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)     

Sustained effects of plasma norepinephrine levels on femoral-radial pressure gradient after cardiopulmonary bypass

In order to determine the influence of the sympathetic nervous system upon the femoral-radial artery pressure gradient after cardiopulmonary bypass (CPB), we examined plasma norepinephrine levels in 34 adult male patients undergoing coronary artery bypass grafting. Cardiovascular parameters, including systolic arterial pressure, mean arterial pressure, cardiac index (CI), systemic vascular resistance index (SVRI), pulmonary artery pressure (PAP), hemoglobin (Hb) and peak dP/dt of radial and femoral artery pressures were measured after sternotomy, and immediately after the discontinuation of CPB and 90min after CPB. Plasma norepinephrine levels were measured after sternotomy, after aortic declamping and 90min after CPB.The patients were divided into two groups. Group A consisted of 17 patients whose femoral minus radial systolic pressure difference was 15mmHg or more at 90min after CPB, while Group B consisted of 17 patients with the difference less than 15mmHg. Group A patients had significantly longer time values in the duration of both CPB (Group A 175 ± 10min; Group B 115 ± 12min, P 0.001) and aortic cross clamping (Group A 116 ± 7min, Group B 71 ± 9min, P 0.001).Although there was no significant difference in Hb or PAP of 90min after CPB in Groups A and B, the following values, listed in the order of A to B, were obtained; CI, 2.79 ± 0.10 versus 3.46 ± 0.16l·min^–1·m^–2 (P 0.01); mean radial artery pressure (MRP), 58.7 ± 2.4 versus 65.1 ± 1.8mmHg (P 0.05); peak dP/dt of radial artery pressure, 568 ± 64 versus 1026 ± 61mmHg·sec^–1 (P 0.001); and plasma norepinephrine concentration, 1.81 ± 0.25 versus 0.98 ± 0.10ng·ml^–1 (P 0.01), which were statistically significant.The higher femoral-radial artery pressure gradient after CPB was observed in patients with both a longer CPB time and a higher plasma norepinephrine concentration. These results suggest that a marked constriction of peripheral arteries might have produced a damped transmission of the pressure pulse to the radial artery.(Nakayama R, Goto T, Kukita I, et al.: Sustained effects of plasma norepinephrine levels on femoral-radial pressure gradient after cardiopulmonary bypass. J Anesth 7: 8–15, 1993)     

The effect of vagal afferent on total vascular compliance in rats

This study was designed to investigate the effect of vagal afferent stimulation on total vascular compliance (TVC). Rats were anesthetized with sodium pentobarbital and artificially ventilated, TVC was determined together with stressed and unstressed blood volumes by measuring mean circulatory filling pressure (Pmcf) at three different levels of circulating blood volume. Measurements was repeated with the intact vagus, after vagotomy and during stimulation of vagal afferents. Vagotomy caused no change in TVC, Pmcf, and stressed and unstressed blood volumes. On the other hand, electrical stimulation of the vagal afferents for 30sec increased TVC from 3.03 ± 0.51 to 3.39 ± 0.44ml·mmHg^–1·kg^–1 (P 0.05) and decreased Pmcf from 7.83 ± 1.40 to 7.22 ± 1.21mmHg (P 0.05). Neither stressed nor unstressed blood volume was changed by vagal stimulation. These results indicate that excitation of vagal afferent causes venodilation and increases TVC without changing stressed and unstressed blood volumes.(Kinoshita T: The effect of vagal afferent on total vascular compliance in rats. J Anesth 7: 198–205, 1993)     

Decreased Tissue Inhibitor of Metalloproteinase-2/Matrix Metalloproteinase Ratio in the Acute Phase of Aortic Dissection

Purpose Aortic dissection is characterized by fragility of the tunica media, and matrix metalloproteinases (MMPs) are enzymes that degrade the extracellular matrix of the aorta. This study examines MMPs in patients with acute aortic dissection (AAD) in an attempt to elucidate the mechanisms of their actions.Methods Enzyme-linked immunosorbent assays were used to measure the quantification of MMP-2, MMP-9, and the tissue inhibitor of metalloproteinase (TIMP)-2 in 30 patients with AAD, 12 patients with abdominal aortic aneurysm (AAA), and 16 control (CON) patients who underwent coronary artery bypass grafting.Results MMP-2 and TIMP-2 were significantly lower in the AAD group than in the CON group, at 36 ± 19 vs 58 ± 30 (P 0.01) and at 21 ± 25 vs 216 ± 130 (P 0.001), respectively. The TIMP-2/MMP-2 ratio was 3.7 ± 1.7 in the CON group and 0.9 ± 0.8 in the AAD group (P 0.001 vs CON), and the TIMP-2/MMP-9 ratio was 200 ± 170 in the CON group and 37 ± 80 in the AAD group (P 0.001 vs CON).Conclusion Low TIMP-2/MMP-2 and TIMP-2/MMP-9 ratios might play an important role in the onset of aortic dissection, when the tunica media becomes fragile with chronic breakage and degradation of the extracellular matrix.     

Insulin-like growth factor-I increases p21 expression and attenuates cisplatin-induced acute renal injury in rats

Background Exogenous insulin-like growth factor-I (IGF-I) promotes recovery from ischemic renal injury, but its effect on cisplatin (CDDP)-induced nephrotoxicity and its mechanisms for the attenuation of renal injury are unknown.Methods We administered recombinant human IGF-I (rhIGF-I, 150µg/day, i.p.) once a day 24h prior to and after CDDP (5mg/kg, i.v.) injection in rats.Results The rhIGF-I treatment significantly decreased serum creatinine (0.92 ± 0.11 vs 1.50 ± 0.15mg/dl; P 0.05), the tubular damage score, and the ratio of apoptotic cells to tubular epithelial cells in the outer stripe of the outer medulla on day 5 (P 0.05). rhIGF-I significantly increased the numbers of p21-positive nuclei (5.15 ± 0.19 vs 3.45 ± 0.42/×400 high-power field (HPF); P 0.05) and proliferating cell nuclear antigen (PCNA)-positive nuclei (28.61 ± 1.89 vs 18.26 ± 2.14/×400 HPF; P 0.05), but decreased the number of cyclin D1-positive cells (3.3 ± 0.3 vs 6.3 ± 1.7/×400 HPF; P 0.05) on day 3. rhIGF-I did not alter 5-bromo-3-deoxyuridine (BrdU) incorporation.Conclusions Our findings suggested that rhIGF-I increased renal p21 and PCNA expression, but reduced cyclin D1 expression in CDDP-treated kidneys. Exogenous rhIGF-I may ameliorate renal damage, in part by stopping the cell cycle at G1/S phase.     

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)     

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)     

Elevation of the extracellular glutamate concentration in the hippocampus after total cerebral ischemia related to the deterioration of the recovery in EEG and evoked potentials in dogs

The concentrations of extracellular glutamate (Glu), aspartate (Asp) and glycine (Gly) were measured by microdialysis method in the cortex and hippocampus before, during and after 15min of total cerebral ischemia in dogs. The correlations between the concentrations of amino acids and the changes in EEG and evoked potentials (EP) after ischemia were evaluated. Total cerebral ischemia was achieved by occluding the ascending aorta and the caval veins. The concentrations of Glu in the hippocampus significantly increased from 1.73 ± 0.59 (mean ± SEM) nmol·ml^–1 at pre-ischemia to 5.46 ± 1.34 (P 0.05) during ischemia and 14.37 ± 3.70 (P 0.01) 0–15min after ischemia, and returned to the pre-ischemic level 30min after ischemia. The concentration of hippocampal Glu 0–15min after ischemia had significant negative correlations with the EEG-EP scores (0 = serious deterioration of electrical function and 6 = normal electrical function) 30min, 3hr and 5hr after ischemia (r = –0.69, P 0.05:r = –0.67, P 0.05:r = –0.70, P 0.05, respectively). The increase of the extracellular Glu concentration in the hippocampus immediately after ischemia may aggravate the neurological outcome after total cerebral ischemia.(Ono K, Iwatsuki N, Tajima T, et al.: Elevation of the extracellular glutamate concentration in the hippocampus after total cerebral ischemia related to the deterioration of the recovery in EEG and evoked potentials in dogs. J Anesth 7: 334–340, 1993)     

The effects of nicardipine given after 10-minutes complete global cerebral ischemia on neurologic recovery in dogs

The effect of nicardipine (NC) on neurologic recovery from ischemic insult after 10-minutes complete global cerebral ischemia was evaluated in dogs by examination of neurologic recovery score (NRS: complete recovery = 100, death = 0). Ischemia was achieved by occlusion of ascending aorta, and NC, 10µg·kg^–1 in bolus followed by infusion of 0.33µg·kg^–1·min^–1 for 2 hours, was administered immediately after re-establishment of circulation. The mortality at 7th day was 2/9 in the control © and 1/9 in the NC group (ns). NRS on 2nd day was 52.3 ± 6.8 in the C and 70.6 ± 6.5 in the NC (P 0.05), but that on 7th day did not differ between the two groups. The numbers of dogs recovered to over 80 in NRS on the 2nd day was 1/9 in the C and 5/9 in the NC (P 0.05), but that on the 7th day increased to 3/9 in the C and remained at 5/9 in the NC (ns). These results suggest that NC accelerates the early neurologic recovery from ischemic damage, but influences little the final outcome.(Iwatsuki N, Ono K, Takahashi M et al.: The effects of Nicardipine given after 10-minutes complete global cerebral ischemia on neurologic recovery in dogs. J Anesth 4: 337–342, 1990)     

Inhibition of Acute Rejection After Skin or Cardiac Transplantation by Administration of Donor Antigens in the Rat

Purpose We examined differences in host immunologic changes induced by the intravenous or intraportal administration of donor antigens at engrafting and evaluated their contribution to graft survival using a rat transplantation model.Methods Lewis rat recipients were given either an intravenous or intraportal injection of donor splenocytes (1 × 10⁸) immediately after receiving skin grafts from Brown Norway donors. The immunologic responses were analyzed by mixed lymphocyte reaction (MLR) and profiles of interferon-, interleukin (IL)-2, and IL-10 in MLR supernatants. The effect on cardiac transplantation of perioperative administration of low-dose FK506 (0.1mg/kg per day) was also examined.Results Mixed lymphocyte reactions using splenocytes and sera from recipients treated intraportally were greatly inhibited. Interferon-, IL-2, and IL-10 levels were significantly higher after intraportal treatment compared with intravenous treatment (P 0.05). When FK506 was injected from day 3, a significant enhancement of cardiac allograft survival was demonstrated by intraportal treatment (16.1 ± 2.9 days) in comparison to the non-treatment (13.0 ± 1.7 days, P 0.05) and intravenous treatment rats (11.7 ± 2.7 days, P 0.05).Conclusions The Th2 deviation induced with intraportal alloantigen administration immediately after engraftment was thus observed to produce a synergistic effect with immunosuppressant treatment to suppress acute rejection.     

Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation

Thirty six patients were received epidural anesthesia with or without buprenorphine (BPN) during upper abdominal surgery. They were divided into three groups of 12 patients as follows; G-I received 20ml of 1% lidocaine epidurally, G-II received 20ml of 1% lidocaine epidurally and 0.6mg BPN intravenously, G-III received 20ml of 1% lidocaine with 0.6mg BPN epidurally. Additional 5ml of 1% lidocaine was given to any patient if systolic blood pressure or heart rate increased 10% compared to control value. Trachea was intubated following anesthetic induction with thiopental. The lungs were ventilated with a mixture of N₂O/O₂ (33%) and pancuronium was used for muscle relaxation. The total required doses of lidocaine in G-II and G-III were decreased 60% compared to control group (G-I) (P 0.05). The mean period of time until the first administration of pentazocine for postoperative pain was 13 ± 10hr (mean ± SD) in G-II and 19 ± 24hr in G-III compared to 5 ± 4hr in G-I (P 0.001). The dose of the administration of pentazocine that was required for pain relief during the first 48 postoperative hr in G-III was 54 ± 10mg (mean ± SD) compared to 150 ± 21mg in G-I (P 0.02) and 106 ± 28mg in G-II (P 0.05). Recovery from anesthesia in G-III was more rapid than that in G-I (P 0.05). The Pa_{CO 2} values in G-II and G-III increased 15% compared to control group at about 4hr and 8hr after administration of BPN, but any clinical treatment was not needed for them. Nonrespiratory side effects, e.g., nausea, vomiting, fatigue and headache, were comparably common in all groups. Mild hematuria associated with acute hypotension occurred in two patients in G-II (17%) immediately after the intravenous injection of 0.6mg of BPN. The results showed that 0.6mg of BPN given epidurally demonstrated better anesthetic and more potent postoperative analgesic effects and lesser side effects than 0.6mg of BPN given intravenously in patients undergoing upper abdominal surgery.(Yonemura E, Fukushima K.: Comparison of anesthetic effects of epidural and intravenous administration of buprenorphine during operation. J Anesth 4: 242–248, 1990)     

The effects of calcitonin on bone resorption in hyperthyroidism: a placebo-controlled clinical study

The effects of intranasal calcitonin on bone metabolism were investigated in patients with hyperthyroidism. Urinary deoxypyridinoline (uDPD) levels were measured as a bone turnover marker and lumbar spine (L2) bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DEXA) in 7 patients who were given only antithyroid drug (group 1), in 10 patients who were given antithyroid drug plus intranasal calcitonin (group 2), and in 10 healthy subjects who were given placebo (group 3) at the beginning and at the end of the study. The study continued until the patients with hyperthyroidism became euthyroidic according to the laboratory values. This period was approximately 3 months in groups 1 and 2. At the beginning of the study, uDPD was 21.5 ± 2.6nM DPD/mM creatinine in group 1, 23.3 ± 3.6nM DPD/mM creatinine in group 2, and 4.3 ± 1.2nM DPD/mM creatinine in group 3. uDPD levels measured in groups 1 and 2 were significantly higher than those in group 3 (P 0.001). Area BMD Z scores of the patients in groups 1 and 2 were significantly lower than the healthy controls (P 0.01, for both). At the end of the study, uDPD was 11.5 ± 1.6nM DPD/mM creatinine in group 1, 5.3 ± 0.6nM DPD/mM creatinine in group 2, and 4.4 ± 1.3nM DPD/mM creatinine in group 3. The levels of uDPD obtained in group 1 were significantly higher than those obtained in groups 2 and 3 (P 0.05, for both). The difference between groups 2 and 3 was not significant. Area BMD Z scores measured at the end of the study were found to be increased in groups 1 and 2 compared to early values, but the values were slightly lower than the normal values. In comparison of early and late uDPD values, the decrease in late period was statistically significant in groups 1 (P 0.05) and 2 (P 0.001). We concluded that bone turnover is high in hyperthyroidism. The treatment of hyperthyroidism decreases the rate of bone turnover, but it is not sufficient to prevent the degradation of bone in hyperthyroidism. The addition of intranasal calcitonin to the treatment of hyperthyroidism prevents the degradation of bone.     

Airway occlusion pressure (P0.1) — A useful predictor for the weaning outcome in patients with acute respiratory failure —

Twenty-five patients who required mechanical ventilatory support (MVS) after major surgery or severe burns were studied to determine whether airway occlusion pressure (P_0.1) is a clinically useful indicator to predict the success or failure of the weaning trial. A total of 33 weaning trials were attempted on these patients. Of the 33 trials, 24 were followed by successful weaning and 9 by failure. Although the success group, when compared with the failure group, had a lower respiratory rate (P 0.001), a lower minute ventilation (P 0.001), a higher maximal voluntary ventilation to minute ventilation ratio (P 0.01) and a higher forced vital capacity (P 0.05), no threshold values separated the success from the failure group. The alveolar-arterial P_{O 2} gradient, with an Fi _{O 2} of 1.0, in weaning success and failure showed no statistical difference. In contrast, all patients in the success group had a P_0.1 of less than 3.5cmH₂O and those in the failure group had a P_0.1 of greater than 3.5cmH₂O (P 0.001). We conclude that P_0.1 is a clinically superior indicator for discontinuing MVS in patients with acute respiratory failure.(Okamoto K, Sato T, Morioka T: Airway occlusion pressure (P_0.1)—A useful predictor for the weaning outcome in patients with acute respiratory failure—. J Anesth 4: 95–101, 1990)     

Suppression of proliferative cholangitis in a rat model by local delivery of paclitaxel

Background. Proliferative cholangitis (PC) leads to biliary stricture, which is the main cause of hepatolithiasis, recurrent cholangitis, and biliary cirrhosis. The aim of this study was to determine whether local delivery of paclitaxel, which inhibits cell proliferation by overstabilization of microtubules, prevents PC in a rat model.Methods. PC was induced by introducing a fine nylon thread into the bile duct in a rat. Paclitaxel (100µl of 10, 100, and 1000µmol/l) or solvent vehicle was administered into the bile duct for 15min. One week after treatment, histopathologic examination and 5-bromodeoxyuridine (BrdU) labeling of the bile duct were performed.Results. In comparison with the control, the mean thickness of the bile duct was reduced by 29% in the 1000µmol/l paclitaxel-treated group (2.61 ± 0.31µm vs 3.67 ± 0.25µm, P 0.05). The luminal area increased (P 0.0001) and the grade of epithelial–glandular proliferation was decreased (P 0.01) as the dose of paclitaxel increased. Ductal fibrosis and inflammatory cell infiltration were similar in both groups. The BrdU labeling index was significantly lower in the paclitaxel-treated group (P 0.05).Conclusions. Local delivery of paclitaxel suppressed PC in a rat model by the inhibition of epithelial–glandular proliferation and may offer an effective therapeutic option for biliary stricture.     

Retrospective study of post-anesthetic mild liver disorder associated with inhalation anesthetics,halothane and enflurane

The incidence of post-anesthetic mild liver disorder (PAMLD) was compared between 928 patients administered halothane and 1766 patients administered enflurane. They were selected from 19504 surgical patients administered general anesthesia at Kyushu University Hospital over the past 6 years and 4 months. They had had normal liver function before operation and had no history of blood transfusion. Alanine aminotransferase (ALT) levels exceeding 70IU·l ^–1 within 180 days after operation were found in 226 patients in the halothane group (24.4%), and in 250 patients in the enflurane group (14.2%) (P 0.01). Both maximum ALT levels and duration of ALT elevation were higher and longer in the halothane group (P 0.01). These results suggest that, not only in the development of fulminant hepatitis but also in PAMLD, enflurane is less hepatotoxic than halothane.(Sakaguchi Y, Inaba S, Umeki Y, et al.: Retrospective study of post-anesthetic mild liver disorder associated with inhalation anesthetics, halothane and enflurane. J Anesth 6: 183–191, 1992)     

The effects of sevoflurane on lidocaine-induced convulsions

The influence of sevoflurane on lidocaine-induced convulsions was studied in cats. The convulsive threshold (mean ± SD) was 41.4 ± 6.5mg·l ^–1 with lidocaine infusion (6mg·kg^–1·min^–1), increasing significantly to 66.6 ± 10.9mg·l ^–1 when the end-tidal concentration of sevoflurane was 0.8%. However, the threshold (61.6 ± 8.7mg·l ^–1) during 1.6% sevoflurane was not significant from that during 0.8% sevoflurane, indicating a celling effect. There was no significant difference in the convulsive threshold between sevoflurane and enflurane. The rise in blood pressure became less marked when higher concentrations of sevoflurane or enflurane were administered and the blood pressure at convulsions decreased significantly in 1.6% sevoflurane, and in 0.8% and 1.6% enflurane. However, there was no significant difference in the lidocaine concentrations measured when the systolic blood pressure became 70mmHg. Apamin, a selective blocker of calcium-dependent potassium channels, was administered intracerebroventricularly in rats anesthetized with 0.8% sevoflurane to investigate the mechanism of the anticonvulsive effects. Apamin (10ng) had a tendency to decrease the convulsive threshold (21.6 ± 2.2 to 19.9 ± 2.5mg·l ^–1) but this was not statistically significant. It is suggested that sevoflurane reduces the convulsive effect of lidocaine toxicity but carries some risk due to circulatory depression.(Karasawa F: The effects of sevoflurane on lidocaine-induced convulsions. J Anesth 5: 60–67, 1991)     

Bone mineral density in women with sarcoidosis

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Almost any organs of the body, but mostly the lungs, are involved. Bone mineral density (BMD) can be affected directly or indirectly in chronic granulomatous systemic diseases such as sarcoidosis. The aim of our study was to evaluate BMD in premenopausal and postmenopausal sarcoidosis patients with or without prednisone treatment and to compare their BMD values with those of a control group having the same menopausal status. Thirty-five premenopausal women (18 untreated, 8 treated, and 9 controls) and 21 postmenopausal women (5 untreated, 5 treated, and 11 controls) were included in the study. All of the patients had a histologically proven diagnosis and were being followed-up at the Sarcoidosis Outpatient Clinic of our unit. BMD of the lumbar (L) spine and femoral neck was measured by dual-energy absorptiometry (DEXA). The subgroups of premenopausals and postmenopausals were compared separately. Comparison among the groups was performed by using analysis of variance. Age, duration of the disease, and body mass index were comparable in treated, untreated, and control subgroups of the pre- and postmenopausal groups, and the subgroups of postmenopausals had comparable durations since menopause. For premenopausals, BMD values at L1–4 were not significantly different among the subgroups (0.920 ± 0.08g/cm², 0.801 ± 0.09g/cm², and 0.910 ± 0.05g/cm², for untreated, treated, and controls, respectively). However, the BMD value at the femoral neck in treated patients (0.921 ± 0.1g/cm²) was significantly lower than the values in untreated patients (1.080 ± 0.2g/cm²; P 0.01) and in controls (1.028 ± 0.17g/cm²; P 0.05). For postmenopausals, the BMD value at L1–4 in controls (1.019 ± 0.07g/cm²) was significantly higher than the values in untreated patients (0.783 ± 0.01g/cm²) and in treated patients (0.751 ± 0.08g/cm²; P 0.001 for both). The BMD value at the femoral neck in controls (0.890 ± 0.1g/cm²) was higher than the values in untreated patients (0.745 ± 0.08g/cm²) and treated patients (0.747 ± 0.1g/cm²), but the difference was not statistically significant (P = 0.06). We concluded that sarcoidosis patients, especially postmenopausal patients with corticosteroid treatment, may have an increased risk of bone mineral loss. Large-scale studies are warranted in order to delineate the exact roles of the disease itself, menopausal status, and corticosteroid treatment in this bone mineral loss.     

Prostaglandin E1 reduces blood loss during and after resection of lumbar herniated disc

Controlled hypotension was employed during resection of lumbar herniated disc on 10 patients. Prostaglandin E₁ (PG) was used as a hypotensive agent. The systolic blood pressure was lowered less than 100mmHg in the hypotensive group. The average blood loss during surgery was 95 ± 41ml for the hypotensive group compared with 154 ± 81ml for the normotensive group (P 0.05). The blood loss after surgery was also significantly less in the hypotensive group than in the normotensive group (P 0.05). We conclude that PG is an effective hypotensive agent on blood loss during and after surgery.(Kashimoto S, Nakamura T, Yamaguchi T: Prostaglandin E₁ reduces blood loss during and after resection of lumbar herniated disc. J Anesth 6: 294–296, 1992)     

Angiogenesis Inhibitor TNP-470 Can Suppress Hepatocellular Carcinoma Growth Without Retarding Liver Regeneration After Partial Hepatectomy

Purpose. We investigated the suppressive effect of the angiogenesis inhibitor TNP-470 on accelerated hepatocellular carcinoma (HCC) growth in the regenerating liver. Methods. After 70% partial hepatectomy (PH), AH-130 cells were injected into the portal vein of Donryu rats. A control group was given the vehicle only, and the treated group was given 10mg/kg TNP-470 subcutaneously every second day, from 24h after tumor implantation, seven times. On day 14, tumor growth was evaluated by the number of foci on the liver surface, liver weight, and the microvessel density of the tumor. Results. The number of foci was significantly less in the treated group (116.5 ± 103.1) than in the control group (319.3 ± 223.1) (P 0.05), as was microvessel density, which was 31.3 ± 14.0/mm² in the treated group and 61.2 ± 18.9/mm² in the control group (P 0.05). The liver tended to weigh less in the treated group (12.15 ± 1.28g) than in the control group (15.22 ± 5.35g). We also assessed whether TNP-470 retards liver regeneration. Seven days after 70% PH, the liver weight in the treated group was similar to that in the control group. Total bilirubin, serum glutamic oxaloacetic transaminase, and serum glutamic pyruvic transaminase were not higher in the treated group than in the control group. Conclusion. TNP-470 can suppress HCC growth without retarding liver regeneration after PH.     

Endocrine and hemodynamic changes during liver surgery in patients with compensated liver cirrhosis

The purpose of this study was to determine hormonal levels in compensated liver cirrhotic patients under general anesthesia before and after liver surgery. We measured plasma norepinephrine, epinephrine, arginine vasopressin, and aldosterone levels and renin activity in non-cirrhotic and compensated cirrhotic patients undergoing liver resection after induction of anesthesia but before skin incision and after the end of operation but before discontinuation of nitrous oxide. We simultaneously measured hemodynamic variables. Plasma levels of norepinephrine (P 0.001), epinephrine (P 0.001), arginine vasopressin (P 0.05), renin (P 0.05) and aldosterone (P 0.001) significantly increased after completion of surgery compared with those before incision in both groups. There was a significant positive correlation between plasma renin and aldosterone (r = 0.56, P 0.01) levels in non-cirrhotics, but no correlation was observed in cirrhotics; and there was a significant positive correlation between plasma norepinephrine and arginine vasopressin (r = 0.45, P 0.05) levels in non-cirrhotics, but no correlation in cirrhotics. Cardiac index and arterial pressure increased after the end of operation (P 0.05). This increase after the operation was the same between cirrhotic and non-cirrhotic groups. There were no changes in heart rate, mean pulmonary arterial pressure, and pulmonary capillary wedge pressure after the end of operation. We conclude that hemodynamic and endocrinological changes were similar between compensated cirrhotic patients and non-cirrhotic patients during liver surgery. Endocrine changes might partly explain the hemodynamic changes during surgery.(Maruyama K, Sakakura S, Nishimura K, et al.: Endocrine and hemodynamic changes during liver surgery in patients with compensated liver cirrhosis. J Anesth 7: 157–166, 1993)