Current studies from this laboratory have indicated altered expression of various cardiac regulatory proteins, which are over-expressed during early, hyperdynamic phase of sepsis but under expressed during the late, hypodynamic phase. The investigators hypothesize that the altered expression of these various cardiac regulatory proteins is responsible for the distinct cardiodynamic states during sepsis, through modifications of the synthesis and/or degradation of their gene transcripts or proteins. The regulatory proteins that would be investigated include the adrenoceptors and their associated G-proteins, as well as the calcium regulatory proteins. The proposed experiments will utilize a complex variety of molecular biological techniques including Western blots, RT-PCR, Northern blots nuclear run off assay and stability studies. Additional studies will include pre-treatment of animals with/ without various inhibitors to mechanistically link the gene transcription and signaling proteins with cardiac contractile function. The results obtained will lay the groundwork for future therapy by drugs or genetic intervention to preserve cardiac function during sepsis.
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