Bioavailability of intravenous fosphenytoin sodium in healthy Japanese volunteers.

To compare and evaluate the bioavailability for intravenous fosphenytoin sodium with that of intravenous phenytoin sodium in Japanese subjects. In study 1, healthy Japanese male volunteers received a 30-min infusion of 375 mg fosphenytoin sodium or an equimolar dose of 250 mg phenytoin by a double-blind, crossover method. In study 2, other healthy Japanese male volunteers received a 30-min or 10-min infusion of 563 mg fosphenytoin sodium, followed by a dose of 750 mg after 2 weeks in an unblinded manner. Comparing with 250 mg phenytoin sodium, 375 mg fosphenytoin sodium exhibited lower total plasma phenytoin C max, whereas the geometric mean ratio of the AUC of total and free phenyotoin for fosphenytoin sodium at a dose of 375 mg was very similar to phenytoin sodium at a equimolar dose of 250 mg (AUC0-t ratio: 0.98 and 1.02, respectively). Therefore, fosphenytoin is almost completely converted to phenytoin in subjects. Fosphenytoin sodium was rapidly converted to phenytoin at doses of 375, 563, and 750 mg. The maximum concentration (C max) of total plasma phenytoin increased in a dose-dependent manner. The area under the plasma concentration-time curve (AUC) increased slightly more than proportionally with the administered dose, and clearance (CL) decreased with increasing dose. Pain and other infusion-site reactions were reported by all 12 subjects with phenytoin sodium, whereas very few symptoms were observed with fosphenytoin sodium. In conclusion, fosphenytoin sodium is considered to be a useful substitute for phenytoin sodium with almost no associated injection-site reactions.

Atrial septal defect in apical hypertrophic cardiomyopathy associated with coronary spasm.

Apical hypertrophic cardiomyopathy (HCM) is a well-known myocardial disease, but the additional coexistence of an atrial septal defect (ASD) and coronary spasm is quite rare. We report here on a 62-year-old man suffering from congestive heart failure due to apical HCM complicated by coronary spasm and secundum-type ASD. The transthoracic, transesophageal echocardiography and cardiac catheterization were useful for diagnosing and evaluating of the patient's status. A calcium channel blocker was given to prevent coronary spasm, and a surgical patch closure operation was successfully performed. Afterwards, his symptoms were alleviated.

Successful catheter ablation of ventricular tachycardia originating from the idiopathic saccular apical left ventricular aneurysm.

Left ventricular (LV) aneurysm has been recognized to frequently become a substrate of ventricular tachyarrhythmias. We report a case of a 66-year-old woman with symptomatic sustained monomorphic ventricular tachycardia (SMVT) originating from saccular apical LV aneurysm without definite underlying diseases. We performed catheter ablation using electroanatomical and conventional bipolar potential mapping. During SMVT, we found an area of fragmented potential -40 ms preceding the earliest wide QRS complex in the area of the apical LV aneurysm. Radiofrequency applications were delivered to this area. Since then, SMVT was no longer inducible by programmed electrical stimulation. The patient has remained free of VT recurrences during a subsequent 12-month follow-up period.

Relation of thoracic aorta calcification on computed tomography and coronary risk factors to obstructive coronary artery disease on angiography.

The aim of this study was to investigate whether thoracic aorta calcification (TAC) on computed tomography (CT) and coronary risk factors had any correlation with obstructive coronary artery disease (CAD) on angiography. A total of 225 consecutive Japanese patients underwent both thoracic conventional helical CT and coronary angiography. The thoracic aorta was divided into 4 locations according to the aortic anatomy (inner curve of the aortic arch, aortic arch but not on the inner curve, ascending aorta, and thoracic descending aorta). The classified TAC and coronary risk factors were evaluated for the presence or absence of obstructive CAD. TAC was detected in 185 patients; 141 of 225 patients had significant obstructive CAD. All of the 13 patients with no TAC and no coronary risk factors had no CAD. The obstructive CAD rate with 1 thoracic calcified location and with no, 1, or 2 coronary risk factors was 10%, 58%, and 90%, respectively, and each showed a significant difference (p < 0.0001). The combinations of TAC and coronary risk factors with obstructive CAD were 1 or 2 thoracic calcified locations with 3 coronary risk factors, and 3 thoracic calcified locations with more than 2 coronary risk factors. Increasing thoracic calcified locations and increasing coronary risk factors indicated a higher likelihood of CAD.

Comparative study of dobutamine stress echocardiography and dual single-photon emission computed tomography (thallium-201 and I-123 BMIPP) for assessing myocardial viability after acute myocardial infarction.

Discordance between the (123)I-labelled 15-iodophenyl-3-R, S-methyl pentadecanoic acid (BMIPP) and (201)Tl findings may indicate myocardial viability (MV). This study compared dobutamine stress echocardiography (DSE) and single-photon emission computed tomography (SPECT) using the dual tracers for assessment of MV and prediction of functional recovery after acute myocardial infarction (AMI). DSE and dual SPECT were studied in 35 patients after AMI, of whom 28 underwent percutaneous coronary intervention in the acute stage. Dual SPECT was performed to compare the defect score of BMIPP and (201)Tl. The left ventricular wall motion score (WMS) was estimated during DSE and 6 months later to assess functional recovery of the infarct area. The rate of agreement of MV between dual SPECT and DSE was 89% (p<0.01), and the sensitivity and specificity of DSE for dual SPECT in MV assessment was 86% and 93%, respectively. The positive and negative predictive values for functional recovery by dual SPECT were 76% and 67%, respectively, and by DSE were 90% and 79%, respectively. Four of 5 patients with positive MV by dual SPECT, but without functional recovery, had residual stenosis of the infarct-related artery. The WMS and defect scores of BMIPP and (201)Tl were significantly smaller in patients with functional recovery than in those without. Assessment of MV using DSE concords with the results of dual SPECT in the early stage of AMI. DSE may have a higher predictive value for long-term functional recovery at the infarct area. However, a finding of positive MV by dual SPECT, without functional recovery, may indicate residual stenosis of the infarct-related artery, although the number of cases was small. Combined assessment by dual SPECT and DSE may be useful for detecting MV and jeopardized myocardium. Furthermore, the results suggest that functional recovery of dysfunctional myocardium may depend on the size of the infarct and risk area.