Remodeling of substrate consumption in the murine sTAC model of heart failure
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Authors: Turer, Aslan; Altamirano, Francisco; Schiattarella, Gabriele G.; May, Herman; Gillette, Thomas G.; Malloy, Craig R.; Merritt, Matthew E.
Abstract
Background: Energy metabolism and substrate selection are key aspects of correct myocardial mechanical function. Myocardial preference for oxidizable substrates changes in both hypertrophy and in overt failure. Previous work has shown that glucose oxidation is upregulated in overpressure hypertrophy, but its fate in overt failure is less clear. Anaplerotic flux of pyruvate into the tricarboxylic acid cycle (TCA) has been posited as a secondary fate of glycolysis, aside from pyruvate oxidation or lactate production. Methods and results: A model of heart failure that emulates both valvular and hypertensive heart disease, the severe transaortic constriction (sTAC) mouse, was assayed for changes in substrate preference using metabolomic and carbon-13 flux measurements. Quantitative measures of O-2 consumption in the Langendorff perfused mouse heart were paired with C-13 isotopomer analysis to assess TCA cycle turnover. Since the heart accommodates oxidation of all physiological energy sources, the utilization of carbohydrates, fatty acids, and ketones were measured simultaneously using a triple-tracer NMR method. The fractional contribution of glucose to acetyl-CoA production was upregulated in heart failure, while other sources were not significantly different. A model that includes both pyruvate carboxylation and anaplerosis through succinyl-CoA produced superior fits to the data compared to a model using only pyruvate carboxylation. In the sTAC heart, anaplerosis through succinyl-CoA is elevated, while pyruvate carboxylation was not. Metabolomic data showed depleted TCA cycle intermediate pool sizes versus the control, in agreement with previous results. Conclusion: In the sTAC heart failure model, the glucose contribution to acetyl-CoA production was significantly higher, with compensatory changes in fatty acid and ketone oxidation not reaching a significant level. Anaplerosis through succinyl-CoA is also upregulated, and is likely used to preserve TCA cycle intermediate pool sizes. The triple tracer method used here is new, and can be used to assess sources of acetyl-CoA production in any oxidative tissue.
Design, fabrication and implementation of smart three axis compliant interconnects for ultra-thin chip stacking technology
56TH ELECTRONIC COMPONENTS & TECHNOLOGY CONFERENCE 2006, VOL 1 AND 2, PROCEEDINGS
Authors: Arunasalam, Parthiban; Ackler, Harold D.; Sammakia, Bahgat G.
Abstract
This paper reports the current status of a novel MEMS based ultra-high density compliant interconnect technology that was proposed in the last Electronic Components and Technology Conference (ECTC) [1]. This MEMS-based interconnect, which we call Smart Three Axis Compliant (STAC) interconnects are directly fabricated onto electrical contact pads or thru-silicon vias on die at the wafer-level. These interconnects are initially bound to the die by a chemically soluble release layer. The "free" end of the interconnect is bonded to a contact pad on a package substrate or other die at the wafer level or die level, and the release layer is dissolved to free the interconnect from the substrate, thereby permitting it to accommodate relative displacements. The paper will clearly show successfully fabricated STAC interconnects at 50micron pitch on a silicon die bonded onto an ultra-thin glass die.