Active fixation mechanism complicates coronary sinus lead extraction and limits subsequent reimplantation targets.

INTRODUCTION: Implantation of cardiac resynchronization therapy (CRT) devices is technically challenging and can be limited by lead dislodgement. The Attain Starfix active fixation coronary sinus (CS) lead (model 4195, Medtronic, Minneapolis, MN, USA) was introduced to reduce the rate of lead dislodgement, but the active fixation mechanism presents additional difficulties should these leads require extraction. METHODS: CS lead extraction procedures at our institution from 2003 to 2011 were reviewed. Procedural variables were compared between extraction of the Starfix lead and passive fixation CS leads. Attempts at reimplantation post Starfix lead extraction were examined. RESULTS: Four Starfix CS leads were extracted in four patients during this time period. The mean implant duration was 784 days (range, 392-1,029 days). The indication for extraction was infection in all four cases. Mean total procedure time was 141.5 min (range, 92-205 min). None of the fixation lobes could be retracted in one lead and only the most proximal lobes could be retracted in the remaining three leads. All four leads were removed in their entirety. The excimer laser sheath (Spectranetics Laser Sheath II, Spectranetics Corp., Colorado Springs, CO,USA) was required to remove the lead in all 4 cases (100 %) compared to 25 of 131 (19.1 %) of passive fixation CS lead extractions (mean implant duration, 659 ± 697 days) performed at our institution over the same time period (P < 0.001). In three cases, the laser sheath had to be advanced past the CS ostium to remove the Starfix lead. After extraction, fibrous material which had grown between the lobes of the fixation mechanism was noted in all four cases. No complications occurred. Transvenous CS lead reimplantation was attempted at a median of 7.5 days post extraction in all four patients. The original target branch was occluded in three patients and the main CS in one patient. Reimplantation was successful in another branch of the CS in three of four patients; one underwent minimally invasive epicardial lead placement. CONCLUSIONS: The Starfix active fixation CS lead presents additional procedural complexity and uniform use of excimer laser sheath compared to other CS leads. Reimplantation was not possible in the same venous branch in our experience.

Preservation of function and histologic appearance in the injured glottis with topical mitomycin-C.

OBJECTIVE: To evaluate the functional and histological effects of a single application of topical mitomycin-C after laser injury in the posterior canine glottis. STUDY DESIGN: A prospective, randomized study of 16 canines. METHODS: A supersaturated (1%) solution of topical mitomycin-C was applied to a unilateral, laser-induced injury near the cricoarytenoid joint in eight dogs. The mitomycin-soaked pledget was placed immediately after induction of the injury and was left in contact with exposed cartilage for 3 minutes. The opposite side was not injured to provide an internal control. In eight additional dogs, the same laser injury was allowed to heal untreated. After 6 weeks, the animals were sacrificed and their larynges harvested. Arytenoid adduction sutures were placed bilaterally, and the force required to bring the vocal folds to midline was measured for each side using tensiometry. Gross and microscopic histological analysis was performed. Statistical analysis was accomplished using a two-tailed Student t test of unpaired samples, and the Wilcoxon Signed Rank Test where appropriate. RESULTS: The mitomycin-C treated larynges demonstrated improved cricoarytenoid joint mobility (P = .007), decreased granulation tissue development (P = .03), and complete prevention of secondary "vocal granuloma" formation (P = .0004) when compared with eight dogs with identical laser injuries allowed to heal untreated. No complications were noted. CONCLUSIONS: This study demonstrates functional preservation and improved histological appearance of the injured glottis after a single treatment with topical mitomycin-C. Potential applications of these findings include prophylactic use of topical mitomycin-C on glottic insults that commonly progress from granulation tissue formation to scarring and decreased vocal fold function.

Influence of mechanical stretch on thrombin regulation by fetal mixed lung cells.

Respiratory distress syndrome (RDS) is characterized by intrapulmonary fibrin deposition, which can adversely affect surfactant function, and stimulate fibroblast proliferation, which may contribute to the development of bronchopulmonary dysplasia (BPD). We speculated that the premature lung may have impaired regulation of thrombin, thus making preterm infants susceptible to fibrin formation within the lung. Therefore, we studied the effect of stretch, which simulates fetal breathing movements (FBMs), on the generation and inhibition of a key hemostatic enzyme-thrombin-by rat fetal mixed lung cells (FMLCs). Our results showed that stretch induced glycosaminoglycan production with increased antithrombin activity due to an increase in the concentration of active chondroitin sulfate. Stretch downregulated secretion of tissue factor procoagulant activity, which may lead to decreased thrombin generation on the surface of FMLCs. Overall, stretch enhanced the local control of thrombin by FMLCs. These results suggest that premature infants, who will have experienced less FBM, may have impaired thrombin regulation. Impaired thrombin regulation likely contributes to increased fibrin deposition and, potentially, the development of BPD.

Effect of a novel covalent antithrombin-heparin complex on thrombin generation on fetal distal lung epithelium.

Respiratory distress syndrome is characterized by fibrin deposition in the lung. Fibrin adversely affects surfactant function and stimulates proliferation of fibroblasts. There is evidence that these properties may be important to the development of bronchopulmonary dysplasia. Despite successful initial treatment of neonatal respiratory distress syndrome with surfactant, the incidence of bronchopulmonary dysplasia has not decreased. In previous studies, it has been demonstrated that rat fetal distal lung epithelium (FDLE) possesses both procoagulant and anticoagulant properties. In this report, we have demonstrated (using factor VII-deficient plasma) that tissue factor is expressed on the FDLE surface and promotes thrombin generation. To regulate thrombin within this procoagulant environment, we have developed a novel anticoagulant, antithrombin-heparin covalent complex (ATH) that can be retained within the lung after intrapulmonary instillation. We have demonstrated that ATH was superior to antithrombin plus standard heparin in suppressing thrombin generation (P < 0.001) and prothrombin consumption (P < 0.01) in recalcified defibrinated plasma on the surface of FDLE. Further studies with ATH in vivo need to be performed.

Covalent antithrombin-heparin complexes with high anticoagulant activity. Intravenous, subcutaneous, and intratracheal administration.

Although heparin has been used clinically for prophylaxis and treatment of thrombosis, it has suffered from problems such as short duration within compartments in vivo that require long term anticoagulation. A covalent antithrombin-heparin complex has been produced with high anticoagulant activity and a long half-life relative to heparin. The product had high anti-factor Xa and antithrombin activities compared with noncovalent mixtures of antithrombin and heparin (861 and 753 units/mg versus 209 and 198 units/mg, respectively). Reaction with thrombin was rapid with bimolecular and second order rate constants of 1.3 x 10(9) M-1 s-1 and 3.1 x 10(9) M-1 s-1, respectively. The intravenous half-life of the complex in rabbits was 2.6 h as compared with 0.32 h for similar loads of heparin. Subcutaneous injection of antithrombin-heparin resulted in plasma levels (peaking at 24-30 h) that were still detectable 96 h post-injection. Given the increased lifetime in these vascular and intravascular spaces, use of the covalent complex in the lung was investigated. Activity of antithrombin-heparin instilled into rabbit lungs remained for 48 h with no detection of any complex systemically. Thus, this highly active agent has features required for pulmonary sequestration as a possible treatment for thrombotic diseases such as respiratory distress syndrome.