rhPTH（1-34）治疗OVX大鼠骨质疏松延后效应的初步研究

目的观察重组人甲状旁腺激素（1-34）[rhPTH（1-34）]对卵巢摘除（OVX）大鼠骨质疏松症的治疗作用及停药后效应.方法应用双侧卵巢摘除方法建立模拟绝经后骨质疏松大鼠模型;给予皮下注射20μg/kg/d rhPTH（1-34）治疗8周,观察其骨量、骨生物力学、骨小梁形态计量及骨代谢相关血、尿生化指标,综合评价PTH对模型大鼠的治疗效果;同时观察停药8周后上述指标的变化.结果外源性PTH（1-34）治疗能显著增加模型大鼠的骨量、骨力学性能,改善骨微结构、增加骨转换.用药组的骨密度、股骨三点弯曲与腰椎压缩最大载荷、腰椎骨小梁百分面积显著高于对照组（P＜0.05～0.001）;血ALP（P＜0.05～0.01）与尿Pyd（P＜0.05）保持高水平;PTH停药8周后大鼠股骨与腰椎骨密度、股骨三点弯曲与腰椎压缩最大载荷及腰椎骨小梁百分面积均较停药前显著降低（P＜0.05～0.001）,但仍显著高于OVX对照组（P＜0.05～0.001）.结论外源性PTH（1-34）可显著增加OVX大鼠的骨量,提高骨力学性能,改善骨微结构,对卵巢摘除诱导的大鼠骨质疏松具有明显治疗作用;停药后出现骨量的快速丢失,骨力学性能下降等变化,但仍显示出其对OVX大鼠骨骼的保护作用.     

大豆异黄酮对肾辐射损伤大鼠骨量和骨结构的影响

目的观察大豆异黄酮对肾辐射损伤大鼠骨量、骨生物力学和骨形态计量的影响.方法应用15Gy 137Cs γ射线局部照射大鼠双侧肾脏,建立肾损伤引起继发性骨质疏松模型,以假照射组大鼠为对照.术后7 d开始用药,给予大豆异黄酮(100 mg/kg·d),以萌格旺(0.1 μg/kg·d)为阳性对照药物,治疗3个月后处死大鼠,观察骨量、骨生物力学和骨形态计量学指标改变,综合评价大豆异黄酮对肾辐射损伤性骨质疏松的防治作用.结果肾辐射损伤大鼠骨量、骨生物力学指标较假照射组显著降低(P＜0.05),表明肾辐射损伤引起大鼠继发性骨质疏松模型成功;大豆异黄酮治疗能明显增加模型大鼠的腰椎BMD、股骨干重与灰重,提高股骨三点弯曲最大载荷,增加腰椎骨小梁面积百分比(P＜0.05).结论大豆异黄酮对肾局部辐射损伤诱导骨质疏松模型大鼠的骨量和骨结构有明显改善作用.     

GLP-1受体激动剂利拉鲁肽对糖皮质激素性骨质疏松大鼠的疗效和作用机制研究

目的讨论GLP-1受体激动剂利拉鲁肽对糖皮质激素性骨质疏松(GIOP)大鼠模型骨代谢指标的影响,包括对骨量、骨组织微结构、骨生物力学、骨转换标志物的作用。方法选取30只8周龄雄性SD大鼠,随机分为对照组、地塞米松组、利拉鲁肽干预组,每组各10只。除对照组外,各组均予以地塞米松1 mg/kg肌肉注射(2次/周)诱导糖皮质激素性骨质疏松。利拉鲁肽组同时给予利拉鲁肽200μg/(kg·d)皮下注射干预。对照组给予同等体积0. 9%氯化钠肌肉注射。干预12周后收集两侧股骨和第五腰椎行Micro-CT和骨生物力学检测。同时收集外周血清检测抗酒石酸酸性磷酸酶(Str ACP)、Ⅰ型胶原交联羧基端肽(CTX-1)、碱性磷酸酶(ALP)、和骨钙素(OC)。结果地塞米松组股骨远端干骺端和第五腰椎的骨密度(BMD)、组织骨密度(TMD)、骨体积分数(BV/TV)、骨小梁分离度(Tb.Sp)、骨小梁厚度(Tb.Th)、骨小梁数量(Tb.N)、连接密度(Conn.D)、最大载荷和弹性模量均较对照组明显降低,骨吸收指标Tr ACP、CTX-1显著升高,骨形成指标ALP、OC显著降低(均P0. 05)。利拉鲁肽干预组大鼠的骨密度、骨微结构、骨生物力学指标得到明显改善,且Tr ACP、CTX-1明显降低,ALP、OC明显升高(均P0. 05)。结论利拉鲁肽能对抗糖皮质激素的致骨质疏松作用,改善糖皮质激素造成的骨质疏松状态,机制可能与减少骨吸收以及促进骨形成有关。     

rhPTH_((1-34))治疗OVX大鼠骨质疏松延后效应的初步研究

目的观察重组人甲状旁腺激素(134)[rhPTH(134)]对卵巢摘除(OVX)大鼠骨质疏松症的治疗作用及停药后效应。方法应用双侧卵巢摘除方法建立模拟绝经后骨质疏松大鼠模型;给予皮下注射20μgkgdrhPTH(134)治疗8周,观察其骨量、骨生物力学、骨小梁形态计量及骨代谢相关血、尿生化指标,综合评价PTH对模型大鼠的治疗效果;同时观察停药8周后上述指标的变化。结果外源性PTH(134)治疗能显著增加模型大鼠的骨量、骨力学性能,改善骨微结构、增加骨转换。用药组的骨密度、股骨三点弯曲与腰椎压缩最大载荷、腰椎骨小梁百分面积显著高于对照组(P<0.05～0.001);血ALP(P<0.05～0.01)与尿Pyd(P<0.05)保持高水平;PTH停药8周后大鼠股骨与腰椎骨密度、股骨三点弯曲与腰椎压缩最大载荷及腰椎骨小梁百分面积均较停药前显著降低(P<0.05～0.001),但仍显著高于OVX对照组(P<0.05～0.001)。结论外源性PTH(134)可显著增加OVX大鼠的骨量,提高骨力学性能,改善骨微结构,对卵巢摘除诱导的大鼠骨质疏松具有明显治疗作用;停药后出现骨量的快速丢失,骨力学性能下降等变化,但仍显示出其对OVX大鼠骨骼的保护作用。     

胰岛素对糖尿病鼠骨量和骨生物力学的影响

目的探讨胰岛素对四氧嘧啶糖尿病大鼠骨量和骨生物力学方面的影响。方法将42只雄性SD大鼠分成正常组、糖尿病组和胰岛素治疗组,3个月后处死,测定股骨干及骺端骨量,并对股骨及腰椎进行生物力学测试,评价。结果与正常组比较,糖尿病组骨量明显降低;股骨极限抗弯承载力、腰椎极限抗压承载力和极限抗压强度均显著下降(P<0.01),弹性模量无明显变化。与糖尿病组比较,胰岛素治疗组骨量增加,股骨极限抗弯承载力、腰椎极限抗压承载力和极限抗压强度提高,但弹性模量异常增高(P<0.01)。结论胰岛素可显著增加糖尿病鼠松质骨骨量;明显提高其骨骼的抗压、抗弯能力,但同时出现了腰椎脆性增加的不良作用。     

水飞蓟宾通过PI3K/AKT/FoxO1通路改善骨质疏松大鼠骨代谢和骨量

目的探讨水飞蓟宾对糖皮质激素性骨质疏松(GIOP)大鼠骨量影响以及对PI3K/AKT/Fox O1通路影响。方法将30只12周龄雄性Sprague Dawley大鼠随机分为3组:对照组(n=10);地塞米松组(n=10)及地塞米松+水飞蓟宾组(n=10),对应给予地塞米松及水飞蓟宾治疗。12周后取双侧股骨进行微型计算机断层扫描(Micro-CT)和骨生物力学检测。同时检测抗酒石酸酸性磷酸酶(TRACP)、Ⅰ型胶原交联羧基末端肽(CTX-I)、碱性磷酸酶(ALP)和骨钙素(OC)。蛋白印迹分析大蒜素对PI3K/AKT/Fox O1通路影响。结果地塞米松组大鼠的骨密度(BMD)、骨微观结构和骨生物力学指标均明显低于对照组(P0.05)。骨吸收指标(TRACP和CTX-I)升高,骨形成指标(ALP和OC)降低。水飞蓟宾治疗后骨密度、骨微观结构、骨生物力学指标均有明显改善。与地塞米松组相比,地塞米松+水飞蓟宾组的TRACP和CTX-I显著降低,ALP和OC显著升高。进一步研究表明水飞蓟宾可以通过抑制地塞米松介导PI3K/AKT/Fox O1信号通路上调来调控骨代谢。结论水飞蓟宾可以通过PI3K/AKT/Fox O1信号通路调控骨代谢,提高GIOP大鼠骨密度、骨微观结构和骨强度。     

复方贞术调脂胶囊对糖皮质激素诱导骨质疏松大鼠股骨和腰椎骨密度及生物力学特性的研究

目的观察复方贞术调脂胶囊(FTZ)对糖皮质激素诱导骨质疏松大鼠股骨和腰椎骨密度及生物力学特性的影响。方法SPF级雄性SD大鼠32只,随机等分为4组:Nrm组为正常对照组,Met组为皮下注射甲强龙(Met)5 mg/(kg·d),每周5次,FTZL组和FTZH组在Met组基础上每日分别给予低剂量FTZ(1.5g/kg)和高剂量FTZ(6g/kg)灌胃,实验期为12w。QDR4500A型双能X线骨密度测定仪测定股骨和腰椎骨密度,MTS-858型生物力学实验机测定股骨和腰椎生物力学性能。结果Met组大鼠股骨和腰椎的骨密度、最大载荷、刚度、弹性模量、皮质骨厚度、股骨中段截面面积和椎体横断面面积均显著低于Nrm组相应指标(P0.001,P0.01),股骨骨髓腔面积显著高于Nrm组(P0.01);FTZL组大鼠的股骨骨密度,最大载荷、刚度、弹性模量、皮质骨厚度、股骨中段截面面积和椎体横断面面积较Met组有升高趋势,股骨骨髓腔面积较Met组减少,但两组间各指标均无显著性差异(P0.05);FTZH组大鼠股骨和腰椎的骨密度、最大载荷、刚度、弹性模量、皮质骨厚度和椎体横断面面积显著高于Met组相应指标(P0.01,P0.05),股骨骨髓腔面积显著低于Met组(P0.05),股骨中段截面面积较Met组有增加趋势,但无显著性差异(P0.05),FTZH组腰椎的骨密度和最大荷载显著高于FTZL组(P0.05),余各项指标间无显著性差异(P0.05)。结论高剂量FTZ对改善糖皮质激素诱导骨质疏松大鼠股骨和腰椎的骨密度及生物力学特性效果显著。     

2型糖尿病雌性大鼠骨代谢的特点

目的 研究2型糖尿病雌性大鼠骨密度和骨生物力学等指标的变化及各指标间的相互关系.方法 采用高糖高脂饮食加腹腔注射小剂量链脲佐菌素诱导建立2型糖尿病大鼠模型.20周后处死大鼠,测定股骨和腰椎骨密度(BMD)、骨灰干重比、骨生物力学以及骨代谢相关指标[血清Ca、骨钙素(BGP)、抗酒石酸酸性磷酸酶(TRAP)、尿Ca/肌酐比值、尿羟脯氨酸/肌酐比值],此外还观察了空腹血糖(FPG)、GHbAIc、甘油三脂(TG)、胆固醇(TC)、高密度脂蛋白-胆固醇(HDL-C)、低密度脂蛋白一胆固醇(LDL-c)、血清胰岛素(FINS)、胰岛素样生长因子(IGF)-I等变化.结果 与正常组相比,(1)糖尿病大鼠腰椎和股骨BMD、灰干重比、生物力学指标显著降低;(2)FPG、FINS及HOMA-IR均显著升高,说明存在胰岛素抵抗;(3)血清‘TRAP、TG、代、LDL广C、GHbA1c升高,血清BGP、IGF-I、HDI-C降低,差异均有显著性;(4)BGP与股骨BMD成显著正相关.结论 高糖高脂饲料联合小剂量链脲佐菌素注射,可成功建立2型糖尿病雌性大鼠模型.该模型大鼠具有高血糖、脂质代谢紊乱和胰岛素抵抗特点.2型糖尿病大鼠骨吸收加快而骨形成不足,导致其骨量下降和骨生物力学特性改变.     

重组人甲状旁腺素（1-34)与雌激素对去卵巢大鼠骨代谢的影响

目的观察重组人甲状旁腺素(1-34)与雌激素单用和联用对去卵巢大鼠骨代谢的影响。方法选用雌性4月龄SD大鼠45只,随机分为5组:①假手术(Sham)8只;②去卵巢(OVX)9只;③雌激素治疗组(OVX E)10只:OVX2个月后给予苯甲酸雌二醇治疗6w;④PTH治疗组(OVX PTH)9只:OVX2个月后给予rhPTH(1-34)治疗6w;⑤雌激素与PTH联合治疗组(OVX E PTH)9只:OVX2个月后给予rhPTH(1-34)和E2联合治疗6w。观察各组大鼠胫骨近端松质骨骨小梁形态计量学参数,椎体生物力学指标及部分血清骨生化代谢指标。结果雌激素治疗组和PTH治疗组的骨静态参数均表现为骨量增加;雌激素治疗组的骨形成参数和骨吸收参数降低;PTH治疗组的骨形成指标明显升高,而骨吸收指标虽较Sham高,但较OVX组有所降低;E2与PTH联合治疗组与单用E2组和单用PTH组比较,骨量明显提高,骨转换率参数介于单用E2和单用PTH组之间。3个治疗组的生物力学指标较OVX组均有明显提高,其中E2与PTH联合治疗组改善最明显。结论雌激素和PTH可使去卵巢大鼠松质骨骨量增加和改善生物力学性能,两者联合治疗有协同作用。     

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。     

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.