A porcine model for sequential assessments of cerebral haemodynamics and metabolism

We present a physiologically stable porcine model designed for sequential assessments of pharmacological effects on mean hemispheric cerebral blood flow (CBF) and cerebral metabolic rate for oxygen (CMRO2) at sustained normocapnia. The dynamic influence of continuously administered fentanyl (0.040 mg.kg-1.h-1 i.v.), nitrous oxide (70%) and pancuronium (0.30 mg.kg-1.h-1 i.v.) on these variables was studied in eight normoventilated pigs. CBF was reliably assessable at 10-min intervals by clearance of intra-arterially injected 133Xe, monitored by an extracranial scintillation detector. CMRO2 was calculated from CBF and the simultaneously measured cerebral arteriovenous difference in blood oxygen content. The intracerebral distribution of a contrast medium injected into the external and internal carotid arteries was studied by angiography, and the cerebral venous outflow was investigated by measurements of the distribution of an intra-arterially administered non-diffusible tracer, [99mTc]pertechnetate, to the internal and external jugular veins. After a 3-h equilibration period, CBF and CMRO2 were determined on six occasions over a study period lasting 1 h 40 min. The mean ranges of these variables were 56-60 and 1.9-2.0 ml.100 g-1.min-1, respectively. We conclude that the model enables repeated assessments of CBF and CMRO2 under stable physiological background conditions and thus valid cerebral pharmacodynamic investigations of drugs given for anaesthesia.     

S-nitrosoglutathione-containing hydrogel accelerates rat cutaneous wound repair

BACKGROUND: Nitric oxide (NO) plays a key role in wound repair and S-nitrosothiols like S-nitrosoglutathione (GSNO) are well known NO donors. METHODS: Animals were separated in two groups and submitted to excisional wounds on the dorsal surface at the first day. GSNO (100 microm)-containing hydrogels were topically applied on the wound bed in the GSNO group, daily, during the first 4 days. Control group was topically treated with hydrogel without GSNO for the same period. Wound contraction and re-epithelialization were measured. Animals were sacrificed 21 days after wounding. Samples of lesion and normal tissue were formalin-fixed, paraffin embedded for histological analysis. RESULTS: Wound contraction, measured 14 and 21 days after wounding, was greater in the GSNO group than in the control group (P<0.05 for both). The re-epithelialized wound area, measured 14 days after wounding, was higher in the GSNO group than in the control group (P<0.05). A higher amount of inflammatory cells was observed in superficial and deep areas of the granulation tissue of the control group compared to the GSNO group. Twenty-one days after wounding, thin red-yellow collagen fibers arranged perpendicularly to the surface were found in the granulation tissue of the control group, whereas in the GSNO-treated group collagen fibers were thicker and arranged parallel to the surface. Increased number of mast cells was observed in the GSNO group compared with that in the control group. Vascularization and myofibroblast distribution were similar in both groups. CONCLUSION: Topical application of GSNO-containing hydrogel during the early phases of rat cutaneous wound repair accelerates wound closure and re-epithelialization and affects granulation tissue organization.     

一氧化氮及一氧化氮合酶在遗传性癫痫易感大鼠惊厥发作中的作用

目的：探讨一氧化氮、一氧化氮合酶在遗传癫痫易感大鼠惊厥发作中的变化及作用。方法：选择惊厥评分在30－40的P77PMC大鼠35只，均分A－G7组，A组为对照组、G组预先30min腹腔注射一氧化氮合酶抑制剂L－NAME，分别于铃声刺激致惊后0．5、1、2、4,12h断头处死，取出脑组织分离双侧大脑皮层、海马等组织匀浆，测定一氧化氮及一氧化氮合酶，分别统计并进行t检验。结果：惊厥后0．5－1h皮层、海马一氧化氮、一氧化氮合酶逐渐升高，2h达峰值，4－12h恢复正常，应用L－NAME后，一氧化氮、一氧化氮合酶升高被抑制，但大鼠惊厥评分增高并致1例惊厥后死亡和明显延长惊厥持续时间。结论：惊厥后大鼠体内一氧化氮、一氧化氮合酶合成增加，给予合成酶抑制后能明显下降，但能加重惊厥程度和延长持续时间，提示一氧化氮于惊厥后升高，可能作为内源性抑制性性质，在惊厥发作自行终止机制中具有重要作用。     

Nitric oxide is not involved in the initiation of insulin secretion from rat islets of Langerhans

Summary The involvement of nitric oxide as an intracellular messenger in the control of insulin secretion from pancreatic Beta cells was studied in rat islets of Langerhans by measuring: (i) nitric oxide generation in response to physiological insulin secretagogues; (ii) the effects of inhibitors of nitric oxide synthesis on insulin secretory responses to physiological secretagogues, and on insulin synthesis; (iii) changes in islet cyclic guanosine monophosphate in response to secretagogues; (iv) the effects of exogenous cyclic guanosine monophosphate and dibutyryl cyclic guanosine monophosphate on insulin secretion from electrically permeabilised islets and from intact islets, respectively. These studies produced no evidence that nitric oxide generation is required for the initiation of insulin secretion by common secretagogues. However, the results of our experiments suggest that the generation of nitric oxide may be involved in long-term, glucose-dependent increases in cyclic guanosine monophosphate content of islet cells, although the physiological relevance of these changes requires further investigation.     

Successful weaning from cardiopulmonary bypass after cardiac surgery using inhaled nitric oxide

Two cases of very difficult weaning from cardiopulmonary bypass after cardiac surgery in children with pulmonary hypertension and ventricular dysfunction are reported. Children fail to respond to conventional therapy combining nitrovasodilators and inotropic support and react successfully to combined inhaled nitric oxide (NO) and epinephrine or left atrial infused norepinephrine. Postoperative NO inhalation must be prolonged and no toxicity appears. Pulmonary endothelial function recovers only after several days.     

Should nitrous oxide be discontinued before desflurane after anaesthesia with desflurane/N2O?

Background : The appearance of hypoxaemia immediately after anaesthesia with nitrous oxide may be partially explained by diffusion hypoxia. This study was undertaken to evaluate circulatory and respiratory variables during emergence after desflurane/nitrous oxide anaesthesia, and whether there are any differences depending on which gas is discontinued first. Methods : 20 patients were studied after gynaecological laparoscopic surgery. The depth of anaesthesia was reduced 10 min prior to the emergence by stopping the administration of one of the two inhalational agents. Desflurane was discontinued first in Group 1, nitrous oxide in Group 2. Ventilation was controlled with E'C0₂ maintained at 5% until the administration of the second anaesthetic gas was discontinued. Thereafter, the patients breathed spontaneously. Results : The PaC0₂ at which the respiratory drive reappeared after controlled normoventilation was similar in both groups, 6.1–6.5 kPa, and extubation was performed after 10–11 min. At extubarion, the end–tidal C0₂ and total MAC were similar in the groups, about 6.2 vol% and 0.16, respectively. Mean arterial blood pressure was significantly higher in Group 1. The cardiac output increased in both groups from about 6 1/min at the conclusion of anaesthesia to 9.0 and 7.6 1/min at 15 min in the recovery period. End–tidal O₂ decreased and CO₂ increased in both groups during the first 10 min in the recovery period. pH was reduced at 15 and 30 min in both groups. Conclusion : Irrespective of which agent was discontinued first, there was an increase in cardiac output, decrease in oxygenation and a modest acidosis in the first 30–min recovery period. The only significant difference between the groups was in mean arterial blood pressure in the early emergence phase with a greater MAP when N₂O had been used until the conclusion of anaesthesia.     

一氧化氮在氯胺酮麻醉机制中的作用

目的：了解一氧化氮（ＮＯ）与氯胺酮麻醉作用间的关系。方法：６０只雄性昆明鼠分成４组，Ⅰ组氯胺酮１００ｍｇ／ｋｇ腹腔内注射，Ⅱ组连续３天腹腔内注射Ｎ－硝基左旋精氨酸甲酯（Ｌ－ＮＡＭＥ）５０ｍｇ／ｋｇ后，腹腔内注射氯胺酮１００ｍｇ／ｋｇ，Ⅲ组连续３天腹腔内注射左旋精氨酸３００ｍｇ／ｋｇ后，腹腔内注射氯胺酮１００ｍｇ／ｋｇ，Ⅳ组腹腔内注射氯胺酮１００ｍｇ／ｋｇ后，腹腔１小时内持续给予Ｓ－亚硝酰－Ｎ－乙酰青霉胺（ＳＮＡＰ）３０ｍｇ／ｋｇ。观察各组动物翻正反射丧失和抑制持续时间。结果：各组翻正反射丧失时间无明显差异，为１．３９～２．３０分钟。翻正反射丧失持续时间Ⅰ组４７．７１±５．１７分，Ⅱ组４７．８４±７．９９分，Ⅲ组和Ⅳ组明显比Ⅰ、Ⅱ组短，分别为３１．１４±２．４４和３２．７５±８．１４分（Ｐ＜０．０１）。结论：改变ＮＯ的生成量将影响着氯胺酮引起的小鼠翻正反射抑制的持续时间，ＮＯ在氯胺酮麻醉分子机制中起作用。     

先天性心脏病患儿肺动脉,上腔静脉血一氧化氮含量检测及意义

目的:探讨一氧化氮(NO)与先天性心脏病(CHD)引起的肺动脉高压(PH)发病间的关系。方法:应用NO试剂盒检测了CHD患儿肺动脉及上腔静脉血浆中NO含量。结果;(1)伴PH组肺动脉血浆NO含量明显高于不伴肺动脉高压组(37.58±9.99μmol/L:19.03±15.25μmol/L,P<0.01);(2)在PH组中,肺动脉血浆NO含量明显高于上腔静脉血(P<0.01);而不伴PH组,肺动脉和上腔静脉血浆NO含量无显著性差异(P>0.05)。结论:(1)伴PH的先心患儿肺动脉血浆NO含量升高;(2)NO可能介入了CHD引起的PH发病过程。     

吸入一氧化氮对心瓣膜置换术后肺动脉高压患者血流动力学的影响

目的：观察吸入一氧化氮（ＮＯ）对心瓣膜置换术后肺动脉高压患者血流动力学的影响。方法：选择９例心瓣膜置换术后伴肺动脉高压的病人，吸入ＮＯ０．００３％，观察三个时象点：吸入ＮＯ前；开始吸入ＮＯ后１５分钟；停止吸入ＮＯ后１５分钟。结果：吸入ＮＯ能显著降低肺动脉压和肺循环阻力指数（Ｐ＜０．０１），停止吸入ＮＯ１５分钟后，肺动脉压和肺循环阻力指数恢复到原有水平。在整个观察过程中，心率、平均动脉压、中心静脉压、肺动脉楔压、体循环阻力指数和心脏指数均无显著变化（Ｐ＞０．０５）。结论：吸入ＮＯ具有选择性肺血管扩张作用，是治疗心瓣膜置换术后肺动脉高压的较理想药物。     

Association analysis of CA repeat polymorphism of the endothelial nitric oxide synthase gene with essential hypertension in Japanese

The nitric oxide synthase (NOS) gene is thought to be associated with essential hypertension (EH), because NO is implicated in endothelium-mediated vasodilation. We investigated the possible association between the alleles of simple tandem repeat DNA polymorphism of the endothelial constitutive NOS (cNOS) gene and EH in Japanese subjects. In all, 100 patients with EH and 123 subjects with normal blood pressure were studied. Polymerase chain reaction was used to amplify the CA repeat site in the endothelial cNOS gene and alleles based on the CA repeat number were determined. The allele frequencies in the hypertensive group and normotensive group were then compared. Twenty-three alleles were identified in this study of Japanese subjects. The overall distributions of allele frequencies in the two groups were not significantly different. However, comparing the allele frequencies in the EH group without left ventricular hypertrophy (LVH) and the normotensive group, the overall distributions were significantly different (p = 0.019). The 33-repeat allele was found more frequently in the EH group without LVH than in the normotensive group (p = 0.000047, Odds ratio = 3.71). In conclusion, the 33-repeat allele of the endothelial cNOS gene is associated with EH without LVH, and may be a genetic marker of EH in Japanese subjects.