BEMF对卵巢切除骨质疏松大鼠治疗作用的骨形态计量学研究

目的观察BEMF对OVX—OP大鼠骨形态计量学指标的影响，探讨BEMF对卵巢切除致骨质疏松大鼠的治疗作用及机制。方法6个月龄雌性未孕Wistar大鼠40只，按体质量随机分为卵巢切除组（OVX）、假手术组（Sham）、仿生电磁场治疗组（EM）、雌激素治疗组（E）。术后8周，E组苯甲酸雌二醇肌肉注射，0．5mg／kg，1次，2周。EM组大鼠暴露于仿生电磁场治疗，1h·次^-1·d^-1，OVX、Sham组不予以任何处理，作为对照组。治疗10周后处死各组大鼠，取左侧胫骨进行骨形态计量学测定。结果治疗10周后，EM组大鼠％Tb．Ar、Tb．Th、Tb．N较OVX组显著增加（P〈0．01），Tb．sp显著降低（P〈0．01），与E组变化相似。E组、EM组大鼠成骨细胞数（％L．Pm）低于OVX组（P〈0．01）；EM组、E组仍高于Sham组（P〈0．01）；EM组高于E组（P〈0．01）。E组、EM组破骨细胞数（N．Oc）低于OVX组（P〈0．01）；EM组、E组仍高于Sham组，（P〈0．01）；EM组高于E组，差异非常显著（P〈0．01）。结论BEMF具有增加骨量、改善骨结构的作用；与雌激素的治疗作用存在不同机制。     

DXA测量活体大鼠骨的精密性及骨丢失的检测

目的 了解QDR－4500A型双能X射线吸收法（DXA）测量活体大鼠的精密性和探测去卵巢后大鼠骨丢失的能力。方法 测量15只体重为202－311g的SD大鼠全身、股骨及腰椎的骨密度（BMD）,每只大鼠测量3次,可得变异系数（CV）,15只大鼠CV的平均值为该指标的批内CV。结果 ①全身、股骨、腰椎BMD的批内CV分别为0．71％、2．02％和2．44％。全身BMD的批内CV显著低于股骨和腰椎（P＜0．05）;②全身BMD的批间CV为0．99％,股骨整体为2．81％,腰椎总体（L3－L6）为3．42％;③术后4周去卵巢组全身、股骨、腰椎BMD与假手术组比较无显著性变化,而股骨远侧干骺端BMD低于假手术组（P＜0．05）;④去卵巢后14周腰椎总体（L4－L6）的BMD低于假手术组（P＜0．05）。结论 QDR－4500A型DXA测量大鼠全身、股骨和腰椎BMD有较好的精密性,全身优于局部骨骼;其精密性能满足检出去卵巢后骨丢失。     

外源性PTH对摘卵大鼠骨髓PPARγ mRNA表达的影响

目的观察骨质疏松大鼠骨髓微环境PPARγ mRNA表达变化和PTH治疗绝经后骨质疏松症的分子机制。方法雌性大鼠随机分为Sham、OVX和OVX＋PTH（1-34）20μg组，摘卵12周后给药，药后8周处死，观察骨髓脂肪细胞及PPARγmRNA表达变化。结果OVX组大鼠腰椎骨髓腔内脂肪空泡数较Sham组明显增加（P〈0．001），空泡百分面积为Sham组的26．81倍（P〈0．001）。OVX＋PTH20μg组的脂肪空泡数明显减少（P〈0．001），仅为OVX组的18．7％（P〈0．001）；OVX组骨髓PPARγmRNA表达较Sham组明显升高（P〈0．05—0．001），OVX＋PTH（1-34）20μg组PPARγmRNA表达则较不治疗组明显降低（P〈0．05～0．01）。结论OVX骨质疏松大鼠骨髓微环境PPARγmRNA表达上调，PTH对骨质疏松的促进骨形成作用与其抑制骨髓PPARγmRNA表达有关。     

鹿瓜多肽对去卵巢大鼠骨密度、股骨生物力学及松质骨中BMP2表达的影响

目的鹿瓜多肽（松梅乐）注射液肌注对去卵巢大鼠骨密度、股骨生物力学及松质骨中BMP2表达的影响。方法将8月龄未经产雌性二级SD大鼠30只，随机分为假手术组（SHAM）组、去势组（OVX）、去势＋鹿瓜多肽（OVX＋CCP）组。OVX＋CCP组大鼠术后第1天开始给药，术后20周处死各组大鼠．应用双能X线吸收仪（DEXA）测量各组大鼠股骨粗隆、股骨干中点及第3～5腰椎中点的骨密度（BMD）；应用INSTRON1195电子拉伸试验机检测股骨生物力学性能；利用免疫组织化学染色及图像分析方法对各组大鼠松质骨切片图像进行灰度分析，观察鹿瓜多肽注射液对OVX大鼠松质骨中BMP2表达的影响。结果（1）OVX与SHAM组比较，灰度值降低明显（P〈0．01），而OVX＋CCP组灰度值较去势组降低（P〈0．01），表明OVX大鼠松质骨中骨小梁周围及髓腔中BMP2表达阳性细胞数明显多于SHAM组；而OVX＋CCP组骨小梁周围及髓腔内BMP2表达阳性细胞数多于去势组，且染色加深。（2）与SHAM组相比，OVX组股骨近端、股骨干、腰椎BMD明显降低（P〈0．01）；OVX＋CCP各部位BMD高于去势组（P〈0．01），但未达到SHAM组水平（P〈0．01）；（3）与SHAM比较，去势组大鼠股骨最大载荷、桡度、最大应力、弹性模量均明显下降（P〈0．01），治疗组上述指标高于去势组（P〈0．01），接近对照组水平（P〉0．05）。结论鹿瓜多肽注射液可以抑制和延缓骨质疏松的形成，对雌激素缺乏引起的骨质疏松具有预防作用。     

血清中骨质疏松相关蛋白分子标志物的筛选研究

目的：通过蛋白芯片筛选血清中反映早期绝经后骨质疏松症发生、发展的标志性分子。方法3月龄雌性SD大鼠20只，随机分为卵巢切除（ovariectomized, OVX）组和假手术（sham operation, Sham）组，每组10只，分别进行卵巢去势手术和假手术处理。术后2、4、6、8周对两组大鼠进行活体显微CT扫描，测量股骨远端骨密度及相关松质骨形态计量学动态参数；同时经内眦静脉取血，利用蛋白芯片检测血清中不同蛋白因子的含量。结果显微CT检测结果显示OVX组大鼠骨密度（BMD）、相对骨体积（BV/TV）、骨小梁厚度（Tb.Th）、骨小梁数目（Tb.N）从第4周开始下降，骨小梁分离度（Tb.Sp）开始上升， Sham组未见明显变化；到第8周各指标在OVX组与Sham组之间差异有统计学意义（P＜0.05）。蛋白芯片检测结果显示OVX组中干扰素?γ（IFN?γ）、β神经生长因子（b?NGF）分别从术后4周和6周后开始升高，同Sham组比较均至第8周具有明显差异（P＜0.05）。结论 IFN?γ和b?NGF水平在绝经后骨质疏松早期开始增高，可考虑作为诊断早期绝经后骨质疏松症发生的新型蛋白分子。     

糖皮质激素对成年大鼠骨量的影响

目的利用双能X线吸收法(DXA)探讨成年大鼠接受糖皮质激素后骨量变化的规律。方法 21只44周龄SD雌性大鼠分别假性去卵巢+未注射糖皮质激素(SHAM组)、摘除双侧卵巢(OVX组)或注射甲基强的松龙[2.5 mg/(kg·d)](PRED组),应用扇形束DXA(QDR-4500A)每4周测定一次全身骨密度(BMD)、骨矿含量(BMC)、骨骼面积(AREA);术后12周处死,测定离体腰椎、股骨、胫骨及其兴趣区的BMD、BMC、AREA。压缩试验测定第二腰椎最大载荷和弹性模量。结果 (1)术后8周开始OVX组体重显著重于同龄SHAM组(8周时,P0.05,12周时P0.01),术后4周开始PRED组体重显著轻于同龄SHAM组(P0.05);(2)术后12周OVX组整体BMC显著高于SHAM组(P0.05),术后8、12周OVX组整体BMC显著高于PRED组(P0.05);(3)术后12周OVX组离体第5、6腰椎BMD及第6腰椎BMC显著低于SHAM组和PRED组(P0.05),PRED组离体各腰椎BMD、BMC、AREA与SHAM组无明显差异;(4)术后12周与SHAM组比较,OVX组离体股骨(-7.42%)、股骨远端(-10.85%)和近端(-6.92%)、胫骨近端(-11.40%)BMD显著降低(P0.05),其中股骨、股骨远端、胫骨近端BMC也显著降低(P0.05);(5)术后12周与SHAM组比较,PRED组离体股骨及各区BMD、BMC、AREA无显著性差异,整体胫骨及各区BMD无显著性差异;(6)术后12周与SHAM组比较,OVX组及PRED组胫骨中远端骨量增加;(7)与SHAM组比较,OVX组最大载荷和弹性模量显著降低,PRED组最大载荷显著降低。结论成熟期大鼠接受甲基强的松龙后,皮质骨和松质骨骨量没有显著变化,DXA检查难以发现其骨丢失情况;力学性能改变提示糖皮质激素更多的是引起骨质量的改变而导致了力学性能的下降及骨折的发生。     

降钙素对卵巢切除大鼠股骨骨折愈合的影响

目的观察降钙素对卵巢切除大鼠股骨骨折愈合的作用，为临床上治疗骨质疏松性骨折提供实验依据。方法50只雌性、14周龄SD大鼠共分成5组，每组10只。分成假手术组（Sham，G1），双侧卵巢切除术组（OVX，G2），假手术＋骨折组（Sham＋F，G3），卵巢切除术＋骨折组（OVX＋F，G4），卵巢切除＋骨折＋降钙素药物组（OVX＋F＋CT，G5），骨折组大鼠均采用右股骨中段横行骨折，髓内针固定；降钙素采用皮下给药，隔日1次（16IU·kg^-1）。所有大鼠于术后4周杀死，取右侧股骨标本。然后，分别进行CR摄片、组织形态学观察，并应用双能X线骨密度仪（DEXA）测量右股骨整体、远段和中段骨密度以及BMP-2免疫组化观察，并应用病理图像分析仪对BMP-2免疫组化进行光密度测量。结果（1）OVX组与Sham组比较，BMD显著下降。（2）OVX＋F＋CT组与OVX＋F组比较：骨痂mBMD显著增高；BMP-2的表达无显著性差异。结论降钙素对OVX大鼠股骨骨折具有明显促进骨折愈合的作用，加速编织骨向板层骨的演变过程。     

间歇皮下注射人甲状旁腺激素不同片段(hFTH1-34及 hFTH1-84)对去卵巢大鼠股骨及腰椎骨量的影响

目的 比较间歇皮下注射人甲状旁腺激素不同片段（hPTH1-34)及（hPTH1-84)对完整雌性（Non-OVX)大鼠和去卵巢（OVX）大鼠股骨及腰椎1－4骨矿物含量（BMC）和骨密度（BMD）的影响。方法 Wistar雌性大鼠176只，分为hPTH1-34和hPTH1-84两大组（各80只及96只），每大组及各自分4组（每组各20只或24只），分别为：两组安慰剂组（未切卵巢及切卵巢）用安慰剂（PBS）进行皮下注射，每周3次，共2周；两组治疗组（未切卵巢及切卵巢）用hPTH1-34或hPTH1-84，皮下注射，每周3次，共2周。结果 1．卵巢切除术后3个月大鼠股骨及腰椎1－4BMC和BMD明显下降；2．两种片段的甲状旁腺激素（hPTH1-34及pPTH1-84)间歇注射均能使Non-OVX大鼠和OVX大鼠股骨及腰椎1－4BMC和BMD较相应对照组明显升高；且腰椎1－4较股骨的BMC和BMD升高更明显；3．OVX大鼠治疗后股骨与腰椎1－4BMC和BMD的升高率较Non-OVX大鼠更明显；OVX大鼠在治疗后股骨及腰椎骨量能恢复到去卵巢前水平；4．hPTH1-34较hPTH1-84更明显的使完整大鼠和OVX大鼠股骨BMC和BMD升高。结论 间歇皮下注射人甲状旁腺激素对大鼠股骨及腰椎骨量均有增高作用，尤其对腰椎的骨量以及对去卵巢大鼠骨量升高作用更明显；hPTH1-34片段对大鼠股骨骨量的增高作用强于hPTH1-84片段。     

甲状旁腺激素相关蛋白对去卵巢大鼠骨组织中OPG、RANKL基因表达的影响

目的观察不同剂量间歇性注射甲状旁腺激素相关蛋白氨基端片段1—34（PTHrP1—34）对去卵巢大鼠骨密度及股骨RANKL、OPG基因表达的影响。方法4月龄健康雌性未孕Wistar大鼠60只，随机分为6组，假手术组（Sham组）和卵巢切除＋安慰剂组（Placebo组）给予生理盐水；卵巢切除＋雌激素治疗组（E2组）给予苯甲酸雌二醇注射液；卵巢切除＋PIHrP治疗组分别用20、40、80ktg／kg剂量，每日1次注射PTHrP1—34。给药12周后，测定腰椎L3-6及股骨BMD，利用实时荧光定量RT-PCR方法检测大鼠股骨RANKL、OPG基因表达的水平。结果①BMD结果：PTHrP40组和PTHrPS0组大鼠股骨、腰椎BMD明显高于Placeb0组。②与Sham组相比，Placebo组OPGmRNA明显下降（P〈0．01），RANKLmRNA水平则显著升高（P〈0．01）。E2组OPGmRNA水平较Placebo组明显升高（P〈0．01），RANKLmRNA水平显著下降（P〈0．01）。与Placebo组相比，不同剂量胛HrP（1-34）治疗组OPG、RANKLmRNA水平无明显变化（P〉0．05）。结论PTHrPl—3440或80ug／kg每天皮下注射能提高去卵巢大鼠股骨、腰椎BMD，间歇性注射PTHrP（1-34）对去卵巢大鼠骨组织RANKL、OPGmRNA水平无明显影响。     

狄诺塞麦对去卵巢大鼠股骨干骺端骨缺损修复影响的实验研究

目的研究狄诺塞麦(DMAb)对去卵巢大鼠股骨干骺端骨缺损修复的影响。方法 40只健康雌性SD大鼠随机行假手术(Sham,n=15)和切除双侧卵巢(OVX,n=25)手术,术后12 w每组各取5只大鼠处死取股骨行双能X线骨密度仪检测来确定骨质疏松的建立情况,随后各组大鼠在双侧股骨干骺端建立3 mm圆形缺损,术后随机分成3组:Sham、OVX组及DMAb组。术后第一天DMAb组给予DMAb皮下注射一次,剂量为60 mg,正常饲养12 w后所有大鼠处死取股骨行Micro-CT、骨生物力学、组织切片检测。结果和OVX组、Sham组股骨干骺端缺损愈合相比,DMAb组大鼠股骨干骺端缺损区域有较高的最大载荷、骨密度(BMD)、骨体积分数(BV/TV)、骨小梁厚度(Tb.Th)、骨小粱数量(Tb.N)、连接密度(Conn.D)、骨矿化沉积率(MAR)和较低的骨小粱分离度(Tb.Sp),且各组之间比较差异有统计学意义(P0.05)。结论 DMAb通过增加骨量,促进骨组织矿化及提高骨骼强度来加速去势大鼠股骨干骺端骨缺损的修复。     

Vasopressor hormone response following mesenteric traction during major abdominal surgery

Background : We investigated the vasopressor hormone response following mesenteric traction (MT) with hypotension due to prostacyclin (PGI₂) release in patients undergoing abdominal surgery with a combined general and epidural anesthesia. Methods : In a prospective, randomized, placebo-controlled study we administered 400 mg ibuprofen (i.v.) in 42 patients scheduled for abdominal surgery. General anesthesia was combined with epidural anesthesia (T4-L1). Before as well as 5, 15, 30, 45, and 90 min after MT we recorded plasma osmolality, hemodynamics and measured 6-keto-PGFlα (stabile metabolite of PGI₂), TXB₂ (stabile metabolite of thromboxane A₂) active renin, and arginine vasopressin (AVP) plasma concentrations by radioimmunoassay. Catecholamine levels were assessed by high-pressure liquid chromatography (HPLC) with electrochemical detection. Results : Following MT, arterial hypotension occurred along with a substantial PGI₂ release. This was completely abolished by ibuprofen administration. Although plasma levels of 6-keto-PGF_1α (1133 (708) vs. 60 (3) ng/L, median (median absolute deviation), P=0.0001, placebo vs. ibuprofen) remained significantly elevated, blood pressure was restored within 30 min after MT in the placebo group. At the same point in time plasma concentrations of TXB² (164 (87) vs. 58 (1) ng/L, P=0.0001), epinephrine (46 (33) vs. 14 (6) ng/L, P=0.001), AVP (41 ± (18) vs. 12 (7) ng/L, P=0.0004), and active renin (27 (12) vs. 12 (4) ng/L, P = 0.001) were significantly higher in placebo-treated patients. Conclusion : Under combined general and epidural anesthesia arterial hypotension following MT due to endogenous PGI₂ release is associated with enhanced release of AVP, active renin, epinephrine and thromboxane A₂, presumably contributing to hemodynamic stability within 30 min after MT.     

A Teaspoon Pump for Pumping Blood with High Hydraulic Efficiency and Low Hemolysis Potential

Abstract: Virtually all blood pumps contain some kind of rubbing, sliding, closely moving machinery surfaces that are exposed to the blood being pumped. These valves, internal bearings, magnetic bearing position sensors, and shaft seals cause most of the problems with blood pumps. The original teaspoon pump design prevented the rubbing, sliding machinery surfaces from contacting the blood. However, the hydraulic efficiency was low because the blood was able to "slip around" the rotating impeller so that the blood itself never rotated fast enough to develop adequate pressure. An improved teaspoon blood pump has been designed and tested and has shown acceptable hydraulic performance and low hemolysis potential. The new pump uses a nonrotating "swinging" hose as the pump impeller. The fluid enters the pump through the center of the swinging hose; therefore, there can be no fluid slip between the revolving blood and the revolving impeller. The new pump uses an impeller that is comparable to a flexible garden hose. If the free end of the hose were swung around in a circle like half of a jump rope, the fluid inside the hose would rotate and develop pressure even though the hose impeller itself did not "rotate"; therefore, no rotating shaft seal or internal bearings are required.     

A comparison of the inhibitory effects of four volatile anaesthetics on the metabolism of chlorzoxazone, a substrate for CYP2E1, in rabbits

Background: Halothane inhibits in vitro and in vivo activity of cytochrome P-450 (CYP) 2E1. There are several fluorinated volatile anaesthetics besides halothane, and most of them are defluorinated by CYP2E1. It is unclear whether other fluorinated anaesthetics inhibit the in vivo activity of CYP2E1.
Methods: We compared the inhibitory effects of therapeutic concentrations of four inhalational anaesthetics, halothane, enflurane, isoflurane, and sevoflurane, on chlorzoxazone metabolism in rabbits receiving artificial ventilation.
Results: All four inhalational anaesthetics decreased arterial blood pressure and increased plasma chlorzoxazone concentration. However, no significant differences in the plasma chlorzoxazone concentration were found between the four anaesthetics. The estimated chlorzoxazone clearance increased after beginning inhalation with all four agents, but no significant difference in clearance was noted between agents.
Conclusions: At therapeutic concentrations, the in vivo inhibitory effect on chlorzoxazone metabolism was similar for all four inhalational anaesthetics examined, even though their chemical characteristics and extent of hepatic metabolism differ considerably.     

Microspheres Based Detoxification System: A New Method in Convective Blood Purification

Abstract: A variety of protein-bound or hydrophobic substances, accumulating as a result of pathologic conditions such as exogenous or endogenous intoxications, are removed poorly by conventional detoxification methods because of low accessibility (hemodialysis), insufficient adsorption capabilities (hemosorption), low efficiency (peritoneal dialysis), or economic limitations (high-volume plasmapheresis). Combining advantages of existing methods with microspheric technology, a module-based system was designed. Major operating parameters of the latter can be modified to allow for adjustment to individual clinical situations. An extracorporeal blood circuit including a plasmafilter is combined with a secondary high-velocity plasma circuit driven by a centrifugal pump. Different microspheric adsorbers can be combined in one circuit or applied in sequence. Thus, a prolonged treatment can be tailored using specially designed selective adsorber materials. Comparing this system with existing methods (high-flux hemodialysis, molecular adsorbent recycling system), results from our in vitro studies and animal experiments demonstrate the superior efficiency of substance removal.     

Tissue perfusion in relation to cardiac output during continuous positive-pressure ventilation and administration of propranolol or verapamil

Background : Our objective was to determine whether administration of propranolol or verapamil modifies the hemodynamic adaptation to continuous positive-pressure ventilation (CPPV), in particular the regional distribution of cardiac output (CO).
Methods : General hemodynamics and regional blood flows assessed by microsphere technique (15 (μm) were recorded in 16 anesthetized pigs during spontaneous breathing (SB) and CPPV with 8 cm H₂O end-expiratory pressure (CPPV8) before and after intravenous administration of propranolol (0.3 mg · kg⁻¹ followed by 0.15 mg · kg⁻¹ · h⁻¹, n=8) or verapamil (0.1 mg · kg⁻¹ followed by 0.3 mg · kg⁻¹ · h⁻¹, n=8).
Results : CPPV8 depressed CO by 25% without shifts in its relative distribution with the exception of a noteworthy increase in adrenal perfusion. Propranolol increased arterial blood pressure, and due to a fall in heart rate, CO dropped by 25%. The kidneys and, to a lesser extent, the splanchic region and central nervous system received increased fractions of the remaining CO at the expense of skeletal muscle flow. Similar patterns were seen during SB and CPPV8 such that the combination of propranolol and CPPV8 depressed CO by 50%. The circulatory effects of verapamil were less evident but myocardial perfusion tended to increase.
Conclusions : The combination of propranolol or verapamil with CPPV does not result in any specific hemodynamic interaction in anesthetized pigs, except that the combined effect of propranolol and CPPV may severely reduce CO.     

Bariatric Surgery in Some "Central and East-European (former Eastern bloc)"Countries - Current Status and Prediction for the Next Millennium

Background: Obesity is increasing globallly, including in the formerly "Eastern Bloc" countries. Methods: A survey was made of obesity and bariatric surgery. Results: In the 8 East and Central European countries studied, with total population 300 million, roughly 43% of the population was overweight (BMI 25-30), 23% obese (BMI > 30), with about 15 million people morbidly obese (BMI > 40). From 0-10 morbidly obese individuals/100,000/year undergo bariatric surgery. Conclusion: Most countries were found to provide inadequate treatment for obesity.The majority of the morbidly obese are not treated effectively. However, health-care awareness of obesity and bariatric surgeons are slowly increasing.     

Volatile anaesthetics reduce adhesion of blood platelets under low-flow conditions in the coronary system of isolated guinea pig hearts

Background : Inhibitory effects of volatile anaesthetics on platelet aggregation have been demonstrated in several studies. However, the influence of volatile anaesthetics on intracoronary platelet adhesion has not been elucidated so far.
Methods : Isolated hearts of guinea pigs were perfused with buffer in the absence or presence of volatile anaesthetics (0.5 and 1 MAC) at constant coronary flow rates of 5 ml/min for 25 min, then 1 ml/min for 30 min and again 5 ml/min for 10 min. Before, during and after low-flow perfusion, a bolus of human platelets was applied into the coronary system. To simulate thrombogenic conditions, 0.3 U/ml human thrombin was infused during low-flow perfusion and reperfusion. The number of platelets sequestered to the endothelium was calculated from the difference between coronary in- and output of platelets. The myocardial production of lactate and consumption of pyruvate and coronary perfusion pressure were also determined.
Results : At a flow rate of 5 ml/min only about 3% of the applied platelets did not emerge from the coronary system, in any group. In contrast, 13.1±1.2% (mean±SEM) of infused platelets became adherent in low-flow perfusion in the control group without anaesthetic. The adherence was reduced with each 1 MAC isoflurane (to 6.2±1.2%), sevoflurane (to 4.4±0.9%) or halothane (to 3.2±1.5%) (each P <0.05 vs. control). Volatile anaesthetic, 0.5 MAC, did not inhibit platelet adhesion to a statistically significant extent in any case. Perfusion pressure and metabolic parameters were not statistically different between the control and the hearts exposed to anaesthetics.
Conclusion : Volatile anaesthetics in a concentration of 1 MAC can reduce the adhesion of platelets in the coronary system under reduced flow conditions. This action does not arise from vasodilation or inhibition of ischaemic stress.     

Synergistic interaction between the effects of propofol and midazolam with fentanyl on phrenic nerve activity in rabbits

Background: It has been shown that the depressive effects of both propofol and midazolam on consciousness are synergistic with opioids, but the nature of their interactions on other physiological systems, e. g. respiration, has not been fully investigated. The present study examined the effect of propofol and midazolam alone and in combination with fentanyl on phrenic nerve activity (PNA) and whether such interactions are additive or synergistic. Methods: PNA was recorded in 27 anaesthetised and artificially ventilated rabbits. In three groups, propofol, fentanyl and midazolam were administered intravenously in incremental doses to construct dose-response curves for the depressant effects of each one on PNA. In another two groups, the effect of pretreatment with either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. on the effects of propofol and fentanyl respectively on PNA were studied. Results: Propofol and fentanyl caused a dose-dependent depression of PNA with complete abolition at the highest total doses of 16 mg · kg^?1 i. v. and 32 μg · kg^?1 i. v., respectively. In contrast, midazolam in incremental doses to a total of 0.8 mg · kg^?1 reduced mean PNA by 63%, but approximately 12% of PNA remained at a total dose as high as 6.4 mg · kg^?1. The mean ED₅₀s, calculated from dose-response curves, were 5.4 mg · kg^?1, 3.9 μg · kg^?1 and 0.4 mg · kg^?1 for propofol, fentanyl and midazolam, respectively. Initial doses of either fentanyl 1 μg · kg^?1 i. v. or midazolam 0.05 mg · kg^?1 i. v. acted synergistically with subsequent doses of either propofol or fentanyl to abolish PNA at total doses of 8 mg · kg^?1 and 8 μg · kg^?1, respectively. Conclusion: Fentanyl has a synergistic interaction with both propofol and midazolam on PNA and hence potentially on respiration.     

Influence of dopexamine hydrochloride on haemodynamics and regulators of circulation in patients undergoing major abdominal surgery

Background: Catecholaminergic support is often used to improve haemodynamics in patients undergoing major abdominal surgery. Dopexamine is a synthetic vasoactive catecholamine with beneficial microcirculatory properties. Methods: The influence of perioperative administration of dopexamine on cardiorespiratory data and important regulators of macro- and microcirculation were studied in 30 patients undergoing Whipple pancreaticduodenectomy. The patients received randomized and blinded either 2 μg · kg^?1 · min^?1 of dopexamine (n=15) or placebo (n=15, control group). The infusion was started after induction of anaesthesia and continued until the morning of the first postoperative day. Endothelin-1 (ET-1), vasopressin, atrial natriuretic peptide (ANP), and catecholamine plasma levels were measured from arterial blood samples. Measurements were carried out after induction of anaesthesia, 2 h after onset of surgery, at the end of surgery, 2 h after surgery, and on the morning of the first postoperative day. Results: Cardiac index (CI) increased significantly in the dopexamine group (from 2.61±0.41 to 4.57±0.78 1 · min^?1 · m^?2) and remained elevated until the morning of the first postoperative day. Oxygen delivery index (DO₂I) and oxygen consumption index (VO₂I) were also significantly increased in the dopexamine group (DO₂I: from 416±91 to 717±110 ml/m² · m²; VO₂I: from 98±25 to 157±22 ml/m² · m²), being significantly higher than in the control group. pHi remained stable only in the dopexamine patients, indicating adequate splanchnic perfusion. Vasopressive regulators of circulation increased significantly only in the untreated control patients (vasopressin: from 4.37±1.1 to 35.9±12.1 pg/ml; ET-1: from 2.88±0.91 to 6.91±1.20 pg/ml). Conclusion: Patients undergoing major abdominal surgery may profit from prophylactic perioperative administration of dopexamine hydrochloride in the form of improved haemodynamics and oxygenation as well as beneficial influence on important regulators of organ blood flow.     

Systemic analgesia adapted to the children's condition

A concept of balanced analgesia using nonsteroidal anti-inflammatory drugs (NSAIDs), paracetamol (acetaminophen), opioids, and corticosteroids can also be used in patients with pre-existing illnesses. NSAIDs are the most effective treatment for acute pain of moderate intensity in children; however, these drugs should be avoided in patients at increased risk for serious side effects, e.g. patients with renal impairment, bleeding tendency, or extreme prematurity. NSAIDs can be given with minimal risks to the younger child with mild to moderate asthma, and, in these patients, the use of steroids can be encouraged; in addition to their antiemetic and analgesic action, a beneficial effect on asthma symptoms can be expected. In the non-intubated child with cerebral trauma, exaggerated sedation caused by opioids and increased bleeding tendency caused by NSAIDs must be avoided. In neonates and small infants, the oral administration of sucrose or glucose is helpful to minimize pain reaction during short uncomfortable interventions.