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.     

Time course of saliva and serum melatonin levels after ingestion of melatonin

Abstract Salival and serum melatonin levels after melatonin ingestion were measured by gas chromatography-mass spectrometry. Ingestion of 3 mg melatonin caused a marked increase in serum melatonin (3561 ± 1201 pg/mL) within 20 min, followed by a gradual decrease, but the level still remained higher than the basal level at 240 min after the ingestion. The saliva melatonin 60 min after the ingestion showed the highest level (1177 ± 403 pg/mL) which was one-third of the plasma level. The saliva melatonin level was highly correlated with the serum level throughout the experimental period ( r = 0.82, P = 0.0001). These data indicate that the measurement of saliva melatonin level may be a suitable indicator for the melatonin secretion into general circulation.     

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.     

Successful Stent Implantation in Acute Myocardial Infarction and Successful Directional Coronary Atherectomy of a Stenotic Lesion Involving an Aneurysm in a Woman with Kawasaki Disease of Adult Onset

Our patient was a woman who suffered from Kawasaki disease at the age of 20. Coronary aneurysms were confirmed in the left main trunk and proximal sites of the left anterior descending artery and the circumflex artery by coronary angiography at the age of 21. When she suffered an inferior acute myocardial infarction at the age of 24, two Palmaz-Schatz stents were successfully implanted in the right coronary lesion in order to prevent acute closure. One month later, directional coronary atherectomy was successfully performed to the left anterior descending artery lesion which had a rapid progression of the stenosis, and the pathological examination revealed that the cause of the stenosis was thrombus. She has remained well during the following 2 years.     

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.     

Directional Coronary Atherectomy in Takayasu's Disease

A 44-year-old woman with a history of coronary aorta bypass grafting (CABG)for stenosis of the left main trunk (LMT) due to Takayasu's disease underwent directional coronary atherectomy (DCA) to the LMT lesion under percutaneous cardiopulmonary support because she had angina pectoris and heart failure due to occlusion of the grafts. Three and a half years after the catheter intervention, her clinical condition remains good. DCA may be an alternative to CABG in limited cases with LMT disease.     

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.     

"Fork" Stenting for Bifurcational Lesion

Based on the experience of our in vitro examination to assess the stents for a safe and effective angioplasty through the struts, a Palmaz-Schatz stent was implanted easily and completely from the left main trunk to the left anterior descending coronary artery through the struts of a Wiktor stent implanted from the left main trunk to the circumflex artery in two cases .