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.

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 MIinduced 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 ATRAdependent 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. IntroductionAcute myocardial infarction (MI) is the most common single cause of death worldwide [1,2]. The occlusion of coronary arteries leads to ischemia and necrotic cell death of cardiomyocytes (CMCs). In order to treat this condition, several therapeutic and surgical options are available. Although, medical interventions such as lysis therapy, stentplacement (PCI) or coronary artery bypass grafting (CABG) may

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.

We thank Drs Ahmed and Edelman for their interest in our article. 1 They expressed concerns about a possible bias toward radial artery (RA) use in comparison with right internal thoracic artery (RITA), because more than two thirds of multiple arterial revascularization (MAR) cases have a RA as a second arterial conduit.The proportion of RA and RITA patients directly reflects the current epidemiological distribution of RA and RITA grafts used. In the United States, the RA is used more than twice as frequently as a RITA graft. 2 When applying the inclusion criteria of our study, our institutional MAR rate has been 35% during the past 9 years, reflecting high experience with MAR on a daily routine basis. Only 4 surgeons performed MAR during the whole study period, and there was a high fluctuation of surgeons during this period. Moreover, this further underlines the fact that MAR can be easily performed by surgeons routinely but not exclusively performing coronary surgery, irrespective whether using a RA or a RITA. We limit our results to the shortcomings of an observational study; however, results from randomized, controlled trials are missing. Significant shortcomings exist in randomized, controlled trials, namely unreal overselection of patients, heterogenous surgical techniques (regarding on-and offpump strategy, in situ grafts and t grafts, pedicle/skeletonized), and the problem of crossover is due to intention-to-treat analysis. 3,4 Previous studies have shown that the level of stenosis has an impact on graft patency for arterial grafts. In our study, arterial grafts were exclusively grafted to target areas with at least 80% stenosis (otherwise conventional coronary artery bypass grafting was performed by using a saphenous vein graft not to waste an arterial graft); furthermore, the degree of stenosis was not different in our study within both treatment groups. In addition, moderate supraphysiological distension of the RA after harvesting was performed in all cases.Cardioembolic stroke, as a complication of cardiac surgery, has a tremendous impact on quality of life, leaving a significant proportion of patients with remaining disability. Our study has clearly shown that a reduction of central aortic anastomoses can reduce the risk of aortic plaque rupture in patients undergoing coronary artery bypass grafting. Therefore, the use of 2 in situ internal thoracic artery grafts might possibly be protective, especially for patients with severe aortic sclerosis. Hence, as we have previously shown, modification of surgical technique to produce less aortic manipulation (either on-pump with single-crossclamp or off-pump procedures) in case of heavily calcified aorta should be a mandatory approach in all coronary artery bypass grafting procedures. 5 However, off-pump coronary surgery has a significant limitation. Many previous large studies and meta-analyses have shown offpump surgery to be associated with reduced long-term survival and an increased risk for subsequent revascularization and incomplete revascularization, ...