冠状动脉内支架植入术在冠心病治疗中的应用

报道６８例冠心病患者８０支血管病变植入１１８个支架，植入成功率为９２．１％。其中不稳定心绞痛者占５０％，既往有心肌梗塞史者占４６％，多支病变者占６２．４％，Ｂ２型以上病变占６６．６％，因ＰＴＣＡ术后不良结果而植入支架的病变占２７．５％（２２／８０），因术后急性并发症者１７．５％（１４／８０），Ｄｅｎｏｖｏ病变占５５％（４４／８０）。狭窄程度由术前的８５．５％±１２．９％减至术后的５．８％±１１．４％。术后４周～１年间，６０例患者（８８．２％）症状缓解，６例（８．８％）心绞痛复发，其中４例（５．８％）经冠状动脉造影证实支架部位再狭窄，术后２个月内死亡２例（２．９％），术后１周内发生无Ｑ波心肌梗塞者１例     

经皮冠状动脉腔内成形术后冠状动脉再狭窄的外科治疗

目的：探讨经皮冠状动脉腔内成形术（ＰＴＣＡ）后冠状动脉再狭窄的治疗方法。方法分析２５例ＰＴＣＡ术后冠状动脉再狭窄接受冠状动脉旁路移植手术（ＣＡＢＧ）患的ＰＴＣＡ前后的临床资料。ＰＴＣＡ后心绞痛症状未缓解５例,术后２天至１７个月复发心绞痛２０例,平均再狭窄发生时间ＰＴＣＡ后４．６个月。一次ＰＴＣＡ后选择ＣＡＢＧ１９例,２次４例,３次２例。除ＰＴＣＡ或支架部位处发生再狭窄外,５例狭窄以冠状动脉病     

冠状动脉内支架临床应用的初步报告

本文报道７例冠状动脉内支架临床应用情况，４例Ｇｉａｎｔｕｒｃｏ－Ｒｏｕｂｉｎ支架用于经皮冠状动脉胶内成形术（ＰＴＣＡ）并发冠状动脉急性闭塞或濒临闭塞，其中１例于右冠状动脉内植入２个支架；２例Ｐａｌｍａｚ－Ｓｃｈａｔｚ支架及１例Ｇｉａｎｔｕｒｃｏ－Ｒｏｕｂｉｎ支架用于预防ＰＴＣＡ后再狭窄。７例支架植入均获成功，１例术后股动脉穿刺部位出血，２例腹股沟局部血肿，无其它并发症。     

冠状动脉完全闭塞病变的经皮腔内冠状动脉成形术

我们自１９８７年１２月至１９９３年１０月对５５例５８支冠状动脉完全闭塞病变（ＴＯ）行经皮腔内冠状动脉成形术（ＰＴＣＡ），占同期ＰＴＣＡ总数的１８．２％。患者平均年龄５６．４±７．５岁，心绞痛患者１９例，心肌梗塞患者３６例，其中梗塞后１０小时内行急诊ＰＴＣＡ２例，１个月内和１个月以后行ＰＴＣＡ分别为６例和２８例。ＴＯ平均时间６８．４±４６．６天。完全闭塞和次全闭塞各占６５．５％和３４．５％。结果显示：病例成功率为８９．１％，病变成功率为８７．９％；完全闭塞成功率为８９．５％，次全闭塞成功率为８５．０％。闭塞类型、闭塞时间、闭塞长度等特征对成功率无显著性影响（Ｐ＞０．０５）；血管并发症率为１２．１％（７／５８），处理成功６处，死亡１例。     

补救性经皮冠状动脉腔内成形术治疗急性心肌梗塞

目的探讨补救性经皮冠状动脉腔内成形术（ＰＴＣＡ）在治疗急性心肌梗塞（ＡＭＩ）中的作用。方法对溶栓治疗失败的３６例患者进行补救性ＰＴＣＡ治疗。患者心功能Ｋｉｌｐ分级：Ⅲ级和Ⅳ级４例，Ⅱ级和Ⅰ级３２例。冠状动脉造影显示梗塞相关动脉：前降支１７例，右冠状动脉１４例，回旋支４例，中间动脉１例。ＰＴＣＡ前ＴＩＭＩⅠ级和Ⅰ～Ⅱ级血流各２例，余３２例均为ＴＩＭＩ０级。３６例均进行ＰＴＣＡ治疗，其中１３例患者置入了支架。结果术中除３例失败外，３１例患者病变血管血流达到ＴＩＭＩⅢ级，２例ＴＩＭＩⅡⅢ级，残余狭窄≤５０％，成功率为９１．７％。院内并发症：１例在ＰＴＣＡ成功后当天因顽固性休克和心室纤颤死亡；１例于第３天死于心脏破裂，住院病死率为５．６％。１４例患者在术后１～２个月内复查冠状动脉造影，２例发生再狭窄。结论ＡＭＩ患者在溶栓治疗失败后，在有条件的医院可施行补救性ＰＴＣＡ治疗，成功率高，对改善患者的近期和远期预后可能有利     

多普勒血流速度测定评价冠状动脉成形术与支架术的疗效

目的 经皮冠状动脉成形术（ＰＴＣＡ）与支架术都可有效的恢复冠状动脉狭窄引起的 动因流异常。采用冠状动脉内多普勒血流速度描记技术评价ＰＴＣＡ及支架在恢复冠状动脉血流作用上的特点及差异。方法 冠心病患２１例（男１８例,女３例）,平均年龄（６４．１±５．４）岁,对２３支狭窄的冠状动脉（左前降支１５支,右冠状动脉６支,左回旋支２支）行ＰＴＣＡ之后置入支架２１枚。分析在介入治疗前后ＰＴＣＡ术后、支架术后采     

经皮冠状动脉腔内成形术229例长期预后分析

为了探讨国人经皮冠状动脉腔内成形术（ＰＴＣＡ）后远期疗效及影响疗效的因素，对ＰＴＣＡ成功的２２９例患者用门诊随诊或信访方式进行随访，随访时间０．５～８．４（平均２．３±１．８）年。结果显示：７６例（３３．２％）患者心绞痛症状复发，随访期中死亡２例（０．９％），非致命性急性心肌梗塞６例（２．６％），行冠状动脉旁路移植术４例（１．７％），重复ＰＴＣＡ２９例（１２．７％）。以Ｋａｐｌａｎ－Ｍｅｉｅｒ法计算术后无心脏事件生存率，１年为８４．８％，８年为７０．５％。Ｃｏｘ回归分析表明，术前病变狭窄程度及术后前降支残余狭窄程度与发生心脏事件的相对危险性呈正相关。提示国人ＰＴＣＡ可取得较好远期疗效；术中尽可能减少前降支残余狭窄，可能减少心脏事件发生的相对危险度     

慢性冠状动脉完全闭塞病变的介入治疗

目的探讨慢性冠状动脉完全闭塞病变行ＰＴＣＡ和支架置入治疗的可行性和临床价值。方法对血管完全闭塞病变行ＰＴＣＡ和（或）支架置入治疗,评价其临床效果。结果共对２８例完全闭塞的冠状动脉行ＰＴＣＡ和冠脉内支架治疗。１７支左前降支治疗中,４例失败,植入支架６例。４支左回旋支治疗中,１例失败,置入支架１例。７支右冠状动脉治疗中,３例失败,置入支架２例。成功率为７１．４％,９例病人置入支架（３２．１％）,无严重并发症。随访１～４２个月效果良好。结论对血管完全闭塞病变行ＰＴＣＡ和支架置入治疗,仍有较高的成功率和安全性。     

经皮冠状动脉腔内成形术对冠心病患者心室晚电位的影响

为观察经皮冠状动脉腔内成形术（ＰＴＣＡ）对心室晚电位（ＶＬＰ）的影响，对３８例冠心病患者ＰＴＣＡ前、后的信号平均心电图（ＳＡ－ＥＣＧ）进行定性、定量分析和随访观察。时域分析发现，３例ＶＬＰ阳性中的１例ＰＴＣＡ术后ＶＬＰ消失，有５．７％（２／３５）ＶＬＰ阴性患者术后ＶＬＰ转为阳性；频谱时间标测发现，４例ＶＬＰ阳性中的２例术后ＶＬＰ消失，有１１．８％（４／３４）ＶＬＰ阴性患者术后ＶＬＰ转为阳性；全组患者中，ＰＴＣＡ前、后ＳＡ－ＥＣＧ参数的变化无显著性（Ｐ＞０．０５）。术后随访１０．９±２．５（４～１４）个月，未发生心律失常事件。提示ＰＴＣＡ可使ＶＬＰ阳性的部分患者转阴；使很少部分患者ＶＬＰ阴性转为阳性，提示再灌注可能改善冠心病患者的预后     

冠状动脉成形术TNF的活性及临床意义

为探讨肿瘤坏死因子（ＴＮＦ）在冠状动脉成形术（ＰＴＣＡ），对冠状动脉内膜损伤及再狭窄的相互关系，自１９９５年４月～１９９６年４月，采用Ｌ９２９细胞系测定了３２例ＰＴＣＡ患者ＴＮＦ的活性。观察ＰＴＣＡ术前和术后１、４、８、２４小时周围静脉血ＴＮＦ的动态变化。结果：术前ＴＮＦ活性低，术后４～８小时明显增高（Ｐ＜０．０１），２４小时基本降至术前水平。显示ＴＮＦ活性增高与ＰＴＣＡ术中冠脉内膜损伤有密切关系，可能是参与ＰＴＣＡ后术冠状动脉急性闭塞及迟发性再狭窄的重要因素之一。     

肝炎病毒感染的肾移植受者术后并发症

目的：了解ＨＢｓＡｇ或Ａｎｔｉ－ＨＣＶ阳性对肾移植受者术后并发肝外感染、急性排异及移植肾功能不全的影响。方法：回顾分析１０１例肾移植受者的临床资料。结果：在ＨＢｓＡｇ（＋）与Ａｎｔｉ－ＨＣＶ（＋）组间上述三大并发症发生率差异不显著（Ｐ＞０．０５）；ＨＢｓＡｇ（＋）组或Ａｎｔｉ－ＨＣＶ（＋）组移植肾急性排异及肾功能不全的发生率较高，尽管较阴性组无显著差异（Ｐ＞０．０５），但肝外感染的发生率明显升高（Ｐ＜０．０５）。结论：对ＨＢｓＡｇ（＋）或Ａｎｔｉ－ＨＣＶ（＋）的肾移植受者必须密切监测肝功能，环孢素Ａ（ＣｓＡ）浓度及机体免疫状态，以选择适当的免疫抑制剂方案及剂量     

Silicon-Carbon bond cleavage reactions of Ansa tungstenocene compounds: the [Me2Si] bridge as a site for metallocene functionalization

[Me(2)Si(Cp(Me(2)))(2)]W(H)Cl is obtained via reaction of WCl(6) with a mixture of [Me(2)Si(Cp(Me(2)))(2)]Li(2) and NaBH(4), from which the dichloride [Me(2)Si(Cp(Me(2)))(2)]WCl(2) is obtained via treatment with CHCl(3). [Me(2)Si(Cp(Me(2)))(2)]WCl(2) provides a means to access other ansa tungstenocene compounds, such as [Me(2)Si(Cp(Me(2)))(2)]WH(2), [Me(2)Si(Cp(Me(2)))(2)]WMe(2), and [Me(2)Si(Cp(Me(2)))(2)]WCO. Of most interest, the reactions of [Me(2)Si(Cp(Me(2)))(2)]W(H)Cl with organolithium reagents do not yield simple ansa tungstenocene derivatives. Specifically, the reactions of [Me(2)Si(Cp(Me(2)))(2)]W(H)Cl with MeLi, Bu(n)Li, or PhLi result in the formation of mixed-ring tungstenocene compounds resulting from C-Si cleavage and functionalization of the ansa bridge, namely (Cp(Me(2)))(eta(5),kappa(1)-C(5)H(2)Me(2)SiMe(2)CH(2))WH, (Cp(Me(2)))[eta(5),kappa(1)-C(5)H(2)Me(2)Si(Me)(Bu(n))CH(2)]WH, and (Cp(Me(2)))[eta(5),kappa(1)-C(5)H(2)Me(2)SiMe(2)(C(6)H(4))]WH, respectively. In contrast to the C-Si cleavage achieved by MeLi, Bu(n)Li, and PhLi, the ansa bridge of [Me(2)Si(Cp(Me(2)))(2)]W(H)Cl is inert to Bu(t)Li and the product obtained is the fulvene ("tuck-in") complex [Me(2)Si(Cp(Me(2)))(eta(6)-C(5)MeH(2)CH(2))]WH derived from dehydrohalogenation.     

Antagonistic effects of 24R,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 on L-type Ca2+ channels and Na+/Ca2+ exchange in enterocytes from Atlantic cod (Gadus morhua)

There is mounting evidence that vitamin D and its metabolites play important roles in regulating plasma calcium concentrations in teleost fish as in other vertebrates. The aims of the present study were to elucidate the possible cellular target mechanisms for the rapid actions of 24R,25(OH)(2)D(3), 25(OH)D(3) and 1,25(OH)(2)D(3) in Atlantic cod enterocytes at physiological doses, and to establish the concentration and thus the physiological range of circulating 24R,25(OH)(2)D(3), 25(OH)D(3) and 1,25(OH)(2)D(3) in the Atlantic cod. The plasma concentrations of 25(OH)D(3), 1,25(OH)(2)D(3) and 24R,25(OH)(2)D(3) were 15.3 +/- 2.7nM, 125.1 +/- 12.3pM and 10.1 +/- 23.5nM respectively. Exposure of enterocytes to 10mM calcium (Ca(2+)) evoked an increase in intracellular Ca(2+) concentrations ([Ca(2+)](i)). This increase was suppressed by 24R,25(OH)(2)D(3) dose-dependently, with an EC(50) of 4.9nM and a maximal inhibition of 60%. 24R,25(OH)(2)D(3) (20nM) abolished an increase in [Ca(2+)](i) (approximately 252%) in the control enterocytes exposed to 10microM S(-)-BAYK-8644, suggesting that the hormone acts by inhibiting Ca(2+) entry through L-type voltage-gated Ca(2+) channels. Administration of 20nM 24R,25(OH)(2)D(3) to enterocytes in the absence of extracellular Ca(2+) increased [Ca(2+)](i) by approximately 20%, indicating a release of Ca(2+) from intracellular stores. Administration of 25(OH)D(3) (20nM) resulted in a biphasic change in the enterocyte [Ca(2+)](i): within 1--5s, it decreased to 87 +/- 12nM below its mean basal [Ca(2+)](i) (334 +/- 13nM), followed by a rapid recovery of [Ca(2+)](i) to a new level, 10% lower than the initial [Ca(2+)](i). The rapid decrease, the recovery rate and the final [Ca(2+)](i) were all affected dose-dependently by 25(OH)D(3), with EC(50) values of 8.5, 17.0 and 18.9nM respectively. Furthermore, the effects of 25(OH)D(3) were sensitive to sodium (Na(+)), bepridil (10microM) and nifedipine (5 microM), suggesting that 25(OH)D(3) regulates the activity of both basolateral membrane-associated Na(+)/Ca(2+) exchangers and brush border membrane-associated L-type Ca(2+) channels. Administration of 25(OH)D(3) (10nM) to enterocytes in the absence of extracellular Ca(2+) increased [Ca(2+)](i) by approximately 18%, indicating a release of Ca(2+) from intracellular stores. 1,25(OH)(2)D(3) also affected enterocyte [Ca(2+)](i) in a biphasic manner: the rapid decrease, the recovery rate, and the mean final [Ca(2+)](i) were all affected dose-dependently, with EC(50) values of 8.3, 24.5 and 7.7nM respectively. The high EC(50) values for 1,25(OH)(2)D(3) compared with circulating concentrations of 1,25(OH)(2)D(3) (130pM) suggest that this effect is pharmacological, rather than of physiological relevance in enterocyte Ca(2+) homeostasis of the Atlantic cod. It is concluded that 24R,25(OH)(2)D(3) has a physiological role in decreasing intestinal Ca(2+) uptake via inactivation of L-type Ca(2+) channels, whereas the physiological role of 25(OH)D(3) is to increase enterocyte Ca(2+) transport via activation of Na(+)/Ca(2+) exchangers, concurrent with activation of L-type Ca(2+) channels.     

The nature of analogue-based free thyroxine estimates.

Clinical laboratories often use analogue-based immunoassays to estimate serum free thyroxine (FT(4)) concentrations. These assays yield FT(4) estimates that correlate closely with thyroxine (T(4)) binding protein concentrations. This correlation implies that either T(4) binding proteins or protein bound T(4) contribute to analogue-based FT(4) values. To study the contributions made by T(4) binding proteins to these FT(4) estimates further, four analogue-based FT(4) assays were applied to: (1) FT(4) solutions without T(4) binding proteins, (2) to T(4) binding protein solutions without T(4), and (3) to total T(4) solutions containing T(4) binding protein, FT(4), and protein-bound T(4). The FT(4) estimates obtained with these solutions ranged from 0.2-8.6 ng/dL, when FT(4) concentrations ranged from less than 0.2-12,000 ng/dL. In the FT(4) solutions, gravimetrically determined FT(4) concentrations were 500-12,000 ng/dL (0.5-12.0 microg/dL) without protein-bound T(4), and the FT(4) estimates obtained were 0.3-6.9 ng/dL. In the total T(4) solutions, dialyzable FT(4) concentrations were less than 0.2-59 ng/dL, retained T(4) concentrations were 499.8-11,441 ng/dL, and the analogue-based FT(4) estimates obtained were 0.2-8.6 ng/dL. Similar FT(4) estimates (0.2-8.6 ng/dL and 0.3-6.9 ng/dL) were obtained with similar concentrations of either protein-bound T(4) or FT(4). Similar test results were associated with similar total T(4) concentrations, not similar FT(4) concentrations. Protein-bound T(4) and T(4) binding protein contributed variably to test results. T(4) quantifications included large analytical losses that are unaccounted for. These assays passed tests of correlation with FT(4) concentrations, but they failed tests of specificity for FT(4) and accuracy in T(4) quantification.     

Hydrogen peroxide in the Burkitt's lymphoma cell line Raji provides protection against arsenic trioxide-induced apoptosis via the phosphoinositide-3 kinase signalling pathway

Many anticarcinogenic drugs kill tumour cells by inducing apoptosis. We examined the effects of hydrogen peroxide (H(2)O(2)) on arsenic trioxide (As(2)O(3))-induced cell killing. Low concentrations of H(2)O(2) (200 micromol/l) inhibited the ability of As(2)O(3) to induce apoptosis in the Burkitt's lymphoma cell line Raji. H(2)O(2) altered the form of cell death from apoptosis to pyknosis/necrosis and also lowered the degree of cell killing by As(2)O(3). H(2)O(2) was capable of preventing caspase-3 activation induced by As(2)O(3) in Raji cells. Incubation of cells with a phosphoinositide-3 kinase (PI-3K) inhibitor, wortmannin (100 nmol/l), blocked the effects of H(2)O(2) on As(2)O(3)-induced caspase-3 activation. In addition, the PI-3K inhibitor partially blocked the effects of H(2)O(2) on up-regulation of Bcl-2 and Bcl-X(L) protein expression, down-regulation of Bax protein expression, and phosphorylation of Bcl-2 and IkappaBalpha. This investigation demonstrated for the first time that low concentrations of H(2)O(2) provide protection against the in vivo of As(2)O(3)-induced apoptosis. PI-3K plays a crucial role in enhancing cell survival during H(2)O(2), inhibiting As(2)O(3)-induced apoptosis in the Burkitt's lymphoma cells. As(2)O(3)-induced cancer cell apoptosis may be enhanced by certain antioxidants in the treatment protocol.     

The heart in dermatomyositis and polymyositis

We studied eleven consecutive patients: eight with Dermatomyositis (DM) and three with Polymyositis (PM) from the cardiological point of view through non invasive methods. Nine patients (82%) had some kind of cardiopulmonary complications as shown by any of the used methods. Symptoms: eight (73%) referred some kind of cardiopulmonary symptoms, mainly dyspnea; Physical examination; in seven (64%) was abnormal, detecting increased second pulmonary sound in four (36%), findings of mitral valve prolapse (MVP) in two (18%) and in two (18%) S3 gallop; Electrocardiogram: in seven (64%) was abnormal; six (55%) had some kind of heart enlargement corresponding four (36%) to right atrial or ventricular hypertrophy (RAH & RVH) and two (18%) to left ventricular hypertrophy (LVH), three (27%) had incomplete or complete right bundle branch block, one (9%) had bifascicular block and one (9%) left anterior hemiblock. Two (18%) had sinus tachycardia and two (18%) atrial premature contractions; d) chest ray: six (55%) were abnormal, among them, three (27%) had pulmonary fibrosis, three (27%) had RAH and/or RVH, two (18%) had LVH and one (9%) pericardial effusion; e) Echocardiogram: was abnormal in eight (73%), corresponding three (27%) to RVH, three to MVP which has been considered rare, in two (18%) congestive cardiomyopathy, in two (18%) pericardial effusion and in one (9%) type "A" paradoxical septal movement.     

Expression and cellular distribution of alpha(v)integrins in beta(1)integrin-deficient embryonic stem cell-derived cardiac cells

beta(1)integrin-deficient (beta(1)-/-) ES cells showed increased differentiation of cardiac cells characterized by reduced adhesion and high beating frequency. Whereas in whole embryoid body outgrowths of beta(1)-/- cells maximum levels of alpha(v), beta(3)and beta(5)integrin mRNA were delayed and transiently upregulated, in cardiac clusters isolated from beta(1)-/- cells, only beta(3)integrin mRNA levels were enhanced in comparison to wild-type (wt) cells. To answer the question, whether alpha(v)and beta(3)integrins may compensate, at least partially, the loss of beta(1)integrin function during cardiac differentiation, the distribution of alpha(v)and beta(3)integrins in beta(1)-/- and wt pacemaker-like cardiac cells was analyzed. A different distribution of alpha(v)and beta(3)integrins in beta(1)-/- v wt cardiac cells was found. In wt cardiac cells, beta(1)integrin was localized in specialized subsarcolemmal regions, in particular, at focal contacts and costameres, but alpha(v)integrin was diffusely distributed. In contrast, in beta(1)-/- cardiac cells, alpha(v)integrin was preponderantly localized at cell membranes, focal contacts and costameres. beta(3)integrin displayed a diffuse pattern both in wt and in beta(1)-/- pacemaker-like cells at early differentiation stages, whereas at terminal stages, beta(3)was colocalized with sarcomeres in wt, but not in beta(1)-/- pacemaker-like cells. Quantitative immunofluorescence analysis revealed increased alpha(v)and beta(3)integrin levels in beta(1)-/- pacemaker-like cardiac cells. Our results led us to conclude that altered cellular distribution of alpha(v)integrin and upregulation of beta(3)integrin correlate with growth and survival of beta(1)-/- cardiac pacemaker-like cells at an early developmental state. However, alpha(v)and beta(3)integrins cannot functionally compensate the loss of beta(1)integrin during terminal differentiation of cardiac cells implicating that cardiomyocytes require specific beta(1)integrin functions for cardiac specialization.     

Role of angiotensin II type 2 receptors and kinins in the cardioprotective effect of angiotensin II type 1 receptor antagonists in rats with heart failure

OBJECTIVES: We studied the role of angiotensin II type 2 (AT(2)) receptors and kinins in the cardioprotective effect of angiotensin II type 1 antagonists (AT(1)-ant) in rats with heart failure (HF) after myocardial infarction. BACKGROUND: The AT(1)-ant is as effective as angiotensin-converting enzyme inhibitors in treating HF, but the mechanisms whereby AT(1)-ant exert their benefits on HF in vivo are more complex than previously understood. METHODS: Brown Norway Katholiek rats (BNK), which are deficient in kinins because of a mutation in the kininogen gene, and their wild-type control (Brown Norway [BN]) underwent myocardial infarction. Two months later, they were treated for two months with: 1) vehicle; 2) AT(1)-ant (L158809, Merck, Rahway, New Jersey); 3) AT(1)-ant + AT(2)-ant (PD-123319, Parke Davis, Ann Arbor, Michigan); or 4) AT(1)-ant + kinin B(2) receptor antagonist (B(2)-ant) (icatibant) (only BN). We measured left ventricular weight (LVW) gravimetrically, myocyte cross-sectional area (MCSA) and interstitial collagen fraction (ICF) histologically, and ejection fraction by ventriculography. RESULTS: Development of HF was comparable in BN and BNK rats. The AT(1)-ant reduced LVW and MCSA and the AT(2)-ant blocked these effects in BN rats, but the B(2)-ant did not. The AT(1)-ant reduced LVW and MCSA in BNK rats, and this effect was reversed by the AT(2)-ant. In BN rats, ICF was reduced and LVEF increased by AT(1)-ant, and both AT(2)-ant and B(2)-ant reversed these effects. In BNK rats, the AT(1)-ant failed to reduce ICF, and its therapeutic effect on LVEF was significantly blunted. CONCLUSIONS: In HF, the AT(2) receptor plays an important role in the therapeutic effects of AT(1)-ant, and this effect may be mediated partly through kinins; however, kinins appear to play a lesser role in the antihypertrophic effect of AT(1)-ant.     

Pharmacokinetics of traditional Chinese syndrome and recipe: a hypothesis and its verification (I)

AIM:To propose a hypothesis defining the absorption, distribution, metabolism and elimination of traditional Chinese recipe (TCR)component in blood of healthy subjects and patients, and estimate its correctness.METHODS:The pharmacokinetics (PK) of same dose of drug was studied in the animal model of traditional Chinese syndrome (S)and healthy animals. The classification, termi-nology, concept and significance of the hypothesis were set forth with evidence provided in the present study. The hypotheses consisted of traditional Chinese syndrome PK (S-PK) and traditional Chinese recipe PK (R-PK). Firstly, the observed tetramethylpyrazine (TMP) PK in healthy, chronically reserpinized rats (rat model of spleen deficiency syndrome, RMSDS) and RMSDS treated with Sijunzi decoction (SJZD) for confirmation were used to verify S-PK; secondly, the ferulic acid (FA) PK in healthy and high molecular weight dextran (HMWD)-induced rabbit model with blood stasis syndrome (RDBSS) was also used to verify S-PK; and lastly, TMP PK parameters in serum of healthy rats after orally taken Ligusticum wallichii (LW), LW and Salvia miltiorrhiza (LW&SM) decoctions were compared to verify R-PK.RESULTS:The apparent first-order absorption Ka,(13.61 plus minus 2.56)h(-1) ,area under the blood drug concentration-time curve AUC, (24.88 plus minus 9.76)&mgr;gcenter doth(-1)mL(-1) , maximum drug concentration C(max), (4.82 plus minus 1.23)&mgr;gcenter dotmL(-1) of serum TMP in RMSDS were increased markedly(P< 0.05) compared with those Ka = (5.41 plus minus1.91)h(-1), AUC = (5.20 plus minus 2.57)&mgr;gcenter doth(-1)center dotmL(-1), C(max) = (2.33 plus minus 1.77)&mgr;gcenter dotmL(-1) of healthy rats (HR). The apparent first-order rate constant for alpha and beta distribution phase alpha = (0.38 plus minus 0.09)h(-1), beta = (0.06 plus minus 0.03)h(-1) , the apparent first-order intercompartmental transfer rate constants K10 = (0.24 plus minus 0.07)h(-1), K(12) = (0.11 plus minus 0.02)h(-1), K(21) = (0.11 plus minus 0.02)h(-1) of serum TMP in RMSDS were decreased significantly (P <0.01) compared with those K(10) = (0.88 plus minus 0.20)h(-1), K(12) = (1.45 plus minus 0.47)h(-1), K(21) = (0.72 plus minus 0.22)h(-1) of HR. However, no apparent differences occurred between HR and RMSDS treated with SJZD. The serum FA concentration and its AUC (5.6690 plus minus 2.3541)&mgr;gcenter doth(-1)center dotmL(-1) in RMBSS were also higher than those AUC =(2.7566 plus minus0.8232)&mgr;gcenter doth(-1)center dotmL(-1) of healthy rabbits (P <0.05). The Ka (11.51 plus minus 2.82)h(-1), AUC (0.84 plus minus0.17)&mgr;gcenter doth(-1)center dotmL(-1) of LW & SM-derived TMP in serum were much lower (P <0.05) than those Ka = (19.58 plus minus 4.14)h(-1),AUC = (1.27 plus minus 0.26)&mgr;gcenter doth(-1)center dotmL(-1) of LW-derived TMP in serum after oral decoctions.CONCLUSION:The SDS and blood stasis syndrome state could affect significantly the pharmacokinetic parameters of drugs and the abnormal SDS pharmacokinetic parameters could be normalized by SJZD. The combination of Chinese medicine in TCR could reciprocally affect the pharmacokinetic parameters of other components absorbed into the systemic circulation. These results support the S and R-PK hypothesis.     

Nitroxyl and its anion in aqueous solutions: spin states,protic equilibria,and reactivities toward oxygen and nitric oxide

The thermodynamic properties of aqueous nitroxyl (HNO) and its anion (NO(-)) have been revised to show that the ground state of NO(-) is triplet and that HNO in its singlet ground state has much lower acidity, pKa((1)HNO/(3)NO(-)) approximately 11.4, than previously believed. These conclusions are in accord with the observed large differences between (1)HNO and (3)NO(-) in their reactivities toward O(2) and NO. Laser flash photolysis was used to generate (1)HNO and (3)NO(-) by photochemical cleavage of trioxodinitrate (Angeli's anion). The spin-allowed addition of (3)O(2) to (3)NO(-) produced peroxynitrite with nearly diffusion-controlled rate (k = 2.7 x 10(9) M(-1) x s(-1)). In contrast, the spin-forbidden addition of (3)O(2) to (1)HNO was not detected (k < 3 x 10(5) M(-1) x s(-1)). Both (1)HNO and (3)NO(-) reacted sequentially with two NO to generate N(3)O as a long-lived intermediate; the rate laws of N(3)O formation were linear in concentrations of NO and (1)HNO (k = 5.8 x 10(6) M(-1) x s(-1)) or NO and (3)NO(-) (k = 2.3 x 10(9) M(-1) x s(-1)). Catalysis by the hydroxide ion was observed for the reactions of (1)HNO with both O(2) and NO. This effect is explicable by a spin-forbidden deprotonation by OH(-) (k = 4.9 x 10(4) M(-1) x s(-1)) of the relatively unreactive (1)HNO into the extremely reactive (3)NO(-). Dimerization of (1)HNO to produce N(2)O occurred much more slowly (k = 8 x 10(6) M(-1) x s(-1)) than previously suggested. The implications of these results for evaluating the biological roles of nitroxyl are discussed.