Oral carbonaceous absorbent modifies renal function of renal ablation model without affecting plasma renin-angiotensin system or protein intake

Background. Although it has been repeatedly shown that the oral carbonaceous absorbent AST-120 ameliorates the progression of chronic renal failure, the mechanisms remain unknown.Methods. Male Sprague-Dawley rats (6 weeks old), weighing 180–210g, were 4/5 nephrectomized, and were divided into two groups: one given AST-120 (0.4g/100g body weight BW; n = 9) and the other not given AST-120 (n = 9). Body weight, blood pressure, and serum and urine chemistry, as well as the plasma components of the renin-angiotensin system, were measured for 22 weeks.Results. Proteinuria was significantly greater in the controls than in the AST-120 group (102 ± 22 vs 51 ± 7mg/day at 22 weeks). Urea clearance was lower in the former (3.7 ± 0.4 vs 3.9 ± 0.4ml/min). There were no differences in plasma renin activity (1.4 ± 0.3 vs 1.9 ± 0.4mg/ml per h), or in angiotensin I (756 ± 119 vs 1042 ± 168pg/ml) and II (35.1 ± 7.4 vs 46.6 ± 7.6pg/ml) or angiotensin-converting enzyme activity (39.0 ± 2.4 vs 37.9 ± 2.2IU/l) between the two groups. Protein intake, estimated from urinary urea appearance, was not different. Serum phosphate concentration (6.6 ± 0.3 vs 5.9 ± 0.3mg/dl) was higher in the control than in AST-120, while the urinary phosphate excretion rate (31.5 ± 0.8 vs 28.1 ± 1.8mg/day) tended to be lower in the latter.Conclusions. AST-120 retarded the progression of renal failure in the 4/5 renal ablation model without affecting the plasma renin-angiotensin system or protein intake, both of which were the most important risk factors for the progression of renal failure. We hypothesize that the renal protective effects of the oral absorbent AST-120 may be, at least in part, due to its lowering phosphate absorption from the diet as a phosphorus binder.     

Experimental study of renal disorder caused by oxaliplatin in rat renal cortical slices

Background Oxaliplatin is a newly developed antitumor platinum complex that is known to have low nephrotoxicity. The inhibitory effects of oxaliplatin on several tubular functions were compared with those of cisplatin and carboplatin, using a renal cortical slice system.Methods and results Rat renal cortical slices were incubated with 0.25mM to 2.0mM of oxaliplatin, cisplatin, on carboplatin at 37°C for 120min. Para-amino hippuric acid (PAH) accumulation, gluconeogenesis, and ATP content in the rat renal slices were determined. PAH accumulation was not inhibited by carboplatin, but it was signific-antly inhibited by oxaliplatin and cisplatin. Inhibition of PAH accumulation by cisplatin was greater than that by oxaliplatin. Gluconeogenesis was not decreased by carboplatin, but it was suppressed by oxaliplatin and cisplatin in a dose-dependent manner. The decrease in gluconeogenesis induced by oxaliplatin was significantly greater than that induced by cisplatin. ATP content in the renal slices was decreased by oxaliplatin, cisplatin, and carboplatin to almost the same extent. As an in vivo experiment, 21.6mmole/kg of oxaliplatin, cisplatin, or carboplatin was injected into rats; then blood urea nitrogen (BUN) and serum creatinine were determined on day 4. Significantly elevated levels of BUN and serum creatinine were observed only in the rats injected with cisplatin.Conclusions Oxaliplatin did not cause nephrotoxicity in the in vivo study; however, the nephrotoxic pattern of oxaliplatin observed in the renal cortical-slice system resembled that of cisplatin. The reason why oxaliplatin is less nephrotoxic than cisplatin in vivo could not be fully elucidated in the present experiment using the renal cortical-slice system.     

Tubular PAH transport capacity in human kidney tissue and in renal cell carcinoma: correlation with various clinical and morphological parameters of the tumor

In vitro accumulation ofp-aminohippurate (PAH) was investigated in intact human renal cortical slices of normal kidney tissue and in tissue slices of renal cell carcinoma (RCC). The technique used was established in preliminary experiments on rat kidney tissue slices. In principle, the accumulation capacity is comparable in renal tissue slices of both species (slice to medium accumulation ratios between 4 and 8). In man sex differences in accumulation capacity do not exist. But, as shown in detail for rats, accumulation capacity drops with age. Tissue slices of RCC are unable to accumulate PAH actively; slice to medium ratio reaches about 1 and indicates passive PAH uptake only. Surprisingly, in tumors of stage pTl PAH uptake is lowest, perhaps as a sign of PAH transport out of the cells. There is no difference between peripheral and central parts of RCC. Age and sex are without influence on PAH uptake in RCC tissue slices. Interestingly, the accumulation capacity of intact tissue of kidneys infested with RCC also depends on the severity of the tumor (stage, diameter), but not on grading and formation of metastases.     

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.     

Circulating 1-84 PTH and large C-terminal PTH fragment levels in uremia

Background. The so-called intact parathyroid hormone (iPTH) assay detects large C-terminal PTH fragments that are lacking several N-terminal amino acid residues in addition to 1-84 PTH molecules.Methods. Blood samples were obtained from 65 predialysis patients (male, 35; female, 30) and 109 dialysis patients (male, 73; female, 36). The plasma 1-84 PTH levels were determined by a specific immunoradiometric assay (IRMA).Results. The ratio of 1-84 PTH/iPTH did not show a significant correlation with glomerular filtration rate (GFR) among patients with a GFR of more than 80ml/min, while it showed a positive correlation with GFR among patients with a GFR of less than 80ml/min. The ratio of 1-84 PTH/iPTH demonstrated a significant tendency to decrease in the order of patients with normal renal function (0.928 ± 0.182), those with renal dysfunction (0.836 ± 0.186; P < 0.05 vs patients with GFR > 80ml/min [i.e., normal renal function]), and those with maintenance hemodialysis (0.618 ± 0.123; P < 0.01 vs patients with GFR > 80ml/min). The plasma levels of 1-84 PTH and conventional iPTH showed a close correlation in dialysis patients. Neither 1-84 PTH levels nor secondary parameters calculated from them showed a better correlation with bone metabolic markers than iPTH levels.Conclusions. Circulating large C-terminal PTH fragment levels are increased in uremic patients. However, this noninvasive study failed to demonstrate the superiority of the specific 1-84 assay compared with the conventional iPTH assay to evaluate bone metabolism.     

The intrathecal spread of hyperbaric dibucaine in adolescents

We investigated the spread of spinal anesthesia with hyperbaric dibucaine in 20 adolescents aged 9–18yr and 20 adults aged 23–53yr. No significant difference was found between the two groups with regard to height, whereas a statistical significant was found between the two groups with regard to weight. Spinal anesthesia was conducted with Neo-Percamin S^® injected at the L3–L4 interspace through a 25-gauge spinal needle. Injected volumes of the anesthetic solution were calculated from the patients height at 0.01ml·cm^–1. In adolescents, 1.6 ± 0.1ml (mean ± SD) of the anesthetic solution produced 19.4 ± 1.5 spinal segments blocked. In adults, 1.6 ± 0.1ml of the solution produced 13.4 ± 1.6 spinal segments blocked. A high spinal anesthesia above T5 was achieved in 17 (85%) patients in adolescents, whereas such a high level of spinal anesthesia was not experienced in adults. These results suggest that the hyperbaric dibucaine solution for spinal anesthesia in adolescents may have a tendency to produce an unexpectedly extensive spread of anesthesia.(Hirabayashi Y, Shimizu R: The intrathecal spread of hyperbaric dibucaine in adolescents. J Anesth 7: 167–172, 1993)     

Delayed discharge and acceptability of ambulatory surgery in adult outpatients receiving general anesthesia

Purpose Delay in discharge after ambulatory surgery impairs its cost-effectiveness. However, it is not self-evident that prolonged postoperative stay is associated with low quality of care and patient acceptability of ambulatory surgery. The aims of this study were to document factors affecting delay in discharge, recovery profiles, and patient acceptability in adult outpatients.Methods Perioperative data were collected prospectively on consecutive 726 adult same-day surgical patients receiving general anesthesia. Factors that affected home-readiness, discharge, and unanticipated admission were noted. Patients were followed up 24h after discharge using a standardized questionnaire to identify postdischarge symptoms, patients self-rated resumption of normal activity (RNA) level, and preference of outpatient procedure.Results Eighty-two percent of patients were discharged home <270min after operation, 16% were delayed (270min), and 2% required unanticipated admission. Delayed patients reported postdischarge pain more frequently (53%) and a lower 24-h postoperative RNA level (7.2 ± 1.8) and preference ratio (76%) than no-delay patients (34%, 8.0 ± 1.9, 87%, respectively; P < 0.001). Delay in home-readiness (165min) was mainly due to an adverse symptom, and delay in discharge after reaching home-readiness (150min) was mainly due to a persistent symptom (58%) or a social/system problem (34%). Causes of admission were perioperative complications (80%) or social reasons (20%).Conclusion Delays in discharge are mainly due to adverse symptoms or social/system problems. Delayed discharge is associated with increased postdischarge pain, lower RNA level, and patient acceptability. Appropriate care of postoperative symptoms and system management could prevent delay in discharge and improve patient RNA level and acceptability.This work was presented in part at the 7th Congress of the Japanese Society for Ambulatory Anesthesia at Nagoya, Japan     

Analgesic dose-response relation in cervical epidural block

The relationship between the age and the spread of analgesia from different epidural anesthetic doses was examined by studying analgesic dose responses in cervical epidural analgesia. Two different anesthetic doses (5ml or 10ml) of 2% mepivacaine were injected into the cervical epidural space at a constant pressure (80mmHg) using an intravenous apparatus, and the spread of analgesia to pinprick was assessed. The significant correlation was found between the patients age and the number of spinal segments blocked (5ml:r = 0.8498, P < 0.01, 10ml:r = 0.5988, P < 0.01). The inverse linear relationship was found between the patients age and the segmental dose requirement (5ml:r = –0.6754, P < 0.01, 10ml:r = –0.5784, P < 0.01). Patients under 39 years of age showed a direct relationship between the dose injected and the number of spinal segments blocked, enabling prediction of the number of segments blocked with a given dose of local anesthetic. Doubling the epidural dose approximately doubled the number of spinal segments blocked. The analgesic dose-response relation in patients over 60 years of age differed from that in patients under 39 years of age and doubling the epidural dose did not double the number of spinal segments blocked. Progressively more extensive analgesia was obtained from a given dose of local anesthetic with advancing age. It was difficult to limit the extent of analgesia by injecting a smaller dose of local anaesthetic in the elderly.(Hirabayashi Y, Matsuda I, Inoue S et al.: Analgesic dose-response relation in cervical epidural block. J Anesth 2: 22–27, 1988)     

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)     

Spinous process-plasty following lumbar laminectomy as a contributing factor to spine stability

A 10-year retrospective study of 41 consecutive patients who underwent spinous process-plasty is presented. We carried out laminectomy of the lumbar spine in cases of spinal stenosis, dorsomedial herniated disc and recurrent disc herniation with firm scars (traumatic and tumour cases are not included). To forestall the development of laminectomy's negative effects on spine stability, we initiated the spinous processes' reconstruction. Two groups of patients who underwent laminectomy form the basis of this presentation, one group with spinous process-plasty (41 patients) and the other (11 patients) without it. On postoperative neutral and dynamic X-ray films we paid attention to horizontal displacements larger than 3 mm and to negative intervertebral angular displacement. Considering such criteria, only 3.8% of those with spinous process-plasty developed a radiographic instability in contrast to 25% of patients without spinous process-plasty. These results support the use of this technique, which provides postlaminectomy lumbar spine stability.     

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.     

31P and23Na nuclear magnetic resonance study on forebrain ischemia in rats with shift reagent Dy(TTHA)

³¹P and ²³Na nuclear magnetic resonance (NMR) spectroscopy was employed to study the dynamic changes in intracellular high-energy phosphates and sodium during 15min of forebrain ischemia and recirculation in in vivo rat brain. In the presence of the shift reagent Dysprosium triethylenetetramine-N,N,N,N,N,N-hexaacetic and [Dy(TTHA)], the sodium peak separated into two peaks, unshifted and shifted. During 15min of ischemia, the unshifted sodium peak decreased and the shifted sodium peak increased. With recirculation, the unshifted and the shifted sodium peaks returned to the preischemia level within 10min, but the shifted one increased during 30–60min. Intracellular high-energy phosphates and intracellular pH (pHi) decreased during 15min of ischemia and returned to the preischemia levels within 20min of recirculation. We conclude that the decrease in unshifted sodium peak during ischemia is due to the decrease in subarachnoid sodium and the cellular influx of interstitial sodium would be minimum. The increase in shifted sodium peak during ischemia is considered to be due to the dilatation of cerebral blood vessels and the increase in interstitial sodium which was transported from subarachnoid space.(Kurata M: ³¹P and ²³Na nuclear magnetic resonance study on forebrain ischemia in rats with shift reagent Dy(TTHA). J Anesth 7: 325–333, 1993)     

The N-Methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enfturane-induced opisthotonus in mice

We determined whether enflurane-induced opisthotonus in ddN mice is mediated by N-methyl-D-aspartate (NMDA) receptor using NMDA receptor antagonists dizocilpine (MK-801) and ketamine. Animals were given intraperitoneal injections of 0.2ml saline (control), 2.5 or 5.0mg·kg^–1 dizocilpine in saline, or 20 or 40mg·kg^–1 ketamine is saline 20min prior to exposure to 2.0% enflurane. Incidence of opisthotonus measured during exposure to enflurane for 20min was 49% (n = 51) in saline (control) group, 6.7 (P 0.01 vs control, n = 30) and 15.0% (P 0.01, n = 40) in 2.5 and 5.0mg·kg^–1 dizocilpine group, respectively, and 43.9 (NS, n = 41) and 40.0% (NS, n = 40) in 20 and 40mg·kg^–1 ketamine group, respectively. These results strongly suggest that enflurane-induced opisthotonus is mediated by NMDA receptor. Ketamine failed to suppress significantly due to possibly small dosages. Further, dizocilpine itself produced severe seizures during preenflurane period (30.0 and 40.0% in 2.5 and 5.0mg·kg^–1, respectively), which may be a novel finding.(Komatsu H, Nogaya J, Anabuki D, et al.: The N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (MK-801) suppresses enflurane-induced opisthotonus in mice. J Anesth 7: 519–522, 1993)     

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.     

Plasma concentration for optimal sedation and total body clearance of propofol in patients after esophagectomy

The present study investigated plasma propofol concentration for optimal sedation and total body clearance in patients who required sedation for mechanical ventilation after esophagectomy. Seven patients after esophagectomy were enrolled in this study. Plasma propofol concentrations were measured with high performance liquid chromatography. Total body clearance was calculated from the steady-state concentration. The infusion rate of propofol for achieving the sedation score of level 3 (drowsy, responds to verbal stimulation) was 1.74 ± 0.82mgkg^–1h^–1 (mean ± SD, n = 7) when the plasma propofol concentration and the total body clearance were 0.85 ± 0.24µgml^–1 and 1.83 ± 0.54lmin^–1 (mean ± SD, n =7), respectively.     

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.     

Safety of Contrast Venography prior to Caval Interruption in Patients with Renal Insufficiency

We undertook this study to determine whether the use of contrast venography would adversely affect renal function in patients with renal insufficiency requiring caval interruption. We conducted a retrospective review of all inferior vena cava (IVC) filters inserted at our institution over a 2-year period (January 2002 to January 2004). The indication for caval interruption, insertion technique, type of filter used, pre- and postintervention creatinine level, and the presence of diabetes and hypertension were analyzed. A total of 282 IVC filters were inserted, with 38 of them placed in patients with renal insufficiency as defined by a serum creatinine level of > 1.5 mg/dL. Contrast venography with 15 to 30 mL of iohexol (Omnipaque 300) was used in all cases, and no special measures other than proper hydration were used for renal protection. All filters were successfully deployed. The mean±SD preintervention creatinine level was 2.38±0.79 mg/dL. The mean±SD postintervention creatinine levels at 2 and 30 days were 2.26±0.45 mg/dL and 2.12±0.94 mg/dL, respectively. No patients required hemodialysis following caval interruption, and no adverse effect on renal function was noted. Contrast venography accurately delineates venous anatomy and facilitates proper caval filter placement with no apparent adverse effect on renal function. We believe contrast venography is safe even in the presence of renal insufficiency.     

Comparison of adrenoceptor subtype expression in porcine and human bladder and prostate

We have quantified and characterized ₁-, ₂-and -adrenoceptor subtypes in porcine bladder detrusor and bladder neck, human bladder detrusor, and porcine and human prostate. ₁-, ₂- and -adrenoceptor were identified in radioligand binding studies using [³H]prazosin, [³H]RX 821002 and [¹²⁵I]iodocyanopindolol, respectively, as the radioligands. In porcine male and female detrusor and bladder neck and male prostate, adrenoceptors were detected in the order of abundance > _{2 1} (not detectable), with no major differences between the sexes or between detrusor and bladder neck. In human detrusor and prostate the order of abundance was > _{2 1} (not detectable) and ₁ > ₂. respectively. The ₂-adrenoceptors in all tissues were homogeneously of the _2A-subtype as evidenced by competition binding studies with yohimbine, prazosin, ARC 239 and oxymetazoline. The -adrenoceptors represented a mixed population with a dominance of the ₂-subtype in all tissues as demonstrated by competition binding with ICI 118,551 and CGP 20,712A. We conclude that pigs may be a suitable model for studies of detrusor function with respect to adrenoceptor expression. They may be less suitable for studies of bladder neck or prostate function.     

Suppression of Experimental Aortic Aneurysms: Comparison of Inducible Nitric Oxide Synthase and Cyclooxygenase Inhibitors

The rat model of abdominal aortic aneurysm (AAA) is associated with inflammation, destruction of extracellular matrix, and production of both inducible nitric oxide synthase (iNOS) and matrix metalloproteinase-9 (MMP-9). Indomethacin, a nonselective cyclooxygenase inhibitor, may prevent AAA formation by inhibiting cyclooxygenase-2 (COX-2) activity. We hypothesized that indomethacin, rofecoxib (selective COX-2 inhibitor), and 1400W (selective iNOS activity inhibitor) would decrease aneurysm formation in the rat model. Forty-six male Wistar rats underwent intraaortic elastase infusion in two parallel studies based on medication delivery route. Sixteen rats were randomized to rofecoxib or water by gastric lavage. Thirty rats were randomized to subcutaneous saline, indomethacin, or 1400W. Heart rate, blood pressure and aortic diameters were measured. Western Blot and mRNA analysis for MMP-9 and iNOS was performed on postoperative day 7 aortic segments. Elastin degradation and inflammation were evaluated by immunohistochemistry. Elastase infusion produced AAA in all rats. 1400W significantly limited aneurysm expansion (p=0.01) whereas treatment with indomethacin and rofecoxib did not. Only 1400W significantly increased blood pressure (p < 0.001). Indomethacin alone statistically decreased MMP-9 (p < 0.011). 1400W resulted in greater conservation of aortic elastin than indomethacin (p=0.025). All groups demonstrated statistically similar expression of iNOS. In conclusion, selective iNOS activity inhibitor, 1400W, significantly decreased aneurysm size and preserved aortic elastin without altering MMP-9 levels. Indomethacin significantly decreased MMP-9 expression without decreasing aneurysm size. Rofecoxib did not significantly decrease MMP-9 expression or aneurysm size. Inhibition of iNOS limits aneurysmal expansion by mechanisms other than MMP-9 inhibition. MMP-9 inhibition by indomethacin is not sufficient to limit aneurysm expansion in our model.Presented at the 2002 Lifeline Foundation Research Initiatives in Vascular Disease Conference,Bethesda, MD, April 18-19, 2002.     

Risk-Adjusted Analysis of Outcomes Following Elective Open Abdominal Aortic Aneurysm Repair

The purpose of this study was to describe a method to analyze outcomes following open abdominal aortic aneurysm (AAA) repair while considering the variability in patients preoperative risk. Consecutive patients undergoing elective open infrarenal AAA repair during a 4-year period (2000-2003) were reviewed. Thirty-day or in-hospital mortality was the major outcome variable. Preoperative mortality risk was estimated for each patient using a validated scoring system that considers age, renal dysfunction, and coronary artery and cerebrovascular disease. A risk-adjusted cumulative sum method was used to compare observed versus predicted outcomes by assigning a risk-adjusted score, based on log-likelihood ratios, to each patient. These cumulative scores were sequentially plotted with preset control limits to allow for signaling when results were substantially different than expected (doubling or halving of odds ratios). Four hundred and sixty-three patients were studied with an overall early mortality rate of 4.5% (n=21). Patients were allocated to three different preoperative risk groups (low, n=89; medium, n=160; high, n=214) according to a medical comorbidity-based scoring system. Predicted (P) and observed (O) mortality rates for each group were as follows: low, 2.4% (P) and 2.2% (O); medium, 4.1% (P) and 4.4% (O); high, 9.3% (P) and 5.6% (O). The resulting risk-adjusted scores for each patient were plotted sequentially. This plot was flat for the first year and then adopted a negative slope crossing the lower control limit after 266 patients, indicating improved results compared to those expected. This coincided with the adoption of routine intraoperative cell saver use in our practice. This form of analysis allows for the prospective evaluation of results while considering patient-mix variabilities.Presented at the Twenty-ninth Annual Meeting of the Peripheral Vascular Surgery Society, Anaheim, CA, June 4-5, 2004.