罂粟碱对大鼠单胺神经递质的影响

本文报道用高效液相色谱-电化学检测器方法,研究了罂粟碱对大鼠脑内及心脏单胺神经递质代谢的影响。结果表明:罂粟碱能显著增加大鼠纹状体及边缘区多巴胺代谢物二羟苯乙酸(DOPAC)和高香草酸(HVA),升高约50-70%。5-羟色胺代谢物5-羟吲哚醋酸(5HIAA)增加约30%,而对脑及心脏内的单胺递质本身含量未见有明显影响。     

不同血管保存液对人桡动脉血管移植物的抗痉挛作用

目的 研究不同的血管保存液对人离体桡动脉痉挛的缓解与预防能力。方法 非体外循环冠状动脉旁路手术(OPCAB)19例患者,应用“无接触(No Touch)”外科技术获取自体桡动脉,保留未处理的远段0.8～1.5cm。应用血管环灌流技术(Organ Bath)比较不同保存液的抗痉挛作用和预防痉挛作用。结果 血管环灌流实验显示,在对痉挛状态桡动脉的舒张能力方面,PS、VG、DG、NG溶液均可以在10min内100％舒张血管,舒张曲线显示舒张能力依次为VG、DG、NG、PS,但差异无显著性(P>0.05),在预先浸泡处理桡动脉45～60min后,除对照组(Ringer's Solution)外,所有血管保存液均可以有效地预防离体桡动脉的痉挛,各组间差异无显著性(P>0.05)。结论 罂粟碱溶液、VG、DG、NG溶液均有较好的抗血管痉挛作用,单从抗血管痉挛角度考虑可以用作CABG手术中桡动脉的准备液。     

Changes in cyclic nucleotides during the calcium paradox in the isolated rat heart

Reperfusion of hearts with a Ca²⁺-containing medium after a perfusion period in Ca²⁺-free medium results in irreversible cell damage (calcium paradox). In this investigation we have studied coronary flow and cyclic AMP and cyclic GMP levels after several periods of Ca²⁺-free perfusion in isolated rat hearts. We also investigated the effects of papaverine (Pap), noradrenaline (NA), acetylcholine (ACh) and absence of inorganic phosphate during Ca²⁺-free perfusion on coronary flow (CF) and cyclic nucleotide levels. Inability of the heart to recover contractile activity with development of contracture during the reperfusion period was accepted as indicative of the calcium paradox. Ca²⁺-free perfusion alone and NA and absence of inorganic phosphate during the Ca²⁺-free perfusion period increased CF, whereas Pap and ACh decreased it. However, only Ca²⁺-free perfusion and NA elevated cyclic AMP. On the other hand, Pap and ACh increased cyclic GMP (with a transient rise of cyclic AMP in Pap infusion), and absence of inorganic phosphate decreased both cyclic AMP and cyclic GMP. Pap, ACh and absence of phosphate prevented the calcium paradox. Our study suggests that increased cyclic AMP during the Ca²⁺-free perfusion may contribute, with the other factors, to the occurrence of the calcium paradox.     

Role of Ca channel in the renal autoregulatory vascular response analysed by the use of BAY K 8644

Summary The role of Ca channel and extracellular Ca²⁺ on autoregulation of renal blood flow was investigated in the perfused kidney of the anesthetized dog. The perfusion pressure was changed in the range between 60 and 200 mm Hg. Intra-arterial infusion of nifedipine (5 g/min) increased renal blood flow at a perfusion pressure above 100 mm Hg and inhibited autoregulation. Simultaneous infusion of 5 g/min of BAY K 8644 antagonized the effect of nifedipine. Renal blood flow was increased and autoregulatory relationship between flow and perfusion pressure was inhibited by EDTA (30 mg/min) infusion. The inhibitory effect of EDTA on renal autoregulation was counteracted by simultaneous infusion of CaCl₂ at 30 mg/min, but not counteracted by that of BAY K 8644 (5 g/min). BAY K 8644 also could not antagonize the inhibitory effect of a vasodilator, papaverine (5 mg/min) on renal blood flow autoregulation. These results provide the evidence that the renal autoregulation involves the process of Ca²⁺ influx into the vascular smooth muscle cell through the Ca channels. Send offprint requests to N. Ogawa at the above address     

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     

ST elevation after intracoronary administration of Papaverine for fractional flow reserve estimation

Introduction

Intracoronary (IC) papaverine which is one of the commonly used agents for Fractional Flow Reserve (FFR) estimation has been reported to cause transient ST elevation in some patients. This phenomenon has not been systematically studied.

Material and methods

This is a prospective, observational study. Consecutive patients, who underwent FFR at our institute using IC papaverine from May 2012 to April 2013, were included. FFR was done when clinically indicated. The procedure involved administration of 20 mg papaverine (Paparin^® – Troikaa, Ahmedabad) as a fast bolus by intracoronary route followed by a 10 cc contrast flush, following which pressure measurements were made. Continuous ECG recording by Philips Hemodynamic Laboratory was obtained for all patients throughout the procedure. Post procedure, they were observed for any delayed effects and eventual outcome was documented. Fischer''s mid-p test was used for statistical analysis.

Result

Twenty-five patients (18 males, 7 females, mean age 57.9 ± 20 years) underwent FFR using Papaverine. The mean LVEF was (51 ± 15%). Fourteen patients (56%) developed transient ST elevation ≥0.5 mm in one or more leads which resolved spontaneously in all cases without any sequelae. The presence of a significant lesion either in the coronary artery being evaluated or in a remote coronary artery did not predict the ST elevation. 70.5% of diabetics (p = 0.02), 75% of hypertensives (p = 0.008) and 75% of patients with LVH (p = 0.008) had ST elevation. None of the 5 patients without any one of these comorbidities showed ST elevation.

Conclusion

Transient ST elevation occurs in a significant proportion of cases receiving IC papaverine which is not associated with any adverse clinical outcomes. Micro vascular dysfunction is the most likely mechanism of this phenomenon.     

气相色谱法测定强力枇杷露中薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱的含量

目的：建立气相色谱法同时测定强力枇杷露中薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱四种成分含量的方法。方法：试样用乙酸乙酯振摇提取,色谱柱为100%二甲基聚硅氧烷固定液的毛细管柱,柱温从100℃程序升温至270℃,保持20 min,检测器为 FID。结果：薄荷脑、磷酸可待因、吗啡、盐酸罂粟碱在各自测定范围内有良好线性关系,各成分平均回收率（n=6）在96.76%~113.34%,RSD<6.0%。结论：本方法准确可靠,重现性好,可有效地控制强力枇杷露的质量。     

Effect of intraurethral papaverine on penile erection in rats

OBJECTIVES: The aim of this study is to investigate erectile response to intraurethral administration of papaverine in rats. MATERIAL AND METHODS: Male Sprague-Dawley rats were used in this study. Under urethane anesthesia, penis was exposed and intracavernous pressure (ICP) was recorded through a 23-gauge needle, which was inserted into right corpus cavernosum. Effects of intraurethral application of incremental doses of 0.2 ml papaverine gel (4-17.5 mg) on intracavernosal pressure were observed and compared with those of 0.4 mg papaverine applied into corpus cavernosum. Mean arterial blood pressure (MABP) and heart rate were also monitored. RESULTS: The mean basal ICP was 8.9 +/- 1.8 mm Hg. Intraurethral administration of papaverine did not increase ICP at any doses used in this study. After intracavernous injection of papaverine (0.4 mg), a significant increase in the ICP occurred from resting (8.9 +/- 1.8 mm Hg) to a peak at 57.5 +/- 9.9 mm Hg and persisted for 22.3 +/- 6.7 minutes (p < 0.05). The latter application significantly decreased MABP (22.3 +/- 3.1 mm Hg; p < 0.05). CONCLUSIONS: Intraurethral administration of papaverine does not seem to be an alternative to other erectile dysfunction treatment modalities. However, further studies on animals are necessary at higher concentrations or in combination with other mucosal enhancers to increase the effect of intraurethral administration of papaverine.     

The influence of periarterial papaverine application on intraoperative renal function and blood flow during laparoscopic donor nephrectomy in a pig model

Background: The transplantation of live donor kidneys harvested laparoscopically is associated with a higher incidence of delayed graft function than the transplantation of grafts harvested via the open technique. The delay is believed to be due to a decrease in renal blood flow during laparoscopic donor nephrectomy (LDN). The aim of this study was to evaluate whether renal function and blood perfusion can be enhanced by the periarterial application of papaverine during LDN. Methods: Renal function and blood flow were studied in a porcine model that included a total of 24 pigs (20–30 kg). In 12 of the pigs, urine output and creatinine clearance were determined as measures of renal function. In the other 12 pigs, renal blood flow was determined using fluorescent-labeled microspheres. In each group, the pigs were randomized into two subgroups, one with and one without a perivascular injection of 50 mg papaverine. Results: As compared to the controls, the animals receiving papaverine had a significantly higher urine output (3.1 ± 1.6 vs 0.9 ± 0.45 ml/h/kg; p = 0.02), superior creatinine clearance (2.22 ± 0.5 vs 0.95 ± 0.1 ml/min/kg; p = 0.038), and enhanced renal blood flow (4.9 ± 2.2 vs 2.1 ± 0.8 ml/min/g; p = 0.008). Conclusions: When applied to the tissue surrounding the renal artery, papaverine substantially improves renal function and blood flow during laparoscopic live kidney donation. Whether graft optimization during kidney procurement also translates into improved posttransplantation function remains to be established. Presented at the 8th World Congress of Endoscopic Surgery, Society of American Gastrointestinal Endoscopic Surgeons (SAGES) meeting, New York, NY, USA, 13–16 March     

阴茎海绵体内血管活性剂注射治疗阳萎1354例报告

自1986年4至1989年12月,1354例阳萎病人采用阴茎海绵体内注射摄入罂粟碱和酚妥拉明。1219例(90.03％)治疗有效,注射后阴茎迅速与暂时地勃起,阴茎长度增加5.12～5.24厘米,周径增加2.28～2.63厘米,阴茎变硬,并有平均73～74.5°的勃起角度,平均勃起时间2.5小时。与性刺激同步下足以完成性交需要。失败率9.97％。14例病人(1.03％)发现阴茎持续勃起。随访观察,仅4例病人有局部血肿和1例病人轻度硬结。25例病人能自我注射。注射技术上的改良给予讨论。这项结果提示,血管活性药物阴茎海绵体内注射是一种安全有效的方法,能用于治疗阳萎。