Decreased PGC-1α Post-Cardiopulmonary Bypass Leads to Impaired Oxidative Stress in Diabetic Patients.

BACKGROUND: The mechanism of mitochondrial dysfunction after cardiopulmonary bypass (CPB) in patients with diabetes mellitus lacks understanding. We hypothesized that impaired beta-oxidation of fatty acids leads to worsened stress response in this patient population after cardiac surgery. METHODS: After Institutional Review Board approval, right atrial tissue samples were collected from 35 diabetic patients and 33 nondiabetic patients before and after CPB. Patients with glycated hemoglobin of 6.0 or greater and a clinical diagnosis of diabetes mellitus were considered to be diabetic. Immunoblotting and microarray analysis were performed to assess protein and gene expression changes. Blots were quantified with ImageJ and analyzed using one-way analysis of variance with multiple Student's t test comparisons after normalization. All p values less than 0.05 were considered significant. Immunohistochemistry was performed for cellular lipid deposition assessment. RESULTS: Diabetic patients had significantly lower levels of PGC-1α before and after CPB (p < 0.01 for both) compared with nondiabetic patients. Several upstream regulators of PGC-1α (SIRT1 and CREB) were significantly higher in nondiabetic patients before CPB (p = 0.01 and 0.0018, respectively). Antioxidant markers (NOX4 and GPX4), angiogenic factors (TGF-ß, NT3, and Ang1), and the antiapoptotic factor BCL-xL were significantly lower in diabetic patients after CPB (p < 0.05). The expression of genes supporting mitochondrial energy production (CREB5 and SLC25A40) and angiogenic genes (p < 0.05) was significantly downregulated in diabetic patients after CPB. Immunohistochemistry results showed significantly increased lipid deposition in diabetic myocardial tissue. CONCLUSIONS: Decreased PGC-1α in diabetic patients may lead to impaired mitochondrial function and attenuated antiapoptotic and angiogenic responses after CPB. Therefore, PGC-1α and upstream regulators could serve as a target for improving beta-oxidation in diabetic patients.

Dynamic Three-Dimensional Geometry of the Aortic Valve Apparatus-A Feasibility Study.

OBJECTIVE: To provide (1) an overview of the aortic valve (AV) apparatus anatomy and nomenclature, and (2) data regarding the normal AV apparatus geometry and dynamism during the cardiac cycle obtained from three-dimensional transesophageal echocardiography (3D TEE). DESIGN: Retrospective feasibility study. SETTING: A single-center university teaching hospital. PARTICIPANTS: The study was performed on data of 10 patients with a nonregurgitant, nonstenotic aortic valve undergoing cardiac surgery. INTERVENTIONS: Intraoperative 3D TEE was performed on all the participants using the Siemens ACUSON SC2000 ultrasound system and Z6Ms transducer (Siemens Medical Systems, Mountainview, CA). MEASUREMENTS AND MAIN RESULTS: Dynamic offline analyses were performed with Siemens eSie valve analytical software in a semiautomated fashion. Forty-five parameters were exported of which 13 were selected and analyzed. The cardiac cycle was divided into 4 quartiles to account for frame-rate variations. The annulus, sinus of Valsalva (SoV) and sinotubular junction (STJ) areas, diameter, perimeter and height, aortic leaflet height, leaflet coaptation height, and aortic valve-mitral valve angle changed significantly during the cardiac cycle (p < 0.001). STJ expanded more than both the annulus and the SoV (p < 0.001). The maximum aortic valve leaflet height change was greater in the left and right versus noncoronary leaflet (p < 0.001). CONCLUSIONS: The semiautomated AV apparatus dynamic assessment using eSie valve software is a clinically feasible technique and can be performed readily in the operating room. It has the potential to significantly impact intraoperative decision-making in cases suitable for AV repair. The AV apparatus is a dynamic structure and demonstrates significant changes during the cardiac cycle.