Background-Endocardial fibrous tissue (FT) deposition is a hallmark of endomyocardial fibrosis (EMF). Echocardiog-raphy is a first-line and the standard technique for the diagnosis of this disease. Although late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) allows FT characterization, its role in the diagnosis and prognosis of EMF has not been investigated. Methods and Results-Thirty-six patients (29 women; age, 54Ϯ12 years) with EMF diagnosis after clinical evaluation and comprehensive 2-dimensional Doppler echocardiography underwent cine-CMR for assessing ventricular volumes, ejection fraction and mass, and LGE-CMR for FT characterization and quantification. Indexed FT volume (FT/body surface area) was calculated after planimetry of the 8 to 12 slices obtained in the short-axis view at end-diastole (mL/m 2 ). Surgical resection of FT was performed in 16 patients. In all patients, areas of LGE were confined to the endocardium, frequently as a continuous streak from the inflow tract extending to the apex, where it was usually most prominent. There was a relation between increased FT/body surface area and worse New York Heart Association functional class and with increased probability of surgery (PϽ0.05). The histopathologic examination of resected FT showed typical features of EMF with extensive endocardial fibrous thickening, proliferation of small vessels, and scarce inflammatory infiltrate. In multivariate analysis, the patients with FT/body surface area Ͼ19 mL/m 2 had an increased mortality rate, with a relative risk of 10.8. Conclusions-Our study provides evidence that LGE-CMR is useful in the diagnosis and prognosis of EMF through quantification of the typical pattern of FT deposition. (Circ Cardiovasc Imaging. 2011;4:304-311.)

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Murine ␥-aminobutyric acid (GABA) type A homomeric receptors made of ␤ 1 subunits are profoundly different, when expressed in Xenopus oocytes, from ␤ 3 homomeric receptors. Application of the intravenous general anesthetic pentobarbital, etomidate, or propofol to ␤ 3 homomeric receptors allows current flow. In contrast, ␤ 1 homomers do not respond to any of these agents. Through construction of chimeric ␤ 1 /␤ 3 receptors, we identified a single amino acid that determines the pharmacological difference between the two ␤ subunits. When the serine residue present in the wild-type nonresponsive ␤ 1 subunit is replaced by an asparagine found in the same position in the ␤ 3 subunit, the resulting pointmutated ␤ 1 S265N forms receptors responsive to intravenous general anesthetics, like the wild-type ␤ 3 subunits. Conversely, after mutation of the wild-type ␤ 3 to ␤ 3 N265S, the homomeric receptor loses its ability to respond to these same general anesthetics. Wild-typeto-mutant titration experiments showed that the nonresponsive phenotype is dominant: A single nonresponsive residue within a pentameric receptor is sufficient to render the receptor nonresponsive. In ␣ 1 ␤ x or ␣ 1 ␤ x ␥ 2 heteromeric receptors, the same residue manifests as a partial determinant of the degree of potentiation of the GABA-induced current by some general anesthetics. The location of this amino acid at the extracellular end of the second transmembrane segment, its influence in both homomeric and heteromeric receptor function, and its dominant behavior suggest that this residue of the ␤ subunit is involved in an allosteric modulation of the receptor. Key Words: GABA A receptor-␤ subunit-Gating-Chimera-Site-directed mutagenesis-Intravenous general anesthetics. J. Neurochem. 74, 827-838 (2000).␥-Aminobutyric acid (GABA) type A (GABA A ) receptor is a member of the ligand-gated ion channel superfamily of homologous receptors (Schofield et al., 1987). Binding of the ligand, GABA, to the receptor opens the integral Cl Ϫ channel, driving the membrane potential toward the chloride equilibrium potential, thus reducing the sensitivity of the membrane to the effects of excitatory neurotransmitters. GABA and competitive GABA agonists such as muscimol, as well as antagonists such as bicuculline, bind to the extracellular N-terminal region of both the ␣ subunit (Sigel et al., 1992) and the ␤ subunit (Amin and Weiss, 1993). Similarly, benzodiazepines bind to the N-terminal region of the ␥ subunit (Mihic et al., 1994). General anesthetic drugs of diverse chemical structures, e.g., pentobarbital, propofol, etomidate, and volatile agents such as halothane, directly open the GABA A Cl Ϫ channel in the absence of GABA (Franks and Lieb, 1994). The site on the receptor where these drugs act has not been identified, but recent evidence suggests a critical role of the second transmembrane segment (M2) in the action of volatile general anesthetics, alcohol, and etomidate on GABA A receptors Mihic et al., 1997;Moody et al., 1997).The GABA A receptor is us...