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Background: Selective antegrade cerebral perfusion (SACP) is adopted as an alternative to deep hypothermic circulatory arrest (DHCA) during aortic arch surgery. However, there is still no preclinical evidence to support the use of SACP associated with moderate hypothermia (28–30°C) instead of DHCA (18–20°C). The present study aims to develop a reliable and reproducible preclinical model of cardiopulmonary bypass (CPB) with SACP applicable for assessing the best temperature management. Materials and methods: A central cannulation through the right jugular vein and the left carotid artery was performed, and CPB was instituted. Animals were randomized into two groups: normothermic circulatory arrest without or with cerebral perfusion (NCA vs SACP). EEG monitoring was maintained during CPB. After 10 min of circulatory arrest, rats underwent 60 min of reperfusion. After that, animals were sacrificed, and brains were collected for histology and molecular biology analysis. Results: Power spectral analysis of the EEG signal showed decreased activity in both cortical regions and lateral thalamus in all rats during the circulatory arrest. Only SACP determined complete recovery of brain activity and higher power spectral signal compared to NCA (p < 0.05). Histological damage scores and western blot analysis of inflammatory and apoptotic proteins like caspase-3 and Poly-ADP ribose polymerase (PARP) were significantly lower in SACP compared to NCA. Vascular endothelial growth factor (VEGF) and RNA binding protein 3 (RBM3) involved in cell-protection mechanisms were higher in SACP, showing better neuroprotection (p < 0.05). Conclusions: SACP by cannulation of the left carotid artery guarantees good perfusion of the whole brain in this rat model of CPB with circulatory arrest. The present model of SACP is reliable, repeatable, and not expensive, and it could be used in the future to achieve preclinical evidence for the best temperature management and to define the best cerebral protection strategy during circulatory arrest. [ABSTRACT FROM AUTHOR]

OBJECTIVES To evaluate if pulsatile cardiopulmonary bypass (CPB) has any protective influence on renal function in elderly patients undergoing aortic valve replacement (AVR). METHODS Forty-six patients (≥75 years old) with aortic valve stenosis underwent AVR with either pulsatile perfusion (PP) or non-pulsatile perfusion (NP) during CPB. Haemodynamic efficacy of the blood pump during either type of perfusion was described in terms of the energy equivalent pressure and the surplus haemodynamic energy. Urine samples were collected before surgery, at sternum closure, and at 2 and 18 h of intensive care unit stay to detect acute kidney injury markers. Perioperative urine levels of N-acetyl-β-d-glucosaminidase (NAG), kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin (NGAL) were assessed together with plasma creatinine, creatinine clearance (CCr) and 24-h haemodynamic monitoring. Normally distributed continuous variables were described as mean ± standard deviation and non-normally distributed data were presented as the median [25th–75th percentiles]. RESULTS PP was characterized by a significantly higher amount of surplus haemodynamic energy transferred to the patients (P < 0.001), with lower mean systemic vascular resistance during CPB (P = 0.020) and during 18 h postoperatively (group-P = 0.018). No difference was found between pre- and postoperative CCr in the PP group (71 ± 23 vs 60 ± 35 ml/min, P = 0.27), while its statistically significant perioperative decrement was observed in the NP group (67 ± 24 vs 45 ± 15 ml/min, P < 0.001). The PP group showed significantly lower urinary levels of NAG at 18 h postoperatively (P = 0.008), and NGAL at sternum closure (P = 0.010), 2 h (P < 0.001) and 18 h (P = 0.015) postoperatively. CONCLUSIONS Short-term PP in elderly patients showed higher safety for renal physiology than NP, resulting in better maintenance of glomerular filtration and lower renal tissue injury. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to test whether adenosine triphosphate-sensitive K+ (KATP) channel expression relates to mechanical and hypoxic stress within the left human heart. Background: The KATP channels play a vital role in preserving the metabolic integrity of the stressed heart. However, the mechanisms that govern the expression of their subunits (e.g., potassium inward rectifier [Kir] 6.2) in adult pathologies are mostly unknown. Methods: We collected biopsies from the 4 cardiac chambers and 50 clinical parameters from 30 surgical patients with severe mitral dysfunction. Proteins and messenger ribonucleic acids (mRNAs) of KATP pore subunits and mRNAs of their known transcriptional regulators (forkhead box [FOX] F2, FOXO1, FOXO3, and hypoxia inducible factor [HIF]-1α) were measured respectively by Western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction, and submitted to statistical analysis. Results: In all heart chambers, Kir6.2 mRNA correlated with HIF-1α mRNA. Neither Kir6.1 nor Kir6.2 proteins positively correlated with their respective mRNAs. The HIF-1α mRNA related in the left ventricle to aortic pressure, in the left atrium to left atrial pressure, and in all heart chambers to a decreased Kir6.2 protein/mRNA ratio. Interestingly, in the left heart, Kir6.2 protein and its immunohistochemical detection in myocytes were maximal at low venous PO2. In the left ventricle, the Kir6.2 protein/mRNA ratio was also significantly higher at low venous PO2, suggesting that tissue hypoxia might stabilize the Kir6.2 protein. Conclusions: Results suggest that post-transcriptional events determine Kir6.2 protein expression in the left ventricle of patients with severe mitral dysfunction and low venous PO2. Mechanical stress mainly affects transcription of HIF-1α and Kir6.2. This study implies that new therapies could aim at the proteasome for stabilizing the left ventricular Kir6.2 protein. [Copyright &y& Elsevier]

Objectives: The aim of this study was to test whether adenosine triphosphate-sensitive K(+) (KATP) channel expression relates to mechanical and hypoxic stress within the left human heart., Background: The KATP channels play a vital role in preserving the metabolic integrity of the stressed heart. However, the mechanisms that govern the expression of their subunits (e.g., potassium inward rectifier [Kir] 6.2) in adult pathologies are mostly unknown., Methods: We collected biopsies from the 4 cardiac chambers and 50 clinical parameters from 30 surgical patients with severe mitral dysfunction. Proteins and messenger ribonucleic acids (mRNAs) of KATP pore subunits and mRNAs of their known transcriptional regulators (forkhead box [FOX] F2, FOXO1, FOXO3, and hypoxia inducible factor [HIF]-1α) were measured respectively by Western blotting, immunohistochemistry, and quantitative real-time polymerase chain reaction, and submitted to statistical analysis., Results: In all heart chambers, Kir6.2 mRNA correlated with HIF-1α mRNA. Neither Kir6.1 nor Kir6.2 proteins positively correlated with their respective mRNAs. The HIF-1α mRNA related in the left ventricle to aortic pressure, in the left atrium to left atrial pressure, and in all heart chambers to a decreased Kir6.2 protein/mRNA ratio. Interestingly, in the left heart, Kir6.2 protein and its immunohistochemical detection in myocytes were maximal at low venous PO(2). In the left ventricle, the Kir6.2 protein/mRNA ratio was also significantly higher at low venous PO(2), suggesting that tissue hypoxia might stabilize the Kir6.2 protein., Conclusions: Results suggest that post-transcriptional events determine Kir6.2 protein expression in the left ventricle of patients with severe mitral dysfunction and low venous PO(2). Mechanical stress mainly affects transcription of HIF-1α and Kir6.2. This study implies that new therapies could aim at the proteasome for stabilizing the left ventricular Kir6.2 protein., (Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)