Interim evidence of the renoprotective effect of the angiotensin II receptor antagonist losartan versus the calcium channel blocker amlodipine in patients with chronic kidney disease and hypertension: a report of the Japanese Losartan Therapy Intended for Global Renal Protection in Hypertensive Patients (JLIGHT) Study

Background. Insufficiency of renal function and high blood pressure influence each other and eventually result in life-threatening endstage renal disease. It has been proposed that proteinuria per se is a determinant of the progression of chronic kidney disease (CKD). The therapeutic strategy for patients with proteinuric CKD and hypertension should therefore be targeted with a view not merely toward blood pressure reduction but also toward renoprotection. Methods. We examined the effect of the angiotensin (AT)₁ receptor antagonist losartan and the calcium channel blocker amlodipine, throughout a period of 12 months, on reduction of blood pressure and renoprotection. This was done by assessing amounts of urinary protein excretion, serum creatinine (SCr), and creatinine clearance (CCr) in patients with hypertension (systolic blood pressure [SBP] 140mmHg or diastolic blood pressure [DBP] 90mmHg) and CKD (male, body weight [BW] 60kg: 1.5 SCr < 3.0mg/dl; female or male BW < 60kg: 1.3 SCr < 3.0mg/dl), manifesting proteinuria of 0.5g or more/day. Losartan was administered once daily at doses of 25 to 100mg/day, and amlodipine was given once daily at 2.5 to 5mg/day. No antihypertensive combination therapy was allowed during the first 3-month period. Results. A 3-month interim analysis revealed that, despite there being no difference in blood pressure between the two groups, there was a significant reduction in 24-h urinary protein excretion in the losartan group (n = 43), but there was no change in the amlodipine group (n = 43). Analysis of stratified subgroups with proteinuria of 2g or more/day and less than 2g/day showed that losartan lowered proteinuria by approximately 24% in both subgroups, while amlodipine lowered proteinuria by 10%, but only in the subgroup of less than 2g/day (NS). SCr and CCr did not change throughout the period of 3 months in either group. No severe or fatal adverse event was experienced in either group during the study period. Conclusions. Losartan appeared to be efficacious for renoprotection in patients with proteinuric CKD and hypertension, with the mechanism being independent of its antihypertensive action.     

Percutaneous and Open Renal Revascularizations Have Equivalent Long-Term Functional Outcomes

Atherosclerotic renal artery stenosis is a significant cause of poorly controlled hypertension and progressive renal dysfunction leading to ischemic nephropathy and other end-organ damage. The optimal treatment of renovascular disease contributing to hypertension and renal dysfunction is not known. This study compares the anatomic and functional outcomes of both open and endovascular therapy for chronic, symptomatic atherosclerotic renal artery disease. We performed a retrospective analysis of records from patients who underwent renal arterial interventions, endovascular or open bypass, between January 1984 and January 2004. Principal indications for intervention were hypertension (51%), chronic renal insufficiency (13%), and hypertension and elevated creatinine (36%). A total of 247 patients (109 males; mean age 69±10, range 44–89 years) underwent 314 interventions (109 open procedures; 205 angioplasties, 71% with stent placement). There was a significant difference in 30-day mortality (4% vs. <1%; p < 0.005) between the open and endoluminal groups, but not at 1, 3, or 5 years. Patients in the open group had a higher primary patency rate at 5 years (83±5% vs. 76±6%; p=0.03), but patients in the endoluminal group had a higher assisted primary patency rate at 5 years (92±5% vs. 84±5; p=0.03). There was no significant difference between both treatment groups in cumulative freedom from presenting symptom or in freedom from dialysis and renal-related death. Patients who presented with hypertension were more likely to have shown improvement in their blood pressure with endoluminal intervention at 1, 3, and 5 (59±6% endoluminal vs. 83±5% open; p=0.01) years. From these results we conclude that open repair and endoluminal repair of atherosclerotic renal artery stenosis have similar immediate and long-term functional and anatomic outcomes. Patients who present with hypertension may have greater benefit with an endoluminal repair.Presented at the Twenty-ninth Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, 2004.     

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)     

Comparison between a disposable and an electronic PCA device for labor epidural analgesia

Purpose The aims of the present study were (1) to investigate if a disposable patient-controlled analgesia (PCA) device can be used for labor analgesia and (2) to evaluate the device by midwives and parturients.Methods Forty healthy parturients were divided into two groups and received combined spinal epidural analgesia for labor pain relief. Following intrathecal administration of 3mg ropivacaine and 1.5µg sufentanil, either a disposable PCA device (Coopdech Syrinjector; Daiken Medical, Osaka, Japan) or an electronic PCA device (IVAC PCAM PCA Syringe Pump; Alaris, Basingstoke, UK) was connected to the epidural catheter, and 0.15% ropivacaine with sufentanil 0.75µg/ml was used for continuous infusion and PCA. For an electronic PCA device, continuous infusion rate, bolus dose, lockout time, and hourly limit were set at 4ml/h, 3ml, 15min, and 16ml, respectively. For a disposable PCA device, continuous infusion rate, bolus dose, and an hourly limit were set at 4ml/h, 3ml, and 16ml, respectively, but lockout function was not available.Results No differences were observed between the groups concerning demographic data, obstetric data, and outcome of labor. Anesthetic requirements (disposable, 9.7 ± 4.7ml/h; electronic, 8.2 ± 4.0ml/h) and VAS score during the delivery (disposable, 26 ± 25; electronic, 21 ± 22) were similar between the groups. Midwives praised the disposable PCA device as well as the electronic one.Conclusion The present results imply that the disposable PCA device can be an alternative to the electronic PCA device for labor analgesia.     

Hospital Readmissions Following Abdominal Aortic Aneurysm Repair

In-hospital outcomes associated with abdominal aortic aneurysm (AAA) repair are well described. However, little is known about post-discharge readmission rates, lengths of stay, associated mortality, and costs. We examined 206 consecutive patients who underwent AAA repair at two American hospitals between 1998 and 2000. Index hospitalization and 6-month readmission data were extracted from a resource and cost accounting system used by both hospitals. Among the 206 patients, 183 survived until discharge (mortality rate 11.2%). Among the surviving patients, 38 (21.0%) were readmitted within 6 months. Half of the readmissions occurred within two weeks of discharge, with patients presenting with a diverse array of complications. Nonelective repair and diabetes mellitus were independent predictors of hospital readmission (OR=2.83, 95% CI=1.25-6.40, p=0.01; OR=6.60, 95% CI=1.02-42.4, p=0.047, respectively). For each readmission, the mean length of stay was 10.7±2.5 days and the mean cost was $13,397±3,381. The cumulative number of hospital days during the 6 months post-discharge was 17.7±3.5 days for each readmitted patient and the mean per-patient total cost was $23,262±5,478. The mortality rate among readmitted patients was 13.2%. Overall, readmissions following AAA repair accounted for a cost >50% over and above the cost of the readmitted patients index hospitalization. Hospital readmissions are common during the 6 months following AAA repair. Patients who are readmitted experience long lengths of stay and high mortality rates, and their care incurs high costs.Dr. Eisenberg is a Physician-Scientist of the Quebec Foundation for Health Research. Dr. Pilote is a Physician-Scientist of the Canadian Institutes for Health Research.     

Oral etodolac,a COX-2 inhibitor,reduces postoperative pain immediately after fast-track cardiac surgery

Purpose The present study was designed to evaluate the efficacy of a cyclooxygenase (COX)-2 inhibitor, etodolac, on postoperative pain after fast-track cardiac surgery, and to examine the changes in plasma etodolac concentration after oral administration.Methods Thirty patients scheduled for elective coronary artery bypass grafting (CABG) surgery were randomly assigned preoperatively in a double-blind fashion to receive either vehicle (n = 15) or etodolac 400mg (n = 15) via a gastric tube at the end of the surgery. Standardized fast-track cardiac anesthesia was used. In both groups, postoperative pain was treated with buprenorphine suppository. Visual analogue pain scores (VASs) were recorded immediately after extubation and at 24h after surgery. Plasma etodolac concentration was measured at 1, 2, and 6h after administration (n = 8).Results No difference was detected in time to extubation between the etodolac group (209 ± 85min, mean ± SD) and the vehicle group (207 ± 98min). VASs were significantly lower in the etodolac (2.3 ± 2.1) vs the vehicle group (5.8 ± 2.0) immediately after extubation (P = 0.009), but no difference was detected in pain scores at 24h after surgery, or in the amount of buprenorphine administered in the intensive care unit (ICU), or in the incidence of side effects. Plasma etodolac concentration was within the pharmaceutically recommended range at 1h, 2h, and 6h after administration.Conclusion The oral use of etodolac with rectal buprenorphine reduces pain scores immediately after cardiac surgery without an increase in side effects.     

AneuRx Device Migration: Incidence, Risk Factors, and Consequences

Success after endovascular abdominal aortic aneurysm repair (EVAR) is dependent on device positional stability. The quest for such stability has motivated different endograft designs, and the risk factors entailed remain the subject of debate. This study aims at defining the incidence, risk factors, and clinical implications of device migration after EVAR with the AneuRx® endograft. In this study we included all consecutive 109 patients submitted to primary AneuRx placement for infrarenal aortic or aortoiliac aneurysms. Preoperative computed tomography (CT) scans were reviewed for the following anatomic characteristics: neck length, diameter, angulation, calcification, and thrombus load; and sac diameter and thrombus load. Percentage of device oversizing relative to the proximal neck diameter was determined. All postoperative CT scans were reviewed, and the distance between the lowest renal artery and the craniad end of the device was measured. A 5-mm increase in such distance was considered indicative of device migration. Migration cumulative incidence was estimated by the Kaplan-Meier method, and its association with any of the preoperative anatomical characteristics was tested using Cox proportional hazards models. Median follow-up time was 9 (range, 1-31) months. Migration occurred in nine patients, corresponding to a 15.6% estimated probability of migration at 30 months (SE=5.1%). Migration was associated with the risk of proximal type I endoleak (hazard ratio=3.39, 95% confidence interval=1.46-7.87; p=0.007). This type of endoleak occurred in three of the migration-affected patients (33.3%); all of them were resolved by additional cuff placement at the proximal landing zone. No other migration-related reinterventions were performed. The only significant associations between anatomic factors and device migration probability were the protective effects of longer necks (odds ratio [OR]=0.71 for each additional 5 mm, p=0.045) and longer overlapped portions of neck and device (OR=0.56 for each additional 5 mm, p=0.003). There was a trend toward higher probability of migration among reverse-tapered necks (OR=1.75, p=0.109). Percentage of device oversizing correlated with early neck dilation (between preoperative and first postoperative diameters, correlation coefficient=0.4, p < 0.0001), but not with late neck dilatation (between first postoperative and 1.5-year scan diameters, correlation coefficient=0.29, p=0.112). There was a trend toward higher mean percentage of late dilation among migrators (11.4%, standard error of the mean [SEM] 2.6) than nonmigrators (5.7%, SEM=1) (p=0.08), but both groups had similar mean percentages of early dilation (3%, SEM=1.6%, vs. 5.5%, SEM=0.6%; p=0.365). This result indicates that device migration is not a rare event after AneuRx implantation. This phenomenon is associated with proximal type I endoleaks. Deployment of the endograft immediately below the renal arteries might help to prevent migration, since use of greater lengths of overlapped device relative to the proximal neck has a protective effect. Migration seems to be independent of the degree of device oversizing.Presented at the 29th Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, Sergio M. Sampaio is a recipient of the Edward S. Rogers Clinical Research Fellowship in Vascular Surgery.     

Changes of local brain tissue oxygen pressure after vasopressin during spontaneous circulation

Summary. Background. Brain tissue oxygen pressure (PbtO₂) correlates to cerebral blood flow (CBF) during spontaneous circulation, with one important regulator being nitric oxide (NO). Although it is established that arginine vasopressin (AVP) improves CBF and global cerebral oxygenation during cardiopulmonary resuscitation, it is unknown whether similar beneficial effects are present during spontaneous circulation. The purpose of this study was to investigate the effects of AVP with and without pre-treatment with the NO synthase inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME) on local brain tissue oxygenation in a beating heart model.Methods. Following approval of the Animal Investigational Committee, nine healthy piglets underwent general anaesthesia, and were instrumented with a probe in the cerebral cortex to measure PbtO₂. Each animal was assigned to receive AVP (0.4U·kg^–1), and after a wash-out period, L-NAME (25mg·kg^–1 over 20min) followed by AVP (0.4U·kg^–1). After each AVP administration, nitroglycerine (25µg·kg^–1 over 1min) as a NO donor was infused to test the vascular reactivity independently from NOS inhibition.Findings. Three minutes after administration of AVP, PbtO₂ increased significantly (P<.05; mean±SEM, 31±11 versus 43±14mmHg, +39%), compared with baseline. After pre-treatment with L-NAME, the changes of PbtO₂ after AVP were not significant (32±11 versus 28±10, –13%) when compared with the baseline.Conclusion. In this beating heart porcine model, local brain tissue oxygenation was improved after AVP alone, but not after inhibition of NO synthesis with L-NAME.     

Bench test assessment of the new Raumedic Neurovent-P ICP sensor: a technical report by the BrainIT group

Summary. Background. In clinical practice, fiberberoptic and piezo-electric ICP probes are often used for measuring intracranial pressure (ICP). A number of similar technologies, although performing well in bench test studies, have been shown to exhibit unacceptable zero drift, fragility or both during trials conducted under clinical conditions. Recently, a new technology has become available, the Neurovent-P (Raumedic AG+CO, Raumedic, Germany). As a pre-requisite for a clinical trial, we have conducted and report on bench test studies to confirm the manufacturers long term zero-drift performance for this technology.Method. In a test rig static tests (recording of 20mmHg pressure) and dynamic tests, ranging from 5 to 50mmHg have been performed.Findings. 10 ICP probes have been tested for a total of 60 days. All the catheters, after the connection with the ICU monitor displayed a static pressure of 0±1mmHg and did not required pre-insertion alteration. At five days, mean zero drift was 0.6±0.9mmHg. Overall, zero drift ranged from 0 to 2mmHg. At a fixed static pressure of 20mmHg, the mean recorded value was 20.6±0.8mmHg, ranging from 19 to 23mmHg. A regression analysis of the relationship between the applied pressure and the recorded pressure during the dynamic tests of the 10 catheters yielded a correlation coefficient R² of 0.997. Applying the Altman and Bland method to assess the bias and confidence limits for the Raumedic catheter responses during the dynamic tests against the applied gold-standard hydrostatic column pressures, the average bias of –0.66±0.85mmHg, with 95% CLs of –2mmHg and 1mmHg.Conclusions. Mean zero drift, after five days, was very small and long-term continuous recording of a stable pressure was very precise. The response at dynamic tests, i.e. the changes of pressure in a wide range, was excellent. The average bias of the Raumedic catheter compared with the hydrostatic column is very small. After this bench test, the next and most critical step will be to conduct a trial of this promising technology under more demanding clinical environment.     

Infusion of radiocontrast agents induces exaggerated release of urinary endothelin in patients with impaired renal function

Background The aim of the study was to examine the role of endothelin in radiocontrast-induced nephropathy (RCN) in patients with chronic renal failure.Methods We measured plasma endothelin-1 (ET) and the urinary excretion of endothelin-like immunoreactivity before and after infusion of radio contrast medium (CM) in patients with normal renal function (group N; n = 6; mean serum creatinine concentration, 0.8 ± 0.1 (SEM) mg/dl), and in another group, with renal dysfunction (group R; n = 6; 2.7 ± 0.5mg/dl). Half-normal saline (0.45% NaCl solution) was continuously infused in all patients for 25h, at a rate of 100ml/h; starting from 5h before the infusion of CM.Results Plasma ET in group R (5.2 ± 1.4pg/ml) was significantly higher than in group N (0.9 ± 0.3; P 0.01). Urinary endothelin excretion corrected by creatinine concentration (uET/Cr) in group R (7.9 ± 2.4mg/g Cr) was significantly higher than in group N (1.5 ± 0.4mg/g Cr; P 0.05). Urinary excretion levels of N-acetyl--d-glucosaminidase (NAG) and 2-microglobulin (2M) were also significantly higher in group R (0.8 ± 0.2mU/g Cr and 670 ± 400mg/g Cr, respectively) than in group N (0.3 ± 0.1 and 7.5 ± 2.2, respectively). After CM infusion, uET/Cr in group R significantly increased, to 10.7 ± 2.6mg/g Cr on the next day and returned to baseline level on the third day. NAG and 2M showed a similar pattern, but a significant change in NAG was observed on the second day in group R. In group N, uET/Cr, NAG, and 2M did not change after CM infusion. Plasma ET remained unchanged throughout the observation period of 4 days in both groups. No patient developed pulmonary edema or a significant rise in serum creatinine (more than 0.5mg/dl), caused by infusion of the amount of half-normal saline used.Conclusions In the present study, uET/Cr increased after the administration of CM only in the patients with renal impairment. This difference in endothelin reaction may be a causal one, in that patients with renal insufficiency readily develop RCN. The infusion of half-normal saline starting before CM infusion causes no side effects and is safe for the prevention of CM-induced acute renal failure.     

Seasonal changes of serum 25-hydroxyvitamin D and intact parathyroid hormone levels in a normal Japanese population

We conducted an observational study in order to assess the prevalence of hypovitaminosis D and its seasonal changes, in the Tokai area (N35.3 E137.0), in 197 normal subjects in Japan. The mean serum 25-hydroxyvitamin D (25-OHD) level measured by direct radioimmunoassay (RIA) was lowest at the end of winter, and highest at the end of summer (15.1 ± 7.1ng/ml in March; 21.5 ± 5.5ng/ml in June; 31.6 ± 5.6ng/ml in September; 23.1 ± 5.3ng/ml in December; mean ± SD). The prevalence of hypovitaminosis D (<20ng/ml) was 86.7%, 33.4%, 1.0%, and 26.0% in March, June, September, and December, respectively. Mean plasma intact parathyroid hormone (iPTH) concentration was lowest at the end of summer and highest at the end of winter (28.2 ± 9.3pg/ml in March; 21.7 ± 7.0pg/ml in June; 19.8 ± 6.9pg/ml in September; and 25.7 ± 9.2pg/ml in December; mean ± SD). Serum 25-OHD was inversely associated with iPTH (coefficient, –0.223; r = 0.251; P < 0.001). Serum 25-OHD levels were higher in men than in women. The serum 25-OHD level was positively associated with age, body weight, and body mass index, but not with body fat content. These results suggest a high prevalence of hypovitaminosis D associated with elevation of iPTH in Japan, in winter, even in a sunny area.     

Effects of Cilostazol on Human Venous Smooth Muscle

In this study, we evaluated the effect of therapeutic doses of cilostazol on human venous smooth muscle. Saphenous vein rings (two to four per patient sample) were suspended in tissue baths for isometric tension recordings. At the beginning of the experiment, optimal tension for isometric contraction was achieved for each ring in a stepwise fashion in the presence of norepinephrine (10^–2 M). Norepinepherine was then added cumulatively in half-molar increments and isometric tension developed by the rings was measured, thereby obtaining a dose-response curve. Following washout and reequilibration, the rings were precontracted with a 30-50% submaximal dose of norepinepherine determined from the dose-response curve and allowed to contract until a stable plateau was reached. Cilostazol was then added in a cumulative manner (680-2,720 g/L), and the tension generated was recorded. A total of 76 venous rings were tested, and all relaxed in the presence of cilostazol. The amount of relaxation increased as the concentration of cilostazol increased. Relaxation of 15±1.9% (mean±SEM) at low cilostazol doses (680 g/L) to 37±3% at high cilostazol doses (2,720 g/L) was demonstrated. A second finding of this study was demonstrated when the patient samples were divided according to the presence or absence of risk factors for arteriosclerosis. The specific risk factors examined included diabetes mellitus, smoking, hypercholesterolemia, and hypertension. The presence or absence of hypertension (n=52) or hypercholesterolemia (n=18) did not affect the amount of relaxation of the venous rings. Smokers (n=46) had less relaxation 16±2.4% (680 g/L) to 41±3.6% (2,720 g/L) compared to nonsmokers (n=53) who relaxed 22±3.5% (680 g/L) to 48±5.7% (2720 g/L). This did not reach statistical significance at any concentration cilostazol (p=0.11-0.18). Diabetics (n=53) did have statistically significantly less relaxation at every concentration of cilostazol compared to nondiabetics (n=11, p < 0.05). All venous rings relaxed in the presence of cilostazol. Veins of nondiabetics relaxed statistically significantly more than those of diabetics. Smokers had less relaxation than non-smokers, but this was not statistically significant. We are the first to demonstrate that human venous smooth muscle cells undergo relaxation when exposed to therapeutic concentrations of cilostazol.     

Effect of preanesthetic famotidine on gastric volume and pH

The effect of preanesthetic 20mg of famotidine on gastric fluid volume and pH were studied in patients scheduled for elective surgery. One hundred and twenty-eight patients were divided into four groups-control, intravenous, intramuscular and oral with 32 patients in each group. Patients in placebo group received no famotidine and served as control. Patients in the intravenous and intramuscular groups were administered famotidine one hour before surgery. Patients in the oral group were administered famotidine the night before and on the morning of surgery. Gasric volume in the control group was 19.1 ± 10.8ml; in the intravenous group, 7.4 ± 6.4ml; in the intramuscular group, 7.3 ± 6.9ml; and in the oral group, 7.1 ± 6.9ml. Gastric pH was 3.4 ± 2.3, 6.8 ± 1.1, 6.9 ± 1.6, and 6.7 ± 1.2 in groups one through four, respectively. When compared to the control group, famotidine significantly decreased gastric volume and increased gastric pH. There were no statistical differences among the different modes of administration. No adverse effects were observed in this study. It is concluded that preanesthetic management of 20mg of famotidine reduced the risk of acid aspiration pneumonitis.(Okuda T, Takatsu T, Kumode O et al.: Effect of preanesthetic famotidine on gastric volume and pH. J Anesth 2: 17–21, 1988)     

Inhaled Nitric Oxide Therapy After Fontan-Type Operations

Purpose Inhaled nitric oxide (NO) therapy is a newly developed strategy designed to reduce pulmonary vascular resistance after the Fontan-type operation. We reviewed our experience to evaluate its efficacy and true indications.Methods We retrospectively examined 47 children who received inhaled NO therapy after the Fontan-type operation between August 1996 and December 2002. The maximal dose of NO ranged from 5 to 30ppm (median 10ppm), and the duration of inhaled NO therapy ranged from 5h to 52 days (median 2 days).Results Inhaled NO significantly decreased the central venous pressure (CVP), from 16.2 ± 2.2 to 14.6 ± 2.2mmHg (P < 0.0001), and the transpulmonary pressure gradient between the CVP and left atrial pressure, from 9.9 ± 2.9 to 8.4 ± 2.7mmHg (P < 0.0001). It also increased the systolic systemic arterial pressure from 71.9 ± 15.2 to 76.8 ± 14.5mmHg (P < 0.05). In 26 patients with additional fenestration, inhaled NO led to a significant improvement in SaO₂ from 90.1% ± 9.6% to 93.3% ± 7.9% (P < 0.01). However, patients with a CVP <15mmHg or a transpulmonary pressure gradient <8mmHg, or both, after the Fontan-type operation, showed no significant changes in hemodynamics during inhaled NO therapy.Conclusions We propose that a CVP 15mmHg or a transpulmonary pressure gradient 8mmHg, or both, after Fontan-type operations are appropriate indications for inhaled NO therapy.     

The effects of calcium antagonists on EEG,evoked potentials and neurologic recovery after complete global brain ischemia for 15 minutes in dogs

The effects of three calcium antagonists on the recovery from neurologic damages after complete global brain ischemia were examined by evaluating the change of a electroencephalogram (EEG), evoked potentials (EP) and a neurologic recovery score (NRS) in dogs. Fifteen minutes global brain ischemia was achieved by occluding the ascending aorta and the caval veins. Nicardipine (NC), flunarizine (FL) and diltiazem (DL) were administered with continuous infusions for three days after the ischemia. The EEG-EP scores (0:no response – 6:normal) 3hr after the ischemia were 1.4 ± 0.4 (mean ± SE) in the control, 2.2 ± 0.3 in the NC, 2.2 ± 0.4 in the FL and 2.1 ± 0.2 in the DL. There were no significant differences between the 4 groups. The survival rates on the 7th day after the ischemia were 67% (6/9) in the control, 78% (7/9) in the NC, 56% (5/9) in the FL and 89% (8/9) in the DL. No significant differences were presented between the 4 groups. The NRSs (0:death – 100:normal) on the 7th day were 40.3 ± 7.3 in the control, 59.0 ± 8.5 in the NC, 63.2 ± 9.7 in the FL and 55.7 ± 3.3 in the DL. Each treated group showed a tendency to have a higher NRS than that in the untreated control group. The NRS in all dogs treated by the Ca⁺⁺ antagonists on the 7th day was 58.7 ± 4.1, which was significantly higher than that in the control group (P < 0.05). We conclude that the continuous administration of calcium antagonists for three days after the global brain ischemia would be beneficial for the neurologic recovery.(Ono K, Iwatsuki N, Takahashi M, et al.: The effect of calcium antagonists on EEG, evoked potentials and neurologic recovery after complete global brain ischemia for 15 minutes in dogs. J Anesth 5: 114–122, 1991)     

Multiple endocrine neoplasia type 1 in end-stage renal failure

A 59-year-old woman with chronic renal failure due to type 2 diabetes mellitus (DM) is presented. Her father and a brother had a history of brain tumor. Her blood urea nitrogen and serum creatinine levels were 102mg/dl and 4.5mg/dl, respectively. Her serum Ca²⁺ and Pi were within the normal range (9.4mg/dl and 5.4mg/dl, respectively). Her intact parathyroid hormone (PTH) level was 1730000pg/ml. A ^99mTc-methoxy-isobutylisonitrile scintigraphy showed high uptake in three parathyroid glands. A magnetic resonance image showed microadenoma in the pituitary gland. The serum gastrin level was high. Genetic examination revealed a mutation of the MEN1 gene (894–9 G A). From these findings, she was diagnosed with multiple endocrine neoplasia (MEN) type 1. Subsequently, a parathyroidectomy was performed successfully, a parathyroid gland was transplanted to her right forearm, and her serum Ca²⁺ level was controlled at 8.5–9.0mg/dl. It is very important to identify MEN1 if an end-stage renal disease (ESRD) patient has hyperparathyroidism with multigland involvement. Examination of the MEN1 gene may be valuable to make an accurate diagnosis and choose the appropriate therapy in some ESRD patients with hyperparathyroidism.     

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)     

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)     

Enhancement of lidocaine-induced epidural anesthesia by deoxyaconitine in the rabbit

Purpose.Aconiti tuber has been used in traditional Oriental medicine to alleviate pain. The antinociceptive property of aconiti tuber is due to the action of its extracted alkaloids such as deoxyaconitine. The purpose of this study was to investigate the effect of epidural deoxyaconitine on epidural lidocaine anesthesia. Methods.Five adult rabbits were used. Three different combinations of drugs were injected into the epidural space, in the following order: first (combination A), 1.5ml of 2% lidocaine; second (combination B), 1.5ml of 2% lidocaine and 150µg deoxyaconitine; and third (combination C), 3mg nor-binaltorphimine followed by 1.5ml of 2% lidocaine and 150µg deoxyaconitine 30min later. The latency of onset and the duration of three end-points (sensory loss in the tail, loss of weight-bearing ability, and flaccid paresis of hind limb) were measured. Results.Onset times for the three end-points were not changed by deoxyaconitine or by nor-binaltorphimine. The duration of sensory loss was 27.0 ± 2.7min, the duration of loss of weight-bearing ability was 33.0 ± 2.7min, and the duration of flaccid paresis was 21.0 ± 4.2min in the combination A group. In the combination B group, deoxyaconitine extended the time of sensory loss by 80%, the time of loss of weight-bearing by 50%, and that of flaccid paresis by 60% compared with the combination A group. In the combination C group, this phenomenon was partially antagonized by pretreatment with nor-binaltorphimine, a -opioid antagonist. Conclusions.Based on our observations, deoxyaconitine enhanced epidural lidocaine anesthesia in the rabbit, and this effect seemed to be partly mediated by -opioid receptors.     

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)