Biomedical subjects

M S Chang

Publications and source records attributed to M S Chang.

At least 145 records · Page 8Linked to original sources

PubMed1998

Electrophysiologic characteristics of a dilated atrium in patients with paroxysmal atrial fibrillation and atrial flutter.

This study investigated the difference of atrial electrophysiologic characteristics between a normal and dilated atrium and compared them among patients with paroxysmal atrial fibrillation and flutter. Twenty-seven patients with paroxysmal atrial fibrillation and 28 patients with paroxysmal atrial flutter were divided into four subgroups, according to the presence of a normal atrium or bilateral atrial enlargement. Thirty patients without atrial arrhythmia (20 patients with normal atrium and 10 patients with bilateral atrial enlargement) were included in control group. The atrial refractoriness in patients with a dilated atrium was longer than those with normal atrial size. In patients with paroxysmal atrial fibrillation and patients of control group, the P-wave duration and interatrial conduction velocity with or without atrial enlargement were similar. However, in patients with paroxysmal atrial flutter, P-APCS (86 +/- 10 ms vs. 73 +/- 9 ms, p < 0.05) and P-ADCS (109 +/- 9 ms vs. 95 +/- 9 ms, p < 0.05) in patients with a dilated atrium were longer than in patients with a normal atrium. The patients with paroxysmal atrial fibrillation or atrial flutter all demonstrated longer P-wave duration and interatrial conduction time than control group. Among the groups with a normal atrium or a dilated atrium, atrial refractoriness in patients with paroxysmal atrial flutter was shorter than that in control group. Moreover, in the patients with a normal atrium, the potential minimal wavelength in control group (6.6 +/- 1.7) was longer than that of paroxysmal atrial fibrillation (5.3 +/- 1.1), or atrial flutter (5.0 +/- 1.2). These findings suggest that atrial electrophysiologic characteristics of a dilated atrium were different from those of normal atrium, and these changes were different between paroxysmal atrial fibrillation and flutter. Multiple factors are considered to be related to the genesis of atrial tachyarrhythmias.

Aged↗

PubMed1998

Small intestinal stromal tumors: a clinicopathologic study of 31 tumors.

The biologic behavior of gastrointestinal stromal tumors is difficult to predict, and they can be best studied in a site-specific fashion. The aims of this study are to analyze the clinicopathologic parameters and assess the prognostic value of p53 (DO-7) and Ki-67 (MIB-1) immunoreactivities in small intestinal stromal tumors (SIST). The histopathologic features of 31 SIST were assessed and categorized into two groups as follows. Group A (clinically aggressive) in which death due to tumor, metastasis, recurrence or relapsed melena were seen (n = 15) and group B (clinically benign; n = 16). For both groups, the period of follow-up was 30-144 months. p53 overexpression was observed in four tumors (31%) in group A, and in none in group B. For groups A and B, the mean Ki-67 index was 16.8 +/- 12.5 and 8.4 +/- 12.6, respectively. Statistical analysis revealed that the significant predictors of malignancy were high cellularity (odds ratio (OR) = 999; 95% confidence interval (CI) = 0-999); p53 overexpression (OR = 999; CI = 0-999); size of tumor > or = 5 cm (OR = 18.0; CI = 1.9-171.9); > or = 5 mitoses/50 high-power fields (HPF) (OR = 17.1; CI = 1.8-165.9); pleomorphism (OR = 17.1; CI = 1.8-165.9); and necrosis (OR = 11.9; CI = 2.2-65.1; P < 0.05). High Ki-67 index (> or = 8.4) had a marginal impact on risk (OR = 4.1; CI = 0.8-20.2; P = 0.08). In conclusion, high cellularity, p53 overexpression, size of tumor > or = 5 cm, > or = 5 mitoses/50 HPF, pleomorphism and necrosis are important parameters for the prediction of malignancy in SIST.

Adult↗

PubMed1998

Radiofrequency ablation of idiopathic left ventricular tachycardia with changing ECG morphology.

Idiopathic left ventricular tachycardia is a distinct clinical entity with a typical ECG of right bundle branch block and left axis deviation. We presented a 39-year-old man with idiopathic left ventricular tachycardia, which demonstrated change in the configuration of QRS complex during successive radiofrequency catheter ablation. We proposed that this idiopathic left ventricular tachycardia may have alternative pathways within the reentrant circuit leading to different exits.

Adult↗

PubMed1998

Effects of procainamide and dl-sotalol on the changes of atrial electrophysiology induced by high current stimulation.

The relation between high current atrial stimulation and antiarrhythmic drugs was not clear. We evaluated the effects of procainamide and dl-sotalol on the electrophysiological changes induced by high current stimulation. Effects of high current atrial stimulation on effective refractory period, dispersion of refractoriness, conduction velocity, and wavelength of the earliest atrial premature beat were evaluated at baseline and after infusion of procainamide (10 patients) and dl-sotalol (10 patients). High current atrial stimulation shortened effective refractory period locally (-12% +/- 4.0%, -7.0% +/- 3.0%, -5.1 +/- 3.3%, and -3.0 +/- 2.0%, at 0, 7, 14, and 21 mm from the S1 stimulation site, respectively; P < 0.001); increased the dispersion of refractoriness (from 17.8 +/- 8.5 to 27.4 +/- 12.5 ms, P < 0.001); decreased conduction velocity of the earliest premature beat (from 0.58 +/- 0.10 to 0.52 +/- 0.09 ms, P = 0.01); and decreased wavelength of the earliest atrial premature beat (from 10.9 +/- 2.4 to 8.8 +/- 2.1 cm, P < 0.001). These effects of high current stimulation persisted after procainamide infusion. However, after dl-sotalol infusion, high current atrial stimuli did not change the dispersion of refractoriness (23.1 +/- 10 ms vs 26.4 +/- 10.4 ms; P > 0.05, twice diastolic threshold vs 10 mA); conduction velocity of the earliest premature beat (0.54 +/- 0.06 ms vs 0.50 +/- 0.06 ms, P > 0.05); or wavelength of the earliest premature atrial beat (11.5 +/- 1.6 m/s vs 10.1 +/- 1.7 cm; P > 0.05). Although high current atrial stimulation shortened effective refractory period locally, increased dispersion of refractoriness, and decreased the wavelength of the earliest premature atrial impulse, these effects were abolished by dl-sotalol but not procainamide.

Adult↗

PubMed1998

Conduction properties of the crista terminalis in patients with typical atrial flutter: basis for a line of block in the reentrant circuit.

INTRODUCTION: Previous mapping studies in patients with typical atrial flutter have demonstrated the crista terminalis to be a posterior barrier of the reentrant circuit forming a line of block. However, the functional role of the crista terminalis in patients with or without a history of atrial flutter is not well known. The aim of this study was to determine whether the conduction properties of the crista terminalis are different between patients with and those without a history of atrial flutter. METHODS AND RESULTS: The study population consisted of 12 patients with clinically documented atrial flutter (group 1) and 12 patients with paroxysmal supraventricular tachycardia as well as induced atrial flutter (group 2). A 7-French, 20-pole, deflectable Halo catheter was positioned around the tricuspid annulus. A 7-French, 20-pole Crista catheter was placed along the crista terminalis identified by the recording of double potentials with opposite activation sequences during typical atrial flutter. After sinus rhythm was restored, pacing from the low posterior right atrium near the crista terminalis was performed at multiple cycle length to 2:1 atrial capture. No double potentials were recorded along the crista terminalis during sinus rhythm in both groups. In group 1, the longest pacing cycle length that resulted in a line of block with double potentials along the crista terminalis was 638 +/- 119 msec. After infusion of propranolol, it was prolonged to 832 +/- 93 msec without change of the interdeflection intervals of double potentials. In group 2, the longest pacing cycle length that resulted in a line of block with double potentials along the crista terminalis was 214 +/- 23 msec. After infusion of procainamide, it was prolonged to 306 +/- 36 msec with increase of interdeflection interval of double potentials. CONCLUSION: The crista terminalis forms a line of transverse conduction block during typical atrial flutter. Poor transverse conduction property in the crista terminalis may be the requisite substrate for clinical occurrence of typical atrial flutter.

Adult↗

PubMed1998

Long-term outcome of radiofrequency catheter ablation for typical atrial flutter: risk prediction of recurrent arrhythmias.

INTRODUCTION: Little is known about the predictors of recurrent atrial flutter or fibrillation after successful radiofrequency ablation of typical atrial flutter. In addition, there is only limited evidence suggesting that elimination of atrial flutter would modify the natural history of atrial fibrillation in patients who experienced both of these arrhythmias. The aims of the present study were to investigate the long-term results of radiofrequency catheter ablation and to examine the predictors for late occurrence of atrial fibrillation in a large population with typical atrial flutter. METHODS AND RESULTS: The study population consisted of 144 patients (mean age 56 +/- 18 years) with successful ablation of clinically documented typical atrial flutter. In the first 50 patients, successful ablation was defined as termination and noninducibility of atrial flutter; for the subsequent 94 patients, successful ablation was defined as achievement of bidirectional isthmus conduction block and no induction of atrial flutter. The clinical and echocardiographic variables were analyzed in relation to the late occurrence of atrial flutter or fibrillation. Over the follow-up period of 17 +/- 13 months, 14 (9.7%) patients had recurrence of typical atrial flutter. In the first 50 patients, 8 (16%) had recurrence of atrial flutter, compared with only 6 (6%) of the following 94 patients. Patients with incomplete isthmus block had a significantly higher incidence of recurrent atrial flutter than those with complete isthmus block (6/16 vs 0/78, P < 0.0001) in the following 94 patients. There was no predictor for recurrence of atrial flutter after successful ablation as determined by univariate and multivariate analysis. Although successful ablation of atrial flutter eliminated atrial fibrillation in 45% of patients with a prior history of atrial fibrillation, 31 (21.5%) of 144 patients undergoing this procedure developed atrial fibrillation during the follow-up period. Univariate analysis revealed that three clinical variables were related to the occurrence of atrial fibrillation: (1) the presence of structural heart disease; (2) a history of atrial fibrillation before ablation; and (3) inducible sustained atrial fibrillation after ablation. By multivariate analysis, only a history of atrial fibrillation and inducible sustained atrial fibrillation could predict the late development of atrial fibrillation after atrial flutter ablation. CONCLUSION: Radiofrequency catheter ablation of typical atrial flutter is highly effective and associated with a low recurrence rate of atrial flutter, but atrial fibrillation continues to be a long-term risk for patients undergoing this procedure. The presence of structural heart disease and prior spontaneous or inducible sustained atrial fibrillation increases the risk of developing atrial fibrillation.

Aged↗

PubMed1998

Intracardiac stimulation of human parasympathetic nerve fibers induces negative dromotropic effects: implication with the lesions of radiofrequency catheter ablation.

INTRODUCTION: The dromotropic effects of intracardiac parasympathetic nerve stimulation have not been well studied; furthermore, the effects of radiofrequency ablation lesions on parasympathetic nerve stimulation are not clear. METHODS AND RESULTS: Group I: intracardiac electrical stimulation in the right posteroseptal and anteroseptal areas under different stimulation strengths; group II: intracardiac electrical stimulation before and 10 minutes after intravenous propranolol; group III: intracardiac electrical stimulation before and 5 minutes after intravenous atropine. Among the 10 patients with AV nodal reentrant tachycardia (group IV) and the 10 patients with atrial flutter (group V), atrial fibrillation was induced before and after successful ablation, and intracardiac electrical stimulation in the right posteroseptal area was performed before and after successful ablation. The maximal response and complete decay of the response occurred within 2 to 6 seconds of initiation or termination of parasympathetic nerve stimulation. This negative dromotropic effect disappeared after atropine was administered, but not after propranolol. After successful ablation, parasympathetic stimulation still induced negative dromotropic effects. CONCLUSION: Electrical stimulation of parasympathetic nerve fibers near the posteroseptal and anteroseptal areas could induce a negative dromotropic effect, and this effect was preserved after successful radiofrequency ablation of slow pathway and isthmus conduction.

Adrenergic beta-Antagonists↗

PubMed1998

AV nodal reentrant tachycardia with unusual characteristics: lessons from radiofrequency catheter ablation.

There are still some AV nodal reentrant tachycardias with unusual AV nodal properties that need further study to understand these complexities. Accordingly, the two-dimensional model with alpha and beta pathways in the AV nodal reentrant tachycardia circuit certainly is an oversimplification and does not explain adequately the anatomic and physiologic complexity of the AV junctional area. The modern concept suggests that this arrhythmia takes place in a highly complex three-dimensional model with nonuniform anisotropy and discontinuous conduction property in the AV junctional area. Application of radiofrequency energy within the AV junctional area should always be performed carefully to achieve a successful ablation procedure and to minimize possible injury of AV nodal conduction.

Animals↗

PubMed1998

Focal atrial tachycardia: reanalysis of the clinical and electrophysiologic characteristics and prediction of successful radiofrequency ablation.

INTRODUCTION: Reports about the clinical and electrophysiologic characteristics of focal atrial tachycardia vary widely. Furthermore, the impact of age, gender, associated cardiac diseases, mechanism, location of atrial tachycardia, and the prediction of results of radiofrequency catheter ablation was not clear. The purpose of this study was to further understand the clinical and electrophysiologic characteristics of focal atrial tachycardia and the prediction of results of radiofrequency ablation. METHODS AND RESULTS: We searched the literature published between January 1969 and July 1997 using the key word "atrial tachycardia" from the MEDLINE and National Library of Medicine systems. The items analyzed were age, sex, cardiac disease, mechanism, attack pattern, cycle length, location, number of atrial tachycardias, results of ablation, and recurrence after ablation. Multivariate analysis showed that age and paroxysmal type of tachycardia were independent predictors of nonautomatic mechanism; age and presence of other cardiac diseases were independent predictors of multiple atrial tachycardias, and age also was the independent predictor of right-sided atrial tachycardia. Atrial tachycardia located in the right atrium was the only significant predictor of successful radiofrequency catheter ablation. Other cardiac diseases and multiple atrial tachycardias were the significant predictors of recurrence after initial successful radiofrequency catheter ablation. CONCLUSION: Patient age is closely related to the clinical and electrophysiologic characteristics of atrial tachycardia based on our reanalysis, which found that patient age is an independent predictor of nonautomatic mechanism, right atrial location, existence of multiple atrial tachycardias, and recurrence of atrial tachycardia after initial successful ablation.

Age Factors↗

PubMed1998

Biochemical and pharmacological characteristics of 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline, a new proton-pump inhibitor, in rabbit gastric microsomes and in rats.

We have investigated the properties of the newly synthesized proton-pump inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379-6), on gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid secretion and gastroduodenal lesions in experimental rats. YJA20379-6 markedly inhibited H+/K+-ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6 on the proton pump was approximately 14-times higher than that of omeprazole at pH 7.4. YJA20379-6 given intraduodenally had a potent inhibitory effect on gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg(-1)) but was less active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently protected the gastric mucosa from damage induced by water-immersion stress, indomethacin and absolute ethanol, and the duodenal mucosa from damage induced by mepirizole. Repeated administration of YJA20379-6 also dose-dependently accelerated the spontaneous healing of acetic acid-induced gastric ulcers. These results suggest that YJA20379-6 has potent anti-secretory and anti-ulcer effects which are exerted by suppression of H+/K+-ATPase activity in gastric parietal cells. YJA20379-6 might be useful for the clinical treatment of peptic ulcer diseases.

Animals↗

PubMed1998

The biochemical and pharmacological properties of a newly synthesized H+-K+ ATPase inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol-[1,2-a]benzimidazol e.

This study was designed to determine the effect of a newly synthesized proton pump inhibitor, 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol[1,2-a]be nzimidazole (YJA20379-2), on gastric H(+)-K(+) ATPase activity, acid secretion, and experimental gastroduodenal lesions or ulcers in rats. YJA20379-2 inhibited in a concentration-dependent manner the proton pump (H(+)-K(+) ATPase) activity in isolated hog gastric mucosal microsomes, therefore, confirming its classification as a proton pump inhibitor. The inhibitory efficacy of YJA20379-2 on the proton pump was about eight times higher than that of omeprazole at pH 7.4. The activity of the inhibited enzyme was not restored by dilution and washout method, so this implied that the inhibition of YJA20379-2 is not reversible. YJA20379-2, given intraduodenally or orally, potently suppressed acid secretion in pylorus-ligated rats, with ED50 values of 3.6 and 7.7 mg.kg(-1), respectively. Pretreatment with YJA20379-2 dose dependently protected the gastric mucosa from damage induced by absolute ethanol, water-immersion stress, indomethacin, and the duodenal mucosa from damage induced by mepirizole in rats, with ED50 values of 11.0, 21.0, 0.5, and 18.7 mg.kg(-1), respectively. Repeated administration of YJA20379-2 also dose dependently accelerated spontaneous healing of acetic acid induced gastric ulcers. These results suggest that YJA20379-2 has potent antisecretory and antiulcer effects, which are exerted by suppression of H(+)-K(+) ATPase activity in gastric parietal cells, such that YJA20379-2 may be useful for the clinical treatment of peptic ulcer diseases.

Animals↗

PubMed1998

Differentiating syndrome X from coronary artery disease by treadmill exercise test in patients with chest pain and exercise-induced myocardial ischemia.

Even though the underlying mechanisms of myocardial ischemia may be different, it is difficult to differentiate syndrome X from coronary artery disease (CAD) by means of the treadmill exercise test in elderly patients with chest pain and exercise-induced myocardial ischemia. One hundred sex- and age-matched patients-42 with syndrome X and 58 with CAD-were studied. Another 10 subjects with atypical chest pain, negative treadmill exercise test, and normal-appearing coronary angiograms served as controls. We evaluated the difference in exercise performance between patients with syndrome X and CAD, and the treadmill exercise test was undertaken with modified Bruce protocol within 2 weeks before coronary angiography. Parameters including time to 1 mm ST segment depression (STD), exercise duration (ED), heart rate (HR), systolic blood pressure, rate-pressure product (RPP), and percentage of age-predicted maximum HR (% HR) at different stages of the test were measured and then compared among the three groups of patients. Compared with CAD patients, syndrome X patients had significantly higher HR, % HR, and RPP at the time of 1 mm STD and at peak exercise. The time to 1 mm STD and ED were longer in syndrome X than in CAD patients. However, ED was shorter and HR, % HR, and RPP at peak exercise were similar in syndrome X patients as compared with control subjects. The new criterion of combined ED (> or =315 seconds) and RPP at peak exercise (> or =24,000 beats x mmHg/min) was found to be highly specific (86%) and moderately sensitive (64%) in differentiating syndrome X from CAD patients. The positive likelihood ratio for this criterion was 4.57 and negative likelihood ratio was 0.42. In conclusion, syndrome X patients had better exercise performance than CAD patients, but less ED and similar workload when compared with control subjects. The new criterion proposed in this study may provide a quick and simple way to differentiate syndrome X from CAD in a group of aged and predominantly male patients with chest pain and positive treadmill exercise test.

Adult↗

PubMed1998

Effects of YJA20379-4 on gastric secretion, Helicobacter pylori growth and various gastric and duodenal lesions in rats.

Effects of a newly synthesized antiulcer agent, YJA20379-4, on gastric proton pump (H+/K+-ATPase) activity, Helicobacter pylori (H. pylori) growth, gastric acid secretion, and gastro-duodenal lesions, were examined in comparison with those of omeprazole. YJA20379-4 markedly inhibited the H+/K+-ATPase activity in a concentration-dependent manner and the inhibitory effect was increased under a weak acidic condition; the IC50 values were 32 and 81 microM at pH 6.4 and 7.4, respectively. The inhibition was completely antagonized by 0.5 mM dithiothreitol (DTT). In addition, YJA20379-4 showed a significant anti-H. pylori activity determined by the agar dilution method. The value of minimum inhibitory concentration (MIC, 3.9-11.7 microg/ml) was at least 3 times more potent than that of omeprazole. In pylorus ligated rats, YJA20379-4 inhibited basal gastric acid secretion when administered by the intraduodenal route (ED50: 23.6 mg/kg). In experimental ulcer models, YJA20379-4 administered by the oral route dose-dependently prevented the development of gastro-duodenal lesions in rats. Moreover, repeated administration of YJA20379-4 promoted the healing of gastric ulcers induced by acetic acid. On the basis of the data obtained, it is suggested that YJA20379-4 has a wide spectrum of antiulcer activities, and its mode of antiulcer actions is dependent on the inhibition of H+/K+-ATPase activity and H. pylori growth and the enhancement of a mucosal defense. Thus, YJA20379-4 might prove to be a beneficial therapy for gastritis and peptic ulcer diseases.

Animals↗

PubMed1998

Differential glucose tolerance in dipper and nondipper essential hypertension: the implications of circadian blood pressure regulation on glucose tolerance in hypertension.

OBJECTIVE: The goals of this study were to compare glucose tolerance in dipper and nondipper hypertensive patients and to explore the cause of glucose intolerance in essential hypertension. RESEARCH DESIGN AND METHODS: A total of 50 patients <45 years old who had essential hypertension were recruited and studied by 24-h blood pressure monitoring and an oral glucose tolerance test (OGTT). Autonomic function was assessed with spectral analysis of heart rate variability RESULTS: Dipper hypertensive patients (n=25) had lower nocturnal blood pressure than nondipper (n=25) patients. During OGTT, postprandial glucose levels were higher in the nondippers at 0, 90, and 120 min (all P < 0.05). Nondippers had a higher fasting insulin/glucose ratio than was apparent in normal control subjects. Despite higher postprandial glucose levels, nondippers had lower postprandial insulin levels. These results suggest that nondippers were insulin resistant and that their pancreatic beta-cell function was impaired. For all patients, nocturnal reduction of blood pressure was inversely related to total glucose levels under the OGTT curve and was positively related to postprandial insulin levels. Daytime heart rate did not differ between the dippers and nondippers, but nocturnal heart rate was higher in the nondippers, suggesting that nocturnal sympathetic activities were higher among the nondippers. Spectral analysis of heart rate variability suggests that the nondippers had lower parasympathetic activities and unbalanced sympathetic/parasympathetic outflow. CONCLUSIONS: These findings indicate that nondipper hypertensive patients are more glucose intolerant than are dipper patients. The abnormalities of glucose metabolism in nondippers could be explained by insulin resistance and beta-cell dysfunction. The results of spectral analysis suggest that abnormal autonomic outflow may represent a possible link between hypertension and associated metabolic dysfunction.

Adult↗

PubMed1998

Stability, blood partition, and pharmacokinetics of a new proton pump inhibitor, YJA-20379-8.

Stability, blood partition, and pharmacokinetics (including tissue distribution and biliary excretion) of YJA-20379-8 were studied using an HPLC analysis. YJA-20379-8 was stable for up to 48 h incubation in a water-bath shaker kept at 37 degrees C and at a rate of 50 oscillations per min in pH solutions ranging from 1 to 14. YJA-20379-8 rapidly reached equilibrium between plasma and blood cells of three rabbit blood, and the equilibrium plasma to blood cell concentration ratios were independent of the initial YJA-20379-8 blood concentrations; the mean values were 1.42-1.56 for three rabbit blood at initial YJA-20379-8 blood concentrations of 1-5 micrograms/ml. As expected from blood partition of the drug between plasma and blood cells, there was no in vitro 'blood storage effect' of YJA-20379-8. After intravenous administration of YJA-20379-8, 10, 20, and 50 mg/kg, to rats, the values of t1/2, MRT, Vss, and CL were dose-independent. However, after intravenous administration of the drug, 5, 10, and 20 mg/kg, to rabbits, the values of t1/2, MRT, and Vss were dose-dependent. After oral administration of the drug, 20, 50, and 100 mg/kg, to rats, the F values (9.00, 16.7, and 11.3% for 20, 50, and 100 mg/kg, respectively) were low considering considerable absorption of the drug from rat gastrointestinal tract (98, 80, and 76% for 20, 50, and 100 mg/kg, respectively) and this could be due to hepatic, gastric, and/or intestinal first-pass metabolism. YJA-20379-8 was under detection limit in urine samples and the contribution of biliary excretion of unchanged YJA-20379-8 to nonrenal clearance of the drug was negligible (less than 0.5% of intravenous dose) in rats, suggesting that the CL (or nonrenal clearance) of YJA-20379-8 could represent metabolic clearance in rats. YJA-20379-8 had a good affinity to almost all rat tissues studied and this was supported by a relatively high value of Vss (3.93-3.93 ml/kg) after intravenous administration of the drug to rats.

Administration, Oral↗

PubMed1998

Pharmacokinetics of a new proton pump inhibitor, YJA-20379-8, in rats with 48-hour water deprivation.

The pharmacokinetics of YJA-20379-8 after the intravenous, 20 mg/kg, and oral, 50 mg/kg, administration of the drug, and tissue distribution of YJA-20379-8 after intravenous administration of the drug, 20 mg/kg, to control and 48-h water-deprived rats were reported. After 15-min intravenous infusion of YJA-20379-8, the drug was not detected in urine and less than 0.5% of intravenous dose of the drug was excreted in bile, suggesting that YJA-20379-8 is essentially completely metabolized in rats. Therefore, the CL (clearance) of YJA-20379-8 represents the CLNR (metabolic clearance) of the drug in rats. After oral administration of YJA-20379-8, the F values were low; the values were 21.2 and 19.4% for control and water-deprived rats, respectively. The values were considerably low considering that 93.4 and 84.6% orally administrated YJA-20379-8 were absorbed from rat GI tract of control and water-deprived rats, respectively. This could be due to considerable first-pass (hepatic, gastric, and intestinal) effects. Recently, it was found that gastric and intestinal first-pass effects of YJA-20379-8 were considerable in rats. The amounts of YJA-20379-8 in small intestine, brain, lung, stomach, and kidney increased significantly in water-deprived rats. However, the T/P ratios were comparable (not significantly different) for both groups of rats, indicating that tissue distribution of the drug was not affected by water deprivation.

Administration, Oral↗

PubMed1998

Pharmacokinetic changes of a new proton pump inhibitor, YJA-20379-8, after intravenous and oral administration to rats with uranyl nitrate-induced acute renal failure.

Because the physiological changes that occur in patients with acute renal failure could alter the pharmacokinetics of the drugs used to treat the disease, the pharmacokinetics of YJA-20379-8, a new reversible proton pump inhibitor, were investigated after 15-min intravenous (20 mg/kg) and oral (50 mg/kg) administration to control rats and rats with uranyl nitrate-induced acute renal failure (U-ARF). The impaired kidney function was observed in rats with U-ARF on the basis of physiological parameters. After intravenous administration of YJA-20379-8, the pharmacokinetic parameters were not significantly different between two groups of rats except significant increase in volume of distribution at steady state in rats with U-ARF (8000 versus 4520 ml/min). However, after oral administration to rats with U-ARF, AUC(0-16)hr was significantly smaller (126 versus 293 microg min/ml) and this was due to decreased absorption of YJA-20379-8 from gastrointestinal tract; the percentages of oral dose of YJA-20379-8 recovered from gastrointestinal tract at 24 hr as unchanged drug was significantly greater (19.9% versus 6.61%) in rats with U-ARF.

Acute Kidney Injury↗

PubMed1997

Idiopathic monomorphic ventricular tachycardia: clinical outcome, electrophysiologic characteristics and long-term results of catheter ablation.

Ventricular tachycardia (VT) without structural heart disease or any identifiable predisposing causes for arrhythmia is an uncommon but well-recognized clinical entity. The purpose of this study is to assess the results of catheter ablation therapy and the long-term outcome of patients with idiopathic monomorphic VT in a large patient group. Sixty-one consecutive patients (male/female=40/21; mean age 38+/-16 years) with idiopathic VT underwent electrophysiologic study and an attempt of catheter ablation therapy. The 'left VT' group included 31 patients with QRS morphology of right bundle branch block during VT suggestive of the VT originating from the left ventricle (LV), and the 'right VT' group consisted of 30 patients with QRS morphology of left bundle branch block with normal or right frontal axis deviation suggestive of VT arising from right ventricular outflow tract (RVOT). Idiopathic left VT has sustained VT during the clinical attacks, baseline electrophysiologic study or after isoproterenol infusion; it can be entrained by overdrive ventricular pacing, terminated by verapamil, but not by adenosine (except one case with VT focus at left ventricular free wall). Catheter ablation was successful in 22 (84%) of 26 patients, with recurrence rate of 9%. The successful ablation sites were located at LV inferior-apical septum (16 patients), mid-septum (three patients), high septum (two patients) and high anterior wall (one patient). In the right VT group, 20 (67%) of 30 patients presented clinically repetitive monomorphic VT. Most of the idiopathic right VT (22/30) required isoproterenol to facilitate induction of VT, and were sensitive to both verapamil and adenosine. Successful catheter ablation was achieved in 21 (84%) of 25 patients, with recurrence rate 19%. The successful ablation sites were located at RVOT-septum in 18 patients, and RVOT-free wall in three patients. During a mean follow-up period of 29.2+/-21.7 months (range 1-76 months) after hospital discharge, all patients were alive but one left VT case died of non-cardiovascular cause. We concluded that idiopathic left side and right side VTs have their distinct clinical, electrophysiologic and electropharmacological characteristics suggestive of different underlying mechanisms, and both have a benign prognosis. Furthermore, catheter ablation can be effective in eliminating idiopathic VT originating from the right ventricular outflow tract and left ventricle.

Adult↗