Bioavailability of Bropirimine 250 mg Tablet in Dogs: Effect of Food

The postprandial effect on the bioavailability of bropirimine in dogs after oral administration of bropirimine tablets (Bropirimine 250 mg Tablet) was investigated. At a dose of 500 mg bropirimine (two tablets of bropirimine 250 mg), the maximum plasma concentration under the postprandial condition was about twice that observed under the fasting condition, and the area under the plasma concentration vs time curve under the postprandial condition was also twice that under the fasting condition. The absolute oral bioavailabilities of bropirimine were 41.1% under the fasting condition and 83.5% under the postprandial condition. It is considered that the longer gastric residence time and larger volume of the gastric fluid induced by food-intake caused the increase in dissolution of bropirimine which increased the bioavailability after oral dosing of bropirimine 250-mg tablets.     

Atrial Electrograms and Activation Sequences in the Transition Between Atrial Fibrillation and Atrial Flutter

Transition Between Atrial Fibrillation and Flutter. Introduction: The eletrophysiologic mechanism of atrial fibrillation (AF) has a wide spectrum, and it seems that some atrial regions are essential for the occurrence of a particular type of AF. We focused on one type of AF: AF associated with typical atrial flutter (AFI), which was right atrial (RA) arrhythmia, and sought to investigate intra-atrial electrograms and activation sequences in the transition between AF and AFL.
Methods and Results: Intra-atrial electrograms and activation sequences in the R.A free wall and the septum were evaluated in the transition between AF and AFL in seven patients without organic heart disease (all men; mean age 57 ± 11 years). In five episodes of the conversion of AFL into AF, the AFL cycle length was shortened (from 211 ± 6 msec in stable AFL to 190 ± 15 msec before the conversion, P, 0.001). Interruption of the AFL wavefront and an abrupt activation sequential change induced by a premature atrial impulse resulted in fractionation and disorganization of the septal electrograms. During sustained AF, septal electrograms were persistently fractionated with disorganized activation sequences. However, the RA free-wall electrograms were organized, and the activation sequence was predominantly craniocaudal rather than caudocranial throughout AF. In 12 episodes of the conversion of AF into AFL, the AF cycle length measured in the RA free wall increased (from 165 ± 26 msec at the onset of AF to 180 ± 24 msec before the conversion, P, 0.001). AFL resumed when fractionated septal electrograms were separated and organized to the caudocranial direction, despite the RA free-wall electrograms remaining discrete and sharp with an isoelectric line.
Conclusion: Changes of the electrogram and activation sequence in the atrial septum played an important role in the transition between AF and AFL.     

Echographic Diagnosis of Soft Tissue Tumors in Extremity and Trunk: --Its Clinical Application in Orthopedic Surgery--

In the field of orthopedics, the echographic examination ofsoft tissue tumors by B-mode contact compound scanning is auseful clinical modality. Characteristics of the tumor, suchas whether it is cystic or solid, its border regular or irregular,and delineation of tumor size in three dimensions can be determined.The relationship between the tumor mass and the skin, musclelayer, connective tissue and periosteum can be defined preoperatively.Furthermore, it can be used for an echographic evaluation oftumor regression during antineoplastic treatment with chemotherapyor radiation therapy. Typical echograms of liposarcoma, chordoma,neurinoma, desmoid tumor, rhabdomyosarcoma and gluteal tumor,metastatic lesions from melanoma, lung and skin were demonstrated.The usefulness of this technique in the field of orthopedicsurgery is discussed with a review of literature.     

Cellular Basis for Complex T Waves and Arrhythmic Activity Following Combined IKr and IKs Block

INTRODUCTION: A growing number of cardiomyopathies have been shown to result in a reduction in both I(Kr) and I(Ks) yet little is known about the electrophysiologic and ECG characteristics of combined I(Kr) and I(Ks) block. METHODS AND RESULTS: To address this gap in our knowledge, transmembrane action potentials (APs) from epicardial, M, and endocardial cells were recorded simultaneously, together with a transmural ECG from arterially perfused canine left ventricular wedge preparations exposed to combined I(Kr) (d-sotalol; 100 micromol/L) and I(Ks) (chromanol 293B; 30 to 60 micromol/L) block. Under baseline conditions, the T wave was typically upright; epicardium repolarized first, coinciding with the peak of the T wave, and the M cells repolarized last, coinciding with the end of the T wave (T(end)). Complex (inverted, biphasic, and triphasic) T waves developed following combined I(Kr) and I(Ks) block. M and epicardial APs prolonged dramatically, so that the endocardial AP was now the earliest to repolarize, coinciding with the first nadir of the complex T wave. In the case of biphasic/triphasic or inverted T waves, Tend coincided with repolarization of either M or epicardial cells, whichever was the last to repolarize. QT intervals prolonged from 286+/-13 msec up to 744+/-148 msec and transmural dispersion of repolarization (TDR) increased from 33+/-10 msec up to 244+/-71 msec. Early afterdepolarizations (EADs) developed in M and epicardial cells, evoking extrasystoles that precipitated polymorphic ventricular tachycardia. Acceleration-induced EADs and T wave alternans also were observed. CONCLUSION: Combined I(Kr) and I(Ks) block gives rise to inverted, biphasic, and triphasic T wave morphologies, a dramatic increase in TDR, and a high incidence of EADs. The diversity of T wave morphologies derives from a preferential AP prolongation of different transmural layers leading to variation in the predominance of voltage gradients on either side of the M cell region. Our study provides direct evidence linking EADs that arise in ventricular epicardial and M cells to the triggered beats that precipitate polymorphic ventricular tachycardia. Our results also suggest possible guidelines for the estimation of TDR from complex T waves appearing in the precordial leads of the surface ECG.     

Small Intestinal Absorption of Bropirimine in Rats and Effect of Bile Salt on the Absorption

The intestinal absorption characteristics of a poorly water-soluble drug, bropirimine, were investigated by the in-situ small intestinal loop method using male Sprague-Dawley rats. Bropirimine in solution was well absorbed in the overall small intestine, following first-order kinetics. The rate determining step for the disappearance of bropirimine from the small intestinal loop after dosing in the suspension was the dissolution process from suspension. Bropirimine was solubilized by sodium glycocholate. The disappearance of bropirimine from the small intestinal loop was suppressed by sodium glycocholate contained in the solution, because of the loss of thermodynamic activity of bropirimine after its involvement in the micellar complex, not by the direct effect of bile salt on the permeability of intestinal mucosa. The disappearance of bropirimine was also suppressed by sodium glycocholate contained in the suspension. The suppression by sodium glycocholate seemed to be caused by the greater influence of sodium glycocholate on the thermodynamic activity of bropirimine than on the dissolution from suspension.     

Dynamic Relationship Between the Q-aT Interval and Heart Rate in Patients with Long QT Syndrome During 24-Hour Holter ECG Monitoring

The purpose of this study was to investigate the dynamic relationship between heart rate and the Q-aT interval (the interval from the Q wave to the T wave apex) in patients with long QT syndrome. The QT to heart rate relation is useful for evaluating abnormalities of the ventricular repolarization, but its clinical application to the long QT syndrome requires accurate computer aided measurement of the QT interval and the sampling of a large number of beats. Therefore, the Q-aT interval was used on the basis of some reports that the heart rate dependency of the QT interval was concentrated in the Q-aT interval. Recent advances in the computer technology have allowed analysis of the relationship between the Q-aT and RR intervals on Holter ECG recordings. However, in addition to a prolonged QT interval, most patients with long QT syndrome have bizarre and variable T waves and the influence of this T wave morphology on the Q-aT to heart rate relation has not been clarified. We investigated the dynamic relationship between the Q-aT interval and heart rate in 10 patients with long QT syndrome and 11 control subjects using our original computer algorithm for the analysis of 24-hour Holter ECG recordings. The patients showed morphological T wave changes associated with heart rate changes during Holter recordings and these affected the Q-aT interval. The patients showed the following characteristics in the relationship between the major T wave peak and the RR interval: (1) a modestly decreased correlation between Q-aT and RR than in the control subjects (a median r value of 0.87 vs 0.93; P = 0.001); and (2) a steeper Q-aT/RR slope than in controls (a median slope of 0.24 vs 0.16; P < 0.05). Abnormal and variable T wave morphology in the long QT patients was closely related to a modestly decreased correlation between Q-aT and RR than in the control subjects. The steep Q-aT/RR slope might reflect unstable repolarization of the ventricle, which could act as a substrate for ventricular tachyarrhythmias.     

Asymptomatic Form of Brugada Syndrome

We describe a patient with the asymptomatic form of Brugada syndrome. His electrographical, electropharmacological, and electrophysiological characteristics were similar to those reported in patients with the symptomatic form of Brugada syndrome. We believe that he has the same arrhythmogenic substrate as that of patients with Brugada syndrome. The fact that he had no episode of spontaneous ventricular fibrillation might be explained by his absence of the triggering factors.     

Evaluation of Direct Respiratory Modulation of the QT Interval Variability

To investigate the direct respiration-mediated vagal modulation of the QT interval variability, spectral analyses of the RTp interval (from the R wave peak to the T wave peak) variability (RTpV) and the RR interval variability (RRV) were performed in 12 subjects with normal ventricular repolarization under three conditions while the respiration frequency was kept at 0.2 Hz: during sinus rhythm, during fixed atrial pacing, and during fixed atrial pacing with autonomic blockade. The cross-spectrum between the RRV and RTpV was quantified by the squared coherence. During sinus rhythm the RRV power spectrum showed two peaks: a broad peak in the low frequency (LF) band and a sharp peak at 0.2 Hz which corresponded to the controlled respiration frequency. The RTpV power spectrum showed corresponding peaks to the RRV peaks in both the LF and high frequency (HF) bands with high coherence (mean maximum values of the squared coherence in the LF band 0.59 ± 0.22, and in the HF band 0.74 ± 0.14). During atrial pacing mean total power of the RTpV decreased from during sinus rhythm (from 16.3 ± 5.6 ms² to 12.9 ± 5.4 ms², P < 0.05) and the RTpV spectral peaks were abolished in both the LF and HF bands concordant with disappearance of the RRV peaks. Autonomic blockade gave no additional change to the RTpV power spectrum independently of the RRV during fixed atrial pacing. The present study suggested that the direct respiration-mediated vagal modulation may not affect the short-term variability of the QT interval in subjects without repolarization abnormality.     

Polymorphic Ventricular Tachycardia Induced by Intracoronary Injection of Ioxaglate in a Patient with Borderline QT Prolongation

Ioxaglate-Induced Polymorphic VT. A 68-year-old female patient with borderline QT prolongation developed polymorphic ventricular tachycardia soon alter intracoronary injection of ioxaglate. There was no coronary stenosis or vasospasm. To investigate abnormality of the ventricular repolarization, we recorded the monophasic action potential (MAP) during coronary angiography. Ioxaglate prolonged the MAP duration regionally in the perfused area and produced temporal dispersion of ventricular repolarization.