Changes in brain monoamines and their metabolites during and after hemorrhagic shock in the rat

The alteration of monoamines and their metabolites in the brain during and after hemorrhagic shock in the conscious state was measured in rats. Blood pressure was maintained at 40–70mmHg (5.3–9.3kPa) for 60min by withdrawing 8ml of blood intermittently. The content of monoamines, as well as their metabolites, increased in various brain regions during hemorrhage, compared with the content in the control rats. Sixty min after the end of the bleeding period, almost no significant change in the contents of brain monoamines nor of their metabolites was observed. These results may indicate not only an increased release of monoamines from nerve terminals, but also an increased synthesis of them during hemorrhagic shock. Soon after the bleeding was stopped, the increased monoamine turnover rate returned to almost normal levels.(Mizobe T, Okuda C, Demura H et al.: Changes in brain monoamines and their metabolites during and after hemorrhagic shock in the rat. J Anesth 4: 116–122, 1990)     

Decreased beta-adrenergic receptor

We investigated alterations in the number and affinity of cardiac beta-adrenergic receptors during hemorrhagic shock. Forty male Wistar rats were divided into two groups: (1) a shock group (n = 20), in which mean arterial blood pressure was decreased to 40–50mmHg by bleeding and kept constant for 6h; and (2) a control group (n = 20), which underwent a sham operation. We used (–)[³H]dihydroalprenolol for the determination of the number and affinity of beta-adrenergic receptors in myocardial membranes. An additional 25 rats were used for determination of plasma epinephrine and norepinephrine concentrations. Scatchard analysis showed a 20% reduction (P < 0.05) in beta-adrenergic receptor density in the shock group (70.3 ± 3.5fmol·mg^–1 protein) compared to the control group (90.0 ± 4.8fmol·mg^–1 protein) but no significant change in the affinity (2.52 ± 0.06 vs. 2.31 ± 0.09nmol·l ^–1, control vs. shock). Plasma catecholamine concentrations were increased significantly at 1, 2, 4 and 6h after the start of hypotension. These data suggest that increased levels of plasma catecholamines in hemorrhagic shock may be correlated a significant loss of beta-adrenergic receptors in rat myocardium.(Mizumachi K, Yahagi M, Kawabata H, et al.: Decreased beta-adrenergic receptor density in rat myocardium during hemorrhagic shock. J Anesth 5: 404–411, 1991)     

The effects of dopamine infusion during operation on the postoperative liver dysfunction

Dopamine improves renal function and renal blood flow by increasing cardiac output but its effect to ameriolate postoperative liver dysfunction has not yet been defined. Effect of 3–5µg·kg^–1·min^–1 dopamine was studied in 22 patients who had total gastrectomy (dopamine group), and was compared with 22 patients who underwent the same operation and without dopamine infusion (control group).Liver function was evaluated from serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) values. Although postoperative SGOT and SGPT values in both groups were increased significantly higher than the preoperative values, the increases in SGOT (40 ± 14IU) and SGPT (32 ± 15IU) values in the dopamine group were significantly less than those in the control group (67 ± 27IU, 43 ± 19IU) (P < 0.05, P < 0.01).In conclusion, these results suggested that this observation might be explained by amelioration of the postoperative liver dysfunction by infusion of dopamine. Dopamine infusion at a small dose during upper abdominal surgery is benefitial for liver function.(Sari A, Kawai K, Nagayama M, et al.: The effects of dopamine infusion during operation on the postoperative liver dysfunction. J. Anesth 5: 388–391, 1991)     

The effects of ulinastatin on cardiac and hepatic energy metabolism in rats subjected to hypovolemic shock

Ulinastatin is a trypsin inhibitor extracted from human urine. In this study the effects of ulinastatin on myocardial and hepatic tissue concentrations of creatine phosphate (CP), ATP, ADP, AMP, lactate, pyruvate, and glycogen have been investigated in rats which were in hemorrhagic shock state. Hypovolemia was induced by bleeding from the femoral artery, and systolic blood pressure was maintained 40mmHg for 25min, then ulinastatin 50,000 units·kg^–1 in saline or saline vehicle was intravenously administered. Thereafter the heart and liver were extirpated and frozen quickly with liquid nitrogen. The tissue concentrations of CP, ATP, ADP, AMP, lactate and glycogen were measured enzymatically. Systolic blood pressure elevated significantly after ulinastatin administration. The myocardial tissue CP level was higher in ulinastatin-treated group than that of control group, whereas no significant difference in energy charge between two groups. The hepatic tissue level of AMP, lactate and L/P ratio was lower in ulinastatin-treated group than that of control group, however, no significant difference was found in hepatic tissue level of ATP, ADP and energy charge. From these results it is concluded that ulinastatin can improve the energy metabolism of myocardium to some extent, but not of the liver in rats with hypovolemic shock.(Kashimoto S, Nakagomi M, Nonaka A et al.: The effects of ulinastatin on cardiac and hepatic energy metabolism in rats subjected to hypovolemic shock. J Anesth 4: 40–44, 1990)     

Preventative effect of PGE1 for postoperative liver damage

The efficacy of a low dose of PGE₁-use on the postoperative liver damage was evaluated. PGE₁ was infused in with the mean rate of 0.026µg·kg^–1·min^–1 during surgical procedure to 93 patients under GO-enflurane anesthesia (the PG). Serum GOT, GPT and total bilirubin (TBIL) values measured before, at the end of (End) and 3 days (3d) after the operation were compared to those obtained from 43 patients without PGE₁ administration (the control).This dose of PGE₁ did not change blood pressure and heart rate, but slightly decreased Pa_{O 2}. In patients with preoperative normal values of GOT, GPT and TBIL, increases in GOT, GPT and TBIL observed at End in the PG were significantly lower than those in the control (31.9 vs 72.2IU, 25.9 vs 61.9IU, 0.68 vs 0.83mg·dl^–1, respectively). GOT, GPT and TBIL at 3d significantly increased in both groups, and these levels were identical between the two groups. In patients with preoperative abnormal values, only GOT at End increased in both groups, while no significant difference between the PG and the control group was noted. GOT at 3d and GPT at End and 3d did not significantly changed in either group. These results suggest that the low dose of PGE₁ administered during an operation prevents the development of postoperative liver damage, but does not treat the damaged hepatic cells.(Iwatsuki N, Yasuda A, Tokutomi S, et al.: Preventative effects of PGE₁ for postoperative liver damage. J Anesth 6: 131–137, 1992)     

Cardiac and hepatic metabolism in spontaneously hypertensive rats following acute blood loss

Seven spontaneously hypertensive rats (SHRs) and eight Wistar-St rats were used to assess the influence of hemorrhage on myocardial and hepatic energy metabolism. They received 2% halothane and pancuronium, 0.3mg·kg^–1, during preparation. After discontinuation of halothane, blood (2ml·100g body weight^–1) was gradually withdrawn over a 5min period from a femoral artery. Thirty min after induction of hemorrhage, the heart and liver were removed and myocardial and hepatic metabolites (ATP, lactate, pyruvate and glycogen) were measured by the enzymatic methods. Acidosis and decreased hematocrit were noted in the both groups after hemorrhage. Mean arterial pressure (MAP) in SHR was significantly higher than that in Wistar rat before hemorrhage. However, there were no significant differences in MAP and heart rate between the two groups after hemorrhage. Although there were no significant differences in cardiac metabolites, a significant decrease of hepatic ATP and an increase of hepatic lactate/pyruvate ratio were found in SHR when compared with Wistar rat. These results suggest that human hypertensive disease may run a high risk in connection with acute hemorrhage.(Kashimoto S, Nonaka A, Nakamura T, et al: Cardiac and hepatic metabolism in spontaneously hypertensive rats following acute blood loss. J Anesth 6: 284–288, 1992)     

KB-R9032, newly developed Na<Superscript>+</Superscript>/H<Superscript>+</Superscript> exchange inhibitor,attenuates reperfusion-induced arrhythmias in isolated perfused rat heart

Purpose This study was conducted to elucidate the effects of KB-R9032, a newly developed Na⁺-H⁺ exchange inhibitor, on reperfusion-induced ventricular arrhythmia in the isolated perfused rat heart.Methods Male Wistar rat hearts (n = 48; 12 for each group) were perfused with modified Krebs-Ringers solution equilibrated with 5% carbon dioxide in oxygen by means of the Langendorff technique. An occluder was placed around the left anterior descending coronary artery (LAD). Heart rate, coronary flow, and ECG were monitored. Drug-free perfusate was used for 10min before switching to a perfusate containing various concentrations of KB-R9032. The added concentrations of KB-R9032 varied in the range of 0 (control) to 1 × 10^–5mol·l^–1. Each heart was subjected to regional ischemia (occlusion of LAD for 11min) and to 3min of reperfusion (release of the ligation).Results In the control group, reperfusion-induced ventricular fibrillation (VF) occurred in 91.7%, and the duration was 158.2 ± 14.4s (mean ± SEM); however, 1 × 10^–7, 1 × 10^–6, and 1 × 10^–5mol·l^–1 KB-R9032 reduced the incidence of VF to 75.0%, 42.9%, and 6.7%, respectively (P < 0.05 at 1 × 10^–5mol·l^–1 of KB-R9032) and reduced the duration of VF to 64.8 ± 22.1, 16.8 ± 10.1, and 1.2 ± 1.2s, respectively (P < 0.05 at 1 × 10^–6 and 1 × 10^–5mol·l^–1 of KB-R9032).Conclusion It was shown in this study that the Na⁺/H⁺ exchange inhibitor KB-R9032 suppresses reperfusion arrhythmias in the ischemia-reperfusion model of isolated rat heart.     

Modification of hepatic protein kinase C with phorbol myristate acetate and staurosporine alters hemodynamics in the perfused rat liver

Activation of protein kinase C (PKC) has been implicated in the pathogenesis of endotoxicosis and severe sepsis. Since hepatic blood flow and metabolism have been known to be altered in endotoxicosis and sepsis, we studied the hemodynamic effect of PKC modulation with phorbol 12-myristate 13-acetate (PMA) and staurosporine (St) on the perfused rat liver. The liver was isolated from overnight-fasted male Sprague-Dawley rats and placed in a recirculating perfusion apparatus. The liver was perfused with Krebs-Ringer-bicarbonate solution at a constant pressure of 12cmH₂O. Flow to the liver was continuously monitored with an electric magnetic flowmeter. PMA at an initial concentration of 2 × 10^–8M significantly decreased hepatic flow. Staurosporine (St), a potent PKC inhibitor at 4 × 10^–7M produced a small increase in hepatic flow. Pretreatment with St significantly attenuated the flow reduction by PMA. St significantly suppressed the flow reductions by 4 × 10^–6M of prostaglandin E₂ and D₂. These results suggest that the PKC inside the liver may play an important role in the regulation of hepatic blood flow during endotoxicosis and sepsis.(Inaba H, Araki M, Numai T, et al.: Modification of hepatic protein kinase C with phorbol myristate acetate and staurosporine alters hemodynamics in the perfused rat liver. J Anesth 7: 48–55, 1993)     

Renal tissue gas tensions during hemorrhagic shock

To evaluate the development of renal hypoxia during hemorrhagic shock, fourteen dogs were induced in this study. The animals were divided equally into a group in which mean arterial pressure (MAP) was kept at 50mmHg (group 1), and into another where MAP was kept at 40mmHg for 180mim (group 2). Renal tissue gas tensions were determined by a mass spectrometer. In the 50-mmHg group, renal tissue oxygen tension (Pr_{O 2}) dropped for 15min following hemorrhage, remained constant for 90min, then fell further for 150min before a plateau was established. In the 40-mmHg group, the Pr_{O 2} dropped for 90min before reaching a plateau. The second Pr_{O 2} decline occurred at the same level in both the 50-mmHg group and the 40-mmHg group. The point at which the same Pr_{O 2} level occurred for each group suggests the cessation of oxygen consumption and the conditions of renal hypoxia. It is assumed that renal hypoxia occurs in 120min at a MAP of 50-mmHg and in 60min at a MAP of 40mmHg.(Murakawa K, Izumi R, Kobayashi A: Renal tissue gas tentions during hemorrhagic shock. J Anesth 3: 10–15, 1989)     

Analysis of oxygen transport to the brain when two or more parameters are affected simultaneously

We composed a model, combining oxygen transport system from blood to tissue with the oxygen consumption system at the tissue. The aim of this study is to apply it to the brain tissue under conditions when two or more oxygen transport parameters are affected simultaneously. The following values were assumed. Critical tissue P_{O 2} (Pcrit_{O 2}) 2mmHg; oxygen consumption above this level 3ml·min^–1·100g^–1; diffusion coefficient from blood vessel to tissue (Dvt) 0.2ml·min^–1·mmHg^–1·100g^–1; cerebral bloow flow (CBF) 50ml·min^–1·100g^–1; hemoglobin 15g·100ml^–1. The Hill equation was used for oxygen dissociation curve with n of 2.7 and P₅₀ of 27.0mmHg.The changes of oxygen consumption of the brain (V¨_{O 2}) were analyzed when 2 or more of 5 parameters, Pa_{O 2}, CBF, Dvt, P₅₀ and hemoglobin decreased simultaneously from their respective normal values.As the number of parameters affected increased, the level at which oxygen consumption begins to be affected became higher. With all five parameters combined, a reduction down to 78 per cent of normal resulted in tissue hypoxia. We conclude that the oxygen consumption of the brain is fairly resistant when only one parameter is affected, but it becomes increasingly vulnerable when several parameters are affected simultaneously. A clinically important finding is that the brain is particularly vulnerable to a combination of hypocapnia and a decreased level of 2,3DPG.(Suwa K: Analysis of oxygen transport to the brain when two or more parameters are affected simultaneously. J Anesth 6: 297–304, 1992)     

Cardioprotective effects of KB-R7943, a novel inhibitor of Na+/Ca2+ exchanger, on stunned myocardium in anesthetized dogs

Purpose The present study was carried out to determine the cardioprotective effects of KB-R7943 (KBR), a selective inhibitor of the reverse mode of Na⁺/Ca²⁺ exchanger (NCX), on stunned myocardium in anesthetized dogs.Methods The dogs were allocated to one of three groups (n = 7 for each group), and received drug vehicle (group C), low-dose KBR (5mg·kg^–1 i.v.) (group L) or high-dose KBR (10mg·kg^–1 i.v.) (group H) at 15min before left anterior descending coronary artery (LAD) occlusion. Stunned myocardium was produced by 15-min occlusion of LAD and 90-min reperfusion in all dogs. Regional myocardial contractility was evaluated with segment shortening (%SS).Results Recovery of %SS at 90min after reperfusion was significantly improved in group H (70.8% ± 3.9% of baseline), whereas the recovery was poor in groups C and L (34.3% ± 2.8% and 36.4% ± 5.4% of baseline, respectively). Regional myocardial blood flow showed no significant difference among groups. KBR had no effect on coronary or systemic hemodynamics.Conclusion The results show that preischemic administration of high-dose KBR markedly improves myocardial contractile dysfunction after ischemia-reperfusion in anesthetized dogs, indicating that KBR protects myocardium against the ischemia-reperfusion injury in vivo.     

Propofol inhibits lidocaine metabolism in human and rat liver microsomes

Purpose.When two drugs are metabolized by similar P450 isoforms, one drug inhibits the metabolism of the other when both the present. The metabolism of lidocaine and propofol can be mediated by similar P450 isoforms. Therefore, we investigated the relationship in the metabolism between lidocaine and propofol in both rat and human liver microsomal P450 (CYP) systems in vitro. Methods.(1) Propofol, 4µg·ml^–1, as the substrate and lidocaine (between 0.5 and 8µg·ml^–1) and (2) lidocaine, 4.7µg·ml^–1, as the substrate and propofol (between 0.5 and 40µg·ml^–1) were reacted separately with human and rat microsomes. The concentrations of lidocaine, its major metabolite (monoethylglycinexylidide, MEGX) and propofol were measured using high-pressure liquid chromatography. The metabolism of lidocaine was presented as a reaction activity (MEGX/lidocaine). Results.The dose-dependent inhibitory effects of propofol on lidocaine metabolism were observed in both the human and rat groups. The IC50 (the concentration producing 50% maximal inhibition) of propofol was 5.0µg·ml^–1 and 0.70µg·ml^–1 in the human and the rat groups, respectively. The propofol concentration of 5.0µg·ml^–1 is within the range of clinical doses for humans. On the other hand, lidocaine did not change propofol metabolism. Conclusion.Propofol possesses a dose-dependent inhibitory effect on the metabolism of lidocaine in both human and rat CYP systems in vitro.     

Analysis of oxygen transport and oxygen utilization combined

We propose a model which combines oxygen transport system from blood to tissue with oxygen utilization system at the tissue.The model consists of 3 equations; the relationship between tissue P_{O 2} (Pts_{O 2}) and O₂ utilization (Vrc_{O 2}), diffusion from vessel to tissue, and Fick equation. This model has two advantages. First, it is self-consistent. Varying Vrc_{O 2} varies the oxygen transport. Second, it enables to analyze the effects of various factors of oxygen transport/utilization on other factors.We applied this model to the brain tissue. Following values were assumed. Critical tissue P_{O 2} (Pcrit_{O 2}) 2mmHg; oxygen utilization above this level 3ml·min^–1·100g^–1; diffusion coefficient from blood vessel to tissue (D) 0.2ml·min^–1·mmHg^–1·100g^–1; cerebral blood flow (CBF) 50ml·min^–1·100g^–1; hemoglobin 15g·100ml^–1. Hill equation was used for oxygen dissociation curve with n of 2.7 and P50 of 27.0mmHg.From these, the following values were obtained; Pv_{O 2}, Pts_{O 2} and Vrc_{O 2}. The changes were analyzed for the 5 input values, Pa_{O 2}, CBF, D, P50 and Hb, changing from zero to their respective normal values. A reduction of a single parameter down to 50% of normal barely affected oxygen utilization. A further reduction resulted in significant oxygen utilization. Under conditions studied, a decrease in P50 reduced oxygen utilization faster than that in any other parameters.(Suwa K: Analysis of oxygen transport and oxygen utilization combined. J Anesth 6: 51–56, 1992)     

Dose-finding study of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam

Purpose We investigated the effective and safe dose of intravenous midazolam for sedation and amnesia during spinal anesthesia in patients premedicated with intramuscular midazolam.Methods One hundred and eighty patients aged 20–50 years scheduled for spinal anesthesia received midazolam 0.06mg·kg^–1 and atropine 0.01mg·kg^–1 intramuscularly 15min before entering the operating room. Spinal anesthesia was performed with 0.5% hyperbaric tetracaine. Five minutes after starting surgery, midazolam 0 (control group), 0.01, 0.02, 0.03, 0.04, or 0.05mg·kg^–1 was intravenously administered (30 patients each). Blood pressure, heart rate, respiratory rate, percutaneous oxygen saturation (S_{p O 2}), verbal response, eyelash reflex, and involuntary body movement were measured every 5min for 30min. Memory during surgery was also investigated.Results The number of the patients with loss of verbal response, with loss of eyelash reflex, and with no memory during surgery were significantly larger in the groups receiving midazolam 0.03mg·kg^–1, 0.04mg·kg^–1, and 0.02mg·kg^–1, respectively. The decrease in blood pressure or increase in respiratory rate with decrease in S_{p O 2} was significantly larger in the groups receiving midazolam 0.03mg·kg^–1 or 0.05mg·kg^–1, respectively.Conclusion For sedation and amnesia of the patients aged 20–50 years in spinal anesthesia with about 1h duration receiving intramuscular midazolam 0.06mg·kg^–1 as a premedication, intravenous midazolam 0.02mg·kg^–1 might be effective and safe.     

The relaxing effects of barbiturates in vascular smooth muscle of rat aorta

The effects of thiamylal and pentobarbital on contractions mediated through the influx of extracellular Ca⁺⁺ and the release of intracellularly stored Ca⁺⁺ were compared in rat aortic strips. Thiamylal (3 × 10^–5M to 10^–3M) and pentobarbital (10^–4 to 10^–3M) significantly attenuated the contraction induced by KCl (20mM), and shifted the dose-response curve for Ca⁺⁺ of KCl (20mM)-treated strips downwards and to the right. Caffeine (10^–2M)-induced contraction was significantly attenuated by thiamylal at concentrations greater than 10^–4M and by pentobarbital at 3 × 10^–4M. Only a high concentration (10^–3M) of these barbiturates significantly inhibited the contractions induced by norepinephrine (NE, 10^–6M) in Ca⁺⁺-free medium. Contraction of strips without endothelium by a Ca⁺⁺ ionophore, A23187 (5 × 10^–6M), in the presence of a Ca channel blocker, was relaxed by high concentrations of thiamylal (3 × 10^–4M to 10^–3M) and pentobarbital (10^–3M). It is concluded that thiamylal inhibits contraction through an intracellular action as well as a Ca channel-blocking action in vascular smooth muscle of rat aorta. However, the intracellular action of pentobarbital is less potent than that of thiamylal.(Nishiwada M, Nakamura K, Hatano Y, et al.: The relaxing effects of barbiturates in vascular smooth muscle of rat aorta. J Anesth 5: 380–387, 1991)     

Effects of calcium and temperature on tension in isolated canine coronary artery

The effects of calcium and temperature on the tension of isolated canine coronary arterial strips were studied.In 20mEq·l ^–1 K solution, the tension was significantly increased from 0mg with 0mEq·l ^–1 Ca to 33 ± 18mg with 0.2mEq·l ^–1 Ca at 37°C, from –40 ± 18mg with 0mEq·l ^–1 Ca to –17 ± 11mg with 0.2mEq·l ^–1 Ca at 30°C, from –77 ± 19mg with 0mEq·l ^–1 Ca to –52 ± 17mEq·l ^–1 with 1mEq·l ^–1 Ca at 25°C, from –88 ± 13mg with 0mEq·l ^–1 Ca to –41 ± 18mg with 2mEq·l ^–1 Ca at 20°C, from –125 ± 16mg with 0mEq·l ^–1 Ca to –116 ± 13mg with 2mEq·l ^–1 Ca at 15°C. Ca higher than 0.2mEq·l ^–1 produced a dose-dependent increase in tension between 37°C and 15°C. In spite of the presence of 4mEq·l ^–1 Ca, the development of tension was strongly supressed by lowering the temperature below 20°C, and completely inhibited at 10°C. The rate of a decrease in tension caused by cooling was about 5.5mg·°C^–1.This study demonstrated that Ca²⁺ produced a dose-dependent increase in tension in high-K solution, which was suppressed as the temperature was lowered.(Yoshida K, Fujii Y, Ina H, et al.: Effects of calcium and temperature on tension in isolated canine coronary artery. J Anesth 5: 172–176, 1991)     

The neuromuscular effects of sevoflurane and isoflurane alone and in combination with vecuronium or atracurium in the rat

Sevoflurane was compared to isoflurane anesthesia alone and in combination with atracurium or vecuronium in 84 rats using the sciatic nerve—anterior tibialis muscle preparation. Both bolus injection and infusion rate techniques were used to evaluate these drug interactions. The ED₅₀ (dose which produced a 50% depression of twitch tension) of atracurium was 311 ± 31 and 360 ± 32µg·kg^–1 during 1.25MAC sevoflurane and isoflurane anesthesia respectively. The ED₅₀ of vecuronium was 190 ± 27 and 149 ± 14µg·kg^–1 during 1.25MAC sevoflurane and isoflurane anesthesia respectively. The mean infusion rates of atracurium and vecuronium required to maintain a 50% depression of twitch tension were 5.04 ± 0.7 and 2.02 ± 0.3mg·kg^–1·hr^–1. These infusion rates were 5.04 ± 0.7 and 2.02 ± 0.3mg·kg^–1·hr^–1 during 1.25MAC sevoflurane and 3.73 ± 0.3 and 1.81 ± 0.4mg·kg^–1·hr^–1 during 1.25MAC isoflurane anesthesia respectively. With both atracurium and vecuronium, the infusion rate required to maintain a 50% depression twitch of tension was inversely related to the concentrations of isoflurane and sevoflurane. The authors conclude that sevoflurane is similar in potency to that of isoflurane in augmenting a vecuronium or atracurium induced neuromuscular blockade in a dose-dependent manner.(Shin YS, Miller RD, Caldwell JE, et al.: The neuromuscular effects of sevoflurane and isoflurane alone and in combination with vecuronium or atracurium in the rat. J Anesth 6: 1–8, 1992)     

Preadministration of low-dose ketamine reduces tourniquet pain in healthy volunteers

We evaluated whether preadministration of low-dose ketamine could attenuate tourniquet pain and arterial pressure increase using high tourniquet pressure in ten healthy awake volunteers. Ketamine, 0.1mg·kg^–1, or normal saline was given intravenously in a double-blind fashion before tourniquet inflation with a pressure of 400mmHg at the thigh. Visual analog scale (VAS) scores and systolic blood pressure (SBP) were measured at 5-min intervals. Ketamine significantly reduced VAS scores compared to saline just after tourniquet inflation [90 (64–100) mm, median (range), with saline versus 66 (50–81) mm with ketamine, P < 0.01] and at 30min [92 (61–100) mm with saline versus 70 (50–100) mm with ketamine, P < 0.03), and significantly prolonged tourniquet time (28 ± 6min with saline, mean ± SD, versus 37 ± 7min with ketamine, P < 0.01). SBP (120 ± 9mmHg) significantly increased before tourniquet deflation (133 ± 16mmHg) in the saline trial, but not in the ketamine trial. The results show that preadministration of low-dose ketamine attenuates tourniquet pain and arterial pressure increase during high-pressure tourniquet application and prolongs tourniquet time in healthy volunteers.     

Timing of injection and plasma concentration of lidocaine before endotracheal intubation

The optimal time of intravenous lidocaine for attenuation of pressor responses to laryngoscopy and endotracheal intubation was evaluated in fifty adult patients and the correlation between plasma lidocaine level and its clinical effects were also studied.The plasma lidocaine levels were highest 0.5min after administration of lidocaine 1.5mg·kg^–1 intravenously. However, endotracheal intubation 0.5min after lidocaine administration caused significant increase in mean arterial pressure (MAP) and heart rate (HR). Mean arterial pressure and HR increased with endotracheal intubation following 1, 2 and 3min after lidocaine administration, but the magnitude of increase was not statistically significant. There were no significant differences in MAP changes among these three groups. It was concluded that the plasma lidocaine levels did not correlate with its suppressive effect on circulatory responses due to laryngoscopy and endotracheal intubation. Laryngoscopy and endotracheal intubation should be carried out at least 1min after intravenous lidocaine administration.(Okuda M, Ohi Y, Kurata M et al.: Timing of injection and plasma concentration of lidocaine before endotracheal intubation. J Anesth 4: 150–154, 1990)     

A selective thromboxane synthetase inhibitor,OKY-046, fails to improve blood rheology in endotoxin-shocked rabbits

Effects of a selective thromboxane synthetase inhibitor, (E)-3-[4-(1-imidazolylmethyl)phenyl]-2-propenoic acid hydrochloride monohydrate (OKY-046), were studied hemorheologically in endotoxin shocked-rabbits. The animals were intravenously administrated with 0.1mg of endotoxin 3 times at intervals of 3 days. At 7 days after the last endotoxin injection, endotoxin (0.2mg·kg^–1) was intravenously administrated to induce a shock. OKY-046 (30mg·kg^–1) was administrated after hypotension was developed by the endotoxin treatment and, then, it was continuously injected at 0.03mg·kg^–1·min^–1. Blood pressure remained unchanged and hypotensive was maintained during the treatment with OKY-046. Blood was sampled from the femoral artery 15 (before the administration of OKY-046), 45, and 120 minutes after the final administration of endotoxin. Pa_{O 2} increased, and Pa_{CO 2}, arterial pH, and base excess (BE) decreased during the endotoxin shock. The decrease of pH and BE was prevented by the administration of OKY-046. In the endotoxin-shocked animals, hematocrit, whole blood viscosity, erythrocyte deformability, plasma fluidity, and the ratio of hematocrit to whole blood viscosity showed no significant differences between the OKY-046 treated animals and non-treated ones. These data show that a selective thromboxane synthetase inhibitor (OKY-046) does not improve the blood rheology during endotoxin shock, although it seems to prevent the acidosis in some extent.(Kato T, Hayashi K, Takamizawa K, et al.: A selective thromboxane synthetase inhibitor, OKY-046, fails to improve blood rheology in exdotoxin-shocked rabbits. J Anesth 5: 247–254, 1991)