The aim of this retrospective study was to assess pre- and intraoperative factors leading to neurological complications and early death following repair of acute type A aortic dissection (ATAAD). There were 122 patients (85 male, age: 58.6 ± 12.5 years) with ATAAD, treated consecutively from August 2003 to August 2010. Pre- and intraoperative variables were analysed using a logistic regression model in order to identify risk factors for temporary neurological dysfunction (TND) and adverse outcome (AO), defined as stroke and 30-day mortality. The 30-day mortality rate was 16.4%. Forty-one patients (33.6%) suffered transient neurological dysfunction and 20 (16.4%) had a postoperative stroke. Mean hypothermic circulatory arrest (HCA) temperature was 24 ± 4°C. Selective cerebral perfusion (SCP) was performed in 99 (82%) patients, with a mean SCP flow rate of 10.3 ml/kg/min. The duration of lower body ischaemia (LBI) was 36 ± 27 min, of HCA 8.7 ± 15.5 min and of SCP 34 ± 28 min, respectively. Male gender [odds ratio (OR): 3.30, 95% confidence interval (CI): 1.15–9.47], diabetes (OR: 3.95, 95% CI: 1.18–13.24), compromised consciousness (OR: 6.65, 95% CI: 1.41–31.48) and manifest arterial atherosclerosis (OR: 6.68, 95% CI: 1.31–34.09) were detected as risk factors for TND, whereas a high body mass index (OR: 1.14, 95% CI: 1.01–1.3), a preoperative malperfusion syndrome (OR: 2.28, 95% CI: 0.84–6.18) and left ventricular ejection fraction <50% (OR: 3.84, 95% CI: 1.41–10.43) were detected as independent predictors for an AO. A dissection entry localized in the aortic arch or the descending aorta independently increased the risk for a postoperative stroke. A prolonged LBI increased the risk for AO (OR: 1.02, 95% CI: 1.00–1.04), whereas femoral cannulation showed a trend to an increased stroke incidence (OR: 4.2, 95% CI: 0.8–21.3). Regardless of standardized neuroprotective techniques, treatment of ATAAD remains a high-risk operation. Preoperatively, the presence of a reduced ejection fraction, a malperfusion syndrome or a high body mass index may increase the perioperative risk for an adverse outcome. A dissection ‘entry’ localized in the aortic arch or the descending aorta may increase the risk for postoperative stroke. Intraoperatively, cannulation of the femoral artery and extension of the LBI time over 45 min should be avoided. Especially in patients with manifest preoperative cerebral and/or end-organ malperfusion, the cannulation modality as well as the entire neuroprotective management should be chosen individually, respecting its limitations.

Patients diagnosed with both aortic stenosis (AS) and diabetes mellitus (DM) encounter a distinctive set of challenges due to the interplay between these two conditions. This study aimed to investigate the effects of DM on the left ventricle in AS patients, specifically focusing on the inflammatory response, oxidative stress, and their implications for cardiomyocyte function, titin phosphorylation, and the nitric oxide (NO)-soluble guanylyl cyclase (sGC)-cyclic guanosine monophosphate (cGMP)-protein kinase G (PKG) signaling pathway. Left ventricular myocardial biopsies (in total: n = 28) were obtained from patients with diabetic AS (n = 11) and compared with those from non-diabetic AS patients (n = 17). Enzyme-linked immunosorbent assay (ELISA) demonstrated significantly elevated levels of pro-inflammatory mediators, including high mobility group box protein 1 (HMGB1) and calprotectin, as well as receptors associated with the inflammatory response, such as Toll-like receptor 2 (TLR2), 4 (TLR4), and receptor for advanced glycation endproducts (RAGE). These were correlated with an enhanced NOD-like receptor protein 3 (NLRP3) inflammasome and the release of interleukins (IL) 1, 6, and 18 in diabetic AS patients compared to their non-diabetic counterparts. Additionally, in the diabetic AS cohort, there was an increase in oxidative stress markers (hydrogen peroxide (H2O2), 3-nitrotyrosine, lipid peroxidation (LPO), oxidative glutathione (GSSG)/reduced glutathione (GSH) ratio) within the myocardium and mitochondria, accompanied by impaired NO-sGC-cGMP-PKG signaling, decreased titin phosphorylation, and increased passive stiffness (Fpassive) of cardiomyocytes relative to non-diabetic AS patients. In vitro anti-inflammatory treatment with an IL-6 inhibitor and antioxidant treatment with GSH effectively normalized the elevated Fpassive observed in AS patients with DM to levels comparable to the non-diabetic group. Furthermore, treatment with PKG and the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin also resulted in a reduction of Fpassive in cardiomyocytes from diabetic AS patients, although not to the levels observed in non-diabetic AS patients. DM exacerbates inflammation and oxidative stress in AS patients, leading to impaired NO-sGC-cGMP-PKG signaling and increased cardiomyocyte Fpassive. These conditions are reminiscent of the pathophysiology of heart failure with preserved ejection fraction (HFpEF). These alterations can be ameliorated through anti-inflammatory and antioxidant therapies, indicating potential therapeutic strategies for diabetic patients suffering from AS.

Temporary (TND) or permanent neurologic dysfunctions (PND) represent the main neurological complications following acute aortic dissection repair. The aim of our experimental and clinical research was the improvement and update of the most common neuroprotective strategies which are in present use. Hypothermic circulatory arrest (HCA): Cerebral metabolic suppression at the clinically most used temperatures (18-22°C) is less complete than had been assumed previously. If used as a ‘stand-alone’ neuroprotective strategy, cooling to 15-20°C with a jugular SO₂ ≥ 95% is needed to provide sufficient metabolic suppression. Regardless of the depth of cooling, the HCA interval should not exceed 25 min. After 40 min of HCA, the incidence of TND and PND increases, after 60 min, the mortality rate increases. Antegrade selective cerebral perfusion (ASCP): At moderate hypothermia (25-28°C), ASCP should be performed at a pump flow rate of 10ml/kg/min, targeting a cerebral perfusion pressure of 50-60mmHg. Experimental data revealed that these conditions offer an optimal regional blood flow in the cortex (80±27ml/min/100g), the cerebellum (77±32ml/min/100g), the pons (89±5ml/min/100g) and the hippocampus (55±16ml/min/100g) for 25 minutes. If prolonged, does ASCP at 32°C provide the same neuroprotective effect? Cannulation strategy: Direct axillary artery cannulation ensures the advantage of performing both systemic cooling and ASCP through the same cannula, preventing additional manipulation with the attendant embolic risk. An additional cannulation of the left carotid artery ensures a bi-hemispheric perfusion, with a neurologic outcome of only 6% TND and 1% PND. Neuromonitoring: Near-infrared spectroscopy and evoked potentials may prove the effectiveness of the neuroprotective strategy used, especially if the trend goes to less radical cooling. Conclusion: A short interval of HCA (5 min) followed by a more extended period of ASCP (25 min) at moderate hypothermia (28°C), with a pump flow rate of 10ml/kg/min and a cerebral perfusion pressure of 50 mmHg, represents safe conditions for open arch surgery.

Although hypothermic circulatory arrest (HCA) and selective cerebral perfusion (SCP) are widely used for cerebral protection during aortic arch surgery, these strategies offer no protection for mesenteric ischaemia during prolonged circulatory arrest. This study explored mesenteric haemodynamics, metabolism, oxidative stress and inflammatory response levels during isolated SCP and combined cerebral and lower body perfusion (CLBP) in pigs. Fourteen pigs (35–45 kg) were cooled on CPB to 28°C. After 10 min of HCA, they were randomized to 60 min of isolated SCP (n = 7) and CLBP (n = 7) at low-flow pump rates: 10 ml/kg/min (SCP) and 20 ml/kg/min (LBP). Microspheres were injected at baseline, 5 and 60 min of SCP/CLBP and 5 and 60 min off CPB, to calculate mesenteric regional blood flow (RBF). Lactate levels and Oxy-DNA expression [fluorescence activated cell sorting (FACS)] in the portal venous blood were determined at the same time points. Semi-quantitative assessment of inflammatory cytokines was performed using real-time polymerase chain reaction (PCR) and immunhistochemical analyses. At baseline mesenteric, RBF was 61 ± 31 ml/min/100 g in the jejunum and 78 ± 43 ml/min/100 g in the colon. Whereas SCP provided a residual mesenteric RBF of 5%, CLBP offered 47% of the baseline jejunal (34 ± 10 ml/min/100 g) and 68% of the colonic RBF (52 ± 34 ml/min/100 g; P = 0.001). Lactate levels were significantly higher in then SCP group (15 ± 2 vs. 11 ± 3 mmol/l; P = 0.01). Oxy-DNA increased, reaching 137% of baseline (SCP) and 129% (CLBP) at 60 min SCP/CLBP, but recovered promptly during reperfusion. Real-time PCR revealed a massive increase in early cytokine expression vs. baseline, showing significant higher interleukin (IL) -6 (29 vs.2; P = 0.027) and COX-relative expression (7 vs. 3, P = 0.016) in the SCP group. Immunhistochemical analysis confirmed a higher immunological activity in the SCP group, showing more intensive signal for tumour necrosis factor-α, IL-6 and p38 when compared with the CLBP group. Low-flow CLBP provides a diminished but considerable mesenteric RBF, leading to lower lactate and oxidative stress levels and a diminished local inflammatory response reaction than isolated SCP.