AIAA

Background: The incidence of postoperative cognitive dysfunction (POCD) after cardiac surgery is up to 65% at hospital discharge.1 For a long time it was assumed that POCD is caused by impaired cerebral tissue oxygenation (cSO2) due to the physiological alterations associated with cardiopulmonary bypass (CPB). A recent study showed that preoperative cSO2 and reactivity to O2-administration predicted POCD after on-pump coronary artery bypass grafting (CABG).2 Other (non-randomized) studies have shown correlations between the severity and duration of brain tissue oxygenation and POCD during on- and off-pump CABG.3,4 Our study aimed to compare the depth as well as duration of cerebral tissue desaturations during on- and off-pump CABG, and relate this to the incidence of POCD. Methods: In this ethical committee approved, clinical trial 60 patients undergoing elective CABG under standardized anesthesia (mean age of 63 [SD 9.4]) were randomized to either the on- or off-pump procedure. Primary endpoint was area under the cSO2 curve 600sec.%. cSO2 was measured continuously from preinduction of anesthesia until ICU admission with both Invos and ForeSight cerebral oximeters. After baseline cSO2 measurements (room air) 100% O2 was administered for 5 min to assess O2-reactivity. A validated cognitive testing battery (CogState) comprising 4 tests was used to assess cognitive performance preoperatively and 4 days after surgery. POCD was defined as a decline in performance of >2 SD in ≥2 tests. Results: One procedure was converted from on-pump to off-pump after sternotomy at the discretion of the surgeon, resulting in 29 on-pump and 30 off-pump procedures. Baseline characteristics were similar in both study groups. There was no difference in major complications, nor duration of ICU and hospital admission. The primary endpoint occurred in only 3 patients, of whom 1 patient developed postoperative stroke. Other commonly used cut-off values for cerebral desaturation, e.g. a cSO2 <60% or a 20% decrease from baseline cSO2, showed no difference in AUC (table 1). Postoperative cognitive dysfunction (POCD) occurred in 39% and 45% of on- and off-pump patients respectively (p=0.65). Baseline cSO2 was not predictive of POCD, nor was there any predictive value of O2-reactivity (table 2). Conclusion: This randomized trial showed no difference in the incidence of intraoperative cerebral desaturation and POCD between patients undergoing on-pump and off-pump CABG. Although the incidence of POCD was similar to other published studies, the depth and duration of intraoperative cerebral desaturations was less severe in our study population. This suggests that factors other than CPB and cerebral oxygenation play an important pathophysiological role in the development of POCD. Factors such as inflammatory responses to stress, anesthesia and surgery should be considered.5 References: 1. Ann Thorac Surg 2008; 85: 872-9 2. Anesthesiology 2011; 114: 58-69 3. J Cardiothorac Vasc Anesth 2004; 18: 552-8 4. J Cardiothorac Vasc Anesth 2011; 25: 95-104 5. Anaesthesia 2012; 67: 280-9

Renal Mitochondrial Response to Low Temperature in Non-Hibernating and Hibernating Species

SIGNIFICANCE: Therapeutic hypothermia is commonly applied to limit ischemic injury in organ transplantation, during cardiac and brain surgery and after cardiopulmonary resuscitation. In these procedures, the kidneys are particularly at risk for ischemia/reperfusion injury (IRI), likely due to their high rate of metabolism. Although hypothermia mitigates ischemic kidney injury, it is not a panacea. Residual mitochondrial failure is believed to be a key event triggering loss of cellular homeostasis, and potentially cell death. Subsequent rewarming generates large amounts of reactive oxygen species that aggravate organ injury. Recent Advances: Hibernators are able to withstand periods of profoundly reduced metabolism and body temperature ("torpor"), interspersed by brief periods of rewarming ("arousal") without signs of organ injury. Specific adaptations allow maintenance of mitochondrial homeostasis, limit oxidative stress, and protect against cell death. These adaptations consist of active suppression of mitochondrial function and upregulation of anti-oxidant enzymes and anti-apoptotic pathways. CRITICAL ISSUES: Unraveling the precise molecular mechanisms that allow hibernators to cycle through torpor and arousal without precipitating organ injury may translate into novel pharmacological approaches to limit IRI in patients. FUTURE DIRECTIONS: Although the precise signaling routes involved in natural hibernation are not yet fully understood, torpor-like hypothermic states with increased resistance to ischemia/reperfusion can be induced pharmacologically by 5'-adenosine monophosphate (5'-AMP), adenosine, and hydrogen sulfide (H2S) in non-hibernators. In this review, we compare the molecular effects of hypothermia in non-hibernators with natural and pharmacologically induced torpor, to delineate how safe and reversible metabolic suppression may provide resistance to renal IRI. Antioxid. Redox Signal. 00, 000-000

Off-pump CABG surgery reduces systemic inflammation compared with on-pump surgery but does not change systemic endothelial responses:a prospective randomized study

Coronary artery bypass graft (CABG) surgery can result in severe postoperative organ failure. During CABG surgery, cardiopulmonary bypass (CPB) with cardiac arrest is often used (on-pump CABG), which often results in a systemic inflammatory response. To reduce this inflammatory response, off-pump CABG was reintroduced, thereby avoiding CPB. There is increasing evidence that the endothelium plays an important role in the pathophysiology of organ failure after CABG surgery. In this study, 60 patients who were scheduled for elective CABG surgery were randomized to have surgery for on-pump or off-pump CABG. Blood was collected at four time points: start, end, 6 h, and 24 h postoperatively. Levels of inflammatory cytokines, soluble adhesion molecules, and angiogenic factors and their receptors were measured in the plasma. No differences were found in preoperative characteristics between the patient groups. The levels of tumor necrosis factor-alpha, interleukin 10, and myeloperoxidase, but not interleukin 6, were increased to a greater extent in the on-pump CABG compared with off-pump CABG after sternum closure. The soluble endothelial adhesion molecules E-selectin, vascular cell adhesion molecule 1, and intracellular adhesion molecule 1 were not elevated in the plasma during and after CABG surgery in both on-pump and off-pump CABG. Angiopoietin 2 was only increased 24 h after surgery in both on-pump and off-pump CABG. Higher levels of sFlt-1 were found after sternum closure in off-pump CABG compared with on-pump CABG. Avoiding CPB and aortic cross clamping in CABG surgery reduces the systemic inflammatory response. On-pump CABG does not lead to an increased release of soluble endothelial adhesion molecules in the circulation compared with off-pump CABG