3D-Transesophageal Echocardiography in Paradoxical Low-Flow, Low-Gradient Aortic Stenosis

Background: In paradoxical low-flow, low gradient (PLFLG) aortic stenosis, 2D-transthoracic echocardiography (2D-TTE)may underestimate flow because it assumes a circular left ventricular outflow tract (LVOT) shape. Three-dimensional transesophagealechocardiography (3D-TEE) is a better method to measure LVOT area.Objectives: The aim of this study was to evaluate left ventricular stroke volume index (SVi) by 2D-TTE and 3D-TEE in patientswith normal heart (NH) and with severe aortic stenosis (SAS) and to determine how many patients are categorized asPLFLG by 2D-TTE and 3D-TEE.Methods: Thirty-five patients were evaluated by 2D-TEE and 3D-TEE: NH=17 patients and SAS=18 patients. Left ventricularoutflow tract area was estimated during early systole by 2D-TTE (ES2DLVOT Ar) and by 3D-TEE (ES3DLVOT Ar)planimetry, and as systolic average (Avg 3DLVOT Ar). Each LVOT area was multiplied by its corresponding flow integral toobtain SVi (ES2D-TTE SVi, ES3D-TEE SVi and Avg 3D-TEE SVi) in NH and SAS groups. Paradoxical LFLG was determinedin SAS following standard criterion.Results: NH: ES2DLVOT Ar vs. ES3DLVOT Ar p<0.05; SAS: ES2DLVOT Ar vs. ES3DLVOT Ar p<0.001 and vs. Avg 3DLVOTAr p<0.023; ES2D-TTE SVi vs. ES3D-TEE SVi p<0.002 and vs. Avg 3D-TEE SVi p<0.038. In the NH group, the lower limitof normal SVi for 2D-TTE, ES3D-TEE and Avg 3D-TEE was <34, <38.9 and <35.9 ml/m2, respectively. Three SAS patientswere categorized as PLFLG by 2D-TTE, but none by 3D-TEE.Conclusions: Patients with PLFLG by 2D-TTE couldIntroducción: En la estenosis aórtica (EAo) con bajo flujo/bajo gradiente paradójico (BFBGP), el eco transtorácico 2D (ETT2D)podría subestimar el cálculo de flujo porque asume el tracto de salida del ventrículo izquierdo (TSVI) con una morfologíacircular. El eco transesofágico 3D (ETE3D) es metodológicamente mejor que el 2D para medir el TSVI.Objetivos: Evaluar el volumen eyectivo indexado (VEi) del ventrículo izquierdo por ETT2D y ETE3D en pacientes con corazónnormal (GN) y con EAo grave (GEAo) y determinar cuántos pacientes con BFBGP por ETT2D se consideran también conBFBGP por ETE3D.Material y métodos: Se evaluaron 35 pacientes con ETT2D y ETE3D: GN = 17 pacientes y GEAo = 18 pacientes. Se estimóen ambos grupos el área del TSVI en protosístole por ETT2D (TSVI2Dprot) y por planimetría ETE3D (TSVI3Dprot) y comopromedio sistólico (TSVI3Dprom). Multiplicando cada área del TSVI por su integral de flujo, se obtuvieron los VEi (VEiETT2D prot, VEi ETE3D prot y VEi ETE3D prom) tanto del GN como del GEAo. En el GEAo se determinó BFBGP segúncriterio actual.Resultados: GN: área TSVI ETT2D prot vs. ETE3D prot p < 0,05. GEAo: área TSVI ETT2D prot vs. ETE3D prot p < 0,001y vs. ETE3D prom p < 0,023; VEi ETT2D prot vs. VEi ETE3D prot p < 0,002 y vs. VEi ETE3D prom p < 0,038. En el GN,el VEi en el límite inferior de lo normal por ETT2D, ETE3D prot y ETE3D prom fue < 34, < 38,9 y < 35,9 ml/m2, respectivamente.Tres pacientes del GEAo fueron BFBGP por ETT2D, pero ninguno por ETE3D.Conclusiones: Los pacientes con BFBGP por ETT2D podrían ser reclasificados por el ETE3D. Este hallazgo se relaciona conlas limitaciones del eco 2D para el cálculo del área del TSVI

BK channels affect glucose homeostasis and cell viability of muring pancreatic beta cells

AIMS/HYPOTHESIS: Evidence is accumulating that Ca(2+)-regulated K(+) (K(Ca)) channels are important for beta cell function. We used BK channel knockout (BK-KO) mice to examine the role of these K(Ca) channels for glucose homeostasis, beta cell function and viability. METHODS: Glucose and insulin tolerance were tested with male wild-type and BK-KO mice. BK channels were detected by single-cell RT-PCR, cytosolic Ca(2+) concentration ([Ca(2+)](c)) by fura-2 fluorescence, and insulin secretion by radioimmunoassay. Electrophysiology was performed with the patch-clamp technique. Apoptosis was detected via caspase 3 or TUNEL assay. RESULTS: BK channels were expressed in murine pancreatic beta cells. BK-KO mice were normoglycaemic but displayed markedly impaired glucose tolerance. Genetic or pharmacological deletion of the BK channel reduced glucose-induced insulin secretion from isolated islets. BK-KO and BK channel inhibition (with iberiotoxin, 100 nmol/l) broadened action potentials and abolished the after-hyperpolarisation in glucose-stimulated beta cells. However, BK-KO did not affect action potential frequency, the plateau potential at which action potentials start or glucose-induced elevation of [Ca(2+)](c). BK-KO had no direct influence on exocytosis. Importantly, in BK-KO islet cells the fraction of apoptotic cells and the rate of cell death induced by oxidative stress (H(2)O(2), 10–100 μmol/l) were significantly increased compared with wild-type controls. Similar effects were obtained with iberiotoxin. Determination of H(2)O(2)-induced K(+) currents revealed that BK channels contribute to the hyperpolarising K(+) current activated under conditions of oxidative stress. CONCLUSIONS/INTERPRETATION: Ablation or inhibition of BK channels impairs glucose homeostasis and insulin secretion by interfering with beta cell stimulus–secretion coupling. In addition, BK channels are part of a defence mechanism against apoptosis and oxidative stress