Rationale: Ca 2+ induced Ca 2+ release (CICR) in normal hearts requires close approximation of L-type calcium channels (LTCCs) within the transverse tubules (T-tubules), and Ryanodine receptors (RyR) within the junctional sarcoplasmic reticulum (jSR). CICR is disrupted in cardiac hypertrophy and heart failure, which is associated with loss of T-tubules and disruption of cardiac dyads. In these conditions, LTCCs are redistributed from the T-tubules to disrupt CICR. The molecular mechanism responsible for LTCCs recruitment to and from the T-tubules is not well known. Junctophilin-2 (JPH2) enables close association between T-tubules and the jSR to ensure efficient CICR. JPH2 has a so-called Joining region that is located near domains that interact with T-tubular plasma membrane, where LTCCs are housed. The idea that this Joining region directly interacts with LTCCs and contributes to LTCC recruitment to T-tubules is unknown. Objective: To determine if the Joining region in JPH2 recruits LTCCs to T-tubules through direct molecular interaction in cardiomyocytes to enable efficient CICR. Methods and Results: Modified abundance of JPH2 and redistribution of LTCC were studied in left ventricular hypertrophy in vivo and in cultured adult Feline and rat ventricular myocytes. Protein-protein interaction studies showed that the Joining region in JPH2 interacts with LTCC-α1C subunit and causes LTCCs distribution to the dyads, where they colocalize with RyRs. A JPH2 with induced mutations in the Joining region (mutPG1JPH2) caused T-tubule remodeling and dyad loss, showing that an interaction between LTCC and JPH2 is crucial for T-tubule stabilization. mut PG1JPH2 caused asynchronous Ca 2+ -release with impaired excitation-contraction (EC) coupling after β-adrenergic stimulation. The disturbed Ca 2+ regulation in mut PG1JPH2 overexpressing myocytes caused Calcium/calmodulin-dependent kinase-II activation and altered myocyte bioenergetics. Conclusions: The interaction between LTCC and the Joining region in JPH2 facilitates dyad assembly and maintains normal CIRC in cardiomyocytes.

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We report on the first human implantation of the BCM 3.5 ventricular assist device in a 46-year-old man suffering from terminal stage cardiomyopathy. The circulatory support was used as a bridge to heart transplantation. The patient was in cardiogenic shock and was on assisted circulation for 18 days after which he underwent cardiac transplantation. While receiving support from the ventricular assist device, the patient's condition improved remarkably and 50 days after transplantation he was discharged from hospital. We give a detailed description of the surgical technique, with special emphasis on the procedures for air extraction. We describe the evolution of the hemodynamic status before and after implantation. Final inspection of the device and cannulae after removal showed no thrombi and only small fibrin deposits in the membrane-wall junction.

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