Pulmonary Protection Strategies in Cardiac Surgery: Are We Making Any Progress?

Pulmonary dysfunction is a common complication of cardiac surgery. The mechanisms involved in the development of pulmonary dysfunction are multifactorial and can be related to the activation of inflammatory and oxidative stress pathways. Clinical manifestation varies from mild atelectasis to severe respiratory failure. Managing pulmonary dysfunction postcardiac surgery is a multistep process that starts before surgery and continues during both the operative and postoperative phases. Different pulmonary protection strategies have evolved over the years; however, the wide acceptance and clinical application of such techniques remain hindered by the poor level of evidence or the sample size of the studies. A better understanding of available modalities and/or combinations can result in the development of customised strategies for the different cohorts of patients with the potential to hence maximise patients and institutes benefits

Requirement of JNK1 for endothelial cell injury in atherogenesis

AbstractObjectiveThe c-Jun N-terminal kinase (JNK) family regulates fundamental physiological processes including apoptosis and metabolism. Although JNK2 is known to promote foam cell formation during atherosclerosis, the potential role of JNK1 is uncertain. We examined the potential influence of JNK1 and its negative regulator, MAP kinase phosphatase-1 (MKP-1), on endothelial cell (EC) injury and early lesion formation using hypercholesterolemic LDLR−/− mice.Methods and resultsTo assess the function of JNK1 in early atherogenesis, we measured EC apoptosis and lesion formation in LDLR−/− or LDLR−/−/JNK1−/− mice exposed to a high fat diet for 6 weeks. En face staining using antibodies that recognise active, cleaved caspase-3 (apoptosis) or using Sudan IV (lipid deposition) revealed that genetic deletion of JNK1 reduced EC apoptosis and lesion formation in hypercholesterolemic mice. By contrast, although EC apoptosis was enhanced in LDLR−/−/MKP-1−/− mice compared to LDLR−/− mice, lesion formation was unaltered.ConclusionWe conclude that JNK1 is required for EC apoptosis and lipid deposition during early atherogenesis. Thus pharmacological inhibitors of JNK may reduce atherosclerosis by preventing EC injury as well as by influencing foam cell formation

Postoperative acute kidney injury defined by RIFLE criteria predicts early health outcome and long-term survival in patients undergoing redo coronary artery bypass graft surgery

AbstractObjectiveTo investigate the impact of postoperative acute kidney injury (AKI) on early health outcome and on long-term survival in patients undergoing redo coronary artery bypass grafting (CABG).MethodsWe performed a Cox analysis with 398 consecutive patients undergoing redo CABG over a median follow-up of 7 years (interquartile range, 4-12.2 years). Renal function was assessed using baseline and peak postoperative levels of serum creatinine. AKI was defined according to the risk, injury, failure, loss, and end-stage (RIFLE) criteria. Health outcome measures included the rate of in-hospital AKI and all-cause 30-day and long-term mortality, using data from the United Kingdom's Office of National Statistics. Propensity score matching, as well as logistic regression analyses, were used. The impact of postoperative AKI at different time points was related to survival.ResultsIn patients with redo CABG, the occurrence of postoperative AKI was associated with in-hospital mortality (odds ratio [OR], 3.74; 95% confidence interval [CI], −1.3 to 10.5; P < .01], high Euroscore (OR, 1.27; 95% CI, 1.07-1.52; P < .01), use of IABP (OR, 6.9; 95% CI, 2.24-20.3; P < .01), and reduced long-term survival (hazard ratio [HR], 2.42; 95% CI, 1.63-3.6; P = .01). Overall survival at 5 and 10 years was lower in AKI patients with AKI compared with those without AKI (64% vs 85% at 5 years; 51% vs 68% at 10 years). On 1:1 propensity score matching analysis, postoperative AKI was independently associated with reduced long term survival (HR, 2.8; 95% CI, 1.15-6.7).ConclusionsIn patients undergoing redo CABG, the occurrence of postoperative AKI is associated with increased 30-day mortality and major complications and with reduced long-term survival

NF-κB inhibition prevents acute shear stress-induced inflammation in the saphenous vein graft endothelium

The long saphenous vein (LSV) is commonly used as a conduit in coronary artery bypass grafting. However, long term patency remains limited by the development of vascular inflammation, intimal hyperplasia and accelerated atherosclerosis. The impact of acute exposure of venous endothelial cells (ECs) to acute arterial wall shear stress (WSS) in the arterial circulation, and the subsequent activation of inflammatory pathways, remain poorly defined. Here, we tested the hypothesis that acute exposure of venous ECs to high shear stress is associated with inflammatory responses that are regulated by NF-κB both in-vitro and ex-vivo. Analysis of the LSV endothelium revealed that activation of NF-κB occurred within 30 min after exposure to arterial rates of shear stress. Activation of NF-κB was associated with increased levels of CCL2 production and enhanced binding of monocytes in LSVECs exposed to 6 h acute arterial WSS. Consistent with this, ex vivo exposure of LSVs to acute arterial WSS promoted monocyte interactions with the vessel lumen. Inhibition of the NF-κB pathway prevented acute arterial WSS-induced CCL2 production and reduced monocyte adhesion, both in vitro and in human LSV ex vivo, demonstrating that this pathway is necessary for the induction of the acute arterial WSS-induced pro-inflammatory response. We have identified NF-κB as a critical regulator of acute endothelial inflammation in saphenous vein in response to acute arterial WSS. Localised endothelial-specific inhibition of the NF-κB pathway may be beneficial to prevent vein graft inflammation and consequent failure

Sulforaphane induces neurovascular protection against a systemic inflammatory challenge via both Nrf2-dependent and independent pathways

NIH/NHLBI; German Research Foundation