慢性快速心房起搏心房颤动犬内皮型一氧化氮合酶mRNA表达变化的研究

为研究慢性快速心房起搏心房颤动(简称房颤)犬模型中心内膜内皮型一氧化氮合酶(eNOS)mRNA表达的变化,探讨其与心房结构重构、血栓形成的关系。13只健康犬随机分为假手术组和起搏组,应用埋藏式高频率心脏起搏器快速起搏心房(400次 /分) 6周,取左、右心房,左、右心耳及主动脉内膜。通过逆转录 聚合酶链反应 (RT PCR),以β actin为内参照,测定犬心内膜eNOSmRNA表达的变化,同时检测血浆NO代谢产物硝酸盐 (NOx)的含量。结果:正常犬心脏eNOSmRNA表达存在差异,左房、左心耳明显高于右房、右心耳;起搏 6周后左房、左心耳eNOSmRNA表达起搏组明显低于假手术组,而右房、右心耳、主动脉无明显差别,血浆NOx起搏组亦明显低于假手术组。结论:正常犬心脏eNOS基因表达是不平衡的,左房明显高于右房。房颤犬eNOSmRNA表达降低可能是心房结构重构,血栓形成的重要因素之一。     

阻断迷走神经对心房肌有效不应期及其离散的影响

用动物实验模拟快速房率来观察阻断迷走神经对心房有效不应期 (AERP)及其离散 (dAERP)的影响。用 8只杂种犬自身前后对照 ,观察阻断迷走神经张力不同状态下犬的AERP及dAERP的变化及其关系。结果 :① 80 0次/分的快速心房刺激很快引起AERP缩短 ,dAERP无明显变化。停止刺激后AERP恢复很快 ,dAERP明显升高。②刺激前单用阿托品阻断迷走神经 ,AERP和dAERP无明显变化 ,快速刺激仍能引起AERP缩短 ,刺激终止后dAERP升高不明显。③刺激前联用阿托品和普奈洛尔同时阻滞交感及迷走神经 ,AERP明显升高 ,dAERP无明显变化 ,快速刺激仍能引起AERP缩短 ,刺激终止后dAERP升高不明显。结论 :心房快速刺激时 ,阻断迷走神经不能阻止AERP的缩短 ,交感和迷走神经对快速刺激终止后的dAERP逐渐升高可能有作用     

Difference between electrical remodelling after pulmonary veins and right atrium appendage pacing.

OBJECTIVE: Pulmonary veins (PVs) are important sources of paroxysmal atrial fibrillation (AF). Rapid atrial pacing changes atrial electrophysiology, and facilitates the induction and maintenance of AF. The purpose of our study was to evaluate the changes in atrial effective refractory period (AERP) proprieties and in ionic currents in PVs myocytes from dogs subjected to rapid atrial pacing in PVs and right atrial appendage (RAA) and to relate these changes to the ability to induce AF. METHODS: Twelve mongrel dogs in normal sinus rhythm were paced from the superior left PVs or RAA at 500 bpm for 4 h. Electrophysiological studies were conducted to determine the changes in AERP, dispersion, and rhythm. Ionic currents were evaluated using patch clamp technique in single PVs myocytes in sham-operated dogs, and the results were compared with those from PVs and RAA pacing groups. RESULTS: The presence of rapid atrial pacing was associated with a marked shortening in AERP in both PVs and RAA pacing group with a marked increase in AERP dispersion in PVs pacing. Both L-type calcium current (I(Ca,L)) and the transient outward current (I(to)) were reduced in both groups with an increased significance in PVs pacing group. The density of I(Ca,L) was decreased significantly from (-6.03 +/- 0.63) pA/pF in the control group to (-3.21 +/- 0.34) pA/pF in the PVs pacing group and (-4.75 +/- 0.41) pA/pF in the RAA pacing group (n = 6, P < 0.05), whereas the density of I(to) was decreased significantly from (8.45 +/- 0.71) pA/pF in the control group to (5.21 +/- 0.763) pA/pF in the PVs pacing group and (6.84 +/- 0.69) pA/pF in the RAA pacing group (n = 6, P < 0.05). CONCLUSION: Our findings provide likely ionic mechanisms of shortened repolarization in induced atrial tachycardia with a decrease in I(Ca,L) and I(to) densities, which is the likely mechanism for a decrease in action potential duration rate adaptation in the canine rapid pacing model more pronounced in the PVs pacing group underlying the crucial role of PVs in initiating AF.     

Serological and entomological survey in a zoonotic visceral leishmaniasis focus of North Central Anatolia, Turkey: Corum province

In the present study, we aimed to carry out an epidemiological and entomological survey on a visceral leishmaniasis (VL) focus located on the northern central part of Anatolia, Turkey. Five villages of Corum province, where five confirmed cases of human visceral leishmaniasis (HVL) (one patient/village) were reported between June 1998 and August 2001 were included in the study. A total of 625 children and 131 dogs were sampled and the physical examination was carried out by authorized physicians and veterinarians. An indirect fluorescent antibody test (IFAT) was performed by standard procedures for human and dog sera, while the direct agglutination test (DAT) was only performed for dog sera. Sand fly collection was performed in three villages by CDC miniature light traps. Hepatosplenomegaly and hepatomegaly were detected in two and eight children, respectively. The seropositivity rate among children was found to be 0.16% (1/625) in the region. The seroprevalence of canine infection in these five villages ranged between 0.0% and 28.26%. In two villages, named Ahlatcik and Asagifindikli, no seropositive dogs were found. A total of 1218 sand flies were collected throughout the study. Six species of Phlebotomus were identified: P. transcaucasicus, P. neglectus, P. halepensis, P. tobbi, P. papatasi, and P. jacusieli. P. transcaucasicus was found to be the predominant species in Cevizli (47.44%; 343/723) and Ucoluk (79.95%; 351/439) villages, while P. tobbi was abundant in Kucukerikli (42.85%; 24/56).     

钾离子通道亚单位mRNA在犬左右心室中层心肌中的表达

目的研究犬左右室中层心肌短暂外向钾电流(Ito)、延迟整流钾电流缓慢激活成分(Iks)亚单位mRNA的表达情况,探讨左右室复极异质性的可能分子机制。方法应用逆转录-聚合酶链反应(RT-PCR)半定量分析犬左右室中层心肌Ito的α亚单位(Kv4.3)、β亚单位(KchIP2)、Iks的α亚单位(KvLQT1)mRNA的表达量(以β-actin为内参照)。结果Kv4.3 mRNA水平在左右室中层心肌中表达没有显著性差异(P>0.05),KchIP2 mRNA、Kv-LQT1 mRNA水平在右室中层心肌表达明显高于左室中层心肌(P<0.01或<0.05)。结论KchIP2、KvLQT1 mRNA水平在左右室中层心肌中表达上的差异可能是其离子流差异的分子基础。     

Role of K+ channels in EDHF-dependent relaxation induced by acetylcholine in canine coronary artery

Summary To identify the K⁺ channels responsible for endothelium-derived hyperpolarizing factor (EDHF)-dependent relaxation, we studied the effects of various K⁺ channel blockers on acetylcholine-induced relaxation, which persists even in the presence of both an inhibitor of nitric oxide synthase and that of cyclooxygenase, in canine coronary artery rings. A nonselective K⁺ channel blocker, tetrabutylammonium (TBA), a large and intermediate conductance Ca²⁺-activated K⁺ channel blocker, charybdotoxin (CTX), and a voltage-dependent K⁺ channel blocker, 4-aminopyridine (4-AP), significantly inhibited this residual relaxation. A combined treatment with CTX and 4-AP almost completely blocked the relaxation. Neither a large (iberiotoxin) nor a small (apamin) conductance Ca²⁺-activated K⁺ channel blocker blocked the relaxation. We also investigated effects of K⁺ channel blockers on basal tone to determine whether or not EDHF is involved in regulating basal tone. TBA and CTX substantially raised basal tone to a greater degree in endothelium-intact preparations than in endothelium-denuded preparations. These results indicate that EDHF may exert its relaxing action through intermediate conductance Ca²⁺-activated and voltage-dependent K⁺ channels in canine coronary arteries. In addition, EDHF may play a role in maintaining basal vascular tone. This study was supported in part by a Grant-in-Aid for Scientific Research (B07457167) from the Ministry of Education, Science and Culture of Japan.     

A dual-chambered hemodialyzer for convection-enhanced hemodialysis

Convective clearance during hemodialysis (HD) improves dialysis outcomes in kidney failure patients, and, thus, trials have been undertaken to increase convective mass transfer, which is directly related to internal filtration rates. The authors designed a new hemodialyzer to increase the internal filtration rates, and here describe the hemodialytic efficacy of the devised unit. The developed dual‐chambered hemodialyzer (DCH) contains two separate chambers for dialysate flow within a single housing. By placing a flow restrictor on the dialysate stream between these two chambers, dialysate pressures are regulated independently. Dialysate is maintained at a higher pressure than blood pressure in one chamber, and at a lower pressure in the other chamber. The dialysis performance of the DCH was investigated using an acute canine renal failure model. Urea and creatinine reductions and albumin loss were monitored, and forward and backward filtration rates were measured. No procedurally related malfunction was encountered, and animals remained stable without any complications. Urea and creatinine reductions after 4‐h dialysis treatments were 75.2 ± 6.5% and 67.7 ± 8.9%, respectively. Post‐treatment total protein and albumin levels remained at pretreatment values. Total filtration volume was 4.98 ± 0.5 L over 4 h, whereas the corresponding backfiltration (BF) volume was 4.77 ± 0.6 L. The developed dual‐chamber dialyzer has the benefit of providing independent control of forward filtration and BF rates. HD using this dialyzer provides a straightforward means of increasing the internal filtration and convective dose.     

Comprehensive comparison of canine retraction using NiTi closed coil springs vs elastomeric chains:: A split-mouth randomized controlled trial

ObjectivesTo compare canine retraction using NiTi closed coil springs vs elastomeric chains comprehensively in a split-mouth randomized controlled trial.Materials and MethodsThe canines in 64 quadrants were randomly retracted into the first premolar extraction spaces using NiTi closed coil springs or elastomeric chains, in the maxilla and mandible. The retraction force was 150 g. Cone beam computed tomography scans and study models were obtained before the start of canine retraction and 6 months later. The rate and total amount of canine retraction, canine rotation, tipping, and root resorption were evaluated. A visual analogue scale was used to evaluate patients'' pain experience.ResultsThe two methods were statistically similar for dental changes, rate of canine retraction, and root resorption. However, patients reported significantly more days of pain with the elastomeric chain compared to the NiTi closed coil springs.ConclusionsWithin the constraints of the current study, using either NiTi closed coil springs or elastomeric chains as force delivery systems for canine retraction results in no significant difference in the rate of canine retraction, tipping, rotation, or root resorption. Pain experience during retraction using elastomeric chains is more significant yet needs further investigation.     

Effect of acute endotoxemia on analog estimates of mean systemic pressure

Dynamic estimates of mean systemic pressure based on a Guytonian analog model (Pmsa) appear accurate under baseline conditions but may not remain so during septic shock because blood volume distribution and resistances between arterial and venous beds may change. Thus, we examined the effect of acute endotoxemia on the ability of Pmsa, estimated from steady-state cardiac output, right atrial pressure, and mean arterial pressure, to reflect our previously validated instantaneous venous return measure of mean systemic pressure (Pmsi), derived from beat-to-beat measures of right ventricular stroke volume and right atrial pressure during positive pressure ventilation. We studied 6 splenectomized pentobarbital-anesthetized close chested dogs. Right ventricular stroke volume was measured by a pulmonary arterial electromagnetic flow probe. Instantaneous venous return measure of mean systemic pressure and Pmsa were calculated during volume loading and removal (± 100-mL bolus increments × 5) both before (control) and 30 minutes after endotoxin infusion (endo). Cardiac output increased (2628 ± 905 vs 3560 ± 539 mL/min; P < .05) and mean arterial pressure decreased (107 ± 16 vs 56 ± 12 mm Hg; P < .01) during endo. Changes in Pmsi and Pmsa correlated during both control and endo (r² = 0.7) with minimal bias by Bland-Altman analysis (mean difference ± 95% confidence interval, 0.47 ± 5.04 mm Hg). We conclude that changes in Pmsa accurately tracts Pmsi under both control and endo.     

Differential antagonism by glibenclamide of the relaxant effects of cromakalim,pinacidil and nicorandil on canine large coronary arteries

Summary The relaxant mechanisms of action of cromakalim, pinacidil and nicorandil, potassium channel openers, on large epicardial coronary arteries were investigated in isolated canine left circumflex arteries contracted by 10^–7 mol/l U46619, a thromboxane A₂ analogue, or addition of 25 mmol/l KCl in comparison with nitroglycerin.Cromakalim (3 × 10^–8–3 × 10^–5 mol/l), pinacidil (10^–6–10^–4 mol/l), nicorandil (3 × 10^–6–10^–3 mol/l) and nitroglycerin (3 × 10^–8–10^–5 mol/l) all produced a concentration-dependent relaxation in both U46619- or KCl-contracted arteries. At their maximum effects pinacidil, nicorandil and nitroglycerin produced full relaxation in arteries contracted by either means. In contrast, cromakalim produced about a 73% relaxation in KCl-contracted arteries, although it caused full relaxation in U46619-contracted ones. In the presence of glibenclamide the concentration-relaxation curves for cromakalim in U46619- or KCl-contracted arteries underwent rightward parallel shifts. Schild regression had a slope of 1.00 and yielded a pA₂ of 7.47 for glibenclamide in U46619-contracted arteries, and corresponding values obtained in KCl-contracted arteries were 0.86 (not significantly different from unity) and 7.28. The concentration-relaxation curves for pinacidil in U46619-contracted arteries also underwent rightward parallel shifts in the presence of glibenclamide, however, Schild regression had a slope of 0.60. The concentration-relaxation curves for pinacidil in KCl-contracted arteries underwent rightward parallel shifts only to a limited extent in the presence of glibenclamide. The concentration-relaxation curves for nicorandil and nitroglycerin in U46619- or KCl-contracted arteries were not affected by glibenclamide in concentrations which antagonized cromakalim. The concentration-relaxation curves for nicorandil or nitroglycerin in U46619-contracted arteries were shifted by methylene blue (10^–5 mol/l) to the right without suppression of the their maximum effects. Similar curves for cromakalim were not affected at all by this concentration of methylene blue. The concentration-relaxation curves for nicorandil in U46619-contracted arteries determined in the presence of methylene blue (10^–5 mol/l) and glibenclamide (3 × 10^–7, 10^–6 and 3 × 10^–6 mol/l) were not significantly different from those in the presence of methylene blue alone.These results indicate the following: In canine large epicardial coronary arteries (1) cromakalim produced relaxation by the mechanism antagonized by glibenclamide, probably opening ATP-sensitive potassium channels, (2) pinacidil did so by the mechanism shared with cromakalim and by one not antagonized by glibenclamide as well, and (3) nicorandil did so exclusively by the mechanism of action as a nitrate. Send offprint requests to N. Taira at the above address