Transapical approach for mitral valve repair during insertion of a left ventricular assist device.

BACKGROUND: Severe mitral regurgitation (MR) is common in patients who are undergoing insertion of a left ventricular assist device (LVAD). This study analyzes the outcomes of a transapical approach for edge-to-edge repair of the mitral valve during insertion of a left ventricular assist device in 19 patients with MR. METHODS: This retrospective study includes 19 patients who were implanted between March 21, 2011, and August 31, 2011, at the University of Chicago. Clinical data include preoperative ejection fraction, post- and preoperative pulmonary arterial pressures, cardiopulmonary bypass time, post- and preoperative mitral regurgitation severity, endotracheal CO2, and LVAD pulse index. RESULTS: All of the 19 patients had a reduction in mitral regurgitation. Fourteen of the 19 patients had at least a three-point reduction in MR severity. The average postoperative pulmonary arterial pressure (PAP) decreased after the surgical procedure from 44/22 ± 14/5 mmHg to 57/28 ± 9/5 mmHg. Average CPB time was 128 ± 27 minutes. Average length-of-stay (LOS) was 21 ± 10 days. CONCLUSIONS: Concomitant MV repair using a transapical approach is advantageous for this small cohort of patients. The surgical procedure is less complex and has a shorter CPB time and LOS, and all of the patients demonstrated significant improvement in postoperative MR and moderate improvement in PAP.

HS1 functions as an essential actin-regulatory adaptor protein at the immune synapse.

HS1, the leukocyte-specific homolog of cortactin, regulates F-actin in vitro and is phosphorylated in response to TCR ligation, but its role in lymphocyte activation has not been addressed. We demonstrate that HS1-deficient T cells fail to accumulate F-actin at the immune synapse (IS) and, upon TCR ligation, form actin-rich structures that are disordered and unstable. Early TCR activation events are intact in these cells, but Ca2+ influx and IL-2 gene transcription are defective. Importantly, HS1 tyrosine phosphorylation is required for its targeting to the IS and for its function in regulating actin dynamics and IL-2 promoter activity. Phosphorylation also links HS1 to multiple signaling proteins, including Lck, PLCgamma1, and Vav1, and is essential for the stable recruitment of Vav1 to the IS. Taken together, our studies show that HS1 is indispensable for signaling events leading to actin assembly and IL-2 production during T cell activation.

Dynamin 2 regulates T cell activation by controlling actin polymerization at the immunological synapse.

Actin reorganization at the immunological synapse is required for the amplification and generation of a functional immune response. Using small interfering RNA, we show here that dynamin 2 (Dyn2), a large GTPase involved in receptor-mediated internalization, did not alter antibody-mediated T cell receptor internalization but considerably affected T cell receptor-stimulated T cell activation by regulating multiple biochemical signaling pathways and the accumulation of F-actin at the immunological synapse. Moreover, Dyn2 interacted directly with the Rho family guanine nucleotide exchange factor Vav1, and this interaction was required for T cell activation. These data identify a functionally important interaction between Dyn2 and Vav1 that regulates actin reorganization and multiple signaling pathways in T lymphocytes.