Identification of a Novel Type of cGMP Phosphodiesterase That Is Defective in the Chemotactic stmF Mutants

StmF mutants are chemotactic mutants that are defective in a cGMP phosphodiesterase (PDE) activity. We identified a novel gene, PdeD, that harbors two cyclic nucleotide–binding domains and a metallo-β-lactamase homology domain. Similar to stmF mutants, pdeD-null mutants displayed extensively streaming aggregates, prolonged elevation of cGMP levels after chemotactic stimulation, and reduced cGMP-PDE activity. PdeD transcripts were lacking in stmF mutant NP377, indicating that this mutant carries a PdeD lesion. Expression of a PdeD-YFP fusion protein in pdeD-null cells restored the normal cGMP response and showed that PdeD resides in the cytosol. When purified by immunoprecipitation, the PdeD-YFP fusion protein displayed cGMP-PDE activity, which was retained in a truncated construct that contained only the metallo-β-lactamase domain

Two Years of Experience in the Implantation of Heartmate III.

Left ventricular assist devices as long-term mechanical circulatory support are increasingly used as an option for medically refractory advanced heart failure. Heartmate III is one of the alternative devices for circulatory support in those patients. Analyze a two years Heartmate III implantation Program. From November 2015 to August 2017, Heartmate III was implanted in 16 patients with chronic end-stage heart failure, in 81% (n = 13) as a bridge to transplant and 19% (n = 3) as destination therapy. We did a review off demographic, clinical and surgical data, and we analyzed the overall survival using the Kaplan-Meier method, excluding patients who were transplanted. Heartmate III was implanted in 16 male patients (100%) with age 55.8 ± 11.1 years (limits 38-74 years) and body surface area 2.0 ± 0.19 m2. The baseline hemodynamic data revealed a cardiac index 2.1 ± 0.4 l / min / m2 and a left ventricular ejection fraction of 20.7 ± 7.3%. Ischemic cardiomyopathy was the most common etiology in this chronic heart failure population (n = 9; 56%). Seven patients (44%) were classified INTERMACS 4; five (31%) in profile 2; three (19%) in profile 3 and one (6%) in profile 1. The implantation of the devices was performed under Cardiopulmonary Bypass (78.6 ± 25.7 min), and 25% of the patients (n = 4) had right ventricular dysfunction, requiring postoperative temporary right ventricle support. As complications, 6 patients (38%) manifested bleeding requiring surgery and 2 (12%) reported gastrointestinal bleeding, 4 (25%) developed driveline infection, 3 of them were treated (18%) with conservative therapy and in 1 patient (6%) with driveline transposition. During the total follow-up time (19 months), three patients (18%) were transplanted; two deaths occured due to pulmonary embolism and ischemic stroke respectively; verified by the Kaplan Meier method, an overall survival rate of 92.9 ± 6.9%, stable from 6 months after implantation. The 6 months survival rate of 92.9% proves the efficacy of this therapy for our patients and all of them were INTERMACS profils lower than 4. Despite the small number of patients enrolled and the follow-up duration limiting our study, we demonstrated the first experience of our center in the treatment of high-risk population. In conclusion, we show that the Heartmate III was consistent in low INTERMACS profile patients