Spontaneous and agonist-induced calcium oscillations in single human nonfunctioning adenoma cells

The effects of gonadotropin-releasing hormone (GnRH) and GnRH-associated peptide (GAP) on cytosolic free calcium concentration ([Ca²⁺]_i) were investigated in 20 human nonfunctioning pituitary adenomas. We divided these tumors into three classes according to their response pattern to hypothalamic peptides. In type I adenomas (8 out of 20 adenomas), GnRH and GAP mobilized intracellular calcium ions stored in a thapsigargin (TG)-sensitive store. For the same concentration of agonist, two distinct patterns of GnRH-GAP-induced Ca²⁺ mobilization were observed (1) sinusoidal oscillations, and (2) monophasic transient. The latter is followed by a protein kinase C (PKC)-dependent increase in calcium influx through L-type channels. In type II adenomas (7 out of 20 adenomas), GnRH and GAP only stimulate calcium influx through dihydropyridine-sensitive Ca²⁺ channels by a PKC-dependent mechanism. TG (1 μM) did not affect [Ca²⁺]_i in these cells, suggesting that they do not possess TG-sensitive Ca²⁺ pools. All the effects of GnRH and GAP were blocked by an inhibitor of phospholipase C (PLC), suggesting that they were owing to the activation of the phosphoinositide turnover. Type I and type II adenoma cells showed spontaneous Ca²⁺ oscillations that were blocked by dihydropyridines and inhibition of PKC activity. GnRH and GAP had no effect on the [Ca²⁺]_i of type III adenoma cells that were also characterized by a low resting [Ca²⁺]_i and by the absence of spontaneous Ca²⁺ fluctuations. K⁺-induced depolarization provoked a reduced Ca²⁺ influx, whereas TG had no effect on the [Ca²⁺]_i of type III adenoma cells. The variety of [Ca²⁺]_i response patterns makes these cells a good cell model for studying calcium homeostasis in pituitary cells.     

Transoesophageal echocardiographic evaluation of atrial morphology in children with congenital heart disease.

In a prospective study, atrial morphology was evaluated by both transoesophageal and precordial echocardiography in 86 unoperated children with congenital heart disease (age range = 0.2 to 14.8 years, mean = 3.8 years) to determine what advantages, if any, might be inherent in the transoesophageal approach. The information derived from both ultrasound approaches was correlated and compared to information obtained during subsequent cardiac catheterization (78 patients) and, or, surgical inspection (53 patients). Atrial appendage morphology and hence atrial situs was determined by transoesophageal echocardiography in every case (82 solitus, two right atrial isomerism, two left atrial isomerism). In addition, the transoesophageal approach indicated left juxtaposition in four patients, compared to only one by precordial examination. Probe patency of the foramen ovale was correctly predicted in 21 patients by transoesophageal imaging, but in only 10 by precordial imaging. In two children significant secundum defects, undetected by the precordial route, were identified. Multiple atrial septal defects were correctly defined in four patients by transoesophageal study but in only one by precordial study. Sinus venosus defects were documented in four by the transoesophageal approach, but in only one by the precordial. Primum defects were equally well documented (nine patients) by either technique, but the associated valve leaflet morphology was better documented by transoesophageal study in 5/9. A subtotal cor triatriatum was diagnosed in one child only by transoesophageal investigation. Transoesophageal echocardiography allows a much more detailed evaluation of atrial morphology than precordial imaging even in infants. It provides direct diagnosis of atrial situs, detection of juxtaposed atrial appendages and improved demonstration or definitive exclusion of atrial septal defects.     

Effects of licorice on plasma atrial natriuretic peptide in healthy volunteers

Ingestion of licorice, 100 g daily for 8 weeks, caused a rise in 81% in plasma atrial natriuretic peptide (ANP) concentration in 12 healthy subjects. Mean body weight increment (1.6 kg) correlated with the increase in plasma ANP (r = 0.59; P less than 0.01). The plasma concentrations of antidiuretic hormone, aldosterone, and plasma renin activity decreased. All these hormonal effects, reflecting retention of sodium and fluid volume, were probably due to the known mineralocorticoid properties of licorice. Blood pressure increased transiently and two subjects developed reversible hypertension. The rise in plasma ANP concentration during ingestion of licorice may be considered a physiological response to prevent fluid retention and development of hypertension.     

Transthoracic Doppler echocardiographic measurement of left atrial appendage blood flow velocity: comparison with transoesophageal measurement.

AIM: We validated transthoracic echocardiographic measurements of left atrial appendage flow velocity by comparing them with transoesophageal echocardiographic measurements. METHODS AND RESULTS: Eighty-four consecutive patients (mean age, 64.6 years) with various cardiac diseases, who underwent both transthoracic echocardiography and transoesophageal echocardiography were studied. Thirty-two patients were in sinus rhythm, and the remaining 52 patients were in atrial fibrillation. On transthoracic echocardiography, the transducer was placed somewhat superior and outside from the position viewing the conventional parasternal short-axis image of the aortic valve, so that the angle between left atrial appendage midline and Doppler beam could be narrowed. The left atrial appendage flow velocity pattern was recorded by pulsed Doppler mode with a sampling volume placed at the left atrial appendage orifice on both transthoracic echocardiography and transoesophageal echocardiography. In both approaches, the peak emptying velocity (LAA-E) and the peak filling velocity (LAA-F) of the left atrial appendage were measured. In sinus rhythm, the LAA-E was detectable in 25 of the 32 patients (78.1%) and the LAA-F in 20 of the 32 patients (62.5%). Both LAA-E and LAA-F were detectable in 46 of the 52 patients (88.5%) in atrial fibrillation. Good correlations of LAA-E and LAA-F were observed between transthoracic echocardiography and transoesophageal echocardiography measurements in sinus rhythm (r=0.94, r=0.95, respectively; both, P<0.0001) and in atrial fibrillation (r=0.89, r=0.95, respectively; both, P<0.0001). CONCLUSIONS: The left atrial appendage flow velocities could be sufficiently recorded and assessed by transthoracic echocardiography in 84 Japanese unselected consecutive patients with sinus rhythm or atrial fibrillation.     

Reentry in a morphologically realistic atrial model

INTRODUCTION: Atrial fibrillation is the most common cardiac arrhythmia. In ablation procedures, identification of the reentrant pathways is vital. This has proven difficult because of the complex morphology of the atria. The purpose of this study was to ascertain the role of specific anatomic structures on reentry induction and maintenance. METHOD AND RESULTS: A computationally efficient, morphologically realistic, computer model of the atria was developed that incorporates its major structural features, including discrete electrical connections between the right and left atria, physiologic fiber orientation in three dimensions, muscle structures representing the crista terminalis (CT) and pectinate muscles, and openings for the veins and AV valves. Reentries were induced near the venous openings in the left and right atria, the mouth of the coronary sinus, and the free wall of the right atrium. The roles of certain muscular structures were ascertained by selectively removing the structures and observing how the propagation of activity was affected. CONCLUSION: (1) The muscular sheath of the coronary sinus acts as a pathway for a reentrant circuit and stabilizes any circuits that utilize the isthmus near the inferior vena cava. (2) Poor trans-CT coupling serves to stabilize flutter circuits. (3) Wall thickness is an important factor in the propagation of electrical activity, especially in the left atrium. (4) The openings of the inferior and superior venae cavae form natural anatomic anchors that make reentry easier to initiate by allowing for smaller ectopic beats to induce reentry.     

Drainage of the inferior vena cava to the left atrium

Drainage of the inferior vena cava to the left atrium is an extremely unusual congenital heart disease. We describe a 54-year-old woman, in whom the diagnosis was suggested by transthoracic echocardiography, and then confirmed by a transesophageal exam and magnetic resonance imaging, which also revealed an associated secundum atrial septal defect. Surgical management involved reconstruction of the interatrial septum to include the inferior vena cava in the right atrium. The few previously reported cases in the literature are reviewed.     

Atrial natriuretic peptide augments coronary collateral blood flow: A study during coronary angioplasty

Background and hypothesis: In vitro studies have shown that atrial natriuretic peptide (ANP) causes relaxation of pre-constricted blood vessel strips and inhibits the contraction of isolated vessels in response to norepinephrine and angiotensin II. The present study examined the effects of exogenous ANP on the coronary collateral blood flow during angioplasty. Methods: We studied 15 patients undergoing elective balloon angioplasty during the second and third balloon inflations. A Doppler flow guidewire was advanced distal to the lesion and used for the estimation of coronary blood flow velocity. After the second balloon inflation, 25 ng/kg/min of ANP were administered intracoronarily for 8 min. Electrocardiogram, pressure, and flow velocity were recorded immediately before each balloon deflation. Fourteen other patients served as controls and received normal saline infusion. Results: Velocity time integral increased from 65 ± 40 to 79 ± 46 mm (p < 0.05) during the third balloon inflation, whereas ST deviation decreased from 1.3 ± 0.9 to 0.7 ± 1.0 mV (p< 0.05). These variables did not change in the control group during the two tested balloon inflations. Conclusion: Exogenous ANP augments coronary collateral blood flow and ameliorates myocardial ischemia during angioplasty.     

Pericardial effusion and right-sided pneumothorax resulting from an atrial active-fixation lead.

We report on a patient in whom an active-fixation pre-shaped atrial lead caused perforation of the right atrial wall, pericardium and pleura, resulting in pericardial effusion and right-sided pneumothorax. Chest X-ray did not demonstrate protrusion of the atrial lead outside the cardiac silhouette but computed tomography visualized the tip of the helix of the atrial screw-in electrode outside the contours of the right atrial appendage touching the right upper lobe of the lung. The lead was repositioned with resolution of pericardial effusion and pneumothorax. Due to their proximity to the right lung, high anterolaterally positioned atrial screw-in leads carry a small but definite risk for right-sided pneumothorax.     

Patients with Persistent Atrial Fibrillation Taking Oral Verapamil Exhibit a Lower Atrial Frequency on the ECG

Background: While there is agreement that verapamil attenuates the AF‐ induced refractory period shortening when given before AF induction, controversy exists regarding its effects when given after the onset of persistent AF. This study aimed to compare atrial fibrillatory frequency obtained from the surface ECG in patients with persistent atrial fibrillation (AF) with oral verapamil treatment to those without this treatment. Methods and Results: Surface ECG recordings were performed in 57 patients (34 male, 23 female, mean age 59 ± 11 years) with persistent AF (> 7 days). The frequency content of the fibrillatory baseline was quantified using digital signal processing (filtering, QRST complex averaging and subtraction. Fourier transformation). In 27 patients with verapamil treatment (120 or 240 mg/day for at least 7 days) mean fibrillatory frequency measured 6.4 ± 0.2 Hz, compared to 7.0 ± 0.4 Hz (P = 0.012) in 30 patients without verapamil. In a subset of 20 randomly selected patients (10 with, 10 without verapamil treatment) a 24‐hour Holter ECG recording was performed and fibrillatory frequency determined at 4 PM, 10 PM, 4 AM, and 10 AM. While there was a significant frequency reduction in the verapamil treated patients at night (P = 0.011), it remained constant over time in the other patients. Conclusion: In patients with persistent AF, fibrillatory frequency assessed by spectral analysis of the surface ECG is lower in patients taking verapamil. A.N.E. 2002;7(2):92–97