Midazolam depresses carotid body chemoreceptor activity

BACKGROUND: Although the contribution of the gamma-aminobutyric acid (GABA) receptor system in peripheral chemosensation is unclear, immunohistochemistry has demonstrated the presence of GABA-ergic receptors in mammalian carotid bodies. We hypothesized that an activation of the carotid body GABA receptors would counteract the depolarizing effect of hypoxia. METHODS: The carotid body with arterial supply and the carotid sinus nerve was removed en bloc from New Zealand White rabbits and placed in a perfusion chamber. The carotid body preparation was perfused via the cut common carotid artery with a modified Tyrode's solution at a rate of 3.5-4.5 ml/min with a constant pressure of 45 cmH2O. The carotid sinus nerve firing frequency (Hz) was recorded at two different oxygen tension levels during perfusion with midazolam of 1, 10 and 100 microg/l. RESULTS: The frequency was decreased by midazolam in a dose-dependent manner (n = 8). Firing frequencies (mean +/- SEM) at the low oxygen tension level decreased from 643.13 +/- 67.2 Hz in the control to 554.5 +/- 67.7 Hz (P = 0.054 vs. control), 509.01 +/- 100.5 Hz (P < 0.012 vs. control) and 422.6 +/- 77.3 Hz (P < 0.001 vs. control) during perfusion with midazolam of 1, 10 and 100 microg/l, respectively. CONCLUSION: Midazolam depresses carotid body chemoreceptor activity in a dose-dependent manner.     

Atracurium and vecuronium block nicotine-induced carotid body chemoreceptor responses

BACKGROUND: Vecuronium depresses carotid body chemosensitivity during hypoxia. We hypothesized that this is caused by inhibition of cholinergic transmission of the carotid body. METHODS: The carotid body with its sinus nerve was removed en bloc from thiopentone-anaesthetized adult male New Zealand rabbits and perfused in vitro with modified Tyrodes buffer solution at constant perfusion pressure, temperature, a buffer pH of 7.4 and normocapnia. Chemoreceptor discharge and spike frequencies (fx) were recorded from the whole sinus nerve after administration of 500 microg nicotine, given as duplicated controls and thereafter following 30 min perfusion of equipotent concentrations of atracurium (28.1 microM) or vecuronium(10 microM), after 30 min of neostigmine perfusion (9.2 microM) and finally after 30 min wash-out with buffer solution only. A short-lasting hypoxic test was performed before and at the end of the experimental period to confirm the responsiveness and validity of the preparation. RESULTS: Atracurium (n = 7) and vecuronium (n = 6) reduced chemoreceptor responses to nicotine by 70 +/- 30% and 66 +/- 19% (SEM) (P<0.05). Chemoreceptor discharges showed full recovery after neostigmine in the atracurium group and partial recovery in the vecuronium group (P<0.05). Finally, after wash-out the chemoreceptor responses to nicotine had fully recovered in both groups. CONCLUSION: Atracurium and vecuronium in equipotent concentrations block nicotine-induced chemoreceptor responses of the carotid body.     

Response of the canine bladder base during reflex micturition.

The response of the bladder base to filling and voiding was studied in a surgical dog model in which the bladder base was separated from the main body and closed to form a chamber. In the bladder distension phase there was a reduction in pressure in the bladder base chamber, which implies relaxation of the bladder base. In the expulsion phase the reflex bladder body activity took place with an increase in bladder base pressure, indicating contraction. Relaxation and contraction were blocked by propranolol and phentolamine respectively and both responses were abolished by trimetaphan. It was concluded that the bladder base activity in the micturition cycle is a reflex action mediated via the sympathetic nervous system.     

Fentanyl antagonizes diazepam on carotid sinus baroreflex control of circulation in rabbits

To investigate the effects of a combination of fentanyl and diazepam on carotid sinus baroreflex in conscious rabbits, we examined the responses of mean systemic arterial pressure (MAP), heart rate (HR) and total peripheral resistance (TPR) to bilateral carotid occlusion (BCO). Seven rabbits were given 0.5mg·kg^–1 of diazepam i.v. followed by 10mg·kg^–1 of fentanyl i.v. at 5min intervals (group 1), and the drugs were given in the reverse order to 5 other rabbits (group 2). BCO was repeated in conscious state (control) and after each drug injection. MAP responses did not differ from control response in either group when both drugs were given. In group 1, however, diazepam decreased HR response to 71.4% of control, and increased TPR response by 36%. Fentanyl administration reversed diazepam-induced changes in BCO responses to the control level. In group 2, fentanyl decreased TPR response to 61.6% of control and increased HR response by 41.5%. Administration of diazepam following fentanyl restored HR and TPR responses to control levels. Carotid sinus baroreflex gain was 3.1 ± 0.4 (mean ± SEM) in control and 3.1 ± 0.4 after administration of both drugs in 12 rabbits. The results suggest that a sedative dose of either fentanyl or diazepam antagonizes the other drugs action on the carotid sinus baroreflex. The combination of fentanyl and diazepam has little influence on carotid sinus baroreflex control of the circulation in rabbits.(Sakamoto M, Ohsumi H, Sumida T, et al.: Fentanyl antagonizes diazepam on carotid sinus baroreflex control of circulation in rabbits. J Anesth 7: 210–217, 1993)     

芬太尼抑制体外培养大鼠胰岛动态条件下葡萄糖刺激胰岛素分泌

目的 研究芬太尼对体外培养大鼠胰岛动态条件下葡萄糖刺激胰岛素分泌的抑制作用.方法 根据芬太尼浓度将SD大鼠胰岛随机均分为四组:Ⅰ组((0.3 ng/ml)、Ⅱ组((3.0 ng/ml)、Ⅲ组(30 ng/ml)和Ⅳ组(0 ng/ml).每组胰岛分别按以下3种方式与药物共同培养24 h:单独与芬太尼,芬太尼+0.1 μg/ml纳洛酮和芬太尼+1 μg/ml纳洛酮.每组设6个培养孔,每孔加入胰岛30IEQ,重复3次.检测胰岛细胞活力.动态培养条件下葡萄糖刺激胰岛素释放试验按以下方法进行:先加入2.8mmol/L葡萄糖(低糖)培养液培养,分别于10 min(第一分泌时相)和60 min(第二分泌时相)吸取上清液,然后加入16.7mmol/L(高糖)的培养液继续培养,分别于10 min和60 min吸取上清液,测定胰岛素含量.结果 四组胰岛细胞活力差异无统计学意义.第一和第二分泌时相单独芬太尼培养下,Ⅱ组和Ⅲ组低糖和高糖刺激胰岛素释放量明显低于Ⅳ组(P<0.01),且Ⅲ组高糖刺激胰岛素释放量最低(P<0.05).第一和第二分泌时相芬太尼+0.1 μg/ml纳洛酮培养下,Ⅱ组和Ⅲ组低糖和高糖刺激胰岛素释放量仍明显低于Ⅳ组(P<0.01),且Ⅲ组高糖刺激胰岛素释放量仍最低(P<0.05).第一和第二分泌时相芬太尼+1 μg/ml纳洛酮培养下,各组胰岛素释放量差异无统计学意义.结论 高浓度芬太尼抑制体外培养大鼠胰岛素的分泌,并且对鼠胰岛细胞具有一定的损伤作用.     

The association of carotid artery stenosis with carotid sinus hypersensitivity. Transitory cerebral ischaemic attack provoked by carotid sinus reflex

The association of internal carotid stenosis with the carotid sinus syndrome represents a special clinical entity. Transitory cerebral ischaemic attack (TIA) will usually be manifested by activation of carotid sinus reflex. Eighteen patients were observed suffering from both carotid sinus hypersensitivity and TIA. The patients had had TIA's for many years. Unilateral internal carotid stenosis was detected in 15 cases, while 3 patients had bilateral carotid stenosis. On carotid sinus stimulation, syncope appeared and a TIA could be provoked. The mean duration of the syncopic attack was 5500 ms and was based on sinus arrest in 14 cases and on third degree AV block in 4 cases. In all patients carotid artery disobliteration was performed; in 14 patients pacemaker implantation was necessary, while 4 patients could be treated by atropine medication. The development of a TIA could be abolished in every patient and 14 patients remained totally symptom free.     

The effect of ischemia on canine carotid endothelial permeability

The effect of ischemia on arterial endothelial permeability was assessed by surgically interrupting arterial blood flow for 45 min in the left carotid artery of 12 foxhounds. The right carotid artery served as control. Twenty-four hours before sacrificing the animals at 1 day, 1 week, 1 month, and 3 months postoperatively. Evans blue dye (1.5 ml/kg) was administered intravenously. Carotid arteries were harvested, opened, and scanned with a reflectometer to measure Evans blue dye uptake, and scanning electron microscopy was performed on a section of tissue from each harvested vessel. A statistically significant increase in permeability of the ischemic vessel occurred at 1 day (79 +/- 42% (SD], 1 week (186 +/- 75%), and 1 month (229 +/- 125%), but was not present at 3 months (7 +/- 8%) postinjury. Scanning electron microscopic examination of all specimens was essentially normal. This study demonstrates that arterial endothelium has increased permeability at 1 month following a brief ischemic period. What effect this ischemia-induced endothelial dysfunction will have on lipid uptake by the arterial wall will be the subject of future study.     

Irradiation inhibits vascular anastomotic stenosis in a canine model

Objective  

The graft patency rate after coronary artery bypass grafting (CABG) correlates with anastomotic stenosis. Intracoronary radiation therapy is effective for preventing restenosis after percutaneous coronary intervention (PCI). We postulated that intracoronary radiation therapy could prevent anastomotic stenosis and tested this hypothesis in an animal model.     

Vecuronium directly inhibits hypoxic neurotransmission of the rat carotid body.

Previous studies have suggested that partial neuromuscular blockade by vecuronium may inhibit the chemoreceptor neural response to hypoxia. Because acetylcholine and its receptors are critically involved in the hypoxic neurotransmission of the carotid body, we examined whether vecuronium interferes with nicotinic processes in the carotid body and inhibits the chemoreceptor neural response to hypoxia. The carotid body was harvested from anesthetized adult Wister rats. Carotid sinus nerve activity (CSNA) was recorded in vitro, whereas the carotid body was perfused with Krebs solutions equilibrated with 5% CO(2)/air or 5% CO(2)/N(2). Vecuronium (0.1, 0.5, and 5 microM) was administered via perfusion. Hypoxic perfusion increased CSNA and the response remained stable for two hours. With vecuronium 0.5 and 5 microM, the increase in CSNA (DeltaCSNA) in response to hypoxia was significantly attenuated. The inhibitory effect of vecuronium was dose-related. Acetylcholine and nicotine increased CSNA, and the values of DeltaCSNA were significantly attenuated by vecuronium. These results indicate that vecuronium directly inhibits the carotid body neural response to hypoxia, possibly because of the inhibition of neuronal nicotinic receptors in the carotid body. IMPLICATIONS: We investigated the effect of vecuronium on the chemoreceptor response to hypoxia with perfused rat carotid bodies. The results indicate that vecuronium significantly reduces carotid body neural responses to hypoxia, acetylcholine, and nicotine by inhibiting neuronal nicotinic receptors in the carotid body.     

Fentanyl inhibits the release of [3H]noradrenaline from SH-SY5Y human neuroblastoma cells

We have examined the effect of fentanyl on [³H]noradrenalinerelease in a human neuroblastoma cell preparation, SH-SY5Y.Fentanyl produced a significant, concentration-dependent inhibitionof [³H]noradrenaline release with IC₅₀ values of 5.5 x 10^–6mol litre^–1 and 15.5 x 10^–6 mol litre^–1 forcarbachol- and potassium- evoked release, respectively. Thesmall difference in IC₅₀ between the two evoking stimuli maybe explained by the weak binding affinity of fentanyl to muscarinicreceptors (K_i = 570 nmol litre^–1). The minimum concentrationsat which a significant effect was observed were 0.3 x 0.10^–6mol litre^–1 and 10.0 x 10^–6 mol litre^–1 forcarbachol- and potassium-evoked release, respectively; thesevalues are considerably in excess of the serum concentrationof fentanyl required to produce analgesia. Naloxone failed toantagonize the fentanyl inhibition and, furthermore, morphineand an enkephalin had no effect on evoked release, implyinga non-opioid receptor mediated effect. (Br. J. Anaesth. 1994;72: 98–103)     

Cryopreserved venous homografts as vascular conduits in canine carotid arteries

In this study we evaluated the histologic condition, prostacyclin production, and compliance of morphologically intact cryopreserved venous homografts (CVH) and autografts 3, 6, and 9 months after arterial implantation. Eighteen external jugular veins were cryopreserved and implanted into the carotid arteries of mongrel dogs. All grafts were patent at the time of excision. Electron microscopy documented a disrupted endothelium in the homografts at 3 months that was intact at 9 months. The cellular infiltrate, suggestive of rejection, in the 3-month homografts resolved by 9 months. Prostacyclin production at 3 months was 8.7 +/- 3.2 pg/ml/cm2 compared with 24.1 +/- 9.6 pg/ml/cm2 (p less than 0.025) in the adjacent carotid artery. The prostacyclin production in the 6-month homografts was 21.7 +/- 12.4 pg/ml/cm2, not significantly different from the adjacent carotid artery. The return of prostacyclin paralleled the return of an intact endothelium. Compliance of fresh vein was diminished by cryopreservation, from 1.57 +/- 0.39% radial change/mm Hg (10(-2] to 0.79 +/- 0.21% radial change/mg Hg (10(-2] (p less than 0.02). The compliance of CVH at 3 months (1.7 +/- 1.0) and at 6 months (1.1 +/- 0.42) was not significantly different from cryopreserved veins. These data showed that CVH remained patent in dogs for 9 months, without loss of compliance for 6 months, and developed a morphologically intact and functional endothelium that paralleled the resolution of the inflammatory infiltrate.     

碳化二亚胺交联犬颈总动脉脱细胞基质的组织相容性初步研究

目的应用碳化二亚胺交联同种异体的犬颈总动脉脱细胞基质，对其进行组织相容性评价。方法应用多步骤除垢剂-胰酶作用制备犬颈总动脉脱细胞基质，按脱细胞基质与碳化二亚胺质量比1：1和1：2制备不同交联程度的脱细胞基质。通过体外降解率，细胞毒性MTT实验和大鼠皮下埋置实验对交联效果和组织相容性进行评价。结果经碳化二亚胺交联的脱细胞基质形态上无明显变化，HE染色纤维排列规则无断裂。0．1％Ⅱ型胶原酶作用下，交联的脱细胞基质的降解率较单纯脱细胞基质显著降低，交联程度高的脱细胞基质较交联程度低的脱细胞基质降解率低。细胞毒性MTT结果显示碳化二亚胺交联的脱细胞基质细胞毒性分级为0-1级，无细胞毒性。大鼠皮下埋置实验显示交联的脱细胞基质抵抗组织酶降解的能力显著提高，同时免疫反应减轻。交联程度高，效果越明显。结论碳化二亚胺交联的脱细胞基质具有良好的组织相容性和抗组织酶解能力，作为血管移植物和组织工程化血管的支架材料有广阔的应用前景。