False carina: a distinct variant of tracheal bronchus.

Tracheal-bronchus is an aberrant bronchus arising from the lateral tracheal wall, superior to the carina. A "False-carina" can be classified as a sub-type. This clinical entity will be defined and the clinical presentation, diagnosis and management of five patients with variations of the anatomical definition of a False-carina, identified at our institution, will be reviewed. Congenital bronchial abnormalities, including False-carina, have important implications in the overall management of the airway. Management can range from expectant in asymptomatic patients to surgical intervention in cases of recurrent respiratory infections. Awareness and understanding of this clinical entity allows for timely investigation, diagnosis and appropriate intervention.

Cardiac strangulation following epicardial pacemaker implantation: a rare pediatric complication.

OBJECTIVES: The aim of our study was 2-fold: to determine the incidence of cardiac strangulation (CS) and to develop a clinical pathway to aid in the diagnosis and prognosis of CS. In <2 years, 2 cases of CS occurred in our institution, which caused much alarm and led to the study's objectives. METHODS: All patients who underwent implantation of an epicardial pacemaker from January 1992 to March 2012 were included. There were no exclusion criteria. Health records were used to locate all subjects and gather all retrospective data. Prospectively, subjects without a chest radiograph from the previous 2 years were approached for imaging. RESULTS: This study included 86 patients retrospectively, and 84 patients prospectively. There was a 2.3% incidence, and a 1.2% mortality, related to CS. A pattern of posterior looping of the ventricular lead was seen in radiographs of both CS-diagnosed patients. Five variables were significantly associated with an outcome of CS (P = .0153). CONCLUSIONS: Our data indicate that the 2 cases of CS were not caused by a lack of follow-up but by a lack of consistent imaging for diagnosis. This conclusion is supported by the 8 cases of CS found in the English-language literature. If the patient is age ≤6 months at the time of implantation, particular attention should be given to the placement of leads and follow-up.

Nonuniform and variable arrangements of ryanodine receptors within mammalian ventricular couplons.

RATIONALE: Single-tilt tomograms of the dyads in rat ventricular myocytes indicated that type 2 ryanodine receptors (RYR2s) were not positioned in a well-ordered array. Furthermore, the orientation and packing strategy of purified type 1 ryanodine receptors in lipid bilayers is determined by the free Mg2+ concentration. These observations led us to test the hypothesis that RYR2s within the mammalian dyad have multiple and complex arrangements. OBJECTIVES: To determine the arrangement of RYR2 tetramers in the dyads of mammalian cardiomyocytes and the effects of physiologically and pathologically relevant factors on this arrangement. METHODS AND RESULTS: We used dual-tilt electron tomography to produce en-face views of dyads, enabling a direct examination of RYR2 distribution and arrangement. Rat hearts fixed in situ; isolated rat cardiomyocytes permeabilized, incubated with 1 mmol/L Mg2+, and then fixed; and sections of human ventricle, all showed that the tetramer packing within a dyad was nonuniform containing a mix of checkerboard and side-by-side arrangements, as well as isolated tetramers. Both phosphorylation and 0.1 mmol/L Mg2+ moved the tetramers into a predominantly checkerboard configuration, whereas the 4 mmol/L Mg2+ induced a dense side-by-side arrangement. These changes occurred within 10 minutes of application of the stimuli. CONCLUSIONS: The arrangement of RYR2 tetramers within the mammalian dyad is neither uniform nor static. We hypothesize that this is characteristic of the dyad in vivo and may provide a mechanism for modulating the open probabilities of the individual tetramers.

Kingella kingae endocarditis: A rare case of mitral valve perforation.

Kingella kingae, a HACEK (Haemophilus parainfluenzae, Aggregatibacter actinomycetemcomitans, Aggregatibacter aphrophilus, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) organism, is a common resident of the upper airway in children; it has been associated with endocarditis in children with pre-existing heart conditions. This case report describes K. kingae endocarditis leading to valvular damage in a previously healthy 18-month-old child. Our patient developed a K. kingae bacteremia that was later complicated by meningitis, septic embolic stroke, and endocarditis of the mitral valve, leading to perforation of the posterolateral leaflet. The patient was initially treated conservatively with cefotaxime but, subsequently, required a mitral valve repair with a pericardial patch and annuloplasty. This report draws attention to the need for clinicians to be aware of the potentially serious complications of K. kingae infection in young children. If K. kingae infection is suspected then therapy should be initiated promptly with a ß-lactam, followed by early echocardiographic assessment. This case also highlights the lack of specific guidelines available for K. kingae endocarditis.

Reciprocal regulation of angiopoietin-1 and angiopoietin-2 following myocardial infarction in the rat.

OBJECTIVE: This study sought to characterize changes in the angiopoietin system in a rat model of myocardial infarction (MI). BACKGROUND: Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) bind to the endothelial-specific receptor tyrosine kinase, TIE-2. Ang-2 has been suggested to be an antagonist of TIE-2, possibly acting to release endothelial cells from the tonic stabilizing influence of Ang-1. However, on prolonged exposure, Ang-2 has been shown to acquire agonistic activity at TIE-2, raising the possibility that this isoform may play a direct role in neovascularization. METHODS: Sprague-Dawley rats were subjected to left coronary ligation and myocardial tissues were harvested from the infarct and peri-infarct regions, or from non-infarcted myocardium. Changes in gene expression were determined by RT-PCR and confirmed by Northern analysis. Changes in protein expression were confirmed by Western analysis and immunocytochemistry, and TIE-2 activity was determined by immunoprecipitation with anti-TIE-2 and antiphosphotyrosine immunoblotting. RESULTS: At 24 h, Ang-1 mRNA and protein expression within the infarct and peri-infarct regions were decreased compared to non-infarcted myocardium, whereas Ang-2 mRNA levels were markedly increased and TIE-2 expression was unchanged. Immunohistochemical staining revealed Ang-1 and TIE-2 immunoreactivity localized to vascular endothelium. In the infarct territory, Ang-2 immunostaining was localized primarily to invading leukocytes at 24 h. At 1 week, Ang-1 expression was partially restored, whereas Ang-2 expression remained elevated. At the time of peak elevation in Ang-2, Tie2 phosphorylation was found to be markedly increased, consistent with receptor activation. CONCLUSIONS: Thus, myocardial ischemia induced by left coronary artery ligation resulted in a sustained increase in Ang-2 expression and a reciprocal decrease in Ang-1, consistent with a predominant role for Ang-2 in the angiogenic response to MI.

Protective role of angiopoietin-1 in experimental pulmonary hypertension.

Angiopoietin-1 (Ang-1), a newly discovered ligand of the endothelial-specific tyrosine kinase receptor Tie-2, has been found to promote cell survival, vascular maturation, and stabilization. We hypothesized that Ang-1 gene transfer to the pulmonary microcirculation would improve pulmonary hemodynamics and vascular remodeling in experimental pulmonary hypertension. Rat pulmonary artery smooth muscle cells were transfected with Ang-1 cDNA or null (pFLAG-CMV-1) vector. Syngeneic Fisher 344 rats were treated with monocrotaline (MCT) (75 mg/kg IP) with or without delivery of 5x10(5) Ang-1-transfected cells into the right jugular vein. After 28 days, plasmid-derived Ang-1 mRNA was consistently and robustly detected by reverse transcriptase-polymerase chain reaction in lungs from all animals receiving Ang-1 gene therapy. Tie-2 receptor expression was markedly downregulated in rats treated with MCT, and this was partially restored by gene therapy with Ang-1. Animals receiving MCT exhibited 77% mortality by 28 days. In contrast, in pAng-1-treated animals, the 28-day mortality was only 14% (P<0.0001). In addition, right ventricular systolic pressure was reduced from 52+/-1.3 mm Hg in the MCT-treated group to 38+/-1.3 mm Hg by Ang-1 gene transfer (P<0.01), whereas the measurement of right to left ventricular plus septal weight ratio was also reduced from 0.41+/-0.03 to 0.31+/-0.01 (P<0.05). Moreover, MCT resulted in increased apoptosis, mainly in the microvasculature, and reduced endothelial NO synthase mRNA expression, both of which were prevented by Ang-1 gene transfer. Thus, cell-based gene transfer with Ang-1 improved survival and pulmonary hemodynamics in experimental pulmonary hypertension by a mechanism involving the inhibition of apoptosis and protection of the pulmonary microvasculature.