Paclitaxel-eluting stents reduce neointimal hyperplasia compared to bare metal stents in saphenous vein grafts: intravascular ultrasonography analysis of the SOS (Stenting of Saphenous Vein Grafts) trial.

AIMS: To compare the intravascular ultrasonography (IVUS) findings between saphenous vein grafts (SVG) treated with paclitaxel-eluting stents (PES) vs. bare metal stents (BMS) in the Stenting Of Saphenous Vein Grafts (SOS) trial. METHODS AND RESULTS: Of the 80 SOS trial patients, 38 had both baseline and follow-up IVUS examination and were included in this substudy: 17 patients received 28 BMS in 26 lesions and 21 patients received 30 PES in 28 lesions. Quantitative IVUS analysis was performed to determine the volume of in-stent neointimal hyperplasia (NIH) - defined as the difference between stent volume and lumen volume in the stented segments. Baseline characteristics were similar between patients who did and did not undergo baseline and follow-up IVUS. Patients receiving BMS and PES had similar stent and lumen volumes immediately after stenting. At 12-month follow-up, compared to BMS, PES-treated lesions had significantly less NIH volume (3.4 vs. 21.9 mm³, p<0.001) and neointima hyperplasia progression (1.6 vs. 17.1 mm³, p<0.001). No significant differences were seen in the 5 mm segment proximal and distal to the stent. CONCLUSIONS: Compared to BMS, use of PES in SVG lesions is associated with significantly lower NIH formation, which may help explain the improved clinical outcomes with PES in these lesions.

Relation between the presence and extent of coronary lipid core plaques detected by near-infrared spectroscopy with postpercutaneous coronary intervention myocardial infarction.

We aimed to examine whether an association exists between the presence and extent of coronary lipid core plaques (LCPs) detected by near-infrared spectroscopy (NIRS) performed before percutaneous coronary intervention (PCI) with postprocedural myocardial infarction (MI). NIRS was performed in the native coronary arteries of 30 patients before PCI. Angular extent of LCP, lesion segment lipid core burden index, and block chemogram were evaluated. Cardiac biomarkers were measured before and 16 to 24 hours after PCI to determine occurrence of postprocedural MI. Mean number of 2-mm yellow blocks within the stented lesion was 1.4 ± 2.1 and mean lesion lipid core burden index was 110.3 ± 99. Using a definition of creatine kinase-MB >1 time upper limit of normal (ULN), >2 times ULN, and >3 times ULN, MI after PCI occurred in 23%, 13%, and 10% of patients, respectively. Compared to patients who did not have MI after PCI, those who did had similar clinical characteristics but received more stents and had more blocks within the stented lesion. Creatine kinase-MB increase >3 times ULN was observed in 27% of patients with ≥1 yellow block versus in none of the patients without a yellow block within the stented lesion (p = 0.02). In conclusion, PCI of LCP-positive lesions as assessed by NIRS is associated with increased risk for MI after PCI. NIRS may allow lesion-specific risk stratification before PCI and optimization of PCI strategies for myocardial injury risk minimization.

Intraoperative needle localization during neck reexploration.

BACKGROUND: Recurrent cervical adenopathy can be difficult to identify intraoperatively during a neck reexploration. Although local preoperative imaging techniques are available, these are not useful in the operative theater. METHODS: We introduce an intraoperative technique of ultrasound-guided needle localization to identify and guide the resection of suspicious cervical lymphadenopathy. CONCLUSIONS: This intraoperative approach to localizing the suspicious lymph node under ultrasound-guided needle localization makes surgical extirpation of lymph node metastasis easy.

Metalloproteinase inhibition reduces lung injury and improves survival after cecal ligation and puncture in rats.

BACKGROUND: Neutrophil activation with concomitant matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) release has been implicated in the development of sepsis-induced acute lung injury. We hypothesized that COL-3, a chemically modified tetracycline known to inhibit MMP-2 and MMP-9, would reduce lung injury and improve survival in rats following cecal ligation and puncture (CLP). METHODS: Sprague-Dawley rats were separated into five groups: 1) sham CLP+ carboxymethylcellulose (CMC; vehicle for COL-3, n = 6); 2) sham CLP + COL-3 (n = 6); 3) CLP + CMC (n = 10); 4) CLP + single-dose (SD) COL-3 administered concomitant with CLP (n = 9); and 5) CLP + multiple-dose (MD) COL-3 administered concomitant with CLP and at 24 h after CLP (n = 15). Rats were sacrificed at 168 h (7 days) or immediately after death, with survival defined as hours after CLP. Histological lung assessment was made based on neutrophil infiltration, alveolar wall thickening, and intraalveolar edema fluid. Lung MMP-2 and MMP-9 levels were assessed by immunohistochemistry. MMP-2 and MMP-9 levels were correlated with survival by simple regression analysis. RESULTS: The mortality of rats in the cecal ligation and puncture without treatment group (CLP + CMC) was 70% at 168 h. A single dose of COL-3 in the CLP + COL-3 (SD) group significantly reduced mortality to 54%. Furthermore, with a repeat dose of COL-3 at 24 h after CLP, mortality was significantly reduced to 33%. Pathologic lung changes seen histologically in the CLP + CMC group were significantly reduced by COL-3. A significant reduction in lung tissue levels of MMP-2 and MMP-9 was noted in both groups treated with COL-3. Reduction of MMP-2 and MMP-9 levels correlated with improved survival. CONCLUSION: Inhibition of MMP-2 and MMP-9 by COL-3 in a clinically relevant model of sepsis-induced acute lung injury reduces pulmonary injury and improves survival in a dose-dependent fashion. Our results suggest that prophylactic treatment with COL-3 in high-risk patients may reduce the morbidity and mortality associated with sepsis-induced acute respiratory distress syndrome.

Alveolar inflation during generation of a quasi-static pressure/volume curve in the acutely injured lung.

OBJECTIVE: Lower and upper inflection points on the quasi-static curve representing a composite of pressure/volume from the whole lung are hypothesized to represent initial alveolar recruitment and overdistension, respectively, and are currently utilized to adjust mechanical ventilation in patients with acute respiratory distress syndrome. However, alveoli have never been directly observed during the generation of a pressure/volume curve to confirm this hypothesis. In this study, we visualized the inflation of individual alveoli during the generation of a pressure/volume curve by direct visualization using in vivo microscopy in a surfactant deactivation model of lung injury in pigs. DESIGN: Prospective, observational, controlled study. SETTING: University research laboratory. SUBJECTS: Eight adult pigs. INTERVENTIONS: Pigs were anesthetized and administered mechanical ventilation, underwent a left thoracotomy, and were separated into two groups: control pigs (n = 3) were subjected to surgical intervention, and Tween lavage pigs (n = 5) were subjected to surgical intervention plus surfactant deactivation by Tween lavage (1.5 mL/kg 5% solution of Tween in saline). The microscope was then attached to the lung, and the size of each was alveolus quantified by measuring the alveolar area by computer image analysis. Each alveolus in the microscopic field was assigned to one of three types, based on alveolar mechanics: type I, no visible change in alveolar size during ventilation; type II, alveoli visibly change size during ventilation but do not totally collapse at end expiration; and type III, alveoli visibly change size during tidal ventilation and completely collapse at end expiration. After alveolar classification, the animals were disconnected from the ventilator and attached to a super syringe filled with 100% oxygen. The lung was inflated from 0 to 220 mL in 20-mL increments with a 10-sec pause between increments for airway pressure and alveolar confirmation to stabilize. These data were utilized to generate both quasi-static pressure/volume curves and individual alveolar pressure/area curves. MEASUREMENTS AND MAIN RESULTS: The normal lung quasi-static pressure/volume curve has a single lower inflection point, whereas the curve after Tween has an inflection point at 8 mm Hg and a second at 24 mm Hg. Normal alveoli in the control group are all type I and do not change size appreciably during generation of the quasi-static pressure/volume curve. Surfactant deactivation causes a heterogenous injury, with all three alveolar types present in the same microscopic field. The inflation pattern of each alveolar type after surfactant deactivation by Tween was notably different. Type I alveoli in either the control or Tween group demonstrated minimal change in alveolar area with lung inflation. Type I alveolar area was significantly (p <.05) larger in the control as compared with the Tween group. In the Tween group, type II alveoli increased significantly in area, with lung inflation from 0 mL (9666 +/- 1340 microm2) to 40 mL (12,935 +/- 1725 microm2) but did not increase further (220 mL, 14,058 +/- 1740 microm2) with lung inflation. Type III alveoli initially recruited with a relatively small area (20 mL lung volume, 798 +/- 797 microm2) and progressively increased in area throughout lung inflation (120 mL, 7302 +/- 1405 microm2; 220 mL, 11,460 +/- 1078 microm2) CONCLUSION: The normal lung does not increase in volume by simple isotropic (balloon-like) expansion of alveoli, as evidenced by the horizontal (no change in alveolar area with increases in airway pressure) pressure/area curve. After surfactant deactivation, the alveolar inflation pattern becomes very complex, with each alveolar type (I, II, and III) displaying a distinct pattern. None of the alveolar pressure/area curves directly parallel the quasi-static lung pressure/volume curve. Of the 16, only one type III atelectatic alveolus recruited at the first inflection point and only five recruited concomitant with the second inflation point, suggesting that neither inflection point was due to inflection point was due to massive alveolar recruitment. Thus, the components responsible for the shape of the pressure/volume curve include all of the individual alveolar pressure/area curves, plus changes in alveolar duct and airway size, and the elastic forces in the pulmonary parenchyma and the chest wall.

Positive end-expiratory pressure after a recruitment maneuver prevents both alveolar collapse and recruitment/derecruitment.

We tested the hypothesis that collapsed alveoli opened by a recruitment maneuver would be unstable or recollapse without adequate positive end-expiratory pressure (PEEP) after recruitment. Surfactant deactivation was induced in pigs by Tween instillation. An in vivo microscope was placed on a lung area with significant atelectasis and the following parameters measured: (1) the number of alveoli per field and (2) alveolar stability (i.e., the change in alveolar size from peak inspiration to end expiration). We previously demonstrated that unstable alveoli cause lung injury. A recruitment maneuver (peak pressure = 45 cm H2O, PEEP = 35 cm H2O for 1 minute) was applied and alveolar number and stability were measured. Pigs were then separated into two groups with standard ventilation plus (1) 5 PEEP or (2) 10 PEEP and alveolar number and stability were again measured. The recruitment maneuver opened a significant number of alveoli, which were stable during the recruitment maneuver. Although both 5 PEEP and 10 PEEP after recruitment demonstrated improved oxygenation, alveoli ventilated with 10 PEEP were stable, whereas alveoli ventilated with 5 PEEP showed significant instability. This suggests recruitment followed by inadequate PEEP permits unstable alveoli and may result in ventilator-induced lung injury despite improved oxygenation.

Tidal volume increases do not affect alveolar mechanics in normal lung but cause alveolar overdistension and exacerbate alveolar instability after surfactant deactivation.

OBJECTIVE: We utilized microscopy to measure the impact of increasing tidal volume on individual alveolar mechanics (i.e., the dynamic change in alveolar size during tidal ventilation) in the living porcine lung. DESIGN: In three anesthetized, mechanically ventilated pigs, we observed normal alveoli (n = 27) and alveoli after surfactant deactivation by Tween 20 lavage (n = 26) at three different tidal volumes (6, 12, and 15 mL/kg). Alveolar area was measured at peak inspiration (I) and at end expiration (E) by image analysis and I minus E was calculated as an index of alveolar stability (I-Edelta). MEASUREMENTS AND MAIN RESULTS: In normal alveoli, increasing tidal volume did not change alveolar area at I (6 mL/kg = 9726 +/- 848 microm; 15 mL/kg = 9,637 +/- 884 microm ), E (6 mL/kg = 9747 +/- 800 microm; 15 mL/kg = 9742 +/- 853 microm ), or I-Edelta (6 mL/kg = -21 +/- 240 microm; 15 mL/kg = -105 +/- 229 microm ). In contrast, with surfactant deactivation, increasing tidal volume significantly increased alveolar area at I (6 mL/kg = 11,413 +/- 1032 microm; 15 mL/kg = 13,917 +/- 1214 microm ), at E (6 mL/kg = 10,462 +/- 906 microm; 15 mL/kg = 12,000 +/- 1066 microm ), and I-Edelta (6 mL/kg = 825 +/- 276 microm; 15 mL/kg = 1917 +/- 363 microm ). Moreover, alveolar instability (increased I-Edelta) was significantly increased at all tidal volumes with altered surface tension when compared with normal alveoli. CONCLUSIONS: We conclude that high tidal volume ventilation does not alter alveolar mechanics in the normal lung; however, in the surfactant-deactivated lung, it causes alveolar overdistension and exacerbates alveolar instability.