精氨酸加压素在血管舒张陛休克治疗中的进展

精氨酸加压素(arginine vasopressin,AVP)是一种强有力的血管收缩药,又称为抗利尿激素,用于治疗血管舒张性休克时,可有效提升血压、增加尿量和减少儿茶酚胺用量.现就AVP在血管舒张性休克中的应用作一综述,对其在改善血液动力学、器官灌注、疾病转归等方面的作用进行评估.     

Arginine vasopressin in the treatment of vasodilatory septic shock

Vasodilatory septic shock is characterized by profound vasodilation of the peripheral circulation, relative refractoriness to catecholamines and a relative deficiency of the posterior pituitary hormone, vasopressin. Arginine vasopressin is effective in restoring vascular tone in vasodilatory septic shock and may be associated with decreased mortality in less severe septic shock as well as improved mortality and decreased renal failure in septic shock patients at risk for renal failure.     

小剂量精氨酸加压素在血管扩张性休克病人中的应用

目的观察小剂量精氨酸加压素(arginine vasopressin,AVP)在血管扩张性休克病人治疗中的作用及其并发症。方法对17例血管扩张性休克病人进行了研究。病人均予儿茶酚胺类药物治疗,在充分容量治疗后加用小剂量AVP(<0.04U/min),在维持MAP≥65mmHg的基础上逐步调整儿茶酚胺类药物的剂量。记录AVP治疗前后的血流动力学参数、肾功能、儿茶酚胺类药物的用量、并发症及病人的预后。结果予小剂量AVP治疗后,病人HR和儿茶酚胺类药物的剂量均显著下降(P<0.01),MAP显著升高(P<0.05),心脏指数(CI)显著下降(P<0.01),每搏量指数(SVI)和周身血管阻力指数(SVRI)均显著升高(P<0.05),尿量显著增加(P<0.01),血肌酐(Cr)显著下降(P<0.01),肌酐清除率(CL)显著升高(P<0.01)。结论加用小剂量AVP治疗可明显改善血管扩张性休克病人的血流动力学,可减少儿茶酚胺类药物的需要量,并改善肾功能。     

Arginine vasopressin vs. terlipressin in the treatment of shock states

The synthetic vasopressin analogue, terlipressin, is being increasingly used to treat catecholamine-resistant hypotension in septic shock and other conditions. While terlipressin holds some theoretical and anecdotal advantages over vasopressin, this has not been formally tested in prospective randomised trials. This review analyses the published literature and makes comparisons, where possible, between vasopressin and terlipressin.     

小剂量血管加压素在感染性休克中的应用进展

血管加压素应用于感染性休克可以改善组织灌注,稳定血流动力学.它的主要作用机制是在感染性休克状态下,血浆血管加压素水平的相对性缺乏与血管对血管加压素的敏感性增强.目前研究主张小剂量血管加压素与其他血管活性药物联合使用治疗感染性休克,由于缺乏临床多中心随机对照研究,血管加压素仍是感染性休克的二线升压药.     

Circulating tetrahydrobiopterin concentrations in patients with septic shock

Nitric oxide synthase requires tetrahydrobiopterin for its activity.In animal models of sepsis, changes in circulating tetrahydrobiopterinconcentrations precede increases in nitrate. We measured plasmatetrahydrobiopterin and nitrate concentrations on three consecutivedays in 10 patients with septic shock and 10 critically illcontrol patients. Total nitrate concentration was measured afterreduction of nitrite to nitrate. Tetrahydrobiopterin concentrationswere measured using HPLC. The median (range) APACHE II scorewas 22 (13–27) in the patients with septic shock and 25(7–28) in the control group. The nitrate concentrationwas significantly higher in patients with septic shock thanin controls (P=0.01) on all days but did not change with time.Tetrahydrobiopterin concentrations were highest in the patientswith septic shock on day 1 only (P=0.037). In the seven patientswith renal failure, both nitrate and tetrahydrobiopterin concentrationstended to be higher than in the 13 patients without renal failure.The nitrate concentration correlated with tetrahydrobiopterinconcentration on day 1 only (P=0.05). In patients with septicshock, both tetrahydrobiopterin and total nitrate concentrationswere higher than those in critically ill controls but were increasedmainly in patients with renal failure. In summary, tetrahydrobiopterinconcentration increases during septic shock, in line with increasesin nitrate concentration. However, as for nitrate, concentrationsare affected by renal function. Measurement of tetrahydrobiopterinconcentration is extremely technically demanding and time consumingand offers no advantage over measurement of nitrate concentration. Br J Anaesth 2001; 86: 578–80     

Causes and investigation of shock

Classification of shock according to the situation in which it presents is helpful in developing a diagnostic strategy. Some causes of shock are immediately apparent; others are less so. Diagnosis is part of a process of advanced first aid in which simultaneous assessment, resuscitation, monitoring and risk assessment should take place. Investigations should be targeted towards the clinical situation in which they take place.     

抗氧化剂抑制内毒素性休克大鼠诱导型一氧化氮合酶基因表达

感染性休克时循环机能障碍的显著特点表现为进行性、顽固性低血压,伴对血管活性药物敏感性降低,以至组织器官灌注不足、重要器官机能代谢障碍,病死率仍高达30％～70％。休克时循环机能障碍所涉及的病理生理机制极其复杂,脂质过氧化物的堆积和NO的爆发生成是其中的关键病理因素之一。我们以往的研究中发现抗氧化剂能部分逆转内毒素休克大鼠的血管低反应性,为了进一步探讨其治疗学机制,本实验对抗氧化剂在内毒素性休克大鼠iNOS mRNA表达中的作用进行了观察。     

Arginine vasopressin: a promising rescue drug in the treatment of uncontrolled haemorrhagic shock

Haemorrhagic shock is one of the most frequent types of shock. If haemorrhage cannot be controlled and fluid resuscitation as well as catecholamines are insufficient to stabilize cardiovascular function, uncontrolled haemorrhagic shock occurs. Several approaches have been suggested as promising alternatives to volume resuscitation. The rationale for the use of arginine vasopressin (AVP) is the pharmacologic amplification of the neuroendocrine stress response. AVP-mediated vasoconstriction is the first physiologic step to haemostasis and shifts blood away from the bleeding site towards the heart, lungs and brain. Particularly, when uncontrolled haemorrhage is accompanied by traumatic brain injury this may help to reduce secondary neurological damage. Since AVP can prevent acute death only transiently, it must comprehensively be combined with rapid hospital admission, immediate control of haemorrhage followed by aggressive fluid resuscitation and blood transfusion. This review article summarizes current experimental and clinical evidence on the use of AVP in uncontrolled haemorrhagic shock.     

Arginine vasopressin in vasodilatory shock: effects on metabolism and beyond

PURPOSE OF REVIEW: To describe the effects of arginine vasopressin other than its vasoconstrictive and antidiuretic potential in vasodilatory shock. RECENT FINDINGS: Arginine vasopressin influences substrate metabolism by stimulation of hepatic glucose release, gluconeogenesis, ureogenesis and fatty acid esterification. Although arginine vasopressin is a secretagogue of different hormones, only prolactin increases during arginine vasopressin therapy. Plasmatic and cellular coagulation are affected by arginine vasopressin, resulting in thrombocyte aggregation. Therefore, platelet count typically decreases following arginine vasopressin infusion in critically ill patients. In addition, arginine vasopressin reduces bile flow and may increase bilirubin concentrations. Despite its potential to decrease serum sodium, no change in electrolytes was observed in critically ill patients receiving arginine vasopressin. Although arginine vasopressin is an endogenous antipyretic, body temperature is not decreased by central venous arginine vasopressin infusion. In addition, arginine vasopressin modulates immune function through V1 receptors. Compared with norepinephrine, arginine vasopressin may have protective effects on endothelial function. Net arginine vasopressin effects on gastrointestinal motility seem to be inhibitory and are dose dependent. SUMMARY: Except for its antidiuretic and vasoconstrictive actions, the effects of arginine vasopressin in patients with vasodilatory shock have so far only been partially examined. Potential influences of arginine vasopressin on metabolism and immune, liver and mitochondrial function remain to be assessed in future studies.     

Arginine vasopressin release inhibitor RU51599 attenuates brian oedema following transient forebrain ischaemia in rats

Summary RU51599 is an arginine vasopressin (AVP) release inhibitor and a selective kappa opioid agonist which has a pure water diuresis effect without associated electrolyte excretion. The effect of RU51599 on brain oedema following transient forebrain ischaemia in rats was examined. Under microscopy, the visible vertebral arteries at the second vertebra could be easily electrocauterized and completely cut by microscissors to yield complete cessation of circulation of both vertebral arteries. Transient forebrain ischaemia was induced by this improved highly reproducible technique of four-vessel occlusion model. Forty-three male Wistar rats were separated into six groups; saline-treated (1 ml/kg) normal rats (n=10), RU51599-treated (1 mg/kg) normal rats (n=4), saline-treated (1 ml/kg) rats with complete occlusion of both vertebral arteries (n=5), RU51599-treated (1 mg/kg) rats with complete occlusion of both vertebral arteries (n=5), saline-treated (1 ml/kg) rats with both complete occlusion of both vertebral arteries and carotid occlusion bilaterally during 45 minutes followed by 60 minutes of reperfusion (n=11), RU51599-treated (1 mg/kg) rats with both complete occlusion of both vertebral arteries and carotid occlusion bilaterally during 45 minutes followed by 60 minutes of reperfusion (n=8). The brain water content was determined by the dry-wet weight method. Cerebral blood flow was monitored during ischaemia and reperfusion was performed by laser Doppler flowmetry to make sure to obtain reversible forebrain ischaemia. Effects of RU51599 on concentration of glutamate released from the hippocampal CA1 of rats subjected to 5 minutes four-vessel occlusion and 60 minutes of reperfusion were also investigated by the microdialysis method. This modified four-vessel occlusion method produced reversible forebrain ischaemia with a high level of success. Bilateral carotid occlusion followed by 60 minutes reperfusion caused a significant increase in brain water content (P<0.01), which was significantly attenuated by RU51599 (P<0.01). These findings indicate that the AVP-release inhibitor RU51599 reduced brain oedema following transient forebrain ischaemia in rats.     

Impact of vasopressin on hemodynamic and metabolic function in the decompensatory phase of hemorrhagic shock

OBJECTIVES: To explore how the potent vasoconstrictive features of vasopressin impact the rate of cardiovascular collapse and metabolic derangements associated with prolonged hemorrhagic shock. DESIGN: A prospective randomized trial. SETTING: University hospital-based animal laboratory. PARTICIPANTS: Sixteen swine. INTERVENTIONS: Swine were bled in an isobaric fashion to achieve a linear decrease in the mean arterial blood pressure to 40 mmHg. The mean arterial blood pressure was then maintained at 40 mmHg until the onset of cardiovascular decompensation, defined as the need to reinfuse shed blood to maintain the blood pressure at 40 mmHg. Once at the onset of cardiovascular decompensation, animals were randomly assigned to 2 resuscitation groups: the crystalloid group received lactated Ringer's solution and the vasopressin group received lactated Ringer's solution and arginine vasopressin. Resuscitation consisted of infusing lactated Ringer's solution with and without vasopressin (0.05 U/kg/min) to maintain a blood pressure of 70 mmHg for 60 minutes. MEASUREMENTS AND MAIN RESULTS: The rate of crystalloid infusion was compared between groups using an unpaired 2-tailed t test. Metabolic and hemodynamic parameters between groups over time were compared with a repeated measures analysis of variance. Vasopressin decreased the rate of crystalloid infusion during resuscitation by 50%. During resuscitation, the cardiac index in the crystalloid group was restored to near baseline levels and was decreased to near half of baseline levels in the vasopressin group. Animals in the vasopressin group developed a lactic acidemia, but animals in the crystalloid group revealed no change from baseline in the arterial pH and a slight decrease in the plasma lactate. CONCLUSIONS: Administration of vasopressin used as an adjunct to maintain blood pressure in the decompensatory phase of hemorrhagic shock slows cardiovascular collapse, but has an adverse effect on metabolic and hemodynamic function. Further investigation is warranted to clarify the role of vasopressin in the delayed management of severe hemorrhagic shock.     

Early changes of arginine vasopressin and angiotensin II in patients with acute cerebral injury

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盐酸戊乙奎醚对创伤性休克兔肠组织诱导型一氧化氮合酶活性和一氧化氮含量的影响

目的 研究盐酸戊乙奎醚(penehyclidine hydrochloride,PHC)对创伤性休克兔复苏后肠黏膜损伤的保护作用.方法 采用Lamson's法建立创伤性休克动物模型,24只健康日本长耳大白兔,采用随机数字表法分为4组(每组6只):对照组(Con组)、生理盐水复苏组(NS组)、PHC处理组(PHC组)、山莨菪碱(anisodamine,ANI)处理组(ANI组).分别在休克前(T1),休克末(T2),复苏后即刻(T3)、2 h (T4)、4 h(T5)、6 h(T6)等6个时间点动态观察MAP和HR,实验结束后放血处死动物取小肠组织,观察肠组织中诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)活性和一氧化氮(nitric oxide,NO)含量的变化,光镜下检查组织病理学变化. 结果 各实验组动物T2时的MAP显著降低(均≤45 mmHg)(1 mmHg=0.133 kPa);与Con组和PHC组比较,T3-T6时NS组的MAP显著低于T1时,差异有统计学意义(P＜0.05).与Con组和PHC组比较,T3～T6时NS组的HR较T1时显著降低,差异有统计学意义(P＜0.05);NS组、PHC组和ANI组肠组织iNOS活性[(4.39±0.44)、(1.59±0.49)、(1.62±0.62) U/mg]及NO含量[(5.81±0.27)、(2.10±0.24)、(2.15±0.30) μmol/g]与Con组[(0.70±0.24) U/mg、(0.70±0.32)μmol/g]比较,差异有统计学意义(P＜0.05).NS组肠组织iNOS活性及NO含量显著高于PHC组、ANI组,差异有统计学意义(P＜0.05).病理组织学检查显示PHC组和ANI组肠黏膜损伤较NS组显著减轻. 结论 PHC和ANI有助于稳定创伤性休克兔的血流动力学,对创伤性休克造成的肠黏膜损伤有一定的保护作用,其作用机制可能是通过抑制iNOS活性,从而减少NO含量的生成而起作用的.     

Dobutamine compensates deleterious hemodynamic and metabolic effects of vasopressin in the splanchnic region in endotoxin shock

BACKGROUND: Vasopressin is a potent vasopressor in septic shock, but it may impair splanchnic perfusion. We compared the effects of vasopressin alone and in combination with dobutamine on systemic and splanchnic circulation and metabolism in porcine endotoxin shock. METHODS: Twelve pigs were randomized to receive either vasopressin (VASO, n = 6) or vasopressin in combination with dobutamine (DOBU, n = 6) during endotoxin shock (E. coli endotoxin infusion). Endotoxin infusion rate was increased to induce hypotension after which vasoactive drugs were started. We aimed to keep systemic mean arterial pressure (MAP) >70 mmHg by vasopressin; the goal of dobutamine infusion was to prevent decrease in cardiac output often associated with vasopressin infusion. Regional blood flows, oxygen delivery and consumption, arterial and regional lactate concentrations were measured. RESULTS: Mean arterial pressure >70 mmHg was achieved in both the VASO and DOBU groups. After the primary decrease of cardiac output by vasopressin, systemic blood flow remained stable in vasopressin-treated animals. However, vasopressin as a monotherapy decreased portal venous blood flow. This was prevented by dobutamine. Vasopressin also induced splanchnic lactate release and arterial hyperlactatemia, which were not observed when dobutamine was combined with vasopressin. CONCLUSION: Dobutamine prevents adverse hemodynamic and metabolic effects of vasopressin in septic shock.     

Cavernosal tissue nitrite,nitrate, malondialdehyde and glutathione levels in diabetic and non-diabetic erectile dysfunction

The aim of this study is to investigate the role of nitric oxide (NO) stabile end products, membrane lipid peroxidation and antioxidant defensive mechanism in diabetic erectile dysfunction (ED) and compare these parameters with non-diabetic ED groups. We examined the penile cavernosal tissues, obtained from 22 patients who had undergone surgery of penile prostheses implantation, for the nitrite, nitrate, malondialdehyde (MDA) and glutathione (GSH) levels. Eight patients were suffering from diabetic erectile dysfunction (ED) and 14 patients had non-diabetic ED. Nitrite and nitrate levels were lower; MDA and GSH levels were higher in the diabetic group. There were statistically significant differences between diabetic and non-diabetic groups amongst the nitrite (p<0.001), nitrate (p<0.01), MDA (p<0.001) and GSH (p<0.01) levels. Our data provide evidence that NO deficiency, possibly due to the membrane lipid peroxidation and defective antioxidant defensive mechanism, may contribute to the development of diabetic ED and thus is involved in the pathogenesis of ED in diabetic patients.     

Nitrite/nitrate (NOx) levels and hemodynamics during septic shock

Nitric oxide (NO) acts as a vasorelaxant. We investigated the relationship between nitrite/nitrate (NOx), which are the final metabolites of NO, and hemodynamics during septic shock. We also examined tumor necrosis factor α (TNF-α), interleukin-8 (IL-8), and endotoxin. A significant negative correlation was observed between NOx levels and pulmonary capillary wedge pressure (PCWP; r = −0.6075, P = 0.0028). A significant positive correlation was noted between NOx levels and the cardiac index (CI; r = 0.5934, P = 0.0038). A significant negative correlation was found between NOx levels and the systemic vascular resistance index (SVRI; r = −0.4354, P = 0.0485). A significant positive correlation was observed between NOx levels and the stroke volume index (SVI; r = 0.5040, P = 0.0186). A significantly close positive correlation was also observed between TNF-α levels and NOx levels (r = 0.7848, P < 0.0001). These findings suggest that NOx levels are closely associated with hemodynamics during septic shock, resulting in a vascular relaxing effect. Received: July 6, 1999 / Accepted: March 24, 2000