氯胺酮对离体大鼠心室肌细胞瞬时外向钾电流的影响

目的研究氯胺酮对大鼠心室肌细胞瞬时外向钾电流(Ito)的影响。方法酶解法分离大鼠心室肌细胞,采用全细胞膜片钳技术记录Ito,观察50μmol/L氯胺酮对Ito电流-电压曲线以及不同浓度氯胺酮对Ito的影响,并研究氯胺酮对Ito通道动力学的影响。结果钳制电压-40mV,刺激电压 70mV条件下,临床相关浓度的氯胺酮50μmol/L使Ito的电流峰值降低23·4%(P<0·01),冲洗后,Ito能够完全恢复。5、10、50、100、500、1000、5000μmol/L的氯胺酮抑制Ito呈浓度依赖性,电流抑制率分别为(13·8±9·7)%、(17·5±6·7)%、(23·4±8·8)%、(31·5±6·7)%、(63·3±5·5)%、(79·7±2·7)%、(88·9±4·4)%,其半数有效浓度(IC50)为299μmol/L。100μmol/L的氯胺酮对激活曲线没有影响;使Ito的失活曲线明显右移,半数失活电压(V1/2)在给药前后数值分别为(-28·27±0·20)mV和(-25·34±0·27)mV(P<0·01),斜率因子(k)值分别为(3·23±0·46)mV和(3·40±0·55)mV(P>0·05)。结论氯胺酮可明显阻滞大鼠心室肌的Ito,这是氯胺酮延长大鼠心室肌动作电位的机理之一,同时氯胺酮使Ito的失活曲线右移。     

氯胺酮对豚鼠心室肌细胞L-型钙电流的影响

目的观察氯胺酮对豚鼠心室肌细胞膜L-型钙电流(ICa-L)的影响。方法酶解法分离单个心室肌细胞,采用全细胞膜片钳技术,观察100μmol/L氯胺酮在不同钳制电压下以及不同浓度 (50-5 000μmol/L)氯胺酮在+10mV钳制电压下豚鼠心室肌细胞膜ICa-L的变化,并研究100μmol/L氯胺酮对ICa-L稳态激活曲线、稳态失活曲线和稳态失活后恢复曲线的影响。结果 100μmol/L氯胺酮抑制ICa-L,使电流密度-电压曲线上移,但不改变激活电压、峰值电压、翻转电压以及曲线形态;细胞外液冲洗后,ICa-L部分恢复。保持电压-40 mV、钳制电压+10 mV条件下,100-5 000 μmol/L氯胺酮呈浓度依赖性抑制ICa-L,其半数抑制浓度为926．6 μmol/L。100μmol/L氯胺酮对ICa-L激活曲线没有明显影响, 给药前后半数激活电压分别为-2．9±0．6、(-1．4±1．1)mV(P>0．05),斜率因子(k)分别为7．4±0． 5、(8．0±0．3)mV(P>0．05);100μmol/l氯胺酮使ICa-L的稳态失活曲线明显左移,给药前后半数失活电压分别为-14．8±0．8、(-19．6±0．7)mV(P<0．05),k分别为6．2±0．4、(5．9±0．3)mV(P>0．05); 100μmol/l氯胺酮使ICa-L的稳态失活后恢复曲线明显下移。结论氯胺酮可通过作用于L-钙通道的失活态,浓度依赖性地抑制豚鼠心室肌细胞ICa-L,产生负性肌力作用。     

异丙酚对人心房肌细胞瞬时外向整流钾电流的影响

目的 探讨异丙酚对人心房肌细胞瞬时外向整流钾电流(I_(to))的影响.方法 体外循环下行冠状动脉旁路移植术患者,术中于上腔静脉插管前取下右心耳组织,采用急性两步酶解法消化分离成单个心房肌细胞,室温下进行膜片钳全细胞模式记录I_(to).记录不同浓度(25、50、100、150、200 靘ol/L)异丙酚在+50 mV钳制电压下I_(to)的变化,并记录50μmol/L异丙酚对I_(to)激活、失活、失活后再激活动力学的影响.结果 与给药前相比,50、100、150、200 μmol/L异丙酚呈浓度依赖性地抑制I_(to)峰电流密度(P<0.05).给药前、后半数激活电压和斜率因子、半数失活电压和斜率因子、时间常数比较差异无统计学意义(P>0.05).结论 异丙酚可呈浓度依赖性地抑制人心房肌细胞I_(to),产生负性肌力作用,可能是其抗心律失常作用的重要机制之一.     

异丙酚、硫喷妥钠对大鼠心肌细胞钙、钾通道电流的影响

目的 研究异丙酚、硫喷妥钠对大鼠心肌细胞钙、钾通道电流的影响。方法 急性分离大鼠心室肌细胞,采用全细胞膜片钳技术,观察不同浓度异丙酚、硫喷妥钠对大鼠心肌细胞L型钙通道电流(I_(Ca))、延迟整流钾通道电流(IK)的作用。结果 随浓度增加,异丙酚和硫喷妥钠对I_(Ca)的抑制作用逐渐增强,与浓度呈正相关,相关系数分别为0.98、0.97(P<0.01),异丙酚、硫喷妥钠的IC_(50)分别为138.8±9.5、102.4±2.0μmol·L~(-1)。50μmol·L~(-1)异丙酚、100μmol·L~(-1)硫喷妥钠并不影响钙通道激活曲线的形态,但使钙通道稳态失活曲线向超极化方向分别移动3、7mV(P<0.05)。50μmol·L~(-1)异丙酚、100μmol·L~(-1)硫喷妥钠使IK降低10％和24％(P<0.01),250μmol·L~(-1)异丙酚、500μmol·L~1硫喷妥钠使IK进一步降低,较基础值下降了18％和46％(P<0.01)。结论 异丙酚、硫喷妥钠呈浓度依赖地抑制大鼠心肌细胞L型I_(Ca),其抑制作用主要与加快钙通道的失活有关,两药对IK也有抑制作用。     

氯胺酮对大鼠海马锥体神经元电压门控型钠通道的影响

目的研究氯胺酮对大鼠海马锥体神经元电压门控型钠通道的影响。方法急性分离 Wistar 大鼠(鼠龄两周)的海马锥体神经元,应用全细胞膜片钳技术记录电压门控型钠通道电流(INa), 加用不同浓度(50、100、200、500、1000、2000μmol/L)氯胺酮后,计算INa抑制率及半数抑制浓度(IC50); 选择100μmol/L氯胺酮作INa稳态激活及失活曲线。结果50、100、200、500、1000、2000μmol/L氯胺酮对INa的抑制呈浓度依赖性,IC50为(794±21)μmol/L;100μmol/L氯胺酮使INa稳态激活、失活曲线均向超极化方向移动,激活曲线的半数最大激活电位从(-51．6±O．9)．mV移至(-58．5±0．8)mV(P< 0．05),斜率因子(κ)分别为2．0±1．0、(3．2±0．9)mV(P<0．05);失活曲线的半数最大失活电位从 (-66．8±0．8)mV移至(-79．9±0．5)mV(P<0．05),κ分别为-6．6±0．7、(-7．0±0．4)mV(P> 0．05)。结论氯胺酮对电压门控型钠通道有抑制作用,与其全身麻醉作用有关。     

罗比卡因对豚鼠心室肌细胞L型钙通道的影响

目的观察罗比卡因对豚鼠心室肌细胞L型钙通道的影响,探讨其心肌负性肌力作用的机制。方法以急性酶解法获得豚鼠单个心室肌细胞,用全细胞膜片钳技术记录L型钙电流(ICa-L)。结果罗比卡因浓度依赖性阻滞豚鼠心室肌细胞ICa-L,其半最大抑制浓度(IC50)为(212±38)μmol/L,Hill常数为1.15±0.18。罗比卡因100μmol/L使钙电流峰值从(-4.6±1.7)pA/pF减小至(-2.9±0.9)pA/pF(P<0.01),抑制率为(37±3)%;使电流密度-电压曲线上移,但不改变激活电压、最大激活电压和曲线的形状;激活曲线也没有明显改变;使稳态失活曲线向左移,半失活电压由给药前(-11.0±1.0)mV降为给药后(-15.0±0.6)mV(P<0.05);使ICa-L稳态失活后再恢复的时间常数(τ)明显延长,由给药前(260±17)ms增加至给药后(346±32)ms(P<0.05)。结论罗比卡因作用于L型钙通道的失活态,从而抑制了心室肌细胞ICa-L,是其产生负性肌力作用的原因之一。     

氯胺酮对大鼠海马锥体神经元延迟整流钾电流的影响

目的观察氯胺酮对大鼠海马锥体神经元延迟整流钾电流(IK)的影响。方法酶消化法急性分离Wistar大鼠海马锥体神经元,采用全细胞膜片钳技术测定IK。加用不同浓度(10、30、100、300、1000μmol/L)氯胺酮后,计算IK抑制率,建立氯胺酮的浓度-效应曲线,选择30 μmol/L氯胺酮作IK 稳态激活(及失活)曲线。结果10、30、100、300、1 000μmol/L氯胺酮对IK的抑制率分别为(10±4)%、(19±4)%、(31±5)%、(50±7)%、(54±8)%。IC50为(100±18)μmol/L,Hill系数为1.33±0.48。激活曲线的半数最大激活膜电位(V1/2)(1.82±0.20)mV上升到(9.30±1.03)mV(n=8,P<0.05),K从(20.4±2.3)mV移动到(16.6±4.2)mV(P>0.05);失活曲线的V1/2从(-29±4)mV下降到(-73±6) mV(P<0.01),K从(26±6)mV上升到(53±11)mV(P<0.01)。30 μmol/L氯胺酮使IK的稳态激活曲线向去极化方向明显移动;使IK的稳态失活曲线向超极化方向明显移动。结论氯胺酮对IK通道有抑制作用,氯胺酮的对中枢神经系统的作用可能与IK抑制有关。     

咪唑安定对大鼠海马锥体细胞延迟整流K+通道的作用

目的探讨咪唑安定对大鼠海马锥体细胞上延迟整流K+通道(IK)的作用,及在其麻醉作用中的机制.方法急性分离大鼠海马锥体细胞,采用全细胞模式测定延迟外向整流K+电流,钳制电压由-50mV去极化至+30mV,加用不同浓度咪唑安定后测量电流的幅度变化.结果咪唑安定呈剂量性相关抑制延迟外向整流K+通道,EG50(8.31±2.78)×10-8 mol/L,Hill系数0.90±0.16.结论咪唑安定对延迟外向整流K+通道有抑制作用.     

硫喷妥钠对人心肌细胞内向整流钾通道电流的影响

目的 通过观察静脉麻醉药硫喷妥钠对人心肌细胞内向整流钾通道电流(Ik1)的影响,评价其对心肌抑制作用中可能的电生理改变作用。方法 采用急性分离的人心房肌细胞,应用膜片钳全细胞技术记录不同浓度的硫喷妥钠(30μmol/L、100μmol,L、300μmol/L)对细胞膜内向整流钾电流的影响。结果30μmol/L硫喷妥钠轻度抑制Ik1外向成分(+10 mV-+40mv,n=14个细胞,P<0.05),100μmol/L和300μmol/L硫喷妥钠分别同时抑制了Ik1内向(分别在测试电位-70mv--120mV)和外向(测试电位分别为0mV-+40 mV和-10 mv-+40 mv)成分(n=14个细胞,P<0.05)。在测试电位为+20 mV时,三组浓度(30、100、300μmol/L)的硫喷妥钠对电流的抑制率分别为:15.2％±2.1％、42.2％±5.0％和75.4％±5.7％,抑制程度与浓度呈正相关(r=0.968,P<0.05)。给予100μmol/L硫喷妥钠后,静息膜电位(RMP)由给药前的(-69.0±1.0)mV分别降为(-63.2±1.3)mV(n=12个细胞,P<0.05)和(-61.7±0.9)mV(n=9个细胞,P<0.05)。结论临床相关及其高于临床浓度的硫喷妥钠对人心房肌细胞内向整流钾电流有直接的和部分可逆性抑制作用,抑制效应具有浓度依赖性,提示这种改变与硫喷妥钠的心肌抑制作用,尤其是负性变时性作用有关。     

异丙酚对大鼠顶叶皮层神经元延迟整流性钾通道电流的影响

目的 探讨异丙酚对大鼠顶叶皮层神经元延迟整流性钾通道电流(IK)的影响.方法 酶消化法急性分离Wistar大鼠顶叶皮层神经元,随机分为4组,分别为不同浓度异丙酚组(P1-4组):培养皿加入异丙酚,终浓度分别为10、30、100和300 μmol/L.于异丙酚给药前,给药后1 min时采用全细胞膜片钳技术,记录顶叶皮层神经元IK,计算IK抑制率,绘制100 μmol/L异丙酚作用下大鼠皮层神经元延迟整流性钾通道电流-电压曲线、延迟整流性钾通道激活曲线和失活曲线.结果 与给药前比较,各组给药后顶叶皮层神经元IK降低(P<0.01);异丙酚对顶叶皮层神经元IK的抑制率呈浓度依赖性(P<0.01);100 μmol/L异丙酚给药后大鼠顶叶皮层神经元延迟整流性钾通道电流-电压曲线下移,但波形、阈电位没有改变;与给药前比较,100 μmol/L异丙酚给药后延迟整流性钾通道激活和失活曲线的半数激活膜电位、曲线斜率因子差异无统计学意义(P>0.05),激活曲线向右移动大约12 mV,失活曲线向左移动大约6 mV.结论 异丙酚可抑制大鼠顶叶皮层神经元IK,且呈浓度依赖性;100 μmol/L异丙酚可减慢延迟整流性钾通道激活,加速其失活.     

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.     

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.     

Is the recovery profile of mivacurium independent of the rate of decay of its plasma concentration in patients with normal plasma cholinesterase activity?

Background: The duration of action of muscle relaxants is poorly correlated to the rate of decay of their plasma concentration. The plasma concentration of mivacurium may rapidly decrease below its active concentration because of the extensive hydrolysis of mivacurium. By inflating a tourniquet on one upper limb for 3 min after the administration of atracurium, mivacurium or vecuronium, we studied the influence of the initial decline of their plasma concentration on their effect. Methods: In 50 patients anaesthetised with thiopental, isoflurane and fentanyl, the effect of bolus doses of 0.15 or 0.25 mg . kg^?1 mivacurium (MIV 15, MIV 25), 0.3 or 0.5 mg . kg^?1 atracurium (ATR 30, ATR 50) and 0.06 or 0.1 mg . kg^?1 vecuronium (VEC 06, VEC 10) were measured on both arms (evoked response of the adductor pollicis to train-of-four stimulation every 12 s), a tourniquet being applied on one arm just before and during 3 min after the muscle relaxant bolus. Results: Tourniquet inflation of 3 min almost abolished the neuromuscular effect of mivacurium. In the vecuronium groups and in the ATR 50 group, tourniquet inflation did not modify the maximum degree of depression of the twitch response. Also, the duration of action of vecuronium was unaffected by the tourniquet. In the ATR 30 group, times to return of the twitch response to 25% (duration 25%) and 75% (duration 75%) of control response were significantly shorter in the cuffed arm, 23 min vs 27 min, and 41 min vs 45 min, respectively. In the ATR 50 group, only duration 25% was significantly shorter in the cuffed arm (41 min vs 45 min). Conclusion: The results suggest that the rate of decline of the plasma concentration of mivacurium is so rapid, that a very low and almost clinically ineffective concentration is present as soon as 3 min after its administration. The results also indicate that the recovery from a mivacurium-induced neuromuscular blockade is not influenced by the rate of decay of its plasma concentration in patients with genotypically normal plasma cholinesterase.     

Membranes in Artificial Organs

Abstract: Membrane processes play a pivotal and enabling role in modern replacement therapy for acute and chronic organ failure and in the management of immunologic diseases. In fact, virtually all contemporary extracorporeal blood purification methods employ membrane devices, and the next generation of artificial organs and tissue engineering therapies are almost certain to be similarly grounded in membrane technology. In this short essay, we comment on the similarities and differences among synthetic membranes and their natural counterparts and also provide a critical overview of the demographics and technology of hemodialysis, hemofiltration, apheresis, oxygenation, and emerging membrane technologies and applications.     

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.     

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.     

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.     

Dilemma of Membrane Biocompatibility and Reuse

Abstract: Numerous articles have been published on the multiple use of dialyzers and on the effect of different reprocessing chemicals and techniques on the dialyzer biocompatibility and performance. The results often appear contradictory, especially those comparing standard biocompatibility parameters. Despite this confusion, a discerning review of the published works allows certain limited conclusions to be drawn. Reprocessing of used hemodialyzers changes the biocompatibility profile of a dialyzer as defined by the parameters complement activation. leukopenia, and cytokine release. The effect of reprocessing depends on the chemicals and reprocessing technique applied and also on the type of membrane polymer being subjected to the reprocessing procedure. Reports of pyrogenic reactions indicate that the flux of the membrane also influences how suitable it is for safe reuse. An increased risk of allergic and pyrogenic reactions appears to be associated with dialyzer reuse. Furthermore, there has been a lack of investigations into the immunologic effect of the layer of adsorbed and chemically altered proteins that remains on the inner surface of reprocessed dialyzers. We conclude that the clinical benefit of dialyzer reuse cannot be generally accepted from a biocompatibility point of view.     

The analgesic effect of racemic ketamine in patients with chronic ischemic pain due to lower extremity arteriosclerosis obliterans

Background : Ketamine in sub-dissociative doses has been shown to have analgesic and phantom-Limb pain, where conventional treatment has often failed. Chronic ischemic pain due to lower extremity arteriosclerosis obliterans often responds poorly to analgesics, and the pain-generating mechanisms are not well understood.
Methods : Eight patients with rest pain in the lower extremity due to arteriosclerosis obliterans were given sub-dissociative doses of 0.15, 0.30, or 0.45 mg/kg racemic ketamine and morphine 10 mg as a 5-min infusion on four separate days in a cross-over, double-blind, randomised protocol. Plasma levels of (S)- and (R)-ketamine and their nor-metabolites were analysed with an enantioselective high-performance liquid chromatography (HPLC) method. Pain levels were evaluated with a visual analogue scale (VAS).
Results : Individual pain levels were highly variable during and after all the infusions but the pooled pain levels showed a dose-dependent analgesic effect of ketamine with a transient but complete pain relief in all patients at the highest dose (0.45 mg/ kg). Side-effects, mainly disturbed cognition and perception, were pronounced and dose-dependent. Morphine 10 mg had an analgesic peak at 20 min and 5/8 patients had complete pain relief. The remaining 3 patients also had high baseline pain scores, indicating a higher analgesic potency for the 0.30 and 0.45 mg/ kg ketamine doses than for morphine 10 mg.
Conclusion : We have demonstrated a potent dose-dependent analgesic effect of racemic ketamine in clinical ischemic pain. Due to a narrow therapeutic window, this analgesic effect is probably best utilised in combination with other analgesics.