Reduced nitric oxide formation causes coronary vasoconstriction and impaired dilator responses to endogenous agonists and hypoxia in dogs

We investigated the relative contribution of basal and agonist stimulated EDRF/NO release to the adjustment of coronary tone and myocardial perfusion in conscious dogs by inhibiting coronary endothelial NO formation with N^G-nitro-l-arginine methyl ester (l-NAME). Chronically instrumented conscious dogs (n = 9) were prepared for measurement of mean arterial blood pressure (MAP), heart rate (HR), coronary blood flow (CF) and diameter of the left circumflex (CD_LC) and left anterior descending (CD_LAD) coronary artery, respectively. Intracoronary infusions of l-NAME (30.3 mM; 0.25 ml × min^–1) caused significant increases in MAP and decreases in HR. CD_LC decreased by 3.8% from 3.01 ± 0.04 to 2.90±0.04 mm and CF decreases by 30% from 12.9 ± 0.2 to 9.1 ± 0.2 (aU). Peak reactive hyperemia (CF_max) evoked by 20-s-lasting occlusions of the left circumflex coronary artery decreased from 29.9 ± 0.8 to 25.8 ± 1.0 aU and maximal flow-dependent coronary dilation were reduced from 2.04 ± 0.08 to 0.91±0.12% after inhibition of NO-synthesis. Intracoronary infusions of acetylcholine (ACh), Adenosinc (Ado), bradykinin (Bk), and papaverine (Pap) caused dose-dependent increases in CD_LC and CE Infusion of l-NAME nearly abolished the dilator effect of Ado on CD_LC and reduced those to ACh, Bk and Pap. Increases in CF to ACh, Ado and Bk but not to Pap were reduced by l-NAME. Subsequent intracoronary infusions of l-arginine (303 mM; 0.25 ml × min^–1) reduced l-NAME-induced CF-changes partly, but did not reverse coronary constriction. These results suggest that inhibition of the continuous release of nitric oxide markedly reduces myocardial perfusion in vivo. Endogenous dilator mechanisms are likewise impaired. Thus, in the heart, nitric oxide deficiency probably cannot be fully compensated for by counter-regulating mechanisms. Correspondence to: E. Bassenge at the above address     

高+Gz负荷下犬心血管系统反应特性

目的探讨犬＋Ｇｚ负荷中、负荷后心电图、动脉血压反应特性。方法将压力传感器导管置于６只麻醉犬的升主动脉和髂总动脉,以测量犬暴露于＋１Ｇｚ、＋３Ｇｚ、＋５Ｇｚ、＋７Ｇｚ的血压,并采用Ａ导联持续监测心电图。结果（１）Ｐ波高度受＋Ｇｚ负荷的影响,负荷前、后１ｍｉｎ内差异显著（＋Ｇｚ负荷前Ｐ波２．３±０．２ｍＶ,＋３Ｇｚ后４．５±０．５ｍＶ,＋５Ｇｚ后４．８±０．３ｍＶ,＋７Ｇｚ后５．３±０．７ｍＶＰ＜０．０５）。（２）高＋Ｇｚ负荷时,髂总动脉血压表现为平均动脉压增高,脉压减低。（３）＋Ｇｚ终止后,升主动脉血压（ＡＰ）出现一过性增高（＋７Ｇｚ前ＡＰ１７．２９±５．５９／１１．３１±３．８６ｋＰａ,＋７Ｇｚ后第３０ｓ２７．５３±６．１２／２０．６２±１．８６ｋＰａ,Ｐ＜０．０１）。结论Ｐ波高度的变化反映心房移位,这可能是心律失常的原因。在高＋Ｇｚ负荷条件下,心血管功能不全,组织灌注压是一个重要的生理参数。＋Ｇｚ负荷终止后即刻,动脉血压极度增高,为血管性衰竭的表现     

微波消融犬室性心动过速的实验研究

观察微波消融犬室性心动过速（简称室速）疗效和微波消融对血液动力学的影响。健康犬４０只,随机分成５组,Ⅰ组（对照组,ｎ＝８）,Ⅱ、Ⅲ、Ⅳ和Ⅴ组（消融组,ｎ＝８）,由股动脉、股静脉穿刺进行血液动力学监测。用０．０１ｍｌ０．０３％乌头碱注入心室壁诱发室性心动过速。消融释放功率和时间Ⅱ组为４０Ｗ×３０ｓ,Ⅲ组为４０Ｗ×６０ｓ,Ⅳ组为８０Ｗ×３０ｓ,Ⅴ组为８０Ｗ×６０ｓ。结果：自发放微波能量至室速终止时间Ⅱ、Ⅲ组为（１０．１±２．４）ｓ,与对照组比,Ｐ＜０．００１;Ⅳ、Ⅴ组为（５．３±１．５）ｓ,与对照组比,Ｐ＜０．００１。消融前后血液动力学各项指标差异无统计学意义（Ｐ＞０．０５）,消融后组间血液动力学各项指标差异无统计学意义（Ｐ＞０．０５）。微波产生的心肌损伤,显微镜下观察均为凝固性坏死,与周围组织存在清晰的界限。结论：微波消融室速具有较好的疗效,消融能量与时间在一定范围内对血液动力学无明显影响,可望成为室速治疗的１种新方法。     

Lidocaine has a narrow antiarrhythmic dose range against ventricular arrhythmias induced by programmed electrical stimulation in conscious postinfarction dogs

Summary The aim of the present study was to investigate the dose-dependent antiarrhythmic efficacy of lidocaine against electrically induced tachycardias in conscious, chronically instrumented postinfarction dogs. Programmed electrical stimulation (PES) was performed in 16 dogs 8 to 21 days after a 4 h occlusion of the left anterior descending coronary artery (LAD). Infusion of saline in 8 control animals with sustained ventricular tachycardia (SVT) inducible at baseline did not affect subsequent inducibility. In the treatment group 7 of 8 animals responded with SVT and one exhibited ventricular fibrillation at baseline. After an initial bolus of 1 mg/kg lidocaine intravenously (i.v.), the drug was infused at infusion rates of 40, 80 and 120 g/kg/min (i.v.). During 80 g/kg/min lidocaine (mean plasma level 3.5 g/ml) 7 out of 8 animals displayed an antiarrhythmic response; both the lower and the higher infusion rate were associated with a smaller antiarrhythmic efficacy (3 of 8 animals responded to 40 g/kg/min and 4 of 8 to 120 g/kg/min). Licocaine did not affect ventricular refractory periods, but induced an increase in intraventricular conduction time at all infusion rates, from 66.2 ms at baseline to 67.7 ms (p<0.05), 67.7 ms (p<0.05), 70.0 ms (p<0.01) respectively.In conclusion the present study demonstrates that lidocaine is of considerable value in the management of PES-induced ventricular arrhythmias in the postinfarction phase. However there is only a small optimal therapeutic plasma level range, where lidocaine exhibits its antiarrhythmic efficacy against this type of arrhythmia; this makes a carefully titration of the drug necessary both in the experimental and in the clinical setting. Send offprint requests to K. Krejcy at the above address     

Effects of antihistamines,ebastine and terfenadine,on electrocardiogram in conscious dogs and cats

The purpose of this study was to evaluate the effects of ebastine and terfenadine on the electrocardiogram of conscious dogs and cats. In dogs, terfenadine at oral doses of 30 mg/kg twice a day for 7 days prolonged the electrocardiographic QT interval and the corrected QT (QTc) interval on the seventh day, whereas the drug did not affect these parameters on the first day. Plasma concentrations of terfenadine and its active metabolite, fexofenadine, reached 306 and 8,541 ng/mL, respectively, on the seventh day. Ebastine at oral doses of 30 and 100 mg/kg once a day for 7 days was without effect on the QT and QTc intervals, whereas the drug slightly shortened the RR interval. On the seventh day following the dose of 100 mg/kg, plasma concentrations of ebastine and its active metabolite, carebastine, reached 36 and 1,939 ng/mL, respectively. In conscious cats, terfenadine at oral doses of 30 mg/kg twice a day for 7 days prolonged the QT and QTc intervals, QRS duration, JT and the corrected JT intervals. Unexpectedly, terfenadine induced ventricular tachyarrhythmia and premature beats. On the other hand, ebastine at oral doses of 100 mg/kg once a day for 7 days was without effect on the electrocardiographic parameters in cats. These results suggest that the electrocardiographic changes indicative of the proarrhythmic potential of terfenadine can be evaluated in conscious dogs and especially in conscious cats by repeated oral administration, and that ebastine does not induce such changes. 58:209–217, 2003. © 2003 Wiley‐Liss, Inc.     

顺铂缓释剂局部植入药代动力学的实验研究

目的　研究局部植入顺铂缓释剂 (DDPSRP)在大鼠和狗体内的药代动力学。方法　用原子吸收分光光度法 (灯电流 12 5mA ,波长 2 6 5 9nm)测定血浆顺铂 (DDP)的浓度。结果　大鼠皮下植入DDPSRP后 ,DDP可持续缓慢释放 ;狗静脉注射DDP 4mg·kg-1,其时间 -浓度曲线呈二室模型 ;狗肌肉植入 2mg·kg-1DDPSRP后 ,其有效血浆浓度 -时间曲线呈一室模型特点 ,但其维持有效血浆浓度时间 (0 1mg·L-1)长达 16 8～ 2 6 4h。结论　DDPSRP有显著的缓释作用     

上海市2001~2005年狂犬病流行病学特征分析

[目的]分析2001~2005年上海市狂犬病流行病学特征和评价预防、控制策略。[方法]开展病例流行病学调查和间接荧光法测狂犬病毒IgG。[结果]2001~2005年上海市人狂犬病发病仍处于较低水平,共发生内源性病例3例,较前5年(1996~2000年)总计8例下降62.5%,发生外源性病例6例。2001~2005年报告的9例狂犬病病例平均潜伏期84.7 d,平均病程3.6 d,其中88.9%未经任何医疗预防处理。288例可疑犬咬伤者经及时全程医疗预防处理后,均未发病。[结论]严格的犬类管理、及时伤口处理、狂犬病疫苗和抗狂犬病血清注射可以预防狂犬病和降低发病率。     

本地实验犬淋巴细胞染色体核型分析

目的通过犬的染色体核型分析,为诊断犬染色体病以及进行犬的分子细胞学研究奠定了基础。方法采集13条正常本地犬(6条雌性、7条雄性)外周血进行淋巴细胞培养,经秋水仙素处理后制备常规及G带染色体标本并进行核型分析。结果本地犬的染色体形态结构表现出很好的一致性,其染色体数为2n=78,雌性染色体核型为78,XX,雄性染色体核型为78,XY。39对染色体中有38对常染色体均为端着丝粒染色体,长度逐渐递减;1对性染色体为中央着丝粒,X染色体最大并与人X染色体形态极其相似,Y染色体最小。结论染色体G带核型分析发现,可以明确鉴别犬第1～21号常染色体和性染色体,但很难可靠地鉴别其余的17对常染色体。     

大鼠胰腺炎相关性急性肺损伤模型的探讨

目的研究重组纳豆激酶(recombinant nattokinase,r-NK)大剂量重复给药对Beagle犬和小型猪凝血和纤溶系统的不同影响。方法用血球计数仪测定血小板相关参数;用血凝仪采取凝固法依次测定纤维蛋白原(Fib)含量、活化部分凝血酶时间(APTT)、凝血酶原时间(PT)、凝血酶时间 (TT);以ELISA法分别测定纤溶酶原(PLG)、纤溶酶原激活因子(t-PA)活性。结果药物对Beagle 犬和小型猪有相似的血管刺激作用。给药1周后Beagle犬血小板计数下降,PT明显延长,Fib含量明显降低,PLG活性升高。而药物对小型猪的各项参数均无明显影响。结论不同动物对相同剂量r-NK毒性反应存在较大的差异性,r-NK大剂量重复给药可破坏Beagle犬的凝血/纤溶系统平衡,而不影响小型猪凝血/纤溶系统功能。     

采用骨内型牵张器建立垂直向牙槽骨牵张成骨动物模型

【目的】应用自行研制的骨内型牙槽骨牵张器,建立犬垂直向牙槽骨牵张成骨动物模型。【方法】实验动物为中山大学动物中心提供的健康成年杂种犬12只。实验材料为自行设计,纯钛制成的骨内型垂直向牙槽骨牵张器,体部直径3.75mm,长5mm。先拔除犬双侧下颌前磨牙,形成萎缩牙槽嵴的模型。3月后随机选取一侧行骨切开术,植入两枚牵张器。1周后开始牵张,每天1次,每次1mm,共5d;分别在牵张后1、2和3月将动物处死进行临床检查,X线检查和组织学检查。【结果】骨内型垂直牙槽骨牵张器愈合良好。牙槽骨高度平均增加(4.8±0.50)mm。组织学切片显示在牵张区有骨质形成,其骨小梁方向与牵引方向一致。【结论】采用该骨内型牙槽骨牵张器成功建立稳定的、重复性好的犬牙槽骨牵张成骨动物模型,为牙槽骨牵张器的国产化和临床上应用该项技术打下基础。