Early inhibition of endothelial retinoid uptake upon myocardial infarction restores cardiac function and prevents cell, tissue, and animal death.

Physiologically, following myocardial infarction (MI), retinoid levels elevate locally in the infarcted area. Whereas therapeutic systemic application of retinoids was shown to reduce the progression of ventricular dilatation and the onset of heart failure, the role of acute physiologically increased retinoids in the infarction zone is unknown to date. To reveal the role of local retinoids in the MI zone is the central aim of this study. Using human cell culture and co-culture models for hypoxia as well as various assays systems, lentivirus-based transgene expression, in silico molecular docking studies, and an MI model in rats, we analysed the impact of the retinoid all-trans retinoic acid (ATRA) on cell signalling, cell viability, tissue survival, heart function, and MI-induced death in rats. Based on our results, ATRA-mediated signalling does aggravate the MI phenotype (e.g. 2.5-fold increased mortality compared to control), whereas 5'-methoxyleoligin (5ML), a new agent which interferes with ATRA-signalling rescues the ATRA-dependent phenotype. On the molecular level, ATRA signalling causes induction of TXNIP, a potent inhibitor of the physiological antioxidant thioredoxin (TRX1) and sensitizes cells to necrotic cell death upon hypoxia. 5ML-mediated prevention of ATRA effects were shown to be based on the inhibition of cellular ATRA uptake by interference with the cholesterol (and retinol) binding motif of the transmembrane protein STRA6. 5ML-mediated inhibition of ATRA uptake led to a strong reduction of ATRA-dependent gene expression, reduced ROS formation, and protection from necrotic cell death. As 5ML exerted a cardioprotective effect, also independent of its inhibition of cellular ATRA uptake, the agent likely has another cardioprotective property, which may rely on the induction of TRX1 activity. In summary, this is the first study to show i) that local retinoids in the early MI zone may worsen disease outcome, ii) that inhibition of endothelial retinoid uptake using 5ML may constitute a novel treatment strategy, and iii) that targeting endothelial and myocardial retinoid uptake (e.g. via STRA6 inhibition) may constitute a novel treatment target in acute MI.

Second internal thoracic artery versus radial artery in coronary artery bypass grafting: a long-term, propensity score-matched follow-up study.

BACKGROUND: The best second arterial conduit for multiple arterial revascularization (MAR) is still a matter of debate. Previous studies on the benefit of either using the radial artery (RA) or the right internal thoracic artery (RITA) in coronary artery bypass grafting are not conclusive. The aim of our study was to compare the perioperative and long-term outcome of either RA or RITA grafts as second conduits for MAR. METHODS AND RESULTS: A consecutive series of 1001 patients undergoing first nonemergent coronary artery bypass grafting receiving either RA or RITA as second graft for MAR between 2001 and 2010 were studied. There were 277 patients receiving a RITA and 724 patients receiving a RA in addition to a left internal thoracic artery (LITA). Concomitant saphenous vein grafts (SVG) were grafted in addition as necessary. Propensity score-matched analysis was performed to compare the 2 groups, bilateral ITA±SVG (BITA±SVG group) and the LITA+RA±SVG group relative to overall survival and major adverse cardiac and cerebrovascular events-free survival. Hazard ratios and their 95% confidence intervals were estimated by COX regression stratified on matched pairs. The incidence of perioperative major adverse cardiac and cerebrovascular events was significantly lower in the BITA±SVG group (1.4% versus 7.6%, P<0.001). Overall survival (hazard ratio 0.23; 95% confidence interval 0.066-0.81; P=0.022) and major adverse cardiac and cerebrovascular events-free survival (hazard ratio 0.18; 95% confidence interval 0.08-0.42; P<0.001) were significantly better in the BITA±SVG group compared to the LITA+RA±SVG group. CONCLUSIONS: The results of our study provide strong evidence for the superiority of a RITA graft compared to RA as a second conduit in MAR.

A new way to use transit-time flow measurement for coronary artery bypass grafting.

OBJECTIVES: Transit-time flow measurement is a recognized method for graft evaluation in coronary surgery. However, single flow measurement has been associated with a low specificity for detecting graft dysfunction. The goal of this study was to assess the value of transit-time flow measurement for assessing in situ internal mammary artery grafts during non-existent native coronary circulation and the relevance of collateral blood flow in target vessels. METHODS: Between 2014 and 2018, a total of 134 patients undergoing on-pump coronary artery bypass grafting were evaluated using transit-time flow measurement. We analysed 111 single left internal mammary artery and 57 single right internal mammary artery bypasses. Correlations between coronary relevant parameters were calculated using Spearman's ρ coefficient. Risk factors for decreased flow with an arrested heart (FAH) <30 ml/min and an increased pulsatility index (PI) >3.0 as well as flow reduction >30% were calculated. RESULTS: FAH correlated with the diameter of the target vessel (Spearman's ρ = 0.32; P < 0.001), the amount of blood distribution (Spearman's ρ = 0.34; P < 0.001), the PI (Spearman's ρ = 0.19; P = 0.019) and the degree of stenosis (Spearman's ρ = -0.17; P = 0.042). The percentage of flow change was found to correlate with the PI (Spearman's ρ = -0.47; P < 0.0001), the degree of stenosis (Spearman's ρ = 0.42; P < 0.001), the diameter of the target vessel (Spearman's ρ = -0.22; P = 0.008) and the area of blood distribution (Spearman's ρ = -0.19; P = 0.018). A small blood distribution area was the only risk factor for decreased FAH [odds ratio (OR) 8.43, confidence interval (CI) 95% (3.04-23.41); P < 0.001]. Binary logistic regression identified PI [OR 2.05, CI 95% (1.36-3.10); P = 0.001], FAH [OR 0.98, CI 95% (0.97-0.99); P = 0.005] and degree of stenosis [OR 0.95, CI 95% (0.92-0.99); P = 0.011] as risk factors for decreased flow after cardiopulmonary bypass (<30 ml/min). An increased PI (>3) was mainly influenced by percentage of flow change [OR 0.99, CI 95% (0.98-1.00); P = 0.031]. CONCLUSIONS: FAH and percentage of flow change are related to the dimensions of the target vessel and the degree of stenosis. The addition of flow measurements with the heart arrested provides additional information about the bypass graft, the quality of the anastomosis and the physiology of the coronary circulation.

Extra-anatomic carotid bypass in acute aortic dissection type A with carotid artery malperfusion.

Acute aortic dissection type A with subtotal or total occlusion of one carotid artery is a complex situation. An additional extra-anatomic carotid artery bypass can restore carotid artery perfusion after standard emergency surgery with aortic replacement.

Simple adaptations of surgical technique to critically reduce the risk of postoperative sternal complications in patients receiving bilateral internal thoracic arteries.

OBJECTIVES: Limited blood supply to the thoracic chest wall is a known risk factor for sternal wound complications after CABG. Therefore, bilateral internal thoracic arteries are still rarely utilized despite their proven superior graft patency. The aim of our study was to analyse whether modification of the surgical technique is able to limit the risk of sternal wound complications in patients receiving bilateral internal thoracic artery grafting. METHODS: All 418 non-emergent CABG patients receiving bilateral internal thoracic artery CABG procedures (BITA) from January 2001 to January 2012 were analysed for sternal wound complications. Surgical technique together with known risk factors and relevant comorbidity were analysed for their effect on the occurrence of sternal wound complications by means of multivariate logistic regression analysis. RESULTS: Sternal wound complications occurred in 25 patients (5.9%), with a sternal dehiscence rate of 2.4% (10 patients). In multivariate analysis, diabetes (odds ratio [OR]: 4.8, 95% CI: 1.9-11.7, P=0.001), but not obesity (OR: 1.6, 95% CI: 0.7-4.2, P=0.28) or chronic obstructive pulmonary disease (OR: 2.2, 95% CI: 0.87-5.6, P=0.1) was a relevant comorbid condition for sternal complications. Skeletonization of ITA grafts (OR: 0.17, 95% CI: 0.06-0.5, P=0.001) and the augmented use of sternal wires (OR: 0.24, 95% CI: 0.06-0.95, P=0.04) were highly effective in preventing sternal complications. The use of platelet-enriched-fibrin glue (PRF) sealant, however, was associated with more superficial sternal infections (OR: 3.7, 95% CI: 1.3-10.5, P=0.02). CONCLUSIONS: Adjusted for common risk factors, skeletonization of BITA grafts together with augmented sternal wires is effective in preventing sternal complications. The use of PRF sealant, however, increased the risk for superficial wound complications.