Johannes Kalder

The impact of selective visceral perfusion on intestinal macrohemodynamics and microhemodynamics in a porcine model of thoracic aortic cross-clamping.

INTRODUCTIONnDespite its presumed effectiveness and clinical use, the physiology of selective visceral perfusion combined with distal aortic perfusion during open thoracoabdominal aortic surgery has not been characterized. Thus, the aim of this study was to establish a translatable model of thoracic aortic-clamping to assess the effect of selective visceral perfusion with added distal aortic perfusion on local intestinal macrohemodynamics and microhemodynamics, intestinal histopathology, and markers of inflammation and intestinal damage.nnnMETHODSnA thoracolaparotomy was performed in 15 pigs, and the aorta was exposed, including the origins of celiac trunk and superior mesenteric artery. The animals were divided into three cohorts: control (I), thoracic aortic cross-clamping (II), and thoracic aortic cross-clamping with selective visceral perfusion plus distal aortic perfusion using extracorporeal circulation (III). Macrocirculatory and microcirculatory blood flow was assessed by transit time ultrasound volume flow measurements and fluorescent microspheres. Intestinal ischemia-reperfusion injury was determined by the analysis of perioperative intestinal fatty acid-binding protein (IFABP) and interleukin-8 (IL-8) levels and correlated with histopathologic changes.nnnRESULTSnSevere intestinal tissue injury and an inflammatory response were observed in cohort II compared with cohort III for IL-8 (38.2 vs 3.56 pg/mL; P = .04). The procedure in cohort III resulted in a flow and pressure-associated intestinal hypoperfusion compared with cohort I in the superior mesenteric artery (mean blood pressure, 24.1 ± 10.4 vs 67.2 ± 7.4 mm Hg; P < .0001; mean flow rates: 353.3 ± 133.8 vs 961.7 ± 310.8 mL/min; P < .0001). This was paralleled in cohort III vs cohort I by a significant mucosal injury (IFABP, 713 ± 307.1 vs 170 ± 115.4 pg/mL; P = .014) despite a profound recruitment of intestinal microcirculation (338% ± 206.7% vs 135% ± 123.7%; P = .05).nnnCONCLUSIONSnThis study reports a novel large-animal model of thoracic aortic cross-clamping that allows the study of visceral perfusion strategies. However, we demonstrated with IL-8 and IFABP measurements that thoracoabdominal aortic aneurysm surgery with selective visceral perfusion and distal aortic perfusion is superior to the clamp-and-sew technique, even though small intestinal tissue damage cannot be completely avoided by selective visceral perfusion and distal aortic perfusion. In any case, this model seems to be a platform to evaluate and optimize measures for gut wall protection.

Feasibility of combined surgical and endovascular carotid access for interventional treatment of ischemic stroke

Background Rapid recanalization of occluded vessels is crucial for good clinical outcome in acute ischemic stroke. Endovascular treatment is usually performed via a transfemoral approach, but catheterization of the carotid arteries can be problematic in cases of difficult anatomy or vascular pathologies in some cases. Objective To describe our experience with a technique involving surgical access to the carotid artery and consecutive transcarotid endovascular thrombectomy in patients with acute stroke. Methods In a retrospective review of a prospectively maintained registry we identified 6 patients who underwent acute endovascular thrombectomy via a surgical access to the carotid artery. Results Admission National Institute of Health Stroke Scale (NIHSS) ranged from 7 to 23. Intracranial recanalization (thrombolysis in cerebral infarction, TICI≥2b) was achieved in all patients (100%). Recanalization was achieved within 19±5 min after establishing carotid access. One patient developed a small neck hematoma, which was surgically removed without complications. No complications related to endovascular therapy were seen. At 3u2005months’ follow-up, five patients had survived. Three patients (50%) had regained excellent neurological function (modified Rankin Scale, mRS 0–1). Conclusions Surgical carotid access for endovascular stroke treatment is feasible, with considerable advantages, in patients with expected problematic access or for whom transfemoral endovascular carotid access has failed.

Operative and Midterm Outcomes of the Fenestrated Anaconda Stent-Graft in the Endovascular Treatment of Juxtarenal, Suprarenal, and Type IV Thoracoabdominal Aortic Aneurysms

Purpose: To report operative and midterm outcomes of fenestrated endovascular aneurysm repair (FEVAR) with the Anaconda device. Methods: A retrospective analysis was conducted of 39 consecutive patients (median age 74 years; 36 men) treated with the fenestrated Anaconda stent-graft between July 2011 and December 2015 at a single center. Indications for FEVAR were abdominal aortic aneurysms (AAAs) with neck anatomy unsuitable for a standard stent-graft. Median infrarenal neck length was 4 mm (range 0–9). Four (10%) patients presented with type IV thoracoabdominal aortic aneurysm (TAAA), 12 (31%) with suprarenal aneurysms, and 23 (59%) with juxtarenal aneurysms. Four (10%) patients had previous infrarenal aortic repair. Five (13%) patients had an infrarenal neck angulation >60°. A total of 106 fenestrations were incorporated into the stent-grafts (73 renal arteries, 25 superior mesenteric arteries, and 8 celiac trunks). Technical success, perioperative and midterm mortality and morbidity, target vessel patency, endoleaks, and reinterventions were documented. Results: Technical success was 95% (37/39). Three (8%) patients died in-hospital from mesenteric embolism in 2 and renal artery rupture with consequent multiorgan failure in 1. Two (5%) patients suffered an intraoperative embolic stroke. During a median follow-up of 33 months (range 4–55), adjunctive maneuvers were performed in 9 (23%) patients, including reintervention for type II endoleak with enlarged aneurysm sac in 2 (5%). Four additional patients died of causes unrelated to the aortic pathology (overall mortality 18%). In 34 (94%) of the 36 patients seen in follow-up, aneurysm sac size was stable or decreased. Target vessel stent patency was 99% (95/96). Conclusion: FEVAR with the Anaconda device delivers satisfactory short-term technical and clinical success rates in patients with juxtarenal, suprarenal, and type IV TAAA. Midterm efficacy and durability with respect to aneurysm sac regression and target vessel patency appear very good. Overall mortality and the need for reintervention were significant in this patient cohort.

Microcirculatory perfusion shift in the gut wall layers induced by extracorporeal circulation

OBJECTIVEnExtracorporeal circulation (ECC) is regularly applied to maintain organ perfusion during major aortic and cardiovascular surgery. During thoracoabdominal aortic repair, ECC-driven selective visceral arterial perfusion (SVP) results in changed microcirculatory perfusion (shift from the muscularis toward the mucosal small intestinal layer) in conjunction with macrohemodynamic hypoperfusion. The underlying mechanism, however, is unclear. Therefore, the aim of this study was to assess in a porcine model whether ECC itself or the hypoperfusion induced by SVP is responsible for the mucosal/muscular shift in the small intestinal wall.nnnMETHODSnA thoracoabdominal aortic approach was performed in 15 healthy pigs divided equally into three groups: group I, control; group II, thoracic aortic cross-clamping with distal aortic perfusion; and group III, thoracic aortic cross-clamping with distal aortic perfusion and SVP. Macrocirculatory and microcirculatory blood flow was assessed by transit time ultrasound volume flow measurement and fluorescent microspheres. In addition, markers for metabolism and intestinal ischemia-reperfusion injury were determined.nnnRESULTSnECC with a roller pump induced a significant switch from the muscularis and mucosal layer of the small intestine, even with adequate macrocirculation (mucosal/muscular perfusion ratio: group I vs II, P = .005; group I vs III, P = .0018). Furthermore, the oxygen extraction ratio increased significantly in groups II (>30%) and III (>40%) in the beginning of the ECC compared with the control (group I vs II, P = .0037; group I vs III, P = .0062). Lactate concentrations and pH values did not differ between groups I and II; but group III demonstrated a significant shifting toward a lactate-associated acidosis (lactate: group I vs III, P = .0031; pH: group I vs III, P = .0001).nnnCONCLUSIONSnWe demonstrated a significant shifting between the small intestinal gut wall layers induced by roller pump-driven ECC. The shift occurs independently of macrohemodynamics, with a significant effect on aerobic metabolism in the gut wall. Consequently, an optimal intestinal perfusion cannot be guaranteed by a roller pump; therefore, perfusion techniques need to be optimized.

Training a Sophisticated Microsurgical Technique: Interposition of External Jugular Vein Graft in the Common Carotid Artery in Rats

Neointimal hyperplasia is one the primary causes of stenosis in arterialized veins that are of great importance in arterial coronary bypass surgery, in peripheral arterial bypass surgery as well as in arteriovenous fistulas.(1-5) The experimental procedure of vein graft interposition in the common carotid artery by using the cuff-technique has been applied in several research projects to examine the aetiology of neointimal hyperplasia and therapeutic options to address it. (6-8) The cuff prevents vessel anastomotic remodeling and induces turbulence within the graft and thereby the development of neointimal hyperplasia. Using the superior caval vein graft is an established small-animal model for venous arterialization experiment.(9-11) This current protocol refers to an established jugular vein graft interposition technique first described by Zou et al., (9) as well as others.(12-14) Nevertheless, these cited small animal protocols are complicated. To simplify the procedure and to minimize the number of experimental animals needed, a detailed operation protocol by video training is presented. This video should help the novice surgeon to learn both the cuff-technique and the vein graft interposition. Hereby, the right external jugular vein was grafted in cuff-technique in the common carotid artery of 21 female Sprague Dawley rats categorized in three equal groups that were sacrificed on day 21, 42 and 84, respectively. Notably, no donor animals were needed, because auto-transplantations were performed. The survival rate was 100 % at the time point of sacrifice. In addition, the graft patency rate was 60 % for the first 10 operated animals and 82 % for the remaining 11 animals. The blood flow at the time of sacrifice was 8±3 ml/min. In conclusion, this surgical protocol considerably simplifies, optimizes and standardizes this complicated procedure. It gives novice surgeons easy, step-by-step instruction, explaining possible pitfalls, thereby helping them to gain expertise fast and avoid useless sacrifice of experimental animals.

Editor's Choice – Open Thoracic and Thoraco-abdominal Aortic Repair in Patients with Connective Tissue Disease

OBJECTIVE/BACKGROUNDnThe aim is to present current results of open complex aortic repair in patients with connective tissue disease (CTD).nnnMETHODSnThis was a retrospective cross-border, single centre study. From February 2000 to April 2016 72 aortic operations were performed on 65 patients with CTD (41 male, median age 41 years [range 19-70 years]). Fifty-six patients (86%) underwent at least one previous aortic repair (71 open, four endovascular), including 33 patients (51%) operated before at the site of the procedure reported here. The open procedures, counting eight emergency operations (11%), included aortic arch revision (nxa0=xa01; 1%), descending thoracic aortic repair (nxa0=xa011; 15%), TAAA type I repair (nxa0=xa012; 17%), type II repair (nxa0=xa029; 40%), type III repair (nxa0=xa012; 17%), and type IV repair (nxa0=xa05; 7%). Simultaneous repair of the ascending aorta and/or the aortic arch was performed in two (3%) and eight cases (11%), respectively. Seven patients (10%) underwent staged procedures. Median follow-up was 42 months (0.5-180 months).nnnRESULTSnThe in hospital mortality was 14% (nxa0=xa09) as a result of haemorrhage (nxa0=xa03/9), neurological (nxa0=xa03/9),xa0cardiac (nxa0=xa02/9), and pulmonary (nxa0=xa01/9) complications. Paraplegia and paraparesis occurred in one (2%) and three patients (5%), respectively. Seven patients (11%) required temporary dialysis; nonexa0needed permanent dialysis. Major complications were revision surgery for bleeding or haematoma (nxa0=xa020/65),xa0sepsis (nxa0=xa010/65), myocardial infarction/severe cardiac arrhythmia (nxa0=xa02/65), stroke (nxa0=xa02/65),xa0as well as multiorgan failure, abdominal compartment syndrome, mesenteric and peripheral ischaemia (all nxa0=xa01/65). Multivariate analysis identified an operating time >xa07xa0hours (pxa0=xa0.006) as an independent predictor of increased mortality. Freedom from re-intervention was 85%, 1 year survival was 80%, and overall survival was 75%.nnnCONCLUSIONnOpen TAA(A) repair is a durable therapy for patients with CTD. Often being performed as revision surgery, it can be associated with relevant risks and should therefore be reserved for specialised centres. Staged procedures and thus reducing operating time, if applicable, should be preferred.

Intraoperative Neuromonitoring for Prevention of Neurological Complications in Aortic Surgery

AIMnStroke and paraplegia are devastating complications of thoracic and thoracoabdominal aortic surgery. The aim of this study was to analyse the value of transcranial Doppler ultrasound (TCD), electroencephalogram (EEG) and motor-evoked potentials (MEP) in preventing neurological complications. Moreover, the principles, technology and surgical protocols are described.nnnPATIENTS AND METHODSnIn 2009, 22 patients (4 females, 18 males) underwent thoracic or thoracoabdominal open aortic repair. We performed 2 arches with descending aortic replacement, 5 arches with TAAA repair, 2 type II, 9 type III, 3 type IV and one type V TAAA aortic repair. In 6 patients, the neuromonitoring included TCD, EEG and MEPs. In 15 patients only MEP monitoring was necessary. In one patient who was operated on in an emergency setting, neuromonitoring was not performed. The surgical approach was a left thoracotomy in 3 and a left thoracolaparotomy in 19 patients. The surgical protocol included cerebrospinal fluid drainage (n=22), moderate (n=19) or deep hypothermia (n=2), and extracorporeal circulation (n=21) with retrograde aortic perfusion and selective cerebral and/or viscerorenal perfusion.nnnRESULTSnIn 21 patients, the neuromonitoring could be established successfully. Using TCD and EEG, a relevant cerebral ischaemia during supraaortic clamping was excluded. With a mean distal arterial pressure of 60 mmHg, the MEPs remained adequate in 15 patients (68.2%). Increasing of the blood pressure restored the MEPs in one patient. In 5 patients (22.7%), a reimplantation of segmental arteries (n=4) or of the left subclavian artery (n=1) re-established spinal cord perfusion, as indicated by restored MEPs. We had no absent MEPs at the end of the procedures. Delayed paraparesis developed in 2 patients with a haemodynamic instability during the postoperative course. Paraplegia was not observed.nnnCONCLUSIONnTCD, EEG and MEPs are reliable techniques to unmask cerebral or spinal cord ischaemia during aortic surgery. Immediate operative strategies based on neuromonitoring information prevent neurological complications in aortic surgery.

Open Thoracic and Thoraco-abdominal Aortic Repair in Patients with Connective Tissue Disease

Retrospective cross-border, single centre study February 2000 to April 2016 72 aortic operations on 65 patients with CTD 41 male, median age 41 years [range 19–70 years] 56 patients (86%) with previous aortic repair (71 open, 4 endovascular) 33 patients (51%) operated before at the site of the procedure reported here Procedures: 8 emergency operations (11%) Aortic arch revision (n = 1; 1%) Descending thoracic aortic repair (n = 11; 15%) TAAA type I repair (n = 12; 17%), Type II repair (n = 29; 40%) Type III repair (n = 12; 17%) Type IV repair (n = 5; 7%). Ascending aorta and/or the aortic arch (n = 2; 3%) and (n = 8; 11%) 7 patients (10%) underwent staged procedures Median follow-up: 42 months (0.5–180 months)

Macrophage Migration Inhibitory Factor Predicts Outcome in Complex Aortic Surgery

The perioperative inflammatory response is associated with outcome after complex aortic repair. Macrophage migration inhibitory factor (MIF) shows protective effects in ischemia-reperfusion (IR), but also adverse pro-inflammatory effects in acute inflammation, potentially leading to adverse outcome, which should be investigated in this trial. This prospective study enrolled 52 patients, of whom 29 (55.7%) underwent open repair (OR) and 23 (44.3%) underwent endovascular repair (ER) between 2014 and 2015. MIF serum levels were measured until 72 h post-operatively. We used linear mixed models and ROC analysis to analyze the MIF time-course and its diagnostic ability. Compared to ER, OR induced higher MIF release perioperatively; at 12 h after ICU admission, MIF levels were similar between groups. MIF course was significantly influenced by baseline MIF level (P = 0.0016) and acute physiology and chronic health evaluation (APACHE) II score (P = 0.0005). MIF level at 24 h after ICU admission showed good diagnostic value regarding patient survival [sensitivity, 80.0% (28.4–99.5%); specificity, 51.2% (35.1–67.1%); AUC, 0.688 (0.534–0.816)] and discharge modality [sensitivity, 87.5% (47.3–99.7%); specificity, 73.7% (56.9–86.6%), AUC, 0.789 (0.644–0.896)]. Increased perioperative MIF-levels are related to an increased risk of adverse outcome in complex aortic surgery and may represent a biomarker for risk stratification in complex aortic surgery.

The β-D-Endoglucuronidase Heparanase Is a Danger Molecule That Drives Systemic Inflammation and Correlates with Clinical Course after Open and Endovascular Thoracoabdominal Aortic Aneurysm Repair : Lessons Learnt from Mice and Men

Thoracoabdominal aortic aneurysm (TAAA) is a highly lethal disorder requiring open or endovascular TAAA repair, both of which are rare, but extensive and complex surgical procedures associated with a significant systemic inflammatory response and high post-operative morbidity and mortality. Heparanase is a β-d-endoglucuronidase that remodels the endothelial glycocalyx by degrading heparan sulfate in many diseases/conditions associated with systemic inflammation including sepsis, trauma, and major surgery. We hypothesized that (a) perioperative serum levels of heparanase and heparan sulfate are associated with the clinical course after open or endovascular TAAA repair and (b) induce a systemic inflammatory response and renal injury/dysfunction in mice. Using a reverse-translational approach, we assessed (a) the serum levels of heparanase, heparan sulfate, and the heparan sulfate proteoglycan syndecan-1 preoperatively as well as 6 and 72u2009h after intensive care unit (ICU) admission in patients undergoing open or endovascular TAAA repair and (b) laboratory and clinical parameters and 90-day survival, and (c) the systemic inflammatory response and renal injury/dysfunction induced by heparanase and heparan sulfate in mice. When compared to preoperative values, the serum levels of heparanase, heparan sulfate, and syndecan-1 significantly transiently increased within 6u2009h of ICU admission and returned to normal within 72u2009h after ICU admission. The kinetics of any observed changes in heparanase, heparan sulfate, or syndecan-1 levels, however, did not differ between open and endovascular TAAA-repair. Postoperative heparanase levels positively correlated with noradrenalin dose at 12u2009h after ICU admission and showed a high predictive value of vasopressor requirements within the first 24u2009h. Postoperative heparan sulfate showed a strong positive correlation with interleukin-6 levels day 0, 1, and 2 post-ICU admission and a strong negative correlation with lactate clearance during the first 6u2009h post-ICU admission. Moreover, systemic administration of heparanase and heparan sulfate induced an inflammatory response and a small degree of renal dysfunction in mice. In conclusion, these results suggest that heparanase and heparan sulfate exhibit a substantial role as clinically relevant danger molecules and may serve as both, promising biomarkers and therapeutic targets in patients undergoing open or endovascular TAAA repair and, indeed, other conditions associated with significant systemic inflammation.