Electrophysiological Effects of MS-551 in Humans: A Class III Antiarrhythmic Agent

To investigate the clinical effects of MS-551, a Class III antiarrhythmic agent, 11 patients underwent electrophysiological study. MS-551 was given intravenously as an initial dose of 0.2 or 0.3 mg/kg for 5 minutes followed by the continuous infusion at 0.2 or 0.3 mg/kg for 30 minutes, respectively, in all patients. The rate corrected QT interval increased significantly from 3 minutes after the beginning of MS-551 infusion. The sinus heart rate decreased significantly by 8% at 10 minutes after the drug administration (P ± 0.025). Mean PR and QRS intervals, and blood pressure were not significantly affected by the drug. Mean PA, AH, and HV intervals during sinus rhythm were also not affected. The effective refractory periods (ERPs) of the atrium and ventricle were significantly prolonged by 13% from 202 ± 24 ms to 231 ± 26 ms (P ± 0.0005), and by 7% from 238 ± 11 ms to 257 ± 13 ms (P ± 0.002), respectively, by MS-551. The ERP of the atrioventricular node and sinoatrial nodal recovery time were not changed significantly by the drug. This is a report of the effects of MS-551 in humans. This agent could be useful for treatment of tachyarrhythmias by prolongation of ERPs of the atrium and ventricle without significant variations of blood pressure and intracardiac conduction times. It is noteworthy that MS-551 slightly but significantly decreased heart rate.     

CASE REPORT: Steatonecrosis in the upper abdomen following transcatheter arterial embolization for hepatocellular carcinoma

A 66-year-old female with liver cirrhosis was treated by transcatheter arterial embolization (TAE) for a small hepatocellular carcinoma. She developed steatonecrosis with tenderness which occurred in the upper abdomen after TAE. The hepatic falciform artery from the middle hepatic artery was detected by arteriography. Necrosis in the upper abdomen was considered to be due to ischaemic changes caused by micromaterials for embolization of this artery, injuries of hepatic arterial endothelia slowly caused by carcinostatics, and chemotoxicity. It was considered that such complication as observed in this patient should be taken into consideration when performing TAE.     

Aortic aneurysm in a four-year-old child with tuberous sclerosis

We present a case of aortic aneurysm in a four-year-old child complicated with tuberous sclerosis. We used the same general principles as for adult patients and successfully managed our patient. Our methods included the use of isoflurane plus epidural anaesthesia, dopamine to maintain blood pressure, and induced mild hypothermia to reduce brain metabolism and to prevent spinal cord damage during aortic cross-clamping. Intensive monitoring including EEG was beneficial to the anaesthetic management.     

Adenocarcinoma of the female urethral diverticulum treated by multimodality therapy

A 75-year-old female presented with a 7-month history of intermittent macrohematuria and urinary retention. Physical examination revealed a firm, round mass on the anterior vaginal wall. The diagnosis by urethroscopy and radiological evaluation was localized urethral diverticular tumor. Pathological examination of the biopsy specimen revealed adenocarcinoma. The patient received two courses of intra-arterial and systemic chemotherapy using cisplatin, 5-fluorouracil and leucovorin, followed by radiation to the urethra. The tumor shrunk markedly after chemotherapy. The patient underwent total urethrectomy and vesicostomy. Two years after the operation, she had no evidence of recurrence. Adenocarcinoma of the female urethral diverticulum is rare and has been treated by surgery and/or radiation. The present case is the first case of it being treated by multimodality therapy including chemotherapy.     

Electrophysiological Abnormalities of the Atrial Muscle in Patients with Manifest Wolff-Parkinson-White Syndrome Associated with Paroxysmal Atrial Fibrillation

We investigated the electrophysiological properties of the atrial muscle in 33 patients with manifest Wolff-Parkinson-White syndrome. Group I consisted of 13 patients with paroxysmal atrial fibrillation and group II consisted of 20 patients without paroxysmal atrial fibrillation. The anterograde and retrograde effective refractory periods of the accessory pathway and the inducibility of atrioventricular reciprocating tachycardia were not significantly different between the two groups. Endocardial electrograms, obtained by right atrial catheter mapping, were recorded during sinus rhythm from 12 sites of the right atrium in 12 of the 13 group I patients and in all group II patients. An abnormal atrial electrogram was defined as 100 msec or longer in duration, and/or the occurrence of eight or more deflections. Ten (83%) of the 12 group I patients had abnormal atrial electrograms, while only two (10%) of the 20 group II patients had abnormal atrial electrograms, and the difference was significant (P less than 0.01). Thirty-six (26%) of the total 139 electrograms obtained from 12 group I patients and two (1%) of the total 199 electrograms obtained from 20 group II patients fulfilled the criteria for an abnormal atrial electrogram, and the difference was significant (P less than 0.01). The fragmented atrial activity zone, interatrial conduction delay zone, and repetitive atrial firing zone obtained by right atrial extrastimulation were significantly wider in group I than in group II, respectively. It was concluded that electrical abnormalities of the atrial muscle may play an important role in the occurrence of paroxysmal atrial fibrillation in patients with Wolff-Parkinson-White syndrome.     

Effect of FK506 on the activation state of hepatic macrophages in Propionibacterium acnes-treated rats

Activated hepatic macrophages can provoke massive liver necrosis following endotoxin stimulation through microcirculatory disturbances due to sinusoidal fibrin deposition in rats pretreated with heat-killed Propionibacterium acnes. In these rats, FK506 (tachlorinus) administered 24 h before and at the time of endotoxin injection, significantly attenuated liver injury compared with the rats given no FK506. The effect of FK506 on hepatic macrophage activation and its action sites were studied in Propionibacterium acnes-treated rats. When rats received Propionibacterium acnes intravenously, hepatic-mRNA expression of interferon-γ-inducing factor and interleukin-2 and splenic-mRNA expression of interferon-γ were significantly increased compared with normal rats. Hepatic-mRNA expression of CD14, a receptor for lipopolysaccharide and its binding protein complex, was also increased preceding the expressions of the three cytokines in the liver and spleen. FK506 administration attenuated hepatic-mRNA expression of interleukin-2 and both superoxide anions as well as tumour necrosis factor-α production by hepatic macrophages, but did not change CD14-mRNA expression in Propionibacterium acnes-treated rats. It is suggested that a cytokine network through interferon-γ-inducing factor, interferon-γ and interleukin-2 may operate during activation of hepatic macrophages in rats treated with heat-killed Propionibacterium acnes, while CD14 expression on the cells may increase independently of this network. FK506 seems to attenuate such activation by suppressing hepatic interleukin-2 expression, without affecting CD14 expression on the cells.     

Optimal Target Site for Slow AV Nodal Pathway Ablation

INTRODUCTION: Although a variety of ablation techniques have been developed in the treatment of atrioventricular nodal reentrant tachycardia (AVNRT), there have been few reports discussing the location of the optimal target site. Based on our early experiences, we hypothesized that radiofrequency (RF) current applied around the upper margin of the coronary sinus ostium (UCSO) results in the most effective and safe treatment of AVNRT. METHODS AND RESULTS: To confirm our hypothesis, the efficacy of RF currents applied around the UCSO guided by local electrograms in 59 patients (group B: predetermined focal mapping approach) were compared with the outcomes in 60 other patients previously treated with the standard electrogram-guided mapping method starting around the lower margin of the coronary sinus ostium (group A). The precise location of ablation catheters at successful sites (S) was also evaluated. All the patients were successfully treated without complications. Significantly fewer RF pulses and lower energies were needed in group B patients (mean RF applications: 4.3 vs 1.4 applications, mean total energy delivered: 4,699 vs 2,236 J in groups A and B, respectively, P < 0.01). Detailed analyses of the anatomical locations of S using CS venography in group B patients who received only a single RF application (46 patients) revealed that the distance between His and S varied according to the length of Koch's triangle, while that between S and UCSO was relatively constant. In 85 % of these 46 patients, S was located within 5 mm above and below the level of the UCSO. CONCLUSION: RF applications around the UCSO guided by local electrograms yielded excellent outcomes in AVNRT patients with wide varieties in the size of Koch's triangle. The optimal target site was located within 5 mm above and below the level of UCSO along the tricuspid annulus.