Intra-operative blood pressure control by prostaglandin E1 in patients with hypertension and ischemic heart disease

The purpose of this multi-center study was to evaluate the efficacy and safety of prostaglandin E₁ (PGE₁) administration in achieving deliberate hypotension and in treating intraoperative hypertension for patients with a history of hypertension and ischemic heart disease. PGE₁ (0.08µg·kg^–1·min^–1) decreased systolic blood pressure from 125 ± 29 to 106 ± 22mmHg (mean ± SD) in the deliberate hypotension group (n = 158) and from 155 ± 34 to 125 ± 32mmHg in the antihypertension group (n = 55). The heart rate significantly increased from 80 ± 15 to 85 ± 18 beats·min^–1 in the deliberate hypotension group, but was not significantly altered in the antihypertension group. The time required to obtain the desired level of blood pressure was approximately 20min in the deliberate hypotension group. When the infusion was stopped, blood pressure returned approximately to the preinfusion level within about 20min. No rebound hypertension was observed. PGE₁ significantly increased the urine flow in patients who had a low urine flow before PGE₁ infusion. Thirteen out of 213 patients (5.6%) had side effects such as excessive hypotension (1%), phlebitis (3%), and unexpected tachycardia (1%), which were alleviated gradually after discontinuation of PGE₁ infusion. No dysarrhythmia and further ST segment changes in the electrocardiograms were observed. These findings suggest that PGE₁ can be safely used to control arterial blood pressure during surgery in patients having preoperative hypertension and ischemic heart disease.(Hoka S, Yoshitake J, Dan K, et al.: Intra-operative blood pressure control by prostaglandin E₁ in patients with hypertension and ischemic heart disease. A multi-center study. J Anesth 7: 173–183, 1993)     

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)     

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)     

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)     

Positive inotropic effect of nicorandil in adult rats in situ

Purpose Although the cardiac protective and negative inotropic effects of nicorandil via opening the sarcolemmal or mitochondrial K_ATP channel and NO-like action are well known, positive inotropic effects of nicorandil in normal hearts have not been reported. The aim of the current study was to investigate how nicorandil affects left ventricular (LV) function of in situ adult rat hearts through the entire cardiovascular system.Methods We performed simultaneous and continuous measurements of LV pressure (P) by a catheter-tip micromanometer and LV volume (V) using a conductance catheter. We obtained steady-state LV P-V loops and intermittent curvilinear LV end-systolic pressure–volume relations (ESPVRs), LV end-systolic pressure (ESP_mLVV), and systolic pressure–volume area (PVA_mLVV) at midrange LVV (mLVV). We evaluated the effects of nicorandil on LV function by these mechanical indexes sensitively reflecting changes in LV contractility and work capability, preload (end-diastolic volume, EDV), and afterload (effective arterial elastance, Ea).Results Nicorandil (10 and 20µg·kg^–1·min^–1) (blood concentration: 0.53 ± 0.14 and 1.48 ± 0.21µg/ml) largely shifted ESPVR upward and thus significantly increased ESP_0.06, PVA_0.06, stroke volume due to increase in EDV, and ejection fraction without significant changes in Ea and heart rate. In contrast, an NO donor, nitroglycerin (1µg·kg^–1·min^–1), significantly decreased Ea but did not change ESP_0.06, PVA_0.06, and EDV. Furthermore, either a nonselective K_ATP channel blocker, glybenclamide, or a mitochondrial K_ATP channel blocker, 5-hydroxydecanoate, abolished these nicorandil-induced positive inotropic actions.Conclusion These results suggest that nicorandil exhibited positive inotropic actions on LV function of in situ hearts in adult rats with resultant increased preload (EDV).     

Prostaglandin E1 (PGE1) attenuates vasoconstriction induced by PGE2, PGD2 and phorbol myristate acetate in the perfused rat liver

It has been shown that prostaglandins (PGs) produced by Kupffer and endothelial cells play an important role in mediating physiological responses to various immunological stimuli. We studied the effect of prostaglandin E₁ (PGE₁) on the hemodynamic and metabolic changes induced by prostaglandin E₂ (PGE₂), D₂ (PGD₂) and phorbol 12-myristate 13-acetate (PMA), a potent inducer of PGs in the isolated rat liver perfused with Krebs-Ringer-bicarbonate (KRB) solution at a constant pressure of 12cmH₂O. The liver was taken from overnight-fasted male Sprague-Dawley rats weighing 260 to 310g. Both PGE₂ and PGD₂ significantly decreased hepatic flow when their initial concentration was elevated to micromolar range. Although 1 × 10^–6M of PGE₁ did not have a major effect on hepatic flow, it significantly attenuated the declines of hepatic flow produced by 4 × 10^–6M of PGE₂ and PGD₂. However, none of PGs tested influenced glucose and lactate concentrations in the medium. Continuous infusion of PGE₁ into the medium at a rate of 5µg·min^–1 significantly diminished the decreases in hepatic flow and oxygen consumption induced by 2 × 10^–8M of PMA. These results suggest that administration of PGE₁ may preserve hepatic blood flow by modifying the intrahepatic regulatory mechanism involving the activation of Kupffer and endothelial cells.(Inaba H, Araki M, Numai T, et al.: Prostaglandin E₁ (PGE₁) attenuates vasoconstriction induced by PGE₂, PGD₂ and phorbol myristate acetate in the perfused rat liver. J Anesth 7: 56–65, 1993)     

The hemodynamic and metabolic changes in prostaglandin E1-induced hypotension in dogs

The hemodynamic and metabolic changes in hypotensive state induced with prostaglandin E₁ (PGE₁) or trimetaphan (TMT) infusion were investigated in dogs. Mean arterial pressure was decreased by about 50% with 1.58µg/kg/min of PGE₁ or 45µg/kg/min of TMT. Heart rate, pulmonary capillary wedge pressure and central venous pressure remained virtually unchanged in the two groups. Cardiac output was well maintained in PGE₁ group, whereas cardiac output showed the tendency to decline in TMT group.Greater reduction in systemic vascular resistance was seen in PGE₁ group than in TMT group. Pulmonary vascular resistance showed no significant change in PGE₁ group, whereas it increased significantly in TMT group. Gradual decreases in arterial pH, Pa_{O 2} and base excess and slight but significant increase in Pa_{CO 2} was observed in PGE₁ group, and these abnormalities recovered 30min after hypotension. Abnormalities in blood gases and acid-base balance were considerably more severe and prolonged in TMT group compared with those in PGE₁ group. Blood lactate and pyruvate concentrations showed no significant changes in PGE₁ group, whereas substantial elevation was seen in L/P ratio especially 30min after induction of hypotension in TMT group. Oxygen consumption showed minimal changes in PGE₁ group, whereas a significant decrease was observed in TMT group. The conclusions derived from these results are as follows;1) PGE₁ maintained cardiac output better than TMT, probably because of its direct inotropic action on the heart, and of its greater reduction of systemic vascular resistance than TMT.2) PGE₁ seemed to provide the better blood perfusion throughout the body than TMT.3) PGE₁ showed less possibility to produce the metabolic derangement compared with TMT.(Nam YT, Takahashi S, Tominaga M et al.: The hemodynamic and metabolic changes in prostaglandin E₁-induced hypotension. J Anesth 3: 210–217, 1989)     

Conversion of atrial fibrillation to sinus rhythm during landiolol infusion

A 71-year-old woman with a history of persistent atrial fibrillation underwent clipping of a ruptured cerebral artery aneurysm. During the surgery her cardiac rhythm was atrial fibrillation and the ventricular rate increased to 130 beats·min^–1. Administration of landiolol was started with 1-min loading infusion at 0.125mg·kg^–1·min^–1 and continuous infusion at 0.04mg·kg^–1·min^–1, which was effective in controlling the ventricular rate without causing hypotension. Approximately 120min after the landiolol infusion was started, the atrial fibrillation was converted to sinus rhythm. Her sinus rhythm was maintained until she left the operating room, even after discontinuation of landiolol.     

Effects of prostaglandin E1 on left ventricular performance in dogs; comparisons with trinitroglycerin and adenosine triphosphate

To examine the cardiovascular response to prostaglandin E1 infusion, we observed hemodynamic changes including left ventricular diameter (an ultrasonic crystal pair) during PGE₁-induced hypotension in anesthetized open-chest dogs. Left ventricular contractility was assessed primarily by measuring the slope of the left ventricular endsystolic pressure-diameter relation (ESPDR) determined by combining end-systolic points from a vena caval occlusion. The cardiovascular effects of induced hypotension by infusions of trinitroglycerin and adenosine triphosphate were also examined at the equivalent magnitude of hypotension. Approximately 25% reduction of systemic blood pressure was produced by the three agents. PGE₁ significantly increased cardiac output from 1200 ± 132 to 1439 ± 162ml·min^–1 (mean ± SE, P 0.05), stroke volume from 9.1 ± 1.1 to 10.0 ± 1.0ml (P 0.05), and %-diameter shortening from 10.4 ± 0.8 to 14.4 ± 0.8% (P 0.01), but the slope of ESPDR was unchanged. Similar changes were also observed during adenosine triphosphate-induced hypotension. PGE₁ significantly decreased end-diastolic diameter in a similar manner to trinitroglycerin. Thus PGE₁ appears to have little influence on left ventricular contractility aside from its effects on afterload and preload, indicating that it is a useful agent for producing controlled hypotension during anesthesia.(Hoka S, Sato M, Okamoto H, et al.: Effect of prostaglandin E₁ on left ventricular performance in dogs; Comparisons with trinitroglycerin and adenosine triphosphate. J Anesth 6: 45–50, 1992)     

Functional and metabolic effects of propafenone in the rat heart-lung preparation

The effects of propafenone on cardiac function and myocardial metabolism were assessed in the isolated rat heart-lung preparation. Propafenone 0.3, 3 or 30µg·ml^–1 was administered 5min after the start of perfusion. Heart rate decreased in the 30µg·ml^–1 group significantly following the drug administration. The highest dose of propafenone (30µg·ml^–1) reduced cardiac output significantly, and this dose was associated with a higher incidence of arrhythmias than the other groups. Although there were no significant differences in myocardial lactate and glycogen concentrations among groups, ATP content in the 30µg·ml^–1 group was significantly less than that in the control group. As therapeutic plasma concentration of propafenone is about 0.6 (range 0.06 to 1.0) µg·ml^–1, 30µg·ml^–1 is 50 times greater than its concentration. These results suggest that the negative inotropic and chronotropic effects of propafenone are almost same with those of lidocaine which we have previously reported.(Kashimoto S, Oguchi T, Nakamura T, et al.: Functional and metabolic effects of propafenone in the rat heart-lung preparation. J Anesth 5: 392–395, 1991)     

Respiration by tracheal insufflation of oxygen (TRIO) at high flow rates in apneic dogs

Tracheal insufflation of oxygen (TRIO) is a technique in which oxygen is introduced into the trachea at a constant flow rate via a catheter advanced to the level of the carina. We studied the effects of flow rates (0.5, 1.0, 1.5 and 2.0l·kg^–1·min^–1) on arterial blood gases during TRIO in 6 apneic dogs. The constant flow was administered through the tip of a catheter (I.D. 2.0mm) advanced to a site of 1cm above the carina. After 30min of TRIO, the mean Pa_{CO 2} at the flow rates of 0.5, 1.0, 1.5 and 2.0l·kg^–1·min^–1 were 88 ± 20, 76 ± 20, 64 ± 23 and 52 ± 18mmHg, respectively. CO₂ elimination increased as the flow rates increased from 0.5 to 2.0l·kg^–1·min^–1.Based on the above study, we examined the effects of TRIO at a flow rate of 3l·kg^–1·min^–1 in another 5 apneic dogs. TRIO, at a flow rate of 3l·kg^–1·min^–1, was able to maintain normocarbia over 4hr. The mean Pa_{O 2} and Pa_{CO 2} at 4.0hr were 465 ± 77 and 41 ± 4mmHg. Although the mechanism of pulmonary gas exchange during TRIO is unclear, our study is the first to document that normocarbia can be maintained by high-flow TRIO in apneic dots.(Urata K, Okamoto K and Morioka T.: Respiration by tracheal insufflation of oxygen (TRIO) at high flow rates in apneic dogs. J Anesth 5: 153–159, 1991)     

Changes in venous capacitance during prostaglandin E1-induced hypotension; Comparisons with trinitroglycerin

The purpose of this study was to examine the effects of prostaglandin E₁ (PGE₁) on venous capacitance during controlled hypotension. Trinitroglycerin (TNG) was used as a control agent. In rats anesthetized with ketamine, mean arterial pressure was lowered to 70mmHg and subsequently 50mmHg by intravenous infusion of PGE₁ or TNG. Venous capacitance was assessed before and during induced hypotension by measuring the mean circulatory filling pressure (MCFP). MCFP was measured after briefly arresting the circulation by inflating an indwelling balloon in the right atrium. MCFP was significantly decreased by PGE₁ from 7.9 ± 0.3 to 6.9 ± 0.3mmHg at mean arterial pressure of 70mmHg and to 6.9 ± 0.2mmHg at mean arterial pressure of 50mmHg. The decrease in MCFP by PGE₁ at mean arterial pressure of 70mmHg was not significantly different from TNG. However, the decrease in MCFP by PGE₁ at mean arterial pressure of 50mmHg was significantly less than that by TNG. The results suggest that the venous capacitance may be increased by PGE₁ to a similar degree with TNG at doses to produce a comparable level of moderate hypotension, but the increase in venous capacitance may be less in PGE₁ than TNG at doses to produce deep hypotension.(Liang J, Hoka S, Okamoto H, et al.: Changes in venous capacitance during prostaglandin E₁-induced hypotension; comparisons with trinitroglycerin. J Anesth 7: 303–307, 1993)     

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)     

Prevention of succinylcholine-induced myalgia with lidocaine pretreatment

We studied the effects of 3mg·kg^–1 lidocaine iv on the succinylcholine (SCh)-induced myalgia in 94 unpremedicated ambulant patients undergoing dilatation and curettage of the uterus. The post-SCh myalgia was confirmed through interview by telephone. The data were correlated with the degree of fasciculation and changes in the serum electrolytes and creatine kinase (CK) levels following SCh administration. Pretreatment with lidocaine, 3mg·kg^–1 iv, significantly reduced the incidence of myalgia from 40.4% of control group to 12.8% lidocaine-treated group, but not the CK levels. The severity of myalgia was not related to the intensity of fasciculation assessed by visual observation. The pretreatment with lidocaine had no untoward effect on the circulation, although the peak arterial and peak venous lidocaine levels achieved were 29.6 ± 23µg·ml^–1 and 10.1 ± 3.3µg·ml^–1 respectively. These finding indicated that the pretreatment with lidocaine, 3mg·kg^–1 iv, was effective in prevention of SCh-induced myalgia.(Tat-Leang Lee, Tar-Choon Aw: Prevention of succinylcholine-induced myalgia with lidocaine. J Anesth 5: 239–246, 1991)     

Vascular responses to hypercapnia in anesthetized dogs

To evaluate the vascular responses to systemic acute mild hypercapnia (Pa_{CO 2} = 65mmHg), we determined the vascular compliance with the relation between the change in circulating blood volume and the change in central venous pressure during and after fluid infusion in dogs anesthetized with halothane in normocapnia and hypercapnia. Circulating blood volume was measured continuously by ⁵¹Cr-labeled erythrocyte dilution method together with hemodynamic variables. Small reduction in vascular compliance (8.1 ± 1.0ml·mmHg^–1·kg^–1 in normocapnia, 5.8 ± 0.5ml·mmHg^–1·kg^–1 in hypercapnia), large reduction in delayed compliance, which were quantitated by computer simulation using Maxwells viscoelastic model, and significant increase in blood volume in central circulation were observed in hypercapnia. The essential change in hypercapnia was concluded as the vasoconstriction in capacitance vessels. Simultaneously, the reduction of total peripheral resistance (1.09 ± 0.08mmHg·min·kg·ml^–1 in normocapnia, 0.98 ± 0.07mmHg·min·kg·ml^–1 in hypercapnia) with no change in transvascular filtration coefficient (0.14 ± 0.02ml·mmHg^–1·min^–1·kg^–1) suggests the increase in shunt flow in peripheral circulation.(Shigemi K: Vascular responses to hypercapnia in anesthetized dogs. J Anesth 2: 1–7, 1988)     

The effects of a thromboxane A2 receptor antagonist on neurologic recovery after 15 min complete global brain ischemia in dogs

The effects of a thromboxane A₂ receptor antagonist (anti-TXA₂; ONO-3708) on the neurologic recovery after 15min complete cerebral ischemia were investigated in dogs. Complete cerebral ischemia was achieved by occlusion of the trunk of the aorta, the superior and the inferior caval vein. Seventeen dogs were divided into 2 groups; 1) control group (no drug, n = 9), 2) Anti-TXA₂ group (anti-TXA₂ 200mcg·kg^–1 in iv bolus soon after recirculation followed by continuous infusion at a rate of 10mcg·kg^–1·min^–1 for 3 days, n = 8). EEG, auditory brainstem response (ABR), middle latency response (MLR), and somatosensory evoked potential (SEP) recordings were obtained before ischemia, 120min after re-circulation and on the 7th day after ischemia. The neurologic recovery score (NRS) were determined on the 3rd and the 7th day. Impaired EEG score was significantly higher in the anti-TXA₂ group on 7th day after ischemia (P < 0.05). Anti-TXA₂ increased the reappearance rates of the ABR-Vth (P < 0.05) and the SEP-N₃ waves (P < 0.01) at 120min after ischemia. The survival rate tended to be higher in the anti-TXA₂ group. However, NRS did not significantly differ in the groups.(Takahashi M, Iwatsuki N, Ono K, et al.: The effects of a thromboxane A₂ receptor antagonist on neurologic recovery after 15min complete global brain ischemia in dogs. J Anesth 5: 73–78, 1991)     

Difference in the effect of pancuronium and vecuronium on baroreflex control of heart rate in humans

The effects of pancuronium and vecuronium, each in doses of 0.05 and 0.08mg·kg^–1, on the baroreflex control of the heart rate were studied in 40 adult patients of either sex (21 men and 19 women) during stable nitrous oxide-oxygen-fentanyl anesthesia. The blood pressure was elevated by intravenous infusion of phenylephrine (4µg·kg^–1·min^–1) for the pressor test, and lowered by a bolus injection of nitroglycerin (0.3–0.5mg) for the depressor test. Baroreflex sensitivity was judged from the slope of the regression of the systolic blood pressure on the succeeding R-R intervals on the ECG. There was no significant difference between the baseline blood pressure at which both tests were carried out. Nitrous oxide-oxygen-fentanyl anesthesia alone suppressed the baroreflex sensitivity to a level which was at the lower limit of the physiological and non-anesthetized state. The 0.08mg·kg^–1 dose of pancuronium significantly suppressed the reflex sensitivity in both the pressor and depressor tests. However, the 0.05mg·kg^–1 dose of pancuronium and both doses of vecuronium did not cause any significant change in the test results.(Tsuchida H, Seki S, Nakae Y, et al.: Difference in the effect of pancuronium and vecuronium on baroreflex control of heart rate in humans. J Anesth 5: 255–259, 1991)     

Calcium entry blocker nicardipine inhibits sodium and inorganic phosphate reabsorption independent of renal circulation in dogs

The effects of nicardipine on renal function were studied in anesthetized dogs. The changes in the tubular sodium (Na) and inorganic phosphate (PO₄) reabsorption caused by the drug infusion into the renal artery without altered systemic and real circulation were especially evaluated. In dogs receiving a smaller dose of nicardipine (5ng·kg^–1·min^–1) into the left renal artery the blood pressure and renal circulation did not change, but urine volume and urinary Na and PO₄ excretion increased significantly. In dogs receiving a larger dose of nicardipine (50ng·kg^–1·min^–1) into the renal artery, renal plasma flow, urine volume and urinary Na and PO₄ excretion increased significantly, but creatinine clearance did not. The fractional distal Na reabsorption did not change with nicardipine infusion in either group. PO₄ reabsorption is considered to occur mainly in the proximal renal tubule, so its appearance in urine in increased quantities without the changes of systemic and renal circulation suggests proximal activity of the drug.(Goto F, Watanabe I: Calcium entry blocker nicardipine inhibits sodium and inorganic phosphate reabsorption independent of renal circulation in dogs. J Anesth 6: 153–160, 1992)     

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.     

Temperature and humidity of the DrÄger Cato anesthetic machine circuit

Purpose.The DrÄger Cato anesthetic machine (DrÄger, LÜbeck, Germany) effectively humidifies and warms anesthetic gases, because it has a built-in hotplate to heat the breathing system, and expired gas passes through the CO₂ absorbent three times during one breath. In the present study, we measured the temperature and absolute humidity (AH) of the anesthetic circuit in the DrÄger Cato machine with and without heat moisture exchangers (HME), and compared them with those in another anesthetic machine, the Aestiva/5 (Datex-Ohmeda, Helsinki, Finland).Methods.Forty-eight adult patients were randomly assigned to one of eight groups according to the anesthetic machine, fresh gas flow (FGF), and the use of HME (n = 6 each): Cato 0.5l·min^–1 without HME (group 1), Cato 1.0l·min^–1 without HME (group 2), Cato 0.5l·min^–1 with HME (group 3), Cato 1.0l·min^–1 with HME (group 4), Aestiva 0.5l·min^–1 without HME (group 5), Aestiva 1.0l·min^–1 without HME (group 6), Aestiva 0.5l·min^–1 with HME (group 7), and Aestiva 1.0l·min^–1 with HME (group 8). The temperature and AH of the anesthetic gases were measured with a Moiscope (S.K.I. Net, Tokyo, Japan), which was placed between the endotracheal tube and the Y-piece of the anesthetic circuit. The HME was placed between the Moiscope and the Y-piece of the anesthetic circuit. The temperature and AH of the anesthetic gases were measured at 5, 10, and 15min and then every 15min up to 150min after tracheal intubation.Results.Among the groups without HME (groups 1, 2, 5, and 6), the inspired temperatures and AH in groups 1 and 2 were significantly higher than those in groups 5 and 6 at all times during the study period (P 0.01–0.001). The inspired temperatures and AH of the groups with HME (groups 3, 4, 7, and 8), were significantly higher than those in groups 2, 5, and 6 (P 0.01–0.001). Among the groups with HME, the AH in group 3 was significantly higher than that in group 8 until the final study period.Conclusion.The present study indicates that the DrÄger Cato machine was more effective in warming and humidifying respiratory gas than the Aestiva/5, and that Aestiva/5 without HME does not reach the optimal temperature and humidity ranges, even if minimal flow anesthesia (0.5l·min^–1) is performed.