卡维地洛与维司力农:心力衰竭中新的抗心律失常途径(英文)

卡维地洛和维司力农是近年来受到瞩目的慢性充血性心力衰竭治疗药。电生理学研究表明这些药物可适度延长心室肌的动作电位时程(APD)而无明显的逆频度依存性,然而其产生这一作用的离子机制是不同的。卡维地洛可阻断L-型钙电流(I_(Ca)),一过性外向钾电流(I_(to))以及延迟整流钾电流(I_K),特别是其快速激活成份(I_(Kr))。维司力农是一个选择性的I_K阻滞剂,具有独特的药物-通道相互作用。根据维司力农对I_K的电位与时间依存性抑制作用,该药被认为在I_K(主要是I_(Kr))通道处于激活状态时与其结合,而在通道关闭时则发生解离。这些电生理学特性将为器质性心脏病患者理想的抗心律失常药的开发提供新的途径。     

Successful Radiofrequency Current Catheter Ablation of Sustained Ventricular Tachycardia

We performed radiofrequency current catheter ablation in two patients with nonischemic sustained ventricular tachycardia (VT). In one patient, two morphologically distinct VTs were induced by electrical stimulation. One showed right bundle branch block pattern and the other left bundle branch block pattern. The earliest site of activation during each VT was determined at the septum of the right ventricle. However, these two sites were close to the His-bundle elecfrogram recording area. In the other patient, a VT with a left bundle branch block pattern occurred spontaneously after the administration of isoproterenol. The earliest site of activation during VT was determined at the outflow tract of the right ventricle. During tachycardia, radiofrequency current ablation (40 W ± 30 sec) was delivered to the earliest site of activation, A few seconds after fulguration, each VT was terminated and additional radio-frequency currents were given near these sites. After the ablation, VT could not be induced by the electrical stimulations, nor did it recur. No side effects were observed and the atrioventricular conduction remained intact. We feel that nonischemic VTs could possibly be treated by using radiofrequency current catheter ablation.     

Adequacy of Pacing Rate During Exercise in Rate Responsive Ventricular Pacing

Our objective was to determint; the adequate pacing rate during exercise in ventricular pacing by measuring exercise capacity, cardiac output, and sinus node activity. Eighteen patients with complete AV block and an implanted pacemaker underwent cardiopulmonary exercise tests under three randomized pacing rates: fixed rate pacing (VVJ) at 60 beats/min and ventricular rate-responsive pacing (VVIR) programmed to attain a heart rate of about 110 beats/min ar 130 beats/min (VVIR 110 and VVIR 130, respectively) at the end of exercise. Compared with VVI and VVIR 130, VVIR 110 was associated with an increased peak oxygen uptake(VVIR 110:20.3 ± 4.5 vs VVI: 16.9 ± 3.1; P < 0.01; and VVIR 130: 19.0 ± 4.1 mL/min per kg, respectively; P < 0.05) and a higher oxygen uptake at anaerobic threshold (15.3 ± 2.7, 12.7 ± 1.9; P < 0.01, and 14.6 ± 2.6 mL/min per kg; P < 0.05). The atrial rate during exercise expressed as a percentage of the expected maximal heart rate was lower in VVIR 110 than in VVI or VVIR 130 (VVIR 110: 75.9%± 14.6% vs VVI: 90.6%± 12.8%; P < 0.01; VVIR 110 vs VVIR 130: 89.1%± 23.1%; P < 0.05). There was no significant difference in cardiac output at peak exercise between VVIR 110 and VVIR 130. We conclude that a pacing rate for submaximal exercise of 110 beats/min may be preferable to that of 130 beats/min in respect to exercise capacity and sympathetic nerve activity.     

Spontaneous recovery from renal infarction resulting from renal artery dissection

A 31-year-old, previously normotensive healthy man developed right flank pain and was admitted to a medical service. Right renal infarction was suspected by enhanced abdominal computed tomography (CT) and arteriography. Fourteen days after the onset, he was transferred to the Oita University Hospital, Oita, Japan. Renal angiography revealed an isolated renal artery dissection causing renal atrophy due to main stem narrowing of the right renal artery. Renogram and renal scintigram with (99m)Tc-diethylene triamine pentaacetic acid revealed a remarkable decline in the glomerular filtration rate and almost no uptake in the right kidney. Four months later, in spite of our belief that functional recovery could not be expected, intravenous pyelography and enhanced abdominal CT scans revealed a functioning right kidney that had spontaneously recovered from the renal artery dissection through conservative management.     

Incidence and Familial Occurrence of the Congenital Anomalies of the Face, Hand and Foot

We made an epidemiological study of congenital anomalies of the face, hand and foot in newborns from 1973 to 1992 in Miyagi Prefecture which has a population of about two million. In these twenty years 579,766 babies were born in Miyagi Prefecture. Out of these newborns 3,416 babies with 3,759 congenital anomalies of the face, hand and foot were registered. Of all registered congenital anomalies, face anomalies were most commonly encountered, followed by hand and foot anomalies. Among face anomalies, in order of frequency, accessory ear was the most common, next cleft lip with or without cleft palate, cleft palate alone, cryptotia and microtia. The occurrence ratio per 10,000 live births was 9.6 in accessory ear, 6.7 in cleft lip, 6.1 in cleft lip with cleft palate, 4.2 in cleft palate alone, 2.9 in cryptotia, and 1.8 in microtia. In hand and foot anomalies, polydactyly was the most common and syndactyly the next. Incidence ratio of polydactyly was 5.8 in the hand and 6.4 in the foot. Polydactyly was the most frequent in the preaxial ray in the hand and in the postaxial ray in the foot. About half of cases of postaxial polydactyly the foot was associated with syndactyly between the fourth and fifth toe. In addition, we reported on variation of the incidence ratio and familial occurrence of congenital anomalies of the face, hand and foot.     

Ocular Membrane Permeability of Hydrophilic Drugs for Ocular Peptide Delivery

The purpose of this study is to investigate the ocular membrane permeability and the permeation mechanism of hydrophilic drugs such as thyrotropin-releasing hormone (TRH), p-nitrophenyl β-cellopentaoside (PNP) and luteinizing hormone-releasing hormone (LHRH). The penetration of hydrophilic drugs was measured across the isolated corneal and conjunctival membranes of albino rabbits using a two-chamber diffusion glass cell. The corneal permeabilities of hydrophilic drugs were much lower than those of beta blockers reported previously. The corneal penetration of TRH was the highest among the hydrophilic drugs studied. Scraping the corneal epithelium increased the penetration of hydrophilic drugs. Conjunctival membranes showed higher permeability to hydrophilic drugs compared with corneal membranes. The permeability of drugs was also analysed by Fick's equation. The partition parameter and diffusion parameter of TRH, PNP and LHRH in the cornea were lower than those in scraped cornea and conjunctiva. In addition to the data of fluorescein isothiocyanate-dextran reported previously, the permeability coefficient of hydrophilic drugs through the cornea, scraped cornea and conjunctiva correlated with molecular weight of the drugs. The diffusion parameters of hydrophilic drugs decreased with an increase of molecular weight for all ocular membranes. The extent of dependency of partition parameters on the molecular weights of drugs varied according to the ocular membrane. These results indicate that ocular membranes are sufficiently different in permeation character and mechanism to control the extent and pathway for ocular absorption of hydrophilic drugs.     

Intraoperative transesophageal echocardiography for inferior vena caval tumor thrombus in renal cell carcinoma

BACKGROUND: We investigated the advantages of intraoperative transesophageal echocardiography (TEE) during inferior vena caval tumor thrombectomy in renal cell carcinoma (RCC). METHODS: Five patients with RCC that extended into the inferior vena cava (IVC) underwent radical nephrectomy. To remove the tumor thrombus in the IVC, an inflated Fogarty balloon catheter was used to pull the thrombus below the level of the hepatic veins with real-time TEE monitoring. RESULTS: In all cases, TEE monitoring during surgery provided an accurate and excellent view of the IVC thrombus. TEE was particularly helpful for the thrombectomy to minimize hepatic mobilization by using occlusion balloon catheter in two patients whose thrombus extended to the intrahepatic IVC. CONCLUSIONS: Intraoperative real-time TEE monitoring is a safe, minimally invasive technique that can provide accurate information regarding the presence and extent of IVC involvement, guidance for placement of a vena caval clamp, confirmation of complete removal of the IVC thrombus and intervention using catheters to assist in thrombectomy.     

Deficiency of Testosterone Associates with the Substrate of Atrial Fibrillation in the Rat Model

Background: Since the prevalence of atrial fibrillation (AF) increases progressively with aging, especially in men, we hypothesized that testosterone might affect the occurrence of AF.
Methods and Results: We examined the electrophysiological properties of the atria in isolated-perfused hearts of sham-operated male (SM), female (SF), orchiectomized male with and without administration of testosterone (ORCH-T and ORCH), and ovariectomized female (OVX) Sprague-Dawley rats. An electrophysiological study revealed that repetitive atrial responses induced by electrical stimuli significantly increased in ORCH rats without changes in other electrophysiological properties and were abolished by administration of testosterone. To investigate the underlying mechanisms, we evaluated the expression level of calcium-handling proteins. In ORCH rats, the immunoreactive protein level of ryanodine receptor type 2 (RyR2) and sodium–calcium exchanger significantly increased as compared with SM and ORCH-T rats without alterations in the level of FK506-binding protein (FKBP12.6), sarcoendoplasmic reticulum Ca-ATPase, and phospholamban. Immunoprecipitation analysis demonstrated decreased binding of FKBP12.6 to RyR2 in ORCH rats, which was prevented by testosterone. In contrast, the expression levels of these proteins showed no significant differences between SF and OVX rats.
Conclusion: Deficiency of testosterone was arrhythmogenic in rat atria possibly through less binding of FKBP12.6 to RyR2, which could induce feasible calcium leakage from the sarcoendoplasmic reticulum. These results would explain, at least in part, the increase in the prevalence of AF in accordance with the decline of testosterone particularly in elderly men.