Hypothermia improves resistance to ischemia in the cardioplegia-arrested heart. This adaptive process produces changes in specific signaling pathways for mitochondrial proteins and heat-shock response. To further test for hypothermic modulation of other signaling pathways such as apoptosis, we used various molecular techniques, including cDNA arrays. Isolated rabbit hearts were perfused and exposed to ischemic cardioplegic arrest for 2 h at 34 degrees C [ischemic group (I); n = 13] or at 30 degrees C before and during ischemia [hypothermic group (H); n = 12]. Developed pressure, the maximum first derivative of left ventricular pressure, oxygen consumption, and pressure-rate product (P < 0.05) recovery were superior in H compared with in I during reperfusion. mRNA expression for the mitochondrial proteins, adenine translocase and the beta-subunit of F1-ATPase, was preserved by hypothermia. cDNA arrays revealed that ischemia altered expression of 13 genes. Hypothermia modified this response to ischemia for eight genes, six related to apoptosis. A marked, near fivefold increase in transformation-related protein 53 in I was virtually abrogated in H. Hypothermia also increased expression for the anti-apoptotic Bcl-2 homologue Bcl-x relative to I but decreased expression for the proapoptotic Bcl-2 homologue bak. These data imply that hypothermia modifies signaling pathways for apoptosis and suggest possible mechanisms for hypothermia-induced myocardial protection.

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Background-MRI guidance of percutaneous transluminal balloon angioplasty (PTA) of aortic coarctation (CoA) would be desirable for continuous visualization of anatomy and to eliminate x-ray exposure. The aim of this study was (1) to determine the suitability of MRI-controlled PTA using the iron oxide-based contrast medium Resovist (ferucarbotran) for catheter visualization and (2) to subsequently apply this technique in a pilot study with patients with CoA. Methods and Results-The MRI contrast-to-noise ratio and artifact behavior of Resovist-treated balloon catheters was optimized in in vitro and animal experiments (pigs). In 5 patients, anatomy of the CoA was evaluated before and after intervention with high-resolution respiratory-navigated 3D MRI and multiphase cine MRI. Position monitoring of Resovist-treated catheters was realized with interactive real-time MRI. Aortic pressures were continuously recorded.Conventional catheterization was performed before and after MRI to confirm interventional success. During MRI, catheters filled with 25 mol of iron particles per milliliter of Resovist produced good signal contrast between catheters and their background anatomy but no image distortion due to susceptibility artifacts. All MRI procedures were performed successfully in the patient study. There was excellent agreement between the diameters of CoA and pressure gradients as measured during MRI and conventional catheterization. In 4 patients, PTA resulted in substantial widening of the CoA and a decrease in pressure gradients. In 1 patient, PTA was ineffective. Conclusions-The MRI method described represents a potential alternative to conventional x-ray fluoroscopy for catheter-based treatment of patients with CoA. (Circulation. 2006;113:1093-1100.)