understood. Through our work, we have now identified 2 main signaling cascades that are activated during MRP-induced tolerance of phagocytes. We demonstrate that the phosphatidylinositol 3-kinase/AKT/GSK-3ß pathway interferes with NF-κB-driven gene expression and that inhibition of GSK-3ß mimics tolerance in vivo. Moreover, we identified interleukin-10-triggered activation of transcription factors STAT3 and BCL-3 as master regulators of MRP-induced tolerance. Accordingly, patients with dominant-negative STAT3 mutations show no tolerance development. In a clinically relevant condition of systemic sterile stress, cardiopulmonary bypass surgery, we confirmed the initial induction of MRP expression and the tolerance induction of monocytes associated with nuclear translocation of STAT3 and BCL-3 as relevant mechanisms. Our data indicate that the use of pharmacological JAK-STAT inhibitors may be promising targets for future therapeutic approaches to prevent complications associated with secondary hyporesponsiveness during SIRS.

Minimally Invasive Aortic Root Replacement with Valved Conduits through Partial Upper Sternotomy.

BACKGROUND: Minimally invasive surgical access through limited sternotomy reduces trauma and morbidity in cardiosurgical patients. However, until now, it is not the standard access for aortic root replacement. This study details our clinic's experience with minimally invasive implantation of valved conduits through partial upper sternotomy and the comparison to conventional full median sternotomy. METHODS: Between January 2012 and March 2016, a total of 187 patients underwent aortic root replacement with valved conduits in our department. Minimally invasive access through partial upper sternotomy (group A) was performed in 33 patients (9 female, 24 male; mean age: 55.68 ± 13.24 years). Four of these patients received concomitant mitral and tricuspid valve interventions. The results were compared with similar procedures through conventional approach (group B): 25 patients (7 female, 18 male; mean age: 59.09 ± 12.32 years). RESULTS: In all 33 cases of minimally invasive access and 25 cases of conventional approach, aortic root replacement was successful. Operative times were as follows (in minutes; groups A and B)-cardiopulmonary bypass: 166.12 ± 40.61 and 162.88 ± 45.89; cross-clamp time: 122.24 ± 27.42 and 113.44 ± 22.57, respectively. In both groups, two patients needed postoperative reexploration due to secondary bleeding. One multimorbid patient suffered from postoperative stroke and died on the ninth postoperative day due to heart failure. The observed operation times and clinical results after minimally invasive surgery are comparable to conduit implantation through full median sternotomy. CONCLUSIONS: Partial upper sternotomy is a feasible access for safe aortic root replacement with valved conduits. Nevertheless, minimally invasive aortic root replacement is a challenging operative procedure.

Early outcomes in re-do operation after acute type A aortic dissection: results from the multicenter REAAD database.

This study provides early results of re-operations after the prior surgical treatment of acute type A aortic dissection (AAD) and identifies risk factors for mortality. Between May 2003 and January 2014, 117 aortic re-operations after an initial operation for AAD (a mean time from the first procedure was 3.98 years, with a range of 0.1-20.87 years) were performed in 110 patients (a mean age of 59.8 ± 12.6 years) in seven European institutions. The re-operation was indicated due to a proximal aortic pathology in ninety cases: twenty aortic root aneurysms, seventeen root re-dissections, twenty-seven aortic valve insufficiencies and twenty-six proximal anastomotic pseudoaneurysms. In fifty-eight cases, repetitive surgical treatment was subscripted because of distal aortic pathology: eighteen arch re-dissections, fifteen arch dilation and twenty-five anastomotic pseudoaneurysms. Surgical procedures comprised a total of seventy-one isolated proximals, thirty-one isolated distals and fifteen combined interventions. In-hospital mortality was 19.6 % (twenty-three patients); 11.1 % in patients with elective/urgent indication and 66.6 % in emergency cases. Mortality rates for isolated proximal, distal and combined operations regardless of the emergency setting were 14.1 % (10 pts.), 25.8 % (8 pts.) and 33.3 % (5 pts.), respectively. The causes of death were cardiac in eight, neurological in three, MOF in five, sepsis in two, bleeding in three and lung failure in two patients. A multivariate logistic regression analysis revealed that risk factors for mortality included previous distal procedure (p = 0.04), new distal procedure (p = 0.018) and emergency operation (p < 0.001). New proximal procedures were not found to be risk factors for early mortality (p = 0.15). This multicenter experience shows that the outcome of REAAD is highly dependent on the localization and extension of aortic pathology and the need for emergency treatment. Surgery in an emergency setting and distal re-do operations after previous AAD remain a surgical challenge, while proximal aortic re-operations show a lower mortality rate. Foresighted decision-making is needed in cases of AAD repair, as the results are essential preconditions for further surgical interventions.

Minimally Invasive Implantation of HeartWare Assist Device and Simultaneous Tricuspid Valve Reconstruction Through Partial Upper Sternotomy.

Left ventricular assist device (LVAD) implantation is a well-established therapy to support patients with end-stage heart failure. However, the operative procedure is associated with severe trauma. Third generation LVADs like the HeartWare assist device (HeartWare, Inc., Framingham, MA, USA) are characterized by enhanced technology despite smaller size. These devices offer new minimally invasive surgical options. Tricuspid regurgitation requiring valve repair is frequent in patients with the need for mechanical circulatory support as it is strongly associated with ischemic and nonischemic cardiomyopathy. We report on HeartWare LVAD implantation and simultaneous tricuspid valve reconstruction through minimally invasive access by partial upper sternotomy to the fifth left intercostal space. Four male patients (mean age 51.72 ± 11.95 years) suffering from chronic heart failure due to dilative (three patients) and ischemic (one patient) cardiomyopathy and also exhibiting concomitant tricuspid valve insufficiency due to annular dilation underwent VAD implantation and tricuspid valve annuloplasty. Extracorporeal circulation was established via the ascending aorta, superior vena cava, and right atrium. In all four cases the LVAD implantation and tricuspid valve repair via partial median sternotomy was successful. During the operative procedure, no conversion to full sternotomy was necessary. One patient needed postoperative re-exploration because of pericardial effusion. No postoperative focal neurologic injury was observed. New generation VADs are advantageous because of the possibility of minimally invasive implantation procedure which can therefore minimize surgical trauma. Concomitant tricuspid valve reconstruction can also be performed simultaneously through partial upper sternotomy. Nevertheless, minimally invasive LVAD implantation is a challenging operative technique.

Axillary artery cannulation provides balanced cerebral oxygenation.

Deterioration of cerebral performance remains a major problem after cardiac surgery. Axillary artery cannulation can improve clinical outcome, but some experimental series show a malperfusion of the right hemisphere. The aim of our clinical study was to analyze the intraoperative investigation of cerebral oxygenation in two different arterial cannulation sites by use of near-infrared spectroscopic oximetry (NIRO). We compared retrospectively the cerebral saturation of 20 patients with aortic cannulation (group AoC) and 20 patients with right axillary artery cannulation (group AxC) during either valve, coronary artery bypass graft (CABG), combined procedures, or aortic surgery. Patients were monitored with bihemispheric NIRO (NIRO-200, Hamamatsu, Herrsching, Germany). The oxygenation data were calculated as tissue oxygenation index (TOI). And the cardiopulmonary bypass time was considered with special regard to potentially dangerous phases for cerebral desaturation like the starting of the extracorporeal circulation (ECC), cross-clamping, rewarming phase, aortic declamping, and stopping of ECC. Patients were then postoperatively evaluated by a standardized neurological examination. During the entire CPB time and the specific phases potentially at risk for cerebral desaturation, no statistically significant drop of cerebral oxygenation (>20 % for >60 s) was detected after aortic and right axillary artery cannulation, respectively. Furthermore, no significant difference in TOI was found comparing the left and right hemisphere in each group. Postoperatively 2 transient confusional syndromes (CS) were observed after aortic and 3 CS after axillary artery cannulation. Right axillary artery cannulation provides balanced cerebral oxygenation in both hemispheres during extracorporeal circulation and its specific phases potentially at risk for cerebral malperfusion. It might therefore reduce the risk of neurological injury by reduction of solid embolization and maintenance of balanced cerebral oxygenation.

Digital Carotid Compression: A Simple Method to Reduce Solid Cerebral Emboli During Cardiac Surgery.

OBJECTIVES: Serious neurologic injury can be attributed to embolization of solid particles into cerebral vessels during cardiac surgery. Previous studies using transcranial Doppler (TCD) identified arterial cannulation and aortic declamping to be associated with cerebral embolization. The purpose of this study was to investigate the impact of transient compression of the carotid arteries during these maneuvers on the embolic load during cardiac surgery with cardiopulmonary bypass. DESIGN: Prospective, randomized, clinical trial/pilot study. SETTING: Single-center study at a university hospital. PARTICIPANTS: Patients with multiple types of procedures were included and they were prospectively, randomly assigned to group I (n = 20, carotid compression during arterial cannulation and aortic declamping) and group II (n = 20, no carotid compression). INTERVENTIONS: Bilateral continuous monitoring of the middle cerebral arteries was performed with a multirange, multifreqency transcranial Doppler (DopplerBoxX, DWL, Singen, Germany), allowing for discrimination between solid and gaseous emboli. For aortic cannulation the carotid arteries were compressed for 5 seconds and for declamping for 3 seconds, and microemboli signals were detected within the following 45 seconds. MEASUREMENTS AND MAIN RESULTS: A reduction of intraoperative solid emboli was detected in group I compared with group II (26±16 v 38±18; p = 0.04). Looking specifically at the maneuver of arterial cannulation, the observed difference was 0.5±0.8 in group I versus 5.7±5.8 in group II (p<0.0001). During aortic declamping, 6.6±6.2 emboli were encountered in group I and 10.8±5.2 in group II (p = 0.02). The incidence of neurologic events was not significantly different between groups (2 patients in group II had pathologic changes on magnetic resonance imaging). CONCLUSIONS: The data of this preliminary trial demonstrated that transient compression of the carotid arteries during arterial cannulation and aortic declamping led to a decreased number of solid cerebral emboli. Further prospective, randomized clinical studies should be undertaken to investigate the influence of transient carotid artery compression during specific surgical procedures.

Implantation of left ventricular assist devices under extracorporeal life support in patients with heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a rare but life-threatening side effect of heparin therapy. It is a demanding therapeutic challenge in patients undergoing left ventricular assist device (LVAD) implantation. We present our experience with LVAD implantation under extracorporeal life support (ECLS) in patients suffering from HIT. Seven patients (mean age 54.0 ± 16.7 years, 1 female, 6 male patients) suffering from acute heart failure were stabilized with ECLS. Under heparin therapy, they all showed a sudden decrease of mean platelet count (maximum 212.6 ± 41.5 tsd/µl; minimum 30.7 ± 13.1 tsd/µl). Due to the clinical suspicion of HIT anticoagulation was switched from heparin to argatroban (aPTT 70-80 s.). No improvement of cardiac function could be detected under ECLS, so LVAD implantation was indicated. We performed LVAD implantation under ECLS. During LVAD implantation under argatroban (aPTT of 50-60 s.) one patient developed massive intraventricular thrombus formations, so the device had to be removed. In 6 cases, we could successfully perform LVAD implantation under argatroban with a higher aPTT of 70-80 s and modified operative strategy. Four patients needed postoperative re-exploration because of bleeding complications. Perioperative management of LVAD patients under argatroban anticoagulation is very difficult. We were able to minimize the perioperative risk for thrombosis with a target aPTT of 70-80 s. To keep the phase of stasis within the device as short as possible we anastomosed the VAD outflow graft to the ascending aorta first before connecting the device to the apex. However, postoperative bleeding complications are frequent.

Giant Left Atrial Myxoma: Cause for Position-Dependent Nocturnal Dyspnea and Cardiac Murmur.

Primary tumors of the heart are rare. The majority of them are benign, the left atrial myxoma being the most frequent one. Clinical appearance varies from unapparent to life-threatening complications such as stroke, acute heart failure, or even sudden death. Diagnosis and consecutive surgical treatment strongly depend on the clinical symptoms, but their extent does not correlate with the risk for serious complications. Therefore, patients with variable clinical presentation can be especially endangered. Consequent diagnostic and immediate operative therapy is essential.

Redo Operation of Recurrent Giant Coronary Artery Aneurysm: Optimizing Surgical Strategy.

Background Giant coronary artery aneurysms (GCAA) are extremely rare, but they can cause life-threatening complications. Indications for surgical intervention are the occurrence of complications such as fistulas, compression, embolization, or rapid enlargement. The optimal therapeutic approach is still under debate. Until now, there are no publications dealing with the follow-up after surgical treatment. Moreover, the surgical strategy in redo operations has not been described yet. Case Description We report on surgery in a 50-year-old man with a recurrent GCAA after previous dissection and reduction. Conclusion Our recommendation is complete resection and bypassing instead of a mere diameter reduction to avoid further progression of the disease.

Anatomic and flow dynamic considerations for safe right axillary artery cannulation.

OBJECTIVES: Neuroprotection is of paramount interest in cardiac surgery. Right axillary artery cannulation is well established in aortic surgery because it significantly improves survival and outcome, but malperfusion of the right brain after direct cannulation has been reported. Anatomically, 4 vessel segments are potentially amenable for cannulation of the subclavian and axillary arteries. Clinical studies vary widely in dissection sites and cannulation techniques. We investigated critical flow dynamics in the right brain caused by arterial inflow after direct cannulation and specified cannulation positions that provide optimal cerebral perfusion. METHODS: Distances from the lateral margin of the axillary artery and the subclavian artery to the origin of the vertebral artery were measured in 14 human corpses by a flexible ruler. We calculated the hemodynamics within the vertebral artery, depending on different positions of the cannula tip, in a computer-calculated model. RESULTS: The mean distance from the axillary artery to the vertebral artery was 8.5 cm, and the mean distance from the subclavian artery to the vertebral artery was 6.7 cm. Computed flow calculations demonstrated reversed flow in the vertebral artery when the cannula tip was positioned too close to its orifice. To ensure safe supra-aortic flow, a cannula can be inserted securely up to 6.0 cm into the axillary artery and 4.2 cm into the subclavian artery. CONCLUSIONS: Direct cannulation of the right axillary artery can lead to cerebral malperfusion, caused by an obstruction of the vertebral artery's orifice by the arterial cannula or a subclavian steal phenomenon due to flow reversal. The safety of direct axillary artery cannulation can be improved by a well-considered dissecting site and insertion length of the cannula.