Asymmetrical dimethylarginine (ADMA) in critically ill patients: high plasma ADMA concentration is an independent risk factor of ICU mortality

BACKGROUND AND AIMS: Accumulation of asymmetrical dimethylarginine (ADMA) has been linked to endothelial dysfunction, and is an important risk factor for cardiovascular disease. Its elimination from the body is dependent on urinary excretion and degradation by the enzyme dimethylarginine dimethylaminohydrolase. This enzyme is highly expressed in the liver, and in rat studies a high net hepatic uptake of asymmetrical dimethylarginine was found. In critically ill patients, we investigated the relation between indicators of renal and hepatic dysfunction and plasma ADMA concentration, and tested the association between ADMA concentration and outcome. METHODS: We prospectively collected blood samples from a cross-section of critically ill patients (n=52) with clinical evidence of dysfunction of more than two organs. We identified correlates of plasma ADMA concentration with laboratory values, organ failures score and outcome by univariate and multiple regression analyses. RESULTS: In critically ill patients, plasma ADMA concentration was independently related to the presence of hepatic failure (b=0.334, 95% CI: 0.207-0.461; P<0.001), and to lactic acid (b=0.395, 95% CI: 0.230-0.560; P<0.001) and bilirubin (b=0.121, 95% CI: 0.031-0.212; P=0.009) concentration as markers of hepatic function. Twenty-one (40%) patients deceased during their ICU stay. In a logistic regression model, plasma ADMA ranked as the first and strongest predictor for outcome, with a 17-fold (95% CI: 3-100) increased risk for ICU death in patients who were in the highest quartile for ADMA. CONCLUSIONS: In critically ill patients, plasma ADMA concentration is a strong and independent risk factor for ICU mortality, and hepatic dysfunction is the most prominent determinant of ADMA concentration in this population.     

The prominent role of the liver in the elimination of asymmetric dimethylarginine (ADMA) and the consequences of impaired hepatic function

Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), the enzyme which converts the amino acid arginine into nitric oxide (NO). ADMA has been identified as an important risk factor for cardiovascular diseases. Besides the role of ADMA in cardiovascular diseases, it also seems to be an important determinant in the development of critical illness, (multiple) organ failure, and the hepatorenal syndrome. ADMA is eliminated from the body by urinary excretion, but it is mainly metabolized by the dimethylarginine dimethylaminohydrolase (DDAH) enzymes that convert ADMA into citrulline and dimethylamine. DDAH is highly expressed in the liver, which makes the liver a key organ in the regulation of the plasma ADMA concentration. The prominent role of the liver in the elimination of ADMA and the consequences of impaired hepatic function on ADMA levels will be discussed in this article.     

High plasma arginine concentrations in critically ill patients suffering from hepatic failure

OBJECTIVE: In physiological conditions, the liver plays an important role in the regulation of plasma arginine concentrations by taking up large amounts of arginine from the hepatic circulation. When hepatic failure is present, arginine metabolism may be disturbed. Therefore, we hypothesized high arginine plasma concentrations in critically ill patients suffering from hepatic failure. DESIGN: We prospectively collected blood samples from a cross-section of intensive care unit patients. SETTING: Surgical intensive care unit of a Dutch university medical center. SUBJECTS: A total of 52 critically ill patients with clinical evidence of dysfunction of more than two organs were recruited. MEASUREMENTS: Plasma arginine concentrations were determined by HPLC. We identified correlations of arginine concentrations with organ failure scores and laboratory variables by univariate and multiple regression analyses. RESULTS: High plasma arginine concentrations were found in critically ill patients developing organ failure. Patients who were in the highest quartile of plasma arginine concentrations had significantly lower fibrinogen concentrations, higher lactic acid concentrations, and longer prothrombin time. Stepwise multiple regression analysis showed that concentrations of arginine were independently associated with the presence of hepatic failure (P=0.03) and renal failure (P=0.048). In addition, lactic acid proved to be an independent determinant of plasma arginine concentration (P=0.014). CONCLUSIONS: Critically ill patients who suffer from hepatic failure have elevated plasma arginine concentrations. Additional arginine in the treatment of these patients can be harmful, and therefore should not be used as a standard nutritional regimen until further evaluation.     

Imbalance of arginine and asymmetric dimethylarginine is associated with markers of circulatory failure, organ failure and mortality in shock patients

In shock, organ perfusion is of vital importance because organ oxygenation is at risk. NO, the main endothelial-derived vasodilator, is crucial for organ perfusion and coronary patency. The availability of NO might depend on the balance between a substrate (arginine) and an inhibitor (asymmetric dimethylarginine; ADMA) of NO synthase. Therefore, we investigated the relationship of arginine, ADMA and their ratio with circulatory markers, disease severity, organ failure and mortality in shock patients. In forty-four patients with shock (cardiogenic n 17, septic n 27), we prospectively measured plasma arginine and ADMA at intensive care unit admission, Acute Physiology and Chronic Health Evaluation (APACHE) II-(predicted mortality) and Sequential Organ Failure Assessment (SOFA) score, and circulatory markers to investigate their relationship. Arginine concentration was decreased (34·6 (SD 17·9) μmol/l) while ADMA concentration was within the normal range (0·46 (SD 0·18) μmol/l), resulting in a decrease in the arginine:ADMA ratio. The ratio correlated with several circulatory markers (cardiac index, disseminated intravascular coagulation, bicarbonate, lactate and pH), APACHE II and SOFA score, creatine kinase and glucose. The arginine:ADMA ratio showed an association (OR 0·976, 95 % CI 0·963, 0·997, P = 0·025) and a diagnostic accuracy (area under the curve 0·721, 95 % CI 0·560, 0·882, P = 0·016) for hospital mortality, whereas the arginine or ADMA concentration alone or APACHE II-predicted mortality failed to do so. In conclusion, in shock patients, the imbalance of arginine and ADMA is related to circulatory failure, organ failure and disease severity, and predicts mortality. We propose a pathophysiological mechanism in shock: the imbalance of arginine and ADMA contributes to endothelial and cardiac dysfunction resulting in poor organ perfusion and organ failure, thereby increasing the risk of death.     

Molecular aspects of insulin therapy in critically ill patients

PURPOSE OF REVIEW: This review provides an overview of molecular mechanisms involved in beneficial effects of insulin in insulin resistant critically ill patients. RECENT FINDINGS: Intense insulin therapy reduced morbidity in critically ill patients. Insulin acts by two major molecular pathways: reduction of the inflammation process induced by free fatty acid excess in tissues and decrease of reactive oxygen species production induced by hyperglycemia. By these actions, insulin preserves mitochondrial function, enhances adiponectin secretion and probably modulates AMP-activated protein kinase activity, which in turn depletes lipid depots in tissues and restores glucose uptake and oxidation. Furthermore, it was recently established that insulin prevents microcirculation alteration and subsequent cellular hypoxia by reducing inducible nitric oxide synthase expression and activity in the endothelium. So, insulin beneficial effects in critically ill patients are dependent on metabolic and non-metabolic molecular pathways. SUMMARY: Critically ill patients requiring intensive care for more than a few days have a high risk of death. A tight control of glucose levels by intense insulin therapy reduced morbidity in critically ill patients. Unraveling the molecular mechanisms of insulin will provide new insights into the pathogenesis of multiple organ failure and will allow novel therapeutic strategies to manage patients needing intensive care.     

The liver is an important organ in the metabolism of asymmetrical dimethylarginine (ADMA)

BACKGROUND AND AIMS: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) synthase enzymes, whereas symmetrical dimethylarginine (SDMA) competes with arginine transport. Although both dimethylarginines may be important regulators of the arginine-NO pathway, their metabolism is largely unknown. Both dimethylarginines are removed from the body by urinary excretion. However, ADMA is also subject to enzymatic degradation by the enzyme dimethylarginine dimethylaminohydrolase (DDAH), which is highly expressed in the liver. To elucidate the role of the liver in the metabolism of ADMA, we aimed to investigate dimethylarginine handling of the liver in detail. METHODS: Ten male Wistar rats were used for this study. Blood flow was measured using radiolabeled microspheres according to the reference sample method. Concentrations of dimethylarginines were measured by HPLC. The combination of arteriovenous concentration difference and organ blood flow allowed calculation of net organ fluxes and fractional extraction rates. RESULTS:Both the liver (0.89+/-0.11) and the kidney (0.68+/-0.06) showed a high net uptake (nmol/100 g body weight (BW)/min) of ADMA, whereas a significant net uptake of SDMA was only observed in the kidney (0.34+/-0.04). For the liver, fractional extraction rates were 29.5% +/-3.0 for ADMA and 0.0%+/-3.7 for SDMA. Fractional extraction rates of ADMA and SDMA for the kidney were 36.0%+/-2.7 and 31.6%+/-3.8, respectively. CONCLUSIONS:The liver plays an important role in the metabolism of ADMA by taking up large amounts of ADMA from the systemic circulation.     

Elevation of asymmetric dimethylarginine (ADMA) in patients developing hepatic failure after major hepatectomy

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of the arginine-nitric oxide pathway. It is conceivable that its concentration is tightly regulated by urinary excretion and degradation by the enzyme dimethylarginine dimethylaminohydrolase, which is highly expressed in the liver. In rats, we showed a high net hepatic uptake of ADMA. Therefore, we aimed to confirm the role of the liver in humans and hypothesized elevated ADMA levels after major liver resection by a reduction of functional liver mass and injury to the remnant liver. METHODS: Patients undergoing a major hepatic resection (HEP, n = 17) or major abdominal surgery (MAS, n = 12) were included and followed in time. In addition, ADMA levels were measured in 4 patients having severe hepatic failure after a liver resection. Plasma ADMA concentration was measured by high-performance liquid chromatography. RESULTS: Preoperatively and on days 1, 3, and 5, plasma levels of ADMA were higher in HEP patients when compared with MAS patients. In HEP patients with prolonged (>7 days) hepatic injury, ADMA levels were especially elevated. On the first postoperative day, ADMA significantly correlated to bilirubin concentration (r = .528, p < .05) as a marker of postoperative hepatic function. Besides, in patients with severe hepatic failure, ADMA levels were highly elevated. CONCLUSIONS: In the present study, evidence was found for the role of the liver in the elimination of ADMA in humans. Increased levels of ADMA occur in the postoperative course after a major hepatic resection, especially when liver function is severely impaired. Further studies need to assess the role of ADMA in the development of complications after liver surgery.     

Asymmetric dimethylarginine,a biomarker of cardiovascular complications in diabetes mellitus

Cardiovascular(CV) complications are an essential causal element of prospect in diabetes mellitus(DM), with carotid atherosclerosis being a common risk factor for prospective crisis of coronary artery diseases and/or cerebral infarction in DM subjects. From another point of view, asymmetric dimethylarginine(ADMA) has been established as an inhibitor of endogenous nitric oxide synthesis and the relationship between ADMA and arteriosclerosis has been reported. In our study with 87 type 2 DM(T2DM) patients, we have examined whether ADMA and other CV risk factors are the useful predictors of DMCV complications. After the measurement of the respective CV risk factors, we have followed the enrolled T2 DM patients for 5 years. We have finally analyzed 77 patients. DMCV complications developed in 15 cases newly within 5 years, and 4 cases recurred. The concentrations of ADMA in plasma were markedly more elevated in 19 DM patients with CV complications than in 58 DM patients without CV complications. Urinary albumin(U-Alb), mean intimal-medial thickness(IMT) and ankle brachial index(ABI) were also higher in patients with CV complications. Multiple regression analyses showed that U-Alb had an influence on the high level of ADMA(standardized β = 6.59, P = 0.00014) independently of age, systolic BP, fibrinogen, mean IMT, plaque score, and ABI. The review indicates what is presently known regarding plasma ADMA that might be a new and meaningful biomarker of CV complications in DM subjects.     

L'intestin du patient agressé

Multiple organ failure syndrome often complicates the course of critically ill patients. In various experimental models, several features of gut dysfunction have been incriminated in the pathogenesis of this syndrome. This work aims at reviewing the clinical data on gut dysfunction recorded in critically ill patients. An increase in gut permeability and an alteration in intestinal motility have been clearly demonstrated, while bacterial translocation, an immune dysfunction and mucosal hypoperfusion are suggested by indirect arguments. The respective roles of these alterations in the pathogenesis of multiple organ failure syndrome remain to be clarified by further investigations.     

Dangers of growth hormone therapy in critically ill patients

Prolonged length of stay is the major challenge for modern intensive care because of the associated morbidity and the impact on resource utilization. Severe trauma or infection is associated with a catabolic response, which is characterized by increased protein turnover and negative nitrogen balance. Severe catabolism leads to end-organ dysfunction and muscular weakness, prolonging the need for mechanical ventilation. Catabolism cannot be prevented with standard parenteral or enteral nutritional formulas. In order to prevent the complications of catabolism in intensive care patients, recombinant growth hormone has been applied as an experimental therapy for two decades in patients requiring parenteral nutrition and in patients with respiratory failure. Administration of recombinant growth hormone has resulted in positive nitrogen balance, and studies in mechanically ventilated patients suggest that it may shorten the need for ventilatory support. In contrast to the results of these relatively small studies, a recent multinational randomized controlled trial revealed that the administration of recombinant growth hormone (with doses 10-20 times higher than used for replacement therapy) increases mortality of critically ill patients. The excessive mortality in patients treated with recombinant growth hormone was related to infections and development of multiple organ failure, leading to the conclusion that administration of high doses of recombinant growth hormone cannot be recommended for critically ill patients. This review reinforces that conclusion.     

Gut Microbiota and Probiotics/Synbiotics for Modulation of Immunity in Critically Ill Patients

Patients suffering from critical illness have host inflammatory responses against injuries, such as infection and trauma, that can lead to tissue damage, organ failure, and death. Modulation of host immune response as well as infection and damage control are detrimental factors in the management of systemic inflammation. The gut is the motor of multiple organ failure following injury, and it is recognized that gut dysfunction is one of the causative factors of disease progression. The gut microbiota has a role in maintaining host immunity, and disruption of the gut microbiota might induce an immunosuppressive condition in critically ill patients. Treatment with probiotics and synbiotics has been reported to attenuate systemic inflammation by maintaining gut microbiota and to reduce postoperative infectious complications and ventilator-associated pneumonia. The administration of prophylactic probiotics/synbiotics could be an important treatment option for preventing infectious complications and modulating immunity. Further basic and clinical research is needed to promote intestinal therapies for critically ill patients.     

Glutamine supplementation fails to affect muscle protein kinetics in critically ill patients

BACKGROUND: In vitro work suggests that glutamine availability may be an important factor in controlling the rate of muscle protein synthesis. The objective of this study was to determine if enteral administration of glutamine affects muscle protein metabolism in critically ill patients. METHODS: Six postsurgical patients requiring prolonged mechanical ventilation for pneumonia (age, 51 +/- 12 years, Acute Physiology and Chronic Health Evaluation [APACHE] 22 +/- 6, mean +/- SEM) and 6 normal healthy volunteers (age, 33 +/- 4 years) underwent evaluation of whole body and muscle protein metabolism using an 8-hour infusion of d5-phenylalanine, 5(15)N glutamine, and d3-alanine with serial blood sampling from the femoral artery and vein and biopsies from the vastus lateralis muscle. Metabolic measurements were obtained while subjects received Peptamen enterally (Basal Period) and with glutamine supplementation (24 g/3 h; Glutamine Period). RESULTS: Glutamine concentration in muscle was significantly less in the critically ill patients. Glutamine supplementation increased the arterial plasma concentration of glutamine, yet with no demonstratable effect on muscle glutamine concentration or on the rate of muscle protein synthesis in either volunteers or patients. Furthermore, muscle glutamine kinetics (incorporation into muscle, release from muscle, and rate of de novo glutamine synthesis in muscle) were not affected by glutamine supplementation in the critically ill patients. In contrast, there was a significant decrease in these kinetic parameters with glutamine supplementation within the muscle of healthy subjects. Metabolism of alanine was unaffected by administration of glutamine in either group. CONCLUSIONS: Enteral glutamine supplementation to critically ill patients fails to alter muscle glutamine metabolism or muscle protein synthesis. This suggests a possible restriction in transport of glutamine into muscle of critically ill patients.     

Standardized concept for the treatment of gastrointestinal dysmotility in critically ill patients--current status and future options

Inhibition of gastrointestinal motility is a major problem in critically ill patients. Motor stasis gives rise to subsequent complications including intolerance to enteral feeding, enhanced permeability of the atrophic intestinal mucosa and conditions as severe as systemic inflammatory response syndrome, sepsis and multiple organ failure. Although the diagnosis of motility disturbances in critically ill patients is difficult, the type and site of the disturbance are important to consider in the analysis of the condition and in the choice of therapeutic approach. The pharmacological treatment of impaired gastrointestinal motility is difficult to handle for the clinician, because the underlying mechanisms are complex and not fully understood and the availability of pharmacological treatment options is limited. In addition, there is a lack of controlled studies on which to build an evidence-based treatment concept for critically ill patients. Notwithstanding this situation, there has been remarkable progress in the understanding of the integrated regulation of gastrointestinal motility in health and disease. These advances, which largely relate to the organization of the enteric nervous system and its signaling mechanisms, enable the intensivist to develop a standardized concept for the use of prokinetic agents in the treatment of impaired gastrointestinal motility in critically ill patients.     

Asymmetric dimethylarginine--mechanisms and targets for therapeutic management

Evidence has been accrued recently that chronic high levels of asymmetric dimethylarginine (ADMA) can be directly beneficial to the treatment of atherosclerotic vascular disorders thus making the substance a promising new therapeutic target. A therapeutic target can be theoretically each stage in the process of generation and elimination of asymmetric dimethylarginine. The methylation of L-arginine residues is a universal biological process involving hundreds of proteins but still with unknown effects. Interference with these mechanisms can generate ambiguous and speculative discussions. Supplementation with L-arginine seems to be the most natural way to reverse the detrimental effect of ADMA on the endothelium. The enzymatic activity of endogenous nitric oxide synthase is regulated by the ratio between the concentrations of L-arginine (the natural substrate) and that of ADMA (the endogenous inhibitor): in the presence of normal L-arginine levels, any elevation ofADMA levels may cause relative L-arginine deficiency thus attenuating the activity of the endogenous nitric oxide synthase. Target replacement therapy with L-arginine to increase the L-arginine plasma levels results in the normalisation of the L-arginine/ADMA ratio in the presence of higher levels of the latter. There is still some controversy about the effects of the most frequently used drugs on asymmetric dimethylarginine. Most of the relevant studies show that statins do not affect the ADMA levels. On the other hand, patients with high levels of ADMA are resistant to statin therapy--to improve the endothelium-dependent vasodilation they need a combined therapy with L-arginine. The angiotensin-converting enzyme inhibitors and the angiotensin receptor blockers are the most extensively studied substances, the studies predominantly centring on confirming their ADMA reducing effect. Until the specific ADMA-reducing therapy becomes readily available, it is the therapies of modification of the risk factors causing the increase of ADMA or the depletion of L-arginine, and the L-arginine replacement therapy that are the most realistic therapeutic solutions for patients with high plasma levels of ADMA because the synthesis of nitric oxide correlates with the L-arginine/ADMA ratio. A study was conducted in the Surgery of Preventive Cardiology with the Clinic of Cardiology in Plovdiv which included 40 patients with pronounced hypercholesterolemia (HC)--it was found that a one-month therapy with 40 mg simvastatin did not change statistically significantly ADMA plasma levels in spite of the optimal lipid regulation.     

Low plasma concentrations of arginine and asymmetric dimethylarginine in premature infants with necrotizing enterocolitis

Several studies have described reduced plasma concentrations of arginine, the substrate for nitric oxide synthase (NOS) in infants with necrotizing enterocolitis (NEC). No information on the plasma concentrations of the endogenous NOS inhibitor asymmetric dimethylarginine (ADMA) in patients with NEC is currently available. We investigated whether plasma concentrations of arginine, ADMA, and their ratio differ between premature infants with and without NEC, and between survivors and non-survivors within the NEC group. In a prospective case-control study, arginine and ADMA concentrations were measured in ten premature infants with NEC (median gestational age 193 d, birth weight 968 g), and ten matched control infants (median gestational age 201 d, birth weight 1102 g), who were admitted to the Neonatal Intensive Care Unit. In the premature infants with NEC, median arginine and ADMA concentrations (micromol/l), and the arginine:ADMA ratio were lower compared to the infants without NEC: 21.4 v. 55.9, P= 0.001; 0.59 v. 0.85, P=0.009 and 36.6 v. 72.3, P=0.023 respectively. In the NEC group, median arginine (micromol/l) and the arginine:ADMA ratio were lower in non-surviving infants than in surviving infants: 14.7 v. 33.8, P=0.01 and 32.0 v. 47.5, P=0.038 respectively. In premature infants with NEC not only the NOS substrate arginine, but also the endogenous NOS inhibitor ADMA and the arginine:ADMA ratio were lower than in infants without NEC. In addition, low arginine and arginine:ADMA were associated with mortality in infants with NEC. Overall, these data suggest that a diminished nitric oxide production may be involved in the pathophysiology of NEC, but this needs further investigation.     

不对称性二甲基精氨酸与早发型重度子痫前期关系的研究进展

不对称性二甲基精氨酸(ADMA)是内源性一氧化氮合酶(NOS)抑制剂,可抑制NOS活性,减少一氧化氮(NO)合成,导致血管内皮细胞功能障碍。早发型重度子痫前期(EOSP)存在胎盘形态学异常,而晚发型重度子痫前期(LOSP)则无明显胎盘形态学异常。因此,胎盘发生和形成异常,可能是导致EOSP发生的原因。该病患者胎盘血管内皮细胞的二甲基精氨酸二甲胺水解酶(DDAH2)表达水平下降,使ADMA降解减少;而血浆及胎盘ADMA水平增加,可竞争性抑制NOS活性,导致NO生成减少及其生物利用度降低,发生胎盘病变及胎盘血管内皮细胞功能障碍。由此可见,ADMA与EOSP胎盘病理改变的发生、发展密切相关,并已成为目前研究热点。笔者拟就ADMA在EOSP中的作用及其可能机制进行综述。     

The role of L-arginine following trauma and blood loss

PURPOSE OF REVIEW: Vascular endothelial cells control vascular smooth muscle tone via the release of nitric oxide. Following adverse circulatory conditions, namely trauma and hemorrhage, endothelial cell dysfunction occurs, leading to a decrease in the release of endothelium-derived nitric oxide, which contributes to further alterations in tissue perfusion and organ function. RECENT FINDINGS: Early administration of L-arginine (the precursor of nitric oxide) and the substrate for nitric oxide synthase in vascular endothelial cells has been found to restore the depressed organ blood flow and to reduce tissue injury following shock. This improvement in cardiovascular function was associated with restoration of the depressed cell-mediated immune responses and attenuation of the massive inflammatory response encountered under such conditions. Furthermore, the excessive infiltration of the liver with neutrophils following trauma-hemorrhage was decreased by L-arginine administration, thereby reducing hepatic injury. In addition, L-arginine treatment decreased the inflammatory response at the site of trauma and the improved wound-healing process following blood loss. SUMMARY: Despite those promising results in animal models at present, none of the published clinical trials has demonstrated efficacy of L-arginine at doses above standard dietary practices on the outcome in critically ill surgical patients, besides the reduction in infectious complications.     

Polyphenols in the prevention and treatment of sepsis syndromes: Rationale and pre-clinical evidence

Sepsis is the overwhelming systemic response to infection of a normally sterile body compartment. Despite advances in elucidating its pathophysiology, severe sepsis remains a leading cause of death in the critically ill. Polyphenols are a family of chemicals found in food and beverages derived from plants, such as cocoa, green tea, turmeric, and soya, as well as in medicinal herbs. These phytochemicals exhibit anti-inflammatory and vasculoprotective properties in clinical and preclinical studies. The oral or systemic administration of polyphenols protects rodents from endotoxinemia and microbial sepsis. Under these circumstances, polyphenols reproducibly attenuate microvascular hyperpermeability, tissue infiltration by leukocytes, oxidative and nitrosative stress, tissue injury, organ dysfunction, shock and vasoplegia, lactate production, and mortality. Importantly, efficacy is maintained in some cases even when treatment is initiated hours after the onset of sepsis. The inhibition of nuclear factor–κB activation and subsequent expression of inducible nitric oxide synthase, adhesion molecules, and tumor necrosis factor–α by polyphenols is operative in ameliorating the sequelae of sepsis. Enhancement of the endogenous antioxidant capacity probably also contributes to the effectiveness of the polyphenols. Because several of the polyphenols reviewed in this article appear to be safe and to exert anti-inflammatory effects in humans, clinical trials assessing their efficacy in the critically ill are indicated. Whether delivered alone or in combination with nutritional formulas, polyphenols may help to prevent and treat sepsis.     

Low arginine plasma levels in patients after thoracoabdominal aortic surgery

OBJECTIVE: Thoracoabdominal aortic surgery is a high-risk procedure and associated with a significant morbidity and mortality. Ischemia reperfusion of visceral organs and lower extremities is one of the most important determinants of this morbidity. Arginine is the precursor of nitric oxide and arginine plasma levels are important in maintaining organ blood flow. Furthermore, arginine is important in wound healing and the immune system. Because of increased utilization of arginine, low arginine plasma levels could be expected after thoracoabdominal aortic surgery. We therefore measured arginine plasma levels in these patients. DESIGN: Six patients with thoracoabdominal aortic aneurysm were included in this study. SETTING: University Hospital Vrije Universiteit, Department of Surgery, Amsterdam, The Netherlands. SUBJECTS: Six patients undergoing thoracoabdominal aortic surgery. INTERVENTION: Plasma levels of arginine were measured by high-performance liquid chromatography. RESULTS: Very low arginine plasma levels were seen on the first postoperative day. From day 1 arginine slowly increased, but did not reach normal plasma levels on day 6. CONCLUSIONS: A significant decrease of arginine plasma levels was found and because of the fact that arginine has multiple functions, it may be important to keep these arginine plasma levels at normal or even higher levels in patients undergoing major vascular surgery. European Journal of Clinical Nutrition (2000) 54, 615-617.