Conversion of Ouabain-Induced Ventricular Tachycardia in Dogs with Epicardial Lidocaine: Pharmacodynamics and Functional Effects

Epicardial antiarrhythmic drug administration was studied as a therapeutic approach for experimental ventricular tachycardia (VT) in an open-chest dog model. Lidocaine-polyurethane matrices (28%, w/w) were formulated as a model system. Matrices were placed on the left ventricular epicardium in each of 23 anesthetized open-chest dogs with ouabain-induced VT, to evaluate effectiveness in restoring sinus rhythm. Conversion occurred in all animals treated with matrices containing 300 mg or more of lidocaine after 1.5 to 7.0 min. The matrix lidocaine content correlated linearly with the time required for conversion to sinus rhythm (r = 0.75, P = 0.0002); irrespective of matrix size the myocardial/plasma lidocaine ratio was 20.1 ± 4.2 (mean ± SD) at the time of conversion. In a separate series of five dogs without ventricular tachycardia, systolic wall thickening measured with sonomicrometers after 5 min of controlled-release lidocaine administration (500- to 1000-mg matrix lidocaine content, 7.48 ± 3.49-mg/kg dose) was only minimally diminished (–14.1%) and this effect was observed only at the site of matrix placement on the anterior-apical epicardium. In contrast, intracoronary injection of 0.3 or 1.0 mg/kg of lidocaine-HCl resulted in complete elimination of wall thickening or replacement by systolic thinning. Thus epicardial administration of lidocaine from polyurethane matrices was an effective means of treating ouabain-induced ventricular tachycardia. Regional myocardial function in the vicinity of the matrices was modified to a very limited degree, supporting the view that the matrices can be used safely, without serious risk to ventricular contractile performance.     

RELAXATION OF MESENTERIC ARTERY OF STROKE PRONE SPONTANEOUSLY HYPERTENSIVE RATS BY CALCIUM REMOVAL

1. The time courses of the relaxation, induced by removal of extracellular Ca2+, of K-depolarized mesenteric artery preparations from stroke prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) were compared. 2. The time course of the decline in extracellular Ca2+ was estimated from the time course of the relaxation and the concentration-response curve of K(+)-depolarized preparations to Ca2+. The time course of the decline in the intracellular free Ca2+ concentration was also estimated from the reported relation between Ca2+ concentration and the contraction of skinned vascular smooth muscle. 3. The time course of relaxation was exponential, the curve being made up of three components. The time course was slower in preparations from SHRSP, especially the first component of the relaxation curve. 4. The time courses of the decline in the intracellular and extracellular Ca2+ concentrations were also exponential, being made up of three components and were also slower in the preparation made from SHRSP. 5. The wall and muscle layer of the mesenteric arteries used in the present experiments were significantly thicker in the SHRSP preparations. 6. Calculation of the half relaxation time, based on the diffusion of Ca2+ across the blood vessel wall, suggested that the slower relaxation in preparations from SHRSP is due largely to the thicker muscle layer, although differences in Ca2+ sequestration by the smooth muscle cells may also be involved.     

第Ⅲ段肝管空肠吻合解除肝门部胆管恶性梗阻

肝门部胆管恶性梗阻的治疗仍然十分困难。若不解除胆道梗阻,病人很快因肝细胞功能衰竭而死亡。由于肿瘤在肝门部侵润性生长,直接经肝门的手术往往不可能实现。1980～1993年间,我们采用第Ⅲ段肝管空肠吻合术姑息治疗28例肝门部胆管恶性梗阻的黄疸病人。24例为肝门部胆管癌,2例为胆囊癌,2例为胃癌肝门部淋巴结转移。术后19例病人恢复顺利;5例发生并发症,4例病人手术后死亡。24例存活病人中,19例黄疸完全消退3月以上,手术有效率为79％。4例黄疸再次出现,2例因胆管炎需要入院治疗。作者认为:第Ⅲ段肝管空肠吻合术能有效解除不能切除的肝门部恶性肿瘤病人的胆道梗阻。     

安体维康诱导肝细胞凋亡实验研究及临床观察

目的 :评价中药制剂安体维康 ( Antivirus Compound,ATVC)诱导人肝癌细胞凋亡的作用及临床疗效。方法 :采用 MTT(细胞毒 )实验培养人肝癌细胞株 BEL - 740 2细胞 ,加入不同浓度安体维康药液进行培养与对照组进行比较。临床给原发性肝癌 1 0例服用安体维康胶囊 3个月。结果 :安体维康能抑制人肝癌细胞株 BEL- 740 2细胞生长 ,有诱导肝细胞凋亡的作用。其作用强弱在一定程度上存在剂量和时间效应。服用安体维康的肝癌患者临床症状明显改善。结论 :安体维康可诱导人肝癌细胞调亡 ,对原发性肝癌有一定临床疗效     

复合带瓣人工血管替换升主动脉和主动脉瓣(24例报告)

报告２４例升主动脉瘤伴主动脉瓣关闭不全行升主动脉和主动脉瓣替换及冠状动脉开口移植术（Ｂｅｎｔａｌ术２２例，底盘法２例）。１３例伴有升主动脉夹层分离，对其中８例ＤｅＢａｋｅｙＩ型者，以Ｔｅｆｌｏｎ毡条内外加固主动脉切端后吻合。１３例用人工血管周围间隙与右心耳吻合以控制升主动脉吻合之外的出血。３例以人工血管片环包主动脉吻合口控制局部广泛渗血及出血。２例术毕不能脱离体外循环死亡，手术死亡率８３％。随访平均２１８个月，２例死于蛛网膜下腔出血，１例右股动脉栓塞经手术治愈；其余病人康复良好，心功能（ＮＹＨＡ）Ｉ～ＩＩ级。     

小血管套叠粘接吻合法在血液透析者中建立动静脉内瘘的应用

慢性肾病患者常需要建立动静脉内瘘进行透析，常规间断缝合法吻合动静脉难度大、耗时长。为了缩短吻合时间，提高远期通畅率，进行了套叠粘接吻合法建立动静脉内瘘的实验研究，并将这一方法应用于透析患者建立动静脉内瘘的血管吻合。将动脉端套入静脉端，只需吻合两针，用医用胶封闭吻合口。经８个月观察，通畅率达１００％，血流量均超过３００ｍｌ／ｍｉｎ。达到了透析需要。     

The influx of Ca and the release of noradrenaline evoked by the stimulation of presynaptic nicotinic receptors of chick sympathetic neurons in culture are not mediated via L-, N-, or P-type calcium channels

We have shown earlier that nicotinic agonists induce the release of noradrenaline from chick sympathetic neurons in culture in two ways: (a) by activating the postsynaptic nicotinic receptors on nerve cell bodies, giving rise to spreading electrical activity and opening of voltage operated calcium channels in neuronal processes; (b) by activating the presynaptic nicotinic receptors on neuronal processes. In the present work, we investigated the contribution of various pathways to the observed Ca²⁺ influx and subsequent noradrenaline release. Sympathetic neurons in culture were stimulated either by the nicotinic agonist dimethylphenylpiperazinium or electrically, in the presence or absence of tetrodotoxin and of specific blockers of calcium or nicotinic channels, and the effects on [Ca²⁺]_i in the area of neuronal processes and on noradrenaline release were measured. Under control conditions, the N-type channel blocker ω-conotoxin (0.1 μmol/1) diminished the release of noradrenaline and the increase of intraterminal Ca²⁺ by 48% and 55%, respectively, whereas the L-type channel blocker (+)Bay k 8644 (1 μmol/1) diminished the release of noradrenaline by 25% and the increase of [Ca²⁺]_i by 39%. The P-type channel blocker ω-agatoxin (0.3 μmol/1) had no effect. The effects of the L-type channel ligands were complex and could only be explained on the assumption that, at high concentrations, these drugs also act as nicotinic antagonists. Tetrodotoxin blocked the Ca²⁺ response evoked by electrical stimulation whereas DMPP applied in the presence of tetrodotoxin still evoked an increase of [Ca²⁺]_i and the release of noradrenaline (27% and 30% of control without tetrodotoxin, respectively). These residual responses were not blocked by any of the calcium channel blockers used or by their combination. Apparently, a substantial part of the influx of Ca²⁺ induced by the activation of presynaptic nicotinic receptors is not carried by the N-, L- or P-type channels and probably occurs directly via the open channels of nicotinic receptors.     

AUGMENTATION OF ANGIOTENSIN II RELEASE FROM ISOLATED MESENTERIC ARTERIES OF WISTAR-KYOTO AND SPONTANEOUSLY HYPERTENSIVE RATS FOLLOWING NEPHRECTOMY

1. We previously reported that angiotensin II release from the mesenteric arteries of Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) increased in a time-dependent manner as a result of the isolation of the arteries and perfusion. This phenomenon appeared to be due to the withdrawal of circulating angiotensin II (AII). 2. The purpose of the present study was to test the hypothesis that vascular AII generation may be negatively regulated by circulating AII in WKY and SHR, and to clarify the role of this vascular angiotensin II in the sustained hypertension of SHR following nephrectomy. 3. The mesenteric arteries from kidney-intact and nephrectomized WKY and SHR were perfused and the amount of AII released into the perfusate was measured. The effects of the angiotensin converting enzyme inhibitor, captopril, and the effects of supplementation of renal renin and circulating angiotensins to nephrectomized rats, by blood exchange between kidney-intact and nephrectomized rats, on AII release were examined to clarify the pathway of vascular AII generation after nephrectomy. 4. Nephrectomy caused augmentation of vascular AII release both in WKY and SHR in spite of the abolishment of circulating renin. Captopril reduced this enhanced release of AII, but blood exchange did not affect it. There was no significant difference in these responses between WKY and SHR. 5. These results suggest that WKY and SHR have in common a potent pathway for production of vascular AII in response to the withdrawal of circulating AII, although this pathway is not responsible for the sustained hypertension of SHR after nephrectomy. The precise pathophysiological role of this pathway remains to be elucidated.     

VASOCONSTRICTOR RESPONSES TO COMPONENTS OF THE RENIN-ANGIOTENSIN SYSTEM IN CYCLOSPORIN-INDUCED HYPERTENSION IN THE RAT

1. Since plasma renin activity is increased in cyclosporin A (CsA)-induced hypertension in the rat, the role of the vascular renin-angiotensin system (RAS) in CsA-induced hypertension was investigated in rat mesenteric resistance vessels. 2. Female Wistar rats received CsA (10 mg/kg per day, s.c.) or vehicle for 30 days. CsA treatment increased tail-cuff systolic blood pressure (CsA treated 135 ± 3 mmHg vs control 125 ± 1 mmHg, P<0.0001). 3. Mesenteric resistance arteries (200–300 μm) were isolated and mounted in a microvessel myograph. Concentration-response curves to tetradecapeptide renin substrate (10-¹¹-10^?6 mol/L), angiotensin I (10-^l1-10^?6 mol/L) and angiotensin II (10-¹²-10^?6 mol/L) showed no differences between CsA-treated and control groups. 4. Mesenteric vascular angiotensin-converting enzyme (ACE) characteristics were determined by radioligand binding. There were no differences in the content or affinity of ACE between CsA-treated and control rats. 5. These results suggest that the mesenteric vascular RAS does not play a major role in CsA-induced hypertension in the rat.