Dextrose Group Research Articles

Do Adenosine Receptors Play a Role in Amitriptyline‐Induced Cardiovascular Toxicity in Rats?

The aim of the our study was to investigate the role of adenosine receptors on cardiovascular toxicity induced by amitriptyline, a tricyclic antidepressant agent. Therefore, the hypothesis of this study was that adenosine receptor antagonists would improve and/or prevent amitriptyline-induced hypotension and conduction abnormalities in an anesthetized rat model of amitriptyline intoxication. Two separate experimental protocols were performed. Amitriptyline intoxication was induced by the infusion of amitriptyline 0.94 mg/kg/min until 40-45% reduction of mean arterial pressure (MAP). Sodium cromoglycate (10 mg/kg) was injected i.v. to inhibit the A3 receptor-mediated activation of mast cells. In protocol 1, after amitriptyline infusion, while control animals (n=8) were given dextrose solution, treatment groups received a selective adenosine A1 antagonist DPCPX (8-cyclopentyl-1,3-Dipropylxanthine, 20 microg/kg/min, n=8) or a selective A2a antagonist CSC (8-(3-chlorostyryl) caffeine, 24 microg/kg/min, n=8) for 60 minutes. In protocol 2, after the sodium cromoglycate, while control group of rats (n=8) recevied a dextrose solution, treatment groups of rats were administered DPCPX (20 microg/kg/min, n=8) or CSC (24 microg/kg/min, n=8) infusion to block adenosine A1 and A2a receptors for 20 minutes before amitriptyline infusion. After pretreatment with adenosine antagonists, all rats were given a dose of 0.94 mg/kg/min of amitriptyline infusion during 60 minutes. Outcome measures were mean arterial pressure (MAP), heart rate (HR), QRS duration and survival rate. In protocol 1, amitriptyline infusion significantly reduced MAP and prolonged QRS within 15 minutes. HR was not changed significantly during the experiments. While dextrose did not improve MAP and QRS prolongation, DPCPX or CSC administration developed a significant improvement in MAP compared to the dextrose group within 10 min (88.5 +/- 2.8%, 75.6 +/- 4.7% and 50.1 +/- 14.7%, p<0.01, p<0.05, respectively). Both DPCPX and CSC decreased QRS prolongation (p<0.05) and increased median survival time significantly (log-rank test, p<0.00001). In protocol 2, pretreatment with DPCPX or CSC prevented the reduction in MAP due to amitriptyline toxicity compared to rats administered dextrose infusion (99.5 +/- 2.6%, 102.4 +/- 2.6%, 81.8 +/- 5.4, p<0.01 at 30 min; 98.0 +/- 2.9%, 93.5 +/- 6.0%, 64.9 +/- 4.7, p<0.001, p<0.01 at 40 min, respectively). Pretreatment with DPCPX or CSC also prevented the QRS prolongation (p<0.05) and increased median survival time significantly (log-rank test, p<0.0001). Adenosine antagonists were found to be effective in improving hypotension, QRS prolongation and survival time in our rat model of amitriptyline toxicity. Additionally, amitriptyline-induced cardiotoxicity was abolished by pretreatment with adenosine receptor antagonists. These results suggest that adenosine receptors may have a role in the pathophysiology of amitriptyline-induced cardiovascular toxicity. Adenosine A1 and A2a receptor antagonists may be promising agents for reversing amitriptyline-induced cardiovascular toxicity.

Efficacy of preconditioning with N-acetylcysteine against reperfusion injury after prolonged cold ischaemia in rats liver in which glutathione had been reduced by buthionine sulphoximine.

To investigate the ability of N-acetylcysteine (NAC) to prevent cold ischaemic-reperfusion injury and improve hepatic integrity in a glutathione-depleted condition. Open laboratory study. University hospitals, Japan and France. 40 male Wistar rats. To produce a glutathione-depleted liver, buthionine sulphoximine (BSO) was injected intraperitoneally 2 hours before either NAC or 5% dextrose was infused 15 minutes before the liver was harvested. We used an isolated perfused rat liver model that had undergone prolonged hypothermic ischaemia, cold-storage for 48 hours and reperfusion for 120 minutes. Concentrations of hepatic enzymes released into samples of perfusate, concentration of adenosine triphosphate in liver tissue, concentrations of reduced and oxidized glutathione in perfusate, and bile production. The concentrations of the hepatocellular enzymes and oxidised glutathione in the perfusate samples were significantly reduced in the NAC group compared with the 5% dextrose group. Bile production improved significantly in the NAC group compared with the 5% dextrose group. The concentration of reduced glutathione in liver tissue was not increased by NAC. In a glutathione-depleted liver NAC prevented hepatic injury and improved liver integrity after a cold ischaemic-reperfusion injury, by acting not as a substrate for glutathione synthesis but as a direct free radical scavenger.

A randomized controlled trial to evaluate the efficacy and safety of icodextrin in peritoneal dialysis

Background: This article presents the results of two randomized, double-blind, controlled studies conducted to compare the efficacy and long-term safety of icodextrin and 2.5% dextrose for the once-daily long dwell in continuous ambulatory peritoneal dialysis (CAPD) and automated peritoneal dialysis (APD). Methods: Both studies were active-control comparisons of 7.5% icodextrin and 2.5% dextrose for the once-daily long dwell. The efficacy study was a 4-week evaluation of net ultrafiltration and peritoneal clearances of creatinine and urea nitrogen in 175 CAPD patients. The 52-week study in CAPD and APD patients examined the long-term safety of icodextrin and longer term effects, such as body weight and quality of life. Results: Mean net ultrafiltration (587.2 versus 346.2 mL, P < 0.001) and clearances of urea nitrogen (4.5 versus 4.1 mL/min, P < 0.001) and creatinine (4.0 versus 3.5 mL/min, P < 0.001) were increased significantly with icodextrin. Patients receiving icodextrin had no increase in weight after 52 weeks, in contrast to a weight gain of almost 2 kg in the dextrose group (P < 0.05). There were significantly fewer patients reporting edema in the icodextrin group compared with the dextrose group (6.3% versus 17.9%, P < 0.01). There were no statistically significant differences between groups for the incidence and severity of adverse events. There were small decreases in sodium and chloride and increases in alkaline phosphatase with icodextrin. Conclusion: Icodextrin provides patients with greater fluid removal and small solute clearance, no weight gain over 52 weeks, and a decreased risk of edema. Am J Kidney Dis 40:1055-1065. © 2002 by the National Kidney Foundation, Inc.

Early quality of life benefits of icodextrin in peritoneal dialysis

Early quality of life benefits of icodextrin in peritoneal dialysis. The impact of new therapies on patient quality of life (QOL) is emerging as an important indicator of the value of these therapies. In patients on dialysis, previous QOL evaluations have focused mainly on comparative approaches between modalities, or on longitudinal trends within a modality, but few have evaluated technical innovations or introduction of new therapies. The aim of the present study was to assess the early effects of a new dialysis solution (icodextrin) on the QOL of peritoneal dialysis patients. The QOL is compared with that of patients on dextrose, and the impact of demographic, and clinical characteristics on patients' QOL is examined. The kidney disease quality of life questionnaire (KDQOL) was administered to patients who participated in a phase III double-blind, parallel group, active-controlled trial to evaluate the efficacy and safety of a peritoneal dialysis (PD) solution containing icodextrin in comparison with dextrose PD solution. A total of 93 patients (58 icodextrin, and 35 dextrose) completed the questionnaire at both baseline and after 13 weeks. In addition to patients QOL, patients' demographic and clinical characteristics were recorded at both baseline and 13 weeks. Mean change scores from baseline to 13 weeks of icodextrin patients were substantially higher (> or =5) than dextrose, particularly with respect to general health perception, physical functioning, role-physical, and many KDQOL symptom items such as lack of strength, washed out or drained, lack of appetite, faintness or dizziness, dry skin, cramps after an exchange or treatment, cramps during an exchange or treatment, and muscle spasms or twitching. At 13 weeks, icodextrin patients had significantly improved symptoms, and rated their health in general higher than those patients in the dextrose group. Upon multivariate analysis, icodextrin contributed significantly to the improvement of patients' mental health, general health, and symptoms such as muscle spasms or twitching, cramps during an exchange or treatment, cramps after an exchange or treatment, itchy skin, and faintness or dizziness. Peritoneal dialysis patients treated with icodextrin experienced substantial quality of life improvement at 13 weeks after the start of treatment when compared to dextrose patients. Further research is necessary to determine patients' quality of life over time in a longitudinal study setting.

Review of clinical trial experience with icodextrin

Icodextrin-based dialysis solutions have been introduced toneal dialysis (CAPD). A total of 209 patients in theto address an unmet clinical need in peritoneal dialysis, United Kingdom were enrolled and were treated for upnamely the difficulties inherent in ultrafiltration manage- to six months. The objectives of the study were to evalu-ment during the long dwell [1–4]. These solutions take ate the efficacy of 7.5% icodextrin compared with lowadvantage of the physiologic principle of colloid osmosis (1.5%) or high (4.25%) dextrose solutions when the dwelland the high reflection coefficient of the glucose poly- time was 8 or 12 hours overnight. Approximately 40%mers allows for ultrafiltration to proceed with dialysis of patients in the dextrose group used 4.25% dextrosesolutions iso-osmotic to plasma. While the efficacy and bags overnight prior to the study and the other patientssafety of icodextrin have been described in multiple pub- used 1.5% dextrose bags overnight prior to the study.lications (abstracts; Douma et al,

Does Enalapril Prevent Peritoneal Fibrosis Induced by Hypertonic (3.86%) Peritoneal Dialysis Solution?

Peritoneal fibrosis (PF) is one of the most serious causes of failure in continuous ambulatory peritoneal dialysis (PD). Although the underlying mechanism responsible for the genesis of PF is still unknown, transforming growth factor beta (TGFbeta1) has been shown to be associated with PF. Angiotensin converting enzyme inhibitors have been shown to prevent the stimulating effect of growth factors. The aim of the present study was to investigate the effect of enalapril on peritoneal function and morphology in a rat model of experimental PF. Twenty-one albino Wistar rats were divided into three groups: (1) the control group (C) received 10 mL isotonic saline intraperitoneally (i.p.), (2) the dextrose (Dx) group 10 mL 3.86% dextrose PD solution i.p., and (3) the enalapril-treated group (ENA) 10 cc 3.86% dextrose PD solution i.p. plus 100 mg/L enalapril in drinking water. After 4 weeks, a 1-hour peritoneal equilibration test was performed with 20 mL 2.27% dextrose PD solution. Dialysate-to-plasma urea ratio (D/P urea), glucose reabsorption (D1/D0 glucose), ultrafiltration (UF) volume, and levels of dialysate protein, TGFbeta1, and cancer antigen 125 (CA125) were determined. The parietal peritoneum was evaluated histologically by light microscopy. Administration of enalapril resulted in preserved UF (-0.2 +/- 0.7 mL vs 1.7 +/- 0.3 mL, p < 0.05), protein loss (2.3 +/- 0.5 g/L vs 1.6 +/- 0.2 g/L, p > 0.05), and peritoneal thickness (77 +/- 7 microns vs 38 +/- 5 microns, p < 0.001). D/P urea increased significantly in the Dx group (p< 0.05). Both higher levels of TGFbeta1 (undetectable vs 298 +/- 43 pg/mL, p < 0.001) and lower levels of CA125 in dialysate effluent (0.94 +/- 0.5 U/L vs 0.11 +/- 0.1 U/L, p > 0.05) were determined in the Dx group. These findings show that peritoneal morphology and function tests were dramatically deranged in the Dx group. The same properties were partially preserved in the ENA group. The production of TGFbeta1 was significantly reduced but peritoneal thickness was not completely inhibited. In conclusion, by inhibiting the production of TGFbeta1, enalapril can preserve peritoneal histology, peritoneal function, and remodeling of mesothelial cells.

Co-administration of Co-trimoxazole Does Not Augment Tacrolimus-Induced Impairment in Kidney Function in Rats

Co-trimoxazole is an antibiotic that is frequently used in organ transplant patients. Our objective was to determine the effect of co-trimoxazole on tacrolimus-mediated functional impairment of the kidney in rats. Sprague Dawley rats were divided into three groups. Group 1 (dextrose) received 5% dextrose and Group 2 (tacrolimus) received tacrolimus (1 mg/kg/day) as a continuous intravenous infusion for seven days. Group 3 (combination) received tacrolimus as above and co-trimoxazole (30 mg/kg/day trimethoprim and 150 mg/kg/day sulfamethoxazole) intraperitoneally for six or seven days. Biochemical and functional parameters were measured pre- and post-drug infusion. On day 7, glomerular filtration rate (GFR) was evaluated using 3H-inulin. while the effective renal plasma flow (ERPF)/cationic tubular secretion was assessed using 14C-tetraethylammoniumbromide (TEA).GFR (mL/min/kg) as measured by inulin clearance was higher (p ≤ 0.05) in the dextrose (12.0 ± 1.4) group as compared to tacrolimus group (6.0 ± 1.3) and combination group (6.4 ± 1.6), but there was no difference between the tacrolimus and combination group. ERPF/cationic tubular secretion (mL/min/kg) was also significantly higher in the dextrose group (62.6 ± 10.3) as compared to the other two groups. ERPF/cationic tubular secretion was not different between the combination (33.3 ± 5.9) and the tacrolimus (35.1 ± 6.7) groups when there was no co-trimoxazole in the body. However, in the presence of co-trimoxazole ERPF/cationic tubular secretion was significantly reduced in the combination (23.1 ± 3.5) group as compared to the tacrolimus group (35.1 ± 6.7).These results indicate that co-trimoxazole does not further potentiate tacrolimus induced impairment in kidney Junction but is likely to further inhibit cationic tubular secretion in patients on tacrolimus therapy.

Photodynamic therapy of U87 human glioma in nude rat using liposome-delivered photofrin.

Liposomes as photosensitizer carriers may enhance the photodynamic effect on tumors. To test this hypothesis, we treated U87 human glioma in rat brain with photodynamic therapy (PDT) using Photofrin encapsulated in a liposome carrier or Photofrin in dextrose. Nontumored brain was also treated and Photofrin content ratios were measured in tumor and nontumored brain. PDT using the liposome encapsulated photosensitizer significantly increased tumor destruction compared to PDT with Photofrin in dextrose (P = 0.007), whereas no difference in tissue damage was detected in nontumored brain with or without liposome carrier. Photofrin uptake was also significantly elevated in the liposome vehicle group compared to the dextrose (P < 0.05) group. Our data suggest that Photofrin encapsulated in a liposome may enhance the PDT treatment of human brain tumors.

Maternal and neonatal hyponatraemia: a comparison of Hartmanns solution with 5% dextrose for the delivery of oxytocin in labour

We performed a randomised controlled trial to compare the effect on neonatal and maternal serum sodium of using oxytocin in Hartmanns solution compared to the standard 5% Dextrose regimen for induction or augmentation in labour. We found significantly decreased maternal and neonatal serum sodium concentrations in the 5% Dextrose group compared to the Hartmanns group.

Effect of pre-reperfusion portal venous blood flush on early liver transplant function.

Portal venous blood for rinsing out the University of Wisconsin solution (UWs) has the advantages of being a physiological fluid, removing acidotic mesenteric venous blood and perhaps resulting in more stable haemodynamic parameters during reperfusion. A group of 209 consecutive adult OLTs carried out between July 1993 and February 1995 were studied prospectively. The UWs was flushed out with 500 ml portal blood in 95 OLTs (group 1) and with 1.0 L 0.5% dextrose at 37 degrees C in 114 OLTs (group 2). The median day 1 and peak day 1-5 AST levels were significantly elevated in the 5% dextrose group: median 755 (118-11090) vs. 546 (121-6150) IU/I (P = 0.007, Wilcoxon); and median 1095 (159-11090) vs. 744 (157-7870) IU/l (p = 0.008, Wilcoxon), respectively. A median of 5 (0-27) units of blood were transfused in group 1 compared to 4 (0-54) units in group 2 (n.s.). There was no difference in peak bilirubin, lowest day 1-5 PT levels, primary nonfunction, median ITU stay, total inpatient stay and 1-month graft survival between the two groups (89% vs. 88%). Pre-reperfusion blood flush may be associated with less hepatocellular damage, without significant additional blood usage.

Alterations in Nuclear Ploidy and Cell Phase Distribution of Rat Liver Cells in Experimental Alcoholic Liver Disease: Relationship to Antioxidant Enzyme Gene Expression

The ability of a cell to withstand oxidative stress has been hypothesized to be related to its ploidy status. We used the intragastric feeding rat model for alcoholic liver disease to evaluate the relationship between severity of liver injury, antioxidant mRNA levels, and DNA ploidy of liver cells. Rats were fed ethanol with different dietary fats (saturated fat, corn oil, and fish oil); pair-fed control animals received isocaloric amounts of dextrose. All animals were euthanized at 1 month and had evaluation of pathologic changes in the liver, DNA content by flow cytometry, and mRNA levels for catalase and glutathione peroxidase. The fish oil–ethanol group exhibited the most severe pathology, the corn oil–ethanol group had intermediate pathologic changes, and no pathologic changes were seen in the saturated fat–ethanol and dextrose-fed controls. Flow cytometric analysis of propidium iodide-stained nuclei revealed that saturated fat–dextrose and corn oil–dextrose groups had about 65% of cells with (diploid) G1DNA content and about 30% of cells with tetraploid (4C) nuclei. The fish oil–dextrose had a significantly higher (p< 0.001) number of 4C cells (67.4 ± 2.1%) compared to the other two dextrose-fed groups. In the animals showing pathologic liver injury, there was a higher percentage of cells with hypertetraploid nuclei. The highest percentage of these hypertetraploid cells was seen in the fish oil–ethanol group. Catalase and glutathione peroxidase mRNA levels correlated significantly with polyploidy. A significant correlation was seen between the number of cells in the greater than G2+ M phase and glutathione peroxidase mRNA levels (r= 0.91,p< 0.01) and catalase mRNA. The different slopes of correlation analysis between catalase mRNA and dietary fats show that the degree of saturation of fatty acids may influence catalase mRNA expression in cells with different ploidy states. We propose that polyploidization of liver cell nuclei may serve as a defense mechanism against ethanol-induced hepatotoxicity. This defense mechanism may also, in part, account for the antiregenerative effect of ethanol on hepatocytes.

The Effect of Substrate Load and Blood Glucose Management on Cerebral Dysfunction Following Cardiopulmonary Bypass

Seventy patients undergoing elective coronary artery bypass grafting were prospectively randomized into either of two primes: 5% dextrose or Hartmann's solution. The groups were comparable. Neuropsychological assessment was performed before and eight weeks after surgery. During bypass blood glucose concentrations rose to a mean of 26 mmol/L in the 5% dextrose group and 6 mmol/L in the Hartmann's group. No deaths occurred in either group; 2 clinically evident neurological events were noted, both taking place in the hyperglycemic group. Detailed analysis of the results showed differences between the groups. When score changes between tests were assessed it was found that in 17 of the 18 versions of the tests more patients in the hyperglycemic group deteriorated than the normoglycemic controls. With a two-tailed binomial statistic this difference was significant at the 5% level. Learning ability was likewise found to worsen in the hyperglycemic group after surgery.Hyperglycemia may be a detrimental factor in...

AMPA and NMDA receptor antagonists do not decrease hippocampal glutamate concentrations during transient global ischemia.

Increased extracellular concentrations of glutamate during episodes of cerebral ischemia may be due in part to a positive glutaminergic feedback loop. We evaluated the effect of selective AMPA or NMDA receptor antagonists on hippocampal extracellular concentrations of excitatory amino acids during ischemia and reperfusion. Thirteen New Zealand white rabbits were subjected to 10 min of global cerebral ischemia produced by neck tourniquet inflation (20 psi) combined with systemic hypotension during halothane (1-1.5%) anesthesia. Hippocampal extracellular concentrations of glutamate, aspartate, and glycine were monitored using in vivo microdialysis. NBQX (a selective AMPA receptor antagonist), MK801 (a noncompetitive NMDA receptor antagonist), or 5% dextrose was administered starting 1 h before ischemia. The NBQX group (n = 4) received 5 mg.kg-1 of NBQX intravenously (dissolved in 5% dextrose) over 5 min followed by an infusion of 5 mg.kg-1.h-1. The 5% dextrose group (n = 4) received an equivalent volume of 5% dextrose. The peak concentrations of glutamate, aspartate, and glycine in the early reperfusion period were 5-8-fold, 9-10-fold, and 4-5-fold higher than preischemic values, respectively. There were no significant differences, however, among the three groups in the concentrations of glutamate, aspartate, or glycine at any time during the study. These results do not support the existence of a positive feedback loop for glutamate mediated via AMPA or NMDA autoreceptors in the hippocampus during transient global ischemia or reperfusion.

The Effect of Substrate Load and Blood Glucose Management on Cerebral Dysfunction Following Cardiopulmonary Bypass

Seventy patients undergoing elective coronary artery bypass grafting were prospectively randomized into either of two primes: 5% dextrose or Hartmann's solution. The groups were comparable. Neuropsychological assessment was performed before and eight weeks after surgery. During bypass blood glucose concentrations rose to a mean of 26 mmol/L in the 5% dextrose group and 6 mmol/L in the Hartmann's group. No deaths occurred in either group; 2 clinically evident neurological events were noted, both taking place in the hyperglycemic group. Detailed analysis of the results showed differences between the groups. When score changes between tests were assessed it was found that in 17 of the 18 versions of the tests more patients in the hyperglycemic group deteriorated than the normoglycemic controls. With a two-tailed binomial statistic this difference was significant at the 5% level. Learning ability was likewise found to worsen in the hyperglycemic group after surgery. Hyperglycemia may be a detrimental factor in the development of postcardiac surgical intellectual dysfunction. The authors would advocate the avoidance of glucose-containing bypass primes and the close monitoring of blood glucose during cardiopulmonary bypass.

Effect of salt supplementation on amphotericin B nephrotoxicity

It has been suggested that salt loading protects against amphotericin B-induced nephrotoxicity. The influence of saline loading on the nephrotoxic response to amphotericin B (50 mg/dose given i.v. over 4 hr 3 X/week for 10 weeks) was assessed in two groups of ten patients each who were diagnosed with mucocutaneous leishmaniasis. Patients were randomized to receive either 1 liter of 0.9% saline or 1 liter of 5% dextrose in water, administered i.v. over one hour in a double-blinded manner, directly prior to amphotericin B administration. Renal function was monitored on a weekly basis two days after the last dose of amphotericin B. Baseline characteristics were similar in both groups except for a slightly higher serum creatinine concentration (Cr) in the saline group (0.8 +/- 0.05 vs. 0.6 +/- 0.04 mg/dl). Baseline sodium (Na) excretion was relatively high (262 +/- 23 mmol/day in the dextrose group and 224 +/- 17 mmol/day in the saline group). None of the patients sustained an increase in Cr to values greater than 1.7 mg/dl. Although mean Cr remained within normal, there was a significant difference between the two groups over the ten week period, with the dextrose group sustaining a significant increase in Cr and the saline group remaining unchanged. Serum potassium (K) levels fell in both groups necessitating oral K supplementation. The saline group required significantly greater amounts of K supplementation to maintain a normal serum K. Amphotericin B caused a rapid reduction in the acidification ability of the kidney in response to an ammonium chloride load. Under these conditions, the saline group had a poorer ability to acidify the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of dietary carbohydrates on cholesterol metabolism in casein-fed rabbits

Dietary carbohydrates consisting of cornstarch and dextrose, as well as molassesenriched dextrose, were fed to rabbits in a high fat, cholesterol-free casein purified diet in order to evaluate their influence on food intake, and more specifically on the magnitude of the cholesterol response to casein feeding. Food intake and weight gain were similar in all groups, regardless of carbohydrate origin. The non-significant trend in serum cholesterol elevation in the molasses+dextrose group was however translated by a significant increase in its LDL-cholesterol, compared to the cornstarch and dextrose groups. Moreover, the significant increase in HDL-C and 4,3-fold decrease in the LDL-C/HDL-C ratio induced by cornstarch, in comparison to the dextrose and dextrose+molasses groups, suggests that the atherosclerosis risk associated to casein intake may be attenuated by the use of cornstarch. In addition, significantly higher liver cholesterol and TG levels following molasses+dextrose feeding, compared to dextrose and cornstarch, suggests that molasses enhances the effects of casein on serum cholesterol by a series of reactions originating from an increase in this group's hepatic lipids.

Hypertension and progressive glomerular injury caused by focal glomerular ischemia

Sprague-Dawley rats received infusions of 55-microns microspheres (groups 1 and 3) or dextrose (groups 2 and 4) into both renal arteries. Groups 1 and 2 rats were studied over 7 mo. In group 1 rats renal embolization increased the mean arterial pressure (group 1, 140 +/- 4 mmHg; group 2, 118 +/- 2 mmHg) without reducing the glomerular filtration rate (GFR; group 1, 4.69 +/- 0.16 ml/min; group 2, 4.57 +/- 0.22 ml/min). Micropuncture studies showed that systemic hypertension was accompanied by an increase in the glomerular capillary pressure of functioning nephrons in group 1 rats. Morphological studies showed that renal embolization caused both glomerular ischemia (group 1, 11.8 +/- 1.9% of glomeruli; group 2, 0.1 +/- 0.1% of glomeruli) and glomerular segmental sclerosis (group 1, 15.0 +/- 1.0% of glomeruli; group 2, 3.3 +/- 0.2% of glomeruli). Groups 3 and 4 rats were studied over 2 mo. Renal embolization again increased the mean arterial pressure without reducing the GFR in group 3 rats. Morphological studies showed that at 2 mo renal embolization caused glomerular ischemia without glomerular segmental sclerosis. These studies show that focal glomerular ischemia can cause systemic and glomerular capillary hypertension in the absence of a reduction in the GFR. They further show that focal glomerular ischemia can cause progressive sclerotic injury in the remaining, nonischemic portion of the glomerular population.

Influence of hydration on ultrafilterable platinum kinetics and kidney function in patients treated withcis-diamminedichloroplatinum(II)

It has been reported that hypertonic saline provides protection against the renal toxicity of cisplatin (CDDP). We therefore evaluated its influence on the plasma and urinary pharmacokinetics of ultrafilterable platinum and kidney function as estimated by creatinine, inulin and PAH clearance. We undertook a randomized trial including two groups of ten patients receiving 100 mg/m2 CDDP in isotonic (group 1) or hypertonic saline (group 2) by a 20-min infusion. The hydration consisted of dextrose in group 1 and isotonic saline in group 2. Maximal concentration (Cmax), protein binding and cumulative urinary excretion were significantly higher in the dextrose group. Urinary flow decreased in this group but not in the other one. Inulin clearance was higher in the dextrose group than in the saline group and P-aminohippuric acid (PAH) clearance was not significantly different in these groups of patients. Hyponatremia was observed in the dextrose group. These results suggest that hypertonic saline infusion and saline hydration may enhance the diffusion of CDDP into tissues, lowering Cmax and renal excretion of platinum. The reduction of protein binding may indicate a diminution of aquation of CDDP in plasma. Our results suggest that the infusion of CDDP in hypertonic saline with salt hydration could exert a protective effect on the kidney. Moreover, there is a lessening of the risk of cellular hyperhydration. However, the better influence of dextrose hydration on glomerular filtration leads us to recommend a combination of the two methods of hydration for better tolerance and efficacy.

Effect of 18- to 24-hour heparin administration for prevention of restenosis after uncomplicated coronary angioplasty

Smooth muscle cell proliferation induced by intimal denudation similar to that produced by coronary angioplasty has been decreased by early and brief heparin administration in animal models. Heparin might also decrease the incidence of thrombus-induced postdenudation arterial obstruction, albiet at risk of bleeding. To evaluate the risks and benefits of heparin after coronary angioplasty, 416 patients (469 vessel sites) with successful coronary angioplasty without large dissection were randomized to heparin (titrated to paritial thromboplastin time 1.5 to 2.5 times normal) or dextrose administered for 18 to 24 hours. Patients also had recelved heparin during angioplasty (usually 10,000 to 15,000 units), and they received aspirin for a period of 6 months. Heparin and dextrose groups were not different in the percentage of patients with male sex (74% in the heparin group and 75% in the dextrose group, p = NS), postangioplasty tear or dissection (30% in the heparin group and 30% in the dextrose group, p = NS), or postangioplasty percent stenosis >35% (31% in the heparin group and 30% in the dextrose group, p = NS). Partial thromboplastin time during treatment in the heparin group was 56 ± 22 seconds and in the dextrose group 27 ± 9 seconds ( p < 0.001). Late angiographic follow-up (180 ± 81 days) was achieved in 58.4% in the heparin group and 64.5% in the control group. Of patients with late angiographic follow-up, 41.2% and 36.7% randomized to heparin and dextrose, respectively, had documented restenosis (≥50% dimeter stenosis at one or more the sites dilated) ( p = NS). Major bleeding or a fall in hemoglobin ≥3 gm/dl was seen in 8.2% of patients randomized to heparin and in 3.8% of patients randomized to dextrose ( p = 0.09). Thus in the absence of a large dissection after successful angioplasty, heparin given for 18 to 24 hours in doses large enough to prolong clotting and produce a trend toward increased bleeding did not decrease the incidence of late restenosis.

Effect of starvation and total parenteral nutrition on electrolyte homeostasis in normal man.

Elemental balances, and skeletal muscle membrane potential (Em) and biopsy were utilized to evaluate electrolyte homeostasis and body composition in 11 healthy adult volunteers after 10 days of starvation. This controlled, acute malnutrition was followed by refeeding for 10 days with two different, commonly used, total parenteral nutrition (TPN) solutions. Six subjects were refed with crystalline amino acids and dextrose (dextrose group), while five subjects received amino acids, dextrose, and lipid (lipid group). During starvation, negative balances for potassium, phosphorous, magnesium, and nitrogen were observed in both groups. When compared to starvation, total parenteral nutrition produced statistically significant (p less than 0.05) equilibrium or positive electrolyte and nitrogen balances for both, the dextrose and lipid groups. During TPN, there was a significantly (p less than 0.001) positive chloride balance in the lipid group when compared to the dextrose group. At the conclusion of the 10-day period of TPN, there was a decrease (p less than 0.05) in skeletal muscle Em. This change, in concert with the electrolyte balance data obtained during parenteral repletion, lead us to postulate that restoration of lean tissue protein and cellular function does not occur at a rate which might be inferred from the positive nitrogen balance observed in this model. A persistent defect in cellular function which was evident after starvation, suggests that a brief period of TPN is insufficient to restore skeletal muscle integrity.