A novel K(ATP) current in cultured neonatal rat atrial appendage cardiomyocytes.
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The functional and pharmacological properties of ATP-sensitive K(+) (K(ATP)) channels were studied in primary cultured neonatal rat atrial appendage cardiomyocytes. Activation of a whole-cell inward rectifying K(+) current depended on the pipette ATP concentration and correlated with a membrane hyperpolarization close to the K(+) equilibrium potential. The K(ATP) current could be activated either spontaneously or by a hypotonic stretch of the membrane induced by lowering the osmolality of the bathing solution from 290 to 260 mOsm/kg H(2)O or by the K(+) channel openers diazoxide and cromakalim with EC(50) approximately 1 and 10 nmol/L, respectively. The activated atrial K(ATP) current was highly sensitive to glyburide, with an IC(50) of 1.22+/-0.15 nmol/L. Recorded in inside-out patches, the neonatal atrial K(ATP) channel displayed a conductance of 58.0+/-2.2 pS and opened in bursts of 133.8+/-20.4 ms duration, with an open time duration of 1.40+/-0.10 ms and a close time duration of 0.66+/-0.04 ms for negative potentials. The channel had a half-maximal open probability at 0.1 mmol/L ATP, was activated by 100 micromol/L diazoxide, and was inhibited by glyburide, with an IC(50) in the nanomolar range. Thus, pending further tests at low concentrations of K(ATP) channel openers, the single-channel data confirm the results obtained with whole-cell recordings. The neonatal atrial appendage K(ATP) channel thus shows a unique functional and pharmacological profile resembling the pancreatic beta-cell channel for its high affinity for glyburide and diazoxide and for its conductance, but also resembling the ventricular channel subtype for its high affinity for cromakalim, its burst duration, and its sensitivity to ATP. Reverse transcriptase-polymerase chain reaction experiments showed the expression of Kir6.1, Kir6.2, SUR1A, SUR1B, SUR2A, and SUR2B subunits, a finding supporting the hypothesis that the neonatal atrial K(ATP) channel corresponds to a novel heteromultimeric association of K(ATP) channel subunits. (+info)
Left atrial appendage: structure, function, and role in thromboembolism.
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The left atrial appendage (LAA) is derived from the left wall of the primary atrium, which forms during the fourth week of embryonic development. It has developmental, ultrastructural, and physiological characteristics distinct from the left atrium proper. The LAA lies within the confines of the pericardium in close relation to the free wall of the left ventricle and thus its emptying and filling may be significantly affected by left ventricular function. The physiological properties and anatomical relations of the LAA render it ideally suited to function as a decompression chamber during left ventricular systole and during other periods when left atrial pressure is high. These properties include the position of the LAA high in the body of the left atrium; the increased distensibility of the LAA compared with the left atrium proper; the high concentration of atrial natriuretic factor (ANF) granules contained within the LAA; and the neuronal configuration of the LAA. Thrombus has a predilection to form in the LAA in patients with atrial fibrillation, mitral valve disease, and other conditions. The pathogenesis has not been fully elucidated; however, relative stasis which occurs in the appendage owing to its shape and the trabeculations within it is thought to play a major role. Obliteration or amputation of the LAA may help to reduce the risk of thromboembolism, but this may result in undesirable physiological sequelae such as reduced atrial compliance and a reduced capacity for ANF secretion in response to pressure and volume overload. (+info)
Left atrial appendage anatomy and function: short term response to sustained atrial fibrillation.
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OBJECTIVE: To determine whether there is significant atrial or atrial appendage enlargement or functional remodelling as a result of one to two months of sustained atrial fibrillation, a duration similar to that experienced by patients undergoing warfarin anticoagulation before elective cardioversion. METHODS: To test the hypothesis that left atrial and left atrial appendage enlargement develop as a result of short term atrial fibrillation, serial anatomical and functional indices were measured using transoesophageal echocardiography (TOE) in 20 patients with recent onset atrial fibrillation (14 men, six women; mean (SEM) age 67 (2) years). Serial TOE was performed 2.5 months apart in patients with sustained atrial fibrillation. RESULTS: There was no significant change in left atrial area (23.7 cm(2) to 24.1 cm(2), p = 0.98); length (5.7 cm to 5.7 cm, p = 0.48); width (5.2 cm to 5.2 cm, p = 0. 65); volume (83 cm(3) to 87 cm(3), p = 0.51) or left atrial appendage area (7.9 cm(2) to 8.1 cm(2), p = 0.89); length (4.6 cm to 4.5 cm, p = 0.8); or width (2.5 to 2.4 cm, p = 0.87). Peak left atrial appendage velocity ejection (0.2 m/s to 0.2 m/s, p = 0.57), and presence of severe spontaneous echo contrast in the left atrial appendage (n = 15 (75%) to n = 13 (72%)) were also not significantly different. There was no correlation between changes in left atrial or left atrial appendage dimensions. CONCLUSIONS: In the setting of sustained atrial fibrillation, significant left atrial and left atrial appendage functional and anatomical remodelling do not occur with atrial fibrillation of a duration similar to that used for conservative anticoagulation in preparation for cardioversion. (+info)
Echocardiographic assessment of the left atrial appendage.
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The left atrial (LA) appendage is a common source of cardiac thrombus formation associated with systemic embolism. Transesophageal echocardiography allows a detailed evaluation of the structure and function of the appendage by two-dimensional imaging and Doppler interrogation of appendage flow. Specific flow patterns, reflecting appendage function, have been characterized for normal sinus rhythm and various abnormal cardiac rhythms. Appendage dysfunction has been associated with LA appendage spontaneous echocardiographic contrast, thrombus formation and thromboembolism. These associations have been studied extensively in patients with atrial fibrillation or atrial flutter, in patients undergoing cardioversion of atrial arrhythmias and in patients with mitral valve disease. The present review summarizes the literature on the echocardiographic assessment of LA appendage structure, function and dysfunction, which has become an integral part of the routine clinical transesophageal echocardiographic examination. (+info)
Contractile and arrhythmic effects of endothelin receptor agonists in human heart in vitro: blockade with SB 209670.
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It is known that binding sites with endothelin(A) (ET)(A) and ET(B) receptor characteristics coexist in human heart but little is known about the receptors that mediate cardiostimulant effects of ET receptor agonists or their consequences. Functional studies were performed on isolated human cardiac tissues. The maximal positive inotropic effects of ET-1 were right atrium > left atrium = right ventricle. The rank order of potencies of agonists in right atrium was sarafotoxin S6c > ET-1 = ET-2 > or = ET-3. The ET(A) receptor-selective compounds BQ123 (10 microM) and A-127722 (1 microM) only slightly blocked (<0.5 log-unit shift) the effects of lower concentrations of ET-1, and the ET(B) receptor antagonist Ro46-8443 (10 microM) did not cause blockade. SB 209670 caused concentration-dependent rightward shifts of ET-1 and sarafotoxin S6c concentration-effect curves with Schild slopes not different from one and affinities (-logM K(B)) of 7.0 and 7.9, respectively. ET-1 caused arrhythmic contractions in right atrial trabeculae that were prevented by 10 microM SB 209670 but not 10 microM BQ123 or 1 microM A-127722, precluding ET(A) receptors. ET-1 caused a higher incidence of arrhythmic contractions in tissues taken from patients treated with beta-blockers before surgery than in tissues from non-beta blocker-treated patients. Sarafotoxin S6c produced arrhythmias that were prevented by SB 209670. The positive inotropic effects of ET-1 in human right atrial myocardium are mediated mostly by a non-ET(A), non-ET(B) receptor. Ventricular inotropic ET receptors differ from atrial inotropic ET receptors. ET-1 induced arrhythmic contractions in human atria do not appear to be mediated by an ET(A) receptor. (+info)
Ionic mechanisms of electrical remodeling in human atrial fibrillation.
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OBJECTIVES: Atrial fibrillation (AF) is associated with a decrease in atrial ERP and ERP adaptation to rate as well as changes in atrial conduction velocity. The cellular changes in repolarization and the underlying ionic mechanisms in human AF are only poorly understood. METHODS: Action potentials (AP) and ionic currents were studied with the patch clamp technique in single atrial myocytes from patients in chronic AF and compared to those from patients in stable sinus rhythm (SR). RESULTS: The presence of AF was associated with a marked shortening of the AP duration and a decreased rate response of atrial repolarization. L-type calcium current (ICa,L) and the transient outward current (Ito) were both reduced about 70% in AF, whereas an increased steady-state outward current was detectable at test potentials between -30 and 0 mV. The inward rectifier potassium current (IKI) and the acetylcholine-activated potassium current (IKACh) were increased in AF at hyperpolarizing potentials. Voltage-dependent inactivation of the fast sodium current (INa) was shifted to more positive voltages in AF. CONCLUSIONS: AF in humans leads to important changes in atrial potassium and calcium currents that likely contribute to the decrease in APD and APD rate adaptation. These changes contribute to electrical remodeling in AF and are therefore important factors for the perpetuation of the arrhythmia. (+info)
Prognostic value of left atrial appendage function in patients with dilated cardiomyopathy.
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The purpose of the present study was to determine whether parameters of left atrial appendage (LAA) function, assessed by transesophageal echocardiography (TEE), could predict the clinical outcome in patients with dilated cardiomyopathy (DCM). Fifty-five patients (20 had ischemic cardiomyopathy; mean age, 56+/-14 years) who underwent TEE to evaluate LAA function from 1992 to 1996 were studied. After a mean follow-up period of 34+/-13 months, 16 patients died; the cause was cardiac in 14 and noncardiac in 2. Patients who died of cardiac cause had a lower LAA emptying velocity than survivors (38+/-18 vs 54+/-18 cm/s, p=0.01). There were, however, no significant differences between survivors and nonsurvivors with regard to the maximal LAA area (4.3+/-1.3 vs 4.5+/-0.9 cm2, p=0.55), minimal LAA area (2.4+/-1.1 vs 2.9+1.1 cm2, p=0.13), and LAA ejection fraction (46+/-16 vs 36+/-18%, p=0.05). On the Cox proportional hazards model analysis, LAA emptying velocity <50 cm/s (chi-square 5.9, p=0.02), LAA ejection fraction <43% (chi-square 5.6, p=0.02), female gender (chi-square 5.2, p=0.02), pulmonary artery wedge pressure > or =14 mmHg (chi-square 4.8, p=0.03), E/A ratio > or =1.3 (chi-square 4.6, p=0.03), deceleration time <148 ms (chi-square 4.6, p=0.03), and cardiothoracic ratio > or =54% (chi-square 4.3, p=0.04) were significantly related to cardiac death. The stepwise multivariate analysis revealed that LAA emptying velocity (chi-square 6.1, p=0.01) and gender (chi-square 5.4, p=0.02) were the independent predictors for outcome. In conclusion, the parameters of LAA function may be useful predictors of the clinical outcome in patients with DCM. (+info)
Evaluation of right atrial appendage blood flow by transesophageal echocardiography in subjects with a normal heart.
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Right atrial appendage (RAA) blood flow pattern was analyzed in 42 normal subjects-without cardiovascular disease (aged 30 to 48 years, mean 40 +/- 6) who underwent transesophageal echocardiography. RAA flow pattern was demonstrated to be bi-, tri- or quadriphasic and heart rate dependent (p < 0.01) in this study. In 15 subjects (36%), a biphasic pattern was observed. A triphasic pattern was observed in 12 subjects (28%). Fifteen subjects (36%) had a quadriphasic pattern. In these subjects, we observed a pattern consisting of two diastolic forward flow waves, each followed by a backward flow wave. Mean heart rates among subjects with bi-, tri- and quadriphasic patterns were 110 +/- 6, 91 +/- 4 and 72 +/- 13 beats/min, respectively. In the triphasic pattern, the onset of superior vena cava diastolic forward flow began 18 +/- 4 ms after the onset of tricuspid E wave, whereas the first diastolic forward flow wave in the RAA began 40 +/- 7 ms after onset of the tricuspid E wave. A similar relation was also noted in the quadriphasic pattern. This sequence was constant and independent of heart rate (p < 0.05), suggesting a temporal relation between right ventricular relaxation and the first diastolic forward flow wave in the RAA. In normal subjects, the RAA flow pattern is heart rate dependent and three distinct flow patterns can be differentiated. Right ventricular relaxation appears to induce both the superior vena cava diastolic forward flow wave and the first diastolic forward flow wave of the RAA. These results can be used for comparison with patterns found in disease states. (+info)