垂体后叶素和硝酸甘油联合治疗食管静脉曲张破裂大出血

３０例肝硬化食管静脉曲张破裂大出血患者，用垂体后叶素０．２～０．４Ｕ／ｍｉｎ连续静脉滴注和硝酸甘油含服联合治疗。结果表明，近期止血有效申达８０％，死亡率１０％；无一例出现严重心绞痛和心电图异常。     

Absence of relaxation to lactate in human placental vessels of pregnancies with severe preeclampsia

OBJECTIVE: Our objective was to determine whether the observed relaxation to lactate and other agents in placental vessels of normal pregnancies is altered in severe preeclampsia.STUDY DESIGN: Isolated placental arteries and veins from women with severe preeclampsia and uncomplicated term pregnancies were precontracted with prostaglandin F_2α under 5% oxygen and 5% carbon dioxide with the balance nitrogen (Po₂ 35 to 38 torr) and then exposed to lactate (1 to 10 mmol/L, pH 7.4, n = 8 to 15), arachidonic acid (0.01 to 10 μmol/L, n = 6 to 13), nitroglycerin (1 nmol to 1 μmol/L, n = 4 to 12), or forskolin (0.01 to 10 μmol/L, n = 6 to 9). The response to lactate was also examined in placental vessels from appropriate-for-gestational-age preterm deliveries (n = 8) for comparison with a similar group with severe preeclampsia (n = 8). The t test and analysis of variance statistics were used.RESULTS: Relaxation to lactate was markedly inhibited in both placental arteries and veins of women with severe preeclampsia compared with vessels from uncomplicated term or preterm pregnancies. Responses to the other relaxing agents were not altered in the severely preeclampsia vessels.CONCLUSIONS: In severe preeclampsia absence of lactate-induced dilatation of placental vessels may contribute to the fetal complications associated with impaired blood flow and vasospasm.     

硝酸甘油、米力农和尼卡地平缓解桡动脉痉挛作用的比较

目的：比较硝酸甘油、米力农和尼卡地平3种药物对桡动脉的解痉作用。方法：收集手术后多余的人体桡动脉标本，采用器官浴槽方法，比较上述3种药物对预收缩的离体桡动脉的解痉作用。结果：米力农和硝酸甘油对预收缩的桡动脉的舒张作用明显强于尼卡地平；米力农和硝酸甘油的疗效相似。结论：米力农和硝酸甘油更适用于缓解冠状动脉旁路移植术中桡动脉的痉挛。     

Effects of sodium nitroprusside (MR7S1) and nitroglycerin on the systemic,renal, cerebral,and coronary circulation of dogs anesthetized with enflurane

Summary In beagle dogs anesthetized with enfluranenitrous oxide, effects of sodium nitroprusside (SNP; MR7S1) and nitroglycerin (NTG) on hemodynamics and main organ circulation were studied to evaluate their effectiveness and safety as hypotensive agents during anesthesia. SNP (MR7S1) infusion (1–10 g/kg/min) decreased arterial blood pressure in a dose-dependent manner. The hypotension was stable during the infusion. After discontinuation of infusion, the blood pressure rapidly returned to the initial level. The hypotension was associated with decreases in cardiac output and total peripheral resistance. NTG infusion (3–10 g/kg/min) decreased arterial blood pressure, too, but the hypotension was less marked and not dose dependent, and the recovery was slower. Neither drug changed the heart rate. Infusion of SNP (MR7S1) and NTG did not change the hypotension induced by the injection of adenosine, SNP, and NTG. Furthermore, cerebral blood flow, cerebral oxygen consumption, and renal blood flow were unchanged during the hypotension produced by either drug. Coronary blood flow was decreased, but this was due to decreases in cardiac oxygen consumption. In conclusion, SNP (MR7S1) is superior to NTG as a hypotensive agent during anesthesia in efficacy, clear dose dependency, and rapid recovery. The hypotension induced by NTG as well as SNP (MR7S1) seems to have no undesirable effects on the circulation of important organs.     

Role of Relative Changes in Caval Flows for Evaluation of Right Atrial Pressure Shifts Induced by Nitroglycerin

Experiments on cats treated with nitroglycerin showed dynamic relationship between changes in caval venous flows: blood flow increased in the superior vena cava and decreased in the inferior vena cava. Blood pressure in the right atrium either decreased, or increased. No significant changes in total venous return were observed during maximum shifts in right atrial pressure, while contractility of the right ventricular myocardium usually decreased. Our findings suggest that the direction of the right atrial pressure shifts induced by nitroglycerin does not depend on venous return, but is determined by the prevalence of flow changes in the superior vena cava or inferior vena cava.     

硝酸甘油、地塞米松对哮喘肺泡巨噬细胞源性一氧化氮、内皮素的影响

研究哮喘患者肺泡巨噬细胞 (AM)源性一氧化氮 (NO)、内皮素 (ET)的变化及硝酸甘油 (NTG)、地塞米松(DXM)对两者的影响及机制。对 15例轻、中度过敏性支气管哮喘发作期患者的AM(分为未干预组、DXM干预组、NTG干预组 ) ,7名健康自愿受试者的AM(未干预组 )培养 48h ,用镀铜镉还原法、放射免疫法和原位杂交法分别测定AM培养上清液中NO ,ET水平和iNOS mRNA ,ET mRNA的表达。结果发现 ,哮喘AMiNOS mRNA ,ET mRNA表达增强 ,分别导致NO ,ET水平升高 ;NTG以直接作用的方式促进AM源性NO的产生 ,反馈抑制iNOS mRNA表达并明显抑制ETmRNA的表达 ,降低ET的水平 ;DXM降低哮喘AM源性NO ,ET水平及iNOS mRNA ,ET mRNA的表达 ,尤以抑制iNOS mRNA表达和降低NO水平为甚 ,使NO ,ET处于低水平的异常状态。     

Application of Pharmacodynamic Modeling for Designing Time-Variant Dosing Regimens to Overcome Nitroglycerin Tolerance in Experimental Heart Failure

Purpose. Prolonged continuous administration of nitroglycerin (NTG) leads to hemodynamic tolerance. We used a previously developed pharmacokinetic-pharmacodynamic (PK/PD) model of NTG tolerance in experimental heart failure to test whether dosage regimens, designed from this model, may allow avoidance of tolerance development upon continuous NTG inftision. Methods. Simulation experiments (using ADAPT II) were performed to evolve a time-variant infusion regimen that would theoretically provide sustained hemodynamic effect (30% reduction in left ventricular end-diastolic pressure, LVEDP) throughout 10 hours of drug dosing. A computer controlled infusion pump was utilized to deliver this time-variant input. Infusion experiments were then conducted in CHF rats to challenge the predictability of the applied PK/PD model. Results. Simulations showed that exponentially increasing input functions provided more sustained LVEDP effects when compared to linear or hyperbolic input functions delivering the same total NTG dose. A computer-selected infusion regimen of 6.56e^{0.00156×minutes} g/min was anticipated to provide the desired hemodynamic profile in our animal model. Experiments conducted in rats with congestive heart failure (n = 4) confirmed the prediction of sustained hemodynamic effect without tolerance (28 ± 4% reduction in LVEDP at 10 hrs). Conclusions. These findings support the utility of our PK/PD model of NTG tolerance in predicting NTG action, and serve as an example of therapeutic optimization through PK/PD considerations.     

硝酸甘油与美托洛尔预防气管插管所致循环副作用的比较

①目的　比较硝酸甘油与美托洛尔在麻醉诱导中对心率、血压和左室射血功能的影响。②方法　２４例病人随机分为３ 组,每组８ 例。麻醉诱导均选用芬太尼、硫喷妥钠和琥珀酰胆碱。于静脉诱导后分别静注美托洛尔、硝酸甘油和生理盐水,监测气管插管时平均动脉压（ Ｍ Ａ Ｐ）、心率（ Ｈ Ｒ）和每搏量（ Ｓ Ｖ）变化。③结果　插管后美托洛尔组 Ｍ Ａ Ｐ低于对照组, Ｈ Ｒ 低于对照组及硝酸甘油组, Ｓ Ｖ 高于硝酸甘油组,差异均有显著性（ Ｆ＝ ４．０７～５．９６,ｑ＝ ３．４４～４．４９, Ｐ 均＜ ０．０５）。④结论　美托洛尔与硝酸甘油皆可预防气管插管所致的循环副作用,但美托洛尔作用优于硝酸甘油。     

小鼠腹腔注射硝酸甘油后心、脑、肾一氧化氮含量的变化

目的 观察小鼠腹腔注射硝酸甘油（Ｎｉｔ）后心、脑、肾中一氧化氮（ＮＯ）含量随时间、剂量变化的关系,方法 用比色法测定组织中亚硝酸盐含量,间接反映ＮＯ含量。结果 ５ｍｉｎ内心脑组织中ＮＯ含量迅速上升,１０ｍｉｎ后开始下降,２０ｍｉｎ后基本恢复正常。肾中ＮＯ含量于２０ｍｉｎ达到最大值,６０ｍｉｎ后基本恢复正常。在６．０ｍｇ／ｋｇ Ｎｉｔ剂量范围内,心、脑、肾组织中ＮＯ含量呈剂量依赖关系。结论 一氧化氮