乳宁霜的抗炎、镇痛及改善微循环作用研究

目的研究外用中药制剂乳宁霜的抗炎、镇痛及改善微循环作用。方法将动物随机分为对照组、散结乳癖贴膏组和乳宁霜低、高剂量组,通过外涂给药方式,分别考察乳宁霜对二甲苯致小鼠耳廓肿胀、大鼠琼脂性慢性肉芽肿炎症的改善作用;采用灌胃给药或外涂给药方式,以小鼠醋酸扭体法和热板法考察乳宁霜的镇痛作用及抗垂体后叶素致微循环障碍的拮抗作用。结果乳宁霜高、低剂量对二甲苯所致的小鼠耳廓肿胀抑制率分别为46·2%和43·1%,与对照组比较有显著性差异(P<0·01);与对照组比较,乳宁霜能减少琼脂所致大鼠慢性肉芽肿的生成(P<0·01),且效果明显好于散结乳癖贴膏组(P<0·05)。乳宁霜高、低剂量均能延迟小鼠注射醋酸后疼痛出现时间,减少单位时间内动物疼痛反应次数,并提高热板法致痛的痛阈,与对照组和散结乳癖贴膏组比较有显著性差异(P<0·01)。乳宁霜高、低剂量对垂体后叶素所致的小鼠尾部微循环血流量减少率分别为38%和39%,明显低于对照组(P<0·01)。结论乳宁霜具有显著的抗急、慢性炎症和镇痛、改善微循环作用。     

活血颗粒对大鼠肢体缺血再灌注损伤的保护作用

目的：探讨大鼠肢体缺血再灌注损伤前后微循环变化及活血颗粒的保护作用。方法：40只大鼠肢体缺血再灌注损伤，随机分成2组。治疗组与对照组分别在再灌注后灌服活血颗粒，一天3次，连续服用7天，观测微循环的变化。结果：对照组：血流缓慢、红细胞严重聚集、大量白细胞附壁和白色微栓形成，无复流现象严重；治疗组经活血颗粒保护，微循环障碍轻，肌肉等软组织损伤轻，功能恢复满意。结论：活血颗粒对肢体缺血再灌注损伤有保护作用。     

实时心肌声学造影评价2型糖尿病患者心肌微循环的研究

目的应用经静脉实时心肌声学造影，观察2型糖尿病患者心肌微循环灌注的情况。方法选择射血分数大于50％，无冠心病病史，负荷超声或者冠状动脉造影正常，无瓣膜病变，无心房颤动和其他严重心律失常，无先天性心脏病，并排除合并高血压病、肾病、甲状腺功能减退的38例患者作为研究对象；正常对照组20例。经体检、心电图和超声心动图检查无心脏疾患，无高血压病、肾病及甲状腺功能减退病史。均进行实时心肌声学造影，图像存储。结果2型糖尿病患者心肌造影剂灌注的峰值强度A与反映心肌血流速度的k值较正常对照组低（P〈0．01），反映心肌血流量的A·k乘积也明显低于正常对照组（P〈0．01）。结论实时心肌声学造影技术可定量评价2型糖尿病患者心肌微循环灌注的改变。     

Effects of alcohol infusion on smoking-induced cerebrovascular changes in rat in vivo

The combined effects of alcohol and cigarette smoking on the cerebral circulation are unknown. The current study was designed (1) to compare the acute effects on cerebral vessels of cigarette smoking alone with those of alcohol plus cigarette smoking and (2) to clarify the mechanism or mechanisms underlying the cerebrovascular responses. In pentobarbital-anesthetized, mechanically ventilated Sprague–Dawley rats, we measured pial vessel diameters with the use of a cranial window preparation. Rats, pretreated with alcohol (n = 6; 1 g/kg/h, i.v.; 1-h infusion from t = −60 min to t = 0) or with saline (n = 6), were exposed to 60 puffs per minute of mainstream smoke from a 1 mg-nicotine cigarette. Inhalation of smoke caused pial arterioles to constrict at t = 30 s (8.4%) and, subsequently, to dilate (peak at t = 5–10 min; 18.7%). Pretreatment with alcohol caused pial vasodilation (14.0%), and, after inhalation of cigarette smoke, the pial vasodilation occurred earlier (peak at t = 1–5 min; 30.2%) and was larger, without an initial vasoconstriction. The plasma concentration of thromboxane (TX) B₂ (a stable metabolite of TXA₂) increased after this smoking, and alcohol pretreatment attenuated this increase (protocol as above). Cigarette smoking had a significant biphasic effect on cerebral arteriolar tone. However, alcohol suppressed the initial vasoconstriction, probably, at least in part, by attenuating the smoking-induced TXA₂ production.     

Microvascular responses to adenosine help explain functional and pathologic differences between intestinal segments

BACKGROUND: Many physiologic (post-prandial hyperemia), pathologic (inflammatory bowel disease), and clinical (enteral feeding) phenomena involve changes in microvascular blood flow to the intestine. Adenosine (Ado) derived from energy metabolism causes vasodilation and appears to be involved in some of these events. The Ado-mediated control mechanisms appear to vary with the diameter of the microvessels and the function of the tissue. This suggests the possibility that Ado-based microvascular control varies between anatomic intestinal segments and microvascular levels in those intestinal segments. METHODS: In vivo digital intravital microscopy was used to measure the responses of larger distributing (A1) and smaller premucosal (A3) vessels to Ado in intact neurovascular loops of jejunum and terminal ileum of the rat. Dose-response curves to Ado were determined. RESULTS: Microvascular dilation and augmented blood flow to Ado were significantly greater in the jejunum than in the terminal ileum. Ado-induced dilation was greater in the smaller A3 than in the larger A1 microvessels. DISCUSSION: These data indicate (1) different vasodilator mechanisms for the jejunum and the terminal ileum, (2) a greater role for Ado-related microvascular control in the jejunum compared with the ileum, and (3) a greater Ado-related control in the premucosal (A3) vessels. These findings suggest that Ado-mediated microvascular effects could explain why some clinical phenomena vary in intensity in selective intestinal segments, and are likely to involve different microvascular control mechanisms in the different segments. Knowledge of these Ado mechanisms could be beneficial in certain clinical scenarios to control blood flow during pathologic conditions.     

Volume replacement and microhemodynamic changes in polytrauma

Though fluid administration is one of the most basic concepts in resuscitation, there is ongoing controversy and continuing research on the definition of the ideal fluid for resuscitation of trauma and hemorrhage and for intraoperative volume support. In general, crystalloids and colloids, as well as blood, blood substitutes and oxygen therapeutics, are available. This report briefly revisits the physiological mechanisms underlying resuscitation with crystalloids and colloids, emphasizing colloid-supplemented resuscitation with hypertonic saline. Finally, potential applications of oxygen therapeutics are briefly considered.     

Efficiency of small-volume resuscitation in restoration of disturbed skeletal muscle microcirculation after soft-tissue trauma and haemorrhagic shock

Background and aims Despite advances in primary care, trauma in conjunction with shock remains the leading cause for morbidity and mortality of young adults in western countries. Herein, we report on the efficiency of small-volume resuscitation to improve compromised perfusion of traumatised skeletal muscle tissue in shock.Methods In pentobarbital anaesthetised, mechanically ventilated rats, closed soft-tissue trauma of the right hind limb was induced, followed by induction of haemorrhagic shock [mean arterial blood pressure (MAP) 40 mmHg for 1 h]. For resuscitation, animals received saline (four-times the shed blood volume/20 min), 10% hydroxyethyl starch (HES) 200/0.5 (equal to shed blood volume/5 min) or 7.2% sodium chloride/6% hydroxyethyl starch 200/0.5 (HyperHES; 10% of shed blood volume/2 min). At 2 h of resuscitation, traumatised skeletal muscle tissue was analysed by in vivo microscopy. Non-resuscitated animals served as shock controls.Results Despite incomplete restoration of systemic blood pressure, HyperHES was superior to saline, but not to HES, with respect to amelioration of nutritive perfusion. Inflammatory cell response within the traumatised skeletal muscle tissue escaped from the anti-adhesive properties of HyperHES when applied for resuscitation from hypovolaemic shock, and did not differ from values in HES-treated and saline-treated animals.Conclusion Resuscitation with HyperHES is as effective as HES in improving capillary perfusion in traumatised skeletal muscle during haemorrhagic shock. However, because values of functional capillary density in the HyperHES-treated and HES-treated animals were still markedly below those reported in traumatised skeletal muscle of normovolaemic animals, further tools are needed to enhance efficiency in treatment of local skeletal muscle tissue injury during haemorrhagic shock.The paper was presented at the International Symposium on Significance of Musculo-Skeletal Soft Tissue on Pre-Operative Planning, Surgery and Healing, 13–14 February 2003, Berlin, Germany     

Rosiglitazone increases extravasation of macromolecules and endothelial nitric oxide synthase in skeletal muscles of the fructose-fed rat model

Reduced extravasation of macromolecules in skeletal muscle has recently been documented in the fructose-fed rat model, corroborating a hypothesis that a functional obliteration of muscle regional microcirculation might lead to hypertension and restrict access of nutrients and hormones to their target cells. The goal of this study was to assess the impact of a treatment with rosiglitazone on the reduced muscle vasopermeability observed previously in the fructose-fed rat model. Fructose-fed Sprague-Dawley rats were gavaged with rosiglitazone (10 micromol kg(-1) per day; n = 21) or the vehicle only (n = 19) for 3 consecutive weeks before assessing the extravasation of Evans Blue (EB) dye in vivo in distinct muscle groups. Relative to control group, rosiglitazone reduced mean arterial blood pressure (Delta = -16.7%, P < 0.001), plasma insulin (Delta= -39.1%, P < 0.05) and plasma triglyceride (Delta= -32.8 %, P < 0.01) concentrations in a significant manner. Plasma VEGF concentrations were significantly lower in the rosiglitazone-treated animals compared to the control animals (32.7 +/- 0.8 pg ml(-1) versus 46.1 +/- 1.2 pg ml(-1), P < 0.001). While no changes were observed in the lungs or the kidneys, fructose-fed rats treated with rosiglitazone had a 30-50% increase (P < 0.005) in the extravasation of EB regardless of the skeletal muscle group studied (rectus femoris, soleus, gastrocnemius lateralis, vastus lateralis and tibialis cranalis). In homogenates of skeletal muscles (vastus lateralis) of fructose-fed rats, rosiglitazone resulted in a significant increase in NO synthase (NOS) activity (Delta = +41.9 %, P < 0.003) as well as endothelial NOS immunoreactive mass (Delta = +37.8 %, P < 0.01) compared to the control animals. There was no change in the immunoreactive level of the nNOS isoform, the most abundant muscle isoform, or in the immunoreactive levels of VEGF. In conclusion, rosiglitazone appears to restore a vascular dysfunction previously documented in the skeletal muscle microcirculation, as evidenced by improved skeletal muscle vasopermeability and upregulation of the muscle endothelium-NO system in the fructose-fed rat model. These effects on muscle per se might also result in a partial improvement of the insulin resistance phenomenon by improving the distribution of nutrients and insulin to skeletal muscle. This effect appears to be independent of circulating levels of VEGF since changes in plasma concentrations of this permeability factor were lower in the rosiglitazone-treated group.