Total and renal sympathetic nervous system activity in alcoholic cirrhosis

Basal sympathetic nervous system activity was assessed in 8 unmedicated patients with alcoholic cirrhosis using a previously developed radiotracer method for measuring total and renal noradrenaline release to, and clearance from, plasma. Compared to the control group total noradrenaline clearance was significantly increased in the patients with advanced alcoholic cirrhosis (Pugh grade C) [1.89 +/- 0.13 vs 1.51 +/- 0.11 l/min, P less than 0.05) indicating that endogenous plasma noradrenaline levels underestimate total sympathetic nervous system activity in these patients. Renal noradrenaline clearance was similar to controls independent of the severity of the liver disease. Both total and renal noradrenaline release were significantly increased in the patients with cirrhosis. The ratio of renal to total noradrenaline release was similar in cirrhotic (26 +/- 7%) and control (23 +/- 5%) groups. Increased arterial plasma adrenaline levels, indicative of adrenal medullary stimulation, were also evident in the patients with cirrhosis and correlated significantly with total noradrenaline spillover (r = 0.732, P less than 0.05). These results strongly suggest that in patients with cirrhosis, rather than a preferential increase in renal sympathetic tone, the increase is part of a pattern of generalized sympathoadrenomedullary activation. Although renal renin secretion was significantly increased in the cirrhotic group no correlation with renal noradrenaline release was seen (r = 0.199), raising the possibility that in cirrhosis renal sympathetic tone is not a major determinant of renal renin secretion. Finally, renal noradrenaline release did not correlate with renal blood or plasma flow but an influence of the sympathetic nervous system on renal function was suggested by the correlation observed between total noradrenaline spillover and impaired salt (r = -0.683, P less than 0.05) and water excretion (r = -0.702, P less than 0.05) demonstrated in the cirrhotic patients.     

Plasma catecholamine level and portal venous pressure as guides to prognosis in patients with cirrhosis

Circulating noradrenaline is increased in patients with cirrhosis, especially in decompensated patients with ascites. Eighty-one patients with alcoholic cirrhosis were followed for up to 8 years in order to establish a possible relationship between plasma catecholamines, haemodynamics, and routine clinical and biochemical variables and survival. Forty-seven (58%) of the patients died during the follow-up period. Univariate analysis showed that plasma noradrenaline and adrenaline concentrations, portal pressure, indocyanine green clearance, serum sodium, bilirubin, and albumin concentrations, and the presence of ascites or cardiovascular disease were of significant prognostic value. In a multivariate analysis (Cox regression model), plasma noradrenaline concentration, portal pressure, serum bilirubin concentration, and the presence of ascites and cardiovascular disease remained significant independent predictors of survival. The results suggest that determination of the circulating level of noradrenaline and portal pressure may add to the prognostic information on survival obtained from routine tests. Thus, the activity of the sympathetic nervous system may indicate the severity of cirrhosis with respect to survival.     

Renal sympathetic nervous activity in patients with cirrhosis]

This study was designed to evaluate the renal contribution to overall sympathetic nerve hyperactivity and the relationships between renal sympathetic activity and systemic, splanchnic or renal hemodynamics in a series of 55 cirrhotic patients. Plasma noradrenaline concentrations were significantly higher in the renal vein than in the pulmonary artery (803 +/- 54 vs 608 +/- 47 pg/ml, P less than 0.01). These two concentrations were significantly correlated, which suggests that renal sympathetic activity and overall sympathetic activity increase in parallel in patients with cirrhosis. However, the estimated renal net release of noradrenaline was not correlated with plasma noradrenaline concentration in the pulmonary artery, suggesting that overall sympathetic nerve activity is not directly dependent on renal contribution in patients with cirrhosis. Neither plasma noradrenaline concentration in the renal vein nor renal net release of noradrenaline were correlated with systemic. splanchnic or renal hemodynamics. Thus, this study did not show a major role of renal sympathetic activity in the hemodynamic changes in cirrhosis.     

Relative Versus Absolute Carbohydrate-Deficient Transferrin as a Marker of Alcohol Consumption in Patients With Acute Alcoholic Hepatitis

BACKGROUND: Carbohydrate-deficient transferrin has been described as a sensitive and specific marker for alcohol consumption. This study investigated the usefulness of carbohydrate-deficient transferrin as a marker of alcohol consumption in acute alcoholic hepatitis. METHODS: Absolute concentrations (U/I) and relative values (%) of carbohydrate-deficient transferrin determined in serum with commercial assays, as well as conventional markers for alcohol consumption, were compared with the alcohol consumption (as estimated by a questionnaire) in patients with acute alcoholic hepatitis (n = 19), alcoholic liver cirrhosis (n = 37), and nonalcoholic liver diseases (n = 16). RESULTS: The concentration of carbohydrate-deficient transferrin was increased (p < 0.001) in nonabstaining patients (median intake 80 g alcohol/day) with alcoholic liver cirrhosis (45.7 +/- 30 U/l), but not in patients with acute alcoholic hepatitis (20.0 +/- 7.8 U/l) despite higher alcohol consumption (median 130 g/d), nor in abstainers with alcoholic liver cirrhosis (19.4 +/- 6.0 U/l) or nonalcoholic liver disease (18.5 +/- 6.7 U/l). However, the relative values of carbohydrate-deficient transferrin were increased both in acute alcoholic hepatitis (7.9 +/- 2.1%) and nonabstainers with alcoholic liver cirrhosis (7.4 +/- 2.8%), but not in abstainers with alcoholic liver cirrhosis (4.6 +/- 3.5%) or nonalcoholic liver disease (3.8 +/- 0.9%) (p < 0.001). In acute alcoholic hepatitis, the sensitivity and specificity were only 32% and 87% for absolute concentrations, respectively, but 79% and 97% for relative values of carbohydrate-deficient transferrin. The concentrations of carbohydrate-deficient and total transferrin in serum were strongly correlated (r = 0.60; p = 0.008). CONCLUSIONS: The relative value (% of total), but not the absolute concentration, of carbohydrate-deficient transferrin in serum is a useful marker of alcohol consumption in acute alcoholic hepatitis.     

Enhancement of renal function with ornipressin in a patient with decompensated cirrhosis.

An infusion with Ornipressin (8-ornithin vasopressin) in a patient with decompensated alcoholic liver cirrhosis increased urinary volume from 30 ml/h to 500 ml/h, creatinine clearance from 24 to 65 ml/min, and fractional sodium excretion from 0.86% to 11.1%. Free water clearance decreased from -10.2 ml/h to -26.2 ml/h and noradrenaline plasma concentrations dropped from 2.04 to 1.37 ng/ml. After stopping Ornipressin infusion all values returned to initial concentrations. Possible effects are an increase of renal blood flow secondary to an increase in arterial blood pressure, possibly potentiated by the vasodilatory effect of the fall in noradrenaline and/or angiotensin concentration.     

Splanchnic and renal elimination and release of catecholamines in cirrhosis. Evidence of enhanced sympathetic nervous activity in patients with decompensated cirrhosis.

Plasma noradrenaline (NA) and adrenaline (A) concentrations were determined in different vascular areas in 32 patients with cirrhosis and in nine controls during a right sided heart, liver, and renal vein catheterisation. The patients were divided into four groups: (I) Compensated (without ascites); (II) Recompensated on diuretic treatment because of former ascites; (III) Decompensated (with ascites) without treatment and (IV) Decompensated on diuretic treatment. Median arterial noradrenaline concentrations were 1.48, 1.07, 2.66, 4.14 and 2.50 nmol/l in controls, group I, II, III, and IV, respectively, the three last mentioned values being significantly raised (p less than 0.01). Median arterial adrenaline concentrations were not significantly increased. In patients arterial-hepatic venous extraction ratios of noradrenaline and adrenaline were on the average 25% (p less than 0.01) and 20% (p less than 0.02) less than those of the controls, indicating a slightly reduced splanchnic elimination of catecholamines in cirrhoses. In controls and group I significant renal venous-arterial noradrenaline differences were absent (0.00 and 0.03 nmol/l) while renal venous-arterial noradrenaline differences were significantly increased in groups II, III and IV (0.47, 0.53 and 0.68 nmol/l, p less than 0.01), indicating a significant net release of noradrenaline from the kidneys in recompensated and decompensated patients. Renal extraction of adrenaline was normal. In conclusion, increased arterial noradrenaline in decompensated and recompensated cirrhosis is only to a limited extent owing to reduced net splanchnic elimination. More likely the increase is caused by release of noradrenaline from the kidneys and possibly other organs indicating enhanced sympathetic nervous tone in these conditions.     

Changes in pancreatic secretion in alcoholic liver disease

By means of consecutive pancreatic stimulation, we have investigated the presence of changes of pancreatic function in alcoholic patients, with and without alcoholic liver disease, in order to detect functional alterations and possible association of hepatic and pancreatic disease. The patients were 49 chronic alcoholics (8 patients without liver disease, 11 hepatic steatosis, 9 alcoholic hepatitis and 21 alcoholic cirrhosis) and 15 non alcoholic subjects (8 normal controls and 7 cases of non alcoholic cirrhosis). In all the cases two consecutive stimulations were carried out: first with secretin and cholecystokinin (CCK) and second with CCK alone. The total volume and concentration as well as the output of bicarbonate, trypsin, amylase and total proteins were measured in the duodenal juice. Patients with alcoholic cirrhosis had larger volumes of duodenal juice and lower concentrations of bicarbonate, enzymes and proteins. There was also a tendency to larger volume and lower bicarbonate concentration as the hepatic lesion was more severe. Bicarbonate output was significatively higher in patients with alcoholic cirrhosis but for the remaining parameters the outputs were similar in all the groups. In conclusion, the alterations in pancreatic function parallel the severity of the liver disease. None of the patients had changes consistent with chronic pancreatitis.     

Clinical characteristics of nontraumatic rhabdomyolysis in patients with liver cirrhosis]

BACKGROUND/AIMS: Rhabdomyolysis is a serious and lethal condition that can be induced not only by traumatic causes but also by a variety of nontraumatic causes. However, there are few reports about rhabdomyolysis developed in patients with liver cirrhosis. We carried out this study to elucidate the clinical characteristics and courses of rhabdomyolysis in patients with liver cirrhosis. METHODS: We analyzed 19 cases of nontraumatic rhabdomyolysis in patients with liver cirrhosis who had admitted at Korea University Ansan Hospital between October 2001 and September 2004. RESULTS: Alcohol (50%) was the main etiology of rhabdomyolysis in alcoholic liver cirrhosis patients, and the precipitating factors were not apparent (69.2%) in majority of nonalcoholic liver cirrhosis patients with rhabdomyolysis. Nonalcoholic liver cirrhosis patients had complaints of pain referable to the musculoskeletal system, but alcoholic liver cirrhosis patients had no typical complaints. Mortality of rhabdomyolysis in liver cirrhosis patients was high (42.1%), especially in decompensated liver cirrhosis patients (p=0.04). In nonalcoholic liver cirrhosis patients, the development of oliguria (p=0.007) and acute renal failure (p=0.049) in the course of rhabdomyolysis increased the mortality significantly. CONCLUSIONS: In cirrhosis patients, rhabdomyolysis showed a poor prognosis, especially in nonalcoholic liver cirrhosis with oliguria, acute renal failure, or decompensated liver cirrhosis. It is believed that a high clinical suspicion for the occurrence of rhabdomyolysis in liver cirrhosis patients can lead to quicker recognition and better patient care.     

Elevated carboxy terminal cross linked telopeptide of type I collagen in alcoholic cirrhosis: relation to liver and kidney function and bone metabolism

BACKGROUND: The carboxy terminal cross linked telopeptide of type I collagen (ICTP) has been put forward as a marker of bone resorption. Patients with alcoholic liver disease may have osteodystrophy. AIMS: To assess circulating and regional concentrations of ICTP in relation to liver dysfunction, bone metabolism, and fibrosis. METHODS: In 15 patients with alcoholic cirrhosis and 20 controls, hepatic venous, renal venous, and femoral arterial concentrations of ICTP, and bone mass and metabolism were measured. RESULTS: Circulating ICTP was higher in patients with cirrhosis than in controls. No overall significant hepatic disposal or production was found in the patient or control groups but slightly increased production was found in a subset of patients with advanced disease. Significant renal extraction was observed in the controls, whereas only a borderline significant extraction was observed in the patients. Measurements of bone mass and metabolism indicated only a mild degree of osteodystrophy in the patients with cirrhosis. ICTP correlated significantly in the cirrhotic patients with hepatic and renal dysfunction and fibrosis, but not with measurements of bone mass or metabolism. CONCLUSIONS: ICTP is highly elevated in patients with cirrhosis, with no detectable hepatic net production or disposal. No relation between ICTP and markers of bone metabolism was identified, but there was a relation to indicators of liver dysfunction and fibrosis. As the cirrhotic patients conceivably only had mild osteopenia, the elevated ICTP in cirrhosis may therefore primarily reflect liver failure and hepatic fibrosis.     

Correlations of hemodynamic parameters with plasma catecholamines in patients with congestive cardiomyopathy

Noradrenaline and adrenaline blood levels, as well as central hemodynamics (Swan-Ganz semi-floating balloon-tipped catheter), were measured at rest and during moderate exercise in 8 male patients suffering with idiopathic congestive cardiomyopathy (COCM), and in 12 healthy male control subjects. The stroke volume and the cardiac output in COCM were, on the average, one-half that of the control subjects; adrenaline, noradrenaline, pulmonary capillary wedge pressure, as well as the roentgenographically determined heart volume (at rest) in COCM were, on the average, increased more than twice the control values. The noradrenaline and adrenaline responses in COCM reached at the 25-W exercise level the response of controls at the 150-W level. Direct correlations were observed between the cate-cholamine responses and the capillary wedge pressure as well as the heart volume; inverse correlations existed between the catecholamines and the stroke volume or the cardiac output. The results may be indicative of a causal relationship between the reduced function of the left heart and a compensatorily increased sympathetic activity, but they are not at all conclusive for a definite cause-effect response. The differences in catecholamine levels and the correlations are more significant for noradrenaline during both exercise and rest, whereas for adrenaline significance only occurred during exercise. The noradrenaline and adrenaline levels may serve as indicators (especially in the chronic stage) in the diagnosis of reduced left ventricular function.     

Urinary thromboxane B2 and prostaglandin E2 in the hepatorenal syndrome: evidence for increased vasoconstrictor and decreased vasodilator factors

Vasodilatory prostaglandins function to maintain renal perfusion in patients with cirrhosis and ascites. To evaluate the potential contribution of the vasodilator prostaglandin E2 and the vasoconstrictor metabolite thromboxane B2 to the development of the hepatorenal syndrome, we measured urinary excretion of these products in 14 patients with hepatorenal syndrome and in control populations with acute or chronic liver or kidney failure. Radioimmunoassay measurements were confirmed by bioassay and by mass spectrometry. Prostaglandin E2 was decreased compared with healthy controls (2.2 +/- 0.3 vs. 6.3 +/- 0.8 ng/h, p less than 0.01) and compared with acute renal failure (9.6 +/- 2.1 ng/h) and with alcoholic hepatitis (9.2 +/- 3.3 ng/h). Thromboxane B2 concentration was normal in patients with alcoholic hepatitis (0.12 +/- 0.02 vs. 0.15 +/- 0.03 ng/ml) and minimally increased in acute renal failure (0.18 +/- 0.15 ng/ml), but markedly elevated in hepatorenal syndrome (0.69 +/- 0.15 ng/ml, p less than 0.001). Urinary thromboxane B2 concentration fell with improved renal function in 3 patients who survived. These data suggest an imbalance of vasodilator and vasoconstrictor metabolites of arachidonic acid in patients with the hepatorenal syndrome.     

A comparison of sympathoadrenal activity and cardiac performance at rest and during exercise in patients with ventricular demand or atrial synchronous pacing

Cardiac sympathetic function was assessed by measuring the coronary sinus overflow of noradrenaline and dopamine at rest and during supine exercise in eight patients with high degree atrioventricular block treated with dual chamber pacemakers (DDD). Patients exercised (30-60 W) during both ventricular inhibited (VVI) and atrial synchronous (VAT) pacing. During exercise cardiac output increased less markedly in the VVI mode than in the VAT mode. The cardiac output response was entirely stroke volume dependent in the VVI mode and mainly heart rate dependent in the VAT mode. Coronary sinus noradrenaline concentrations were higher in the VVI mode at rest and during exercise. Noradrenaline overflow from the heart was enhanced during VVI pacing and increased from about 100 pmol/min (17 ng/min) at rest to 1087 pmol/min during exercise (60 W) in the VVI mode and 545 pmol/min in the VAT mode. Dopamine overflow from the heart was less than 5 pmol/at rest but increased 2-5 fold during exercise. Also arterial concentrations of catecholamine increased more during exercise in the VVI mode, but the differences between pacing modes were less pronounced. Circulating adrenaline seems to be of little importance for cardiac function under these conditions; in healthy individuals the arterial concentrations of adrenaline attained in this study have small effects. Cardiac noradrenaline overflow correlated with pulmonary capillary venous pressures and atrial rates in both pacing modes, indicating a relation between cardiac sympathetic activity and cardiac function. Enhanced cardiac release of noradrenaline may increase cardiac contractility and thereby partially compensate for the lack of heart rate responsiveness to exercise during VVI pacing.     

A comparison of sympathoadrenal activity and cardiac performance at rest and during exercise in patients with ventricular demand or atrial synchronous pacing.

Cardiac sympathetic function was assessed by measuring the coronary sinus overflow of noradrenaline and dopamine at rest and during supine exercise in eight patients with high degree atrioventricular block treated with dual chamber pacemakers (DDD). Patients exercised (30-60 W) during both ventricular inhibited (VVI) and atrial synchronous (VAT) pacing. During exercise cardiac output increased less markedly in the VVI mode than in the VAT mode. The cardiac output response was entirely stroke volume dependent in the VVI mode and mainly heart rate dependent in the VAT mode. Coronary sinus noradrenaline concentrations were higher in the VVI mode at rest and during exercise. Noradrenaline overflow from the heart was enhanced during VVI pacing and increased from about 100 pmol/min (17 ng/min) at rest to 1087 pmol/min during exercise (60 W) in the VVI mode and 545 pmol/min in the VAT mode. Dopamine overflow from the heart was less than 5 pmol/at rest but increased 2-5 fold during exercise. Also arterial concentrations of catecholamine increased more during exercise in the VVI mode, but the differences between pacing modes were less pronounced. Circulating adrenaline seems to be of little importance for cardiac function under these conditions; in healthy individuals the arterial concentrations of adrenaline attained in this study have small effects. Cardiac noradrenaline overflow correlated with pulmonary capillary venous pressures and atrial rates in both pacing modes, indicating a relation between cardiac sympathetic activity and cardiac function. Enhanced cardiac release of noradrenaline may increase cardiac contractility and thereby partially compensate for the lack of heart rate responsiveness to exercise during VVI pacing.     

Plasma neurotransmitters and cortisol in duodenal ulcer patients

Levels of noradrenaline, adrenaline, dopamine, free serotonin, platelet serotonin, and cortisol were measured in the plasma of duodenal ulcer patients and controls. All subjects received antacids, and these substances were also measured. During relapse, all patients showed raised noradrenaline, adrenaline, dopamine, free serotonin, and cortisol values. In contrast, platelet serotonin showed very low values, which correlated negatively with all the former, except free serotonin. No correlations were found in parameters of the controls. After healing, significant reductions of noradrenaline, adrenaline, dopamine, free serotonin, and cortisol and significant increases of platelet serotonin values were observed. However, only dopamine, free serotonin, and cortisol reached normal values. Noradrenaline and adrenaline remained higher and platelet serotonin lower, both significantly more so than normals. These still-altered parameters showed similar correlations to those found during relapses. The present results demonstrate that some baseline autonomic system imbalance exists in patients, amplified and accentuated during relapse. We discuss the possibility that stress plays some role in triggering duodenal ulcer relapse.This work was supported by a FUNDAIME grant.     

Plasma metallothionein concentration in patients with liver disorders: special emphasis on the relation with primary biliary cirrhosis

The plasma metallothionein concentration was evaluated in healthy subjects and in patients with several types of liver disorders. Plasma metallothionein concentrations in controls varied between 2.4 and 4.8 ng/ml. Patients with disorders associated with increased liver copper concentrations (i.e., primary biliary cirrhosis and primary sclerosing cholangitis) had significantly (both p less than 0.002) elevated plasma metallothionein concentrations (range = 1.8 to 52.2 ng/ml), and a considerable number of these were above the maximum control level (21 of 41 patients). In contrast, patients with liver disorders not associated with increased liver copper concentrations (alcoholic and cryptogenic cirrhosis, and acute viral and chronic active hepatitis) generally had normal plasma metallothionein concentrations and only a few were above the maximum control level (11 of 64 patients, maximum = 8.8 ng/ml). The metallothionein concentrations in plasma samples from patients in stage I or II primary biliary cirrhosis were within or slightly above the control range, whereas most patients in stage III had elevated levels (p less than 0.002), and almost all patients in stage IV had clearly elevated (p less than 0.0001) concentrations. In primary biliary cirrhosis the plasma metallothionein concentration tended to increase during the evolution of the disorder, and the concentration correlated significantly with the serum total bilirubin concentration. In conclusion, the plasma metallothionein concentration is significantly elevated in patients with primary biliary cirrhosis and in patients with primary sclerosing cholangitis. Although related to the histological stage of primary biliary cirrhosis, the measurement of plasma metallothionein concentrations contributes little to the diagnosis or the evaluation of the severity of these disorders.(ABSTRACT TRUNCATED AT 250 WORDS)     

Balance between pro and anti-inflammatory cytokines in patients with acute alcoholic hepatitis

The ability of endogenous IL-10 to modulate inflammatory response and to limit hepatotoxicity has been shown in several models of liver injury. AIMS: The objectives of this study were to evaluate the relationship between liver disease and the balance between pro and anti-inflammatory cytokines in acute alcoholic hepatitis. METHODS: Twenty-five patients with pure steatosis, 17 with cirrhosis and mild acute alcoholic hepatitis (discriminant function value<32) and 41 patients with cirrhosis and severe acute alcoholic hepatitis (discriminant function value >=32) were studied. Plasma levels of interleukin 10 (IL-10) and soluble TNF receptors (TNFsRp75 and 55) were analyzed using ELISA assays. Hepatocyte proliferative activity was assessed with proliferating cell nuclear antigen labeling index (PCNA-LI) on formalin-fixed paraffin embedded liver biopsy specimens. RESULTS: In patients with steatosis, cirrhosis with mild and severe acute alcoholic hepatitis, the plasma levels of IL-10 were higher (P<0.05) than in healthy controls. Between day 1 and day 8, the TNFsRp55/IL-10 ratio increased by 137 +/- 47 in the 10 patients with severe acute alcoholic hepatitis treated with prednisolone who died within 2 months and by 9.3 +/- 14 in the 19 patients still alive at 2 months (P=0.031). In patients with severe acute alcoholic hepatitis, PCNA-LI on liver biopsy was negatively correlated with the TNFsRp55/IL-10 ratio increase from day 1 to day 8 (r=- 0.42, P=0.11). PCNA-LI was positively correlated with TNFsRp75/TNFsRp 55 ratio increase from day 1 to day 15 (r=0.52; p<0.05). CONCLUSION: Our data suggest the anti-inflammatory system is up-regulated in patients with alcoholic liver disease. Nevertheless, in patients with severe acute alcoholic hepatitis, IL-10 production seems insufficient to modulate TNF-alpha cytotoxicity mediated by TNFRp55.     

Biological diagnosis of the type of liver disease in alcoholic patients with abnormal liver function tests

OBJECTIVES: The histological diagnosis of the different stages of alcoholic liver disease is not systematic. The aim of this study was to assess whether common biological features were useful in identifying the different stages. METHODS: One thousand twenty six alcoholic patients with liver histology and without any associated diseases or infections likely to alter serum liver tests were studied. Diagnostic analyses were performed using stepwise discriminant analysis in the entire population and in asymptomatic patients. RESULTS: a) Serum ASAT activity levels were only normal in 39% of the patients with normal histological liver and in 14% of the patients with steatosis; b) liver failure was already present in patients with fibrosis without cirrhosis; c) betagamma block was the only biochemical parameter which confirmed the diagnosis of cirrhosis without biopsy; d) the diagnostic accuracy of common tests was weak for the diagnosis of alcoholic liver disease without cirrhosis but prothrombin time could be useful in excluding the diagnosis of cirrhosis with and without acute alcoholic hepatitis when liver biopsy is not available. CONCLUSION: Only a prothrombin time of 80% with a negative predictive value of 94% and the presence of beta-gamma [corrected] block with a positive predictive value of 98% were useful for assessing the diagnosis of cirrhosis in all patients with alcoholic liver disease.     

Magnesium sulphate infusion suppresses the cardiac release of noradrenaline during a handgrip stress test

BACKGROUND: Magnesium has several important cardiovascular effects, but its effect on cardiac sympathetic efferent neuron activity has not been clarified. Objectives: To examine the effect of magnesium sulphate infusion on cardiac sympathetic efferent postganglionic neuronal liberation of noradrenaline. PATIENTS AND METHODS: Twenty-two patients who underwent cardiac catheterization were randomly allocated to the control group or the magnesium group. Plasma noradrenaline and adrenaline concentrations in the aorta and the coronary sinus were measured. Noradrenaline or adrenaline release from the heart was calculated by dividing the difference in noradrenaline or adrenaline concentration between the aorta and the coronary sinus by that of the aorta. After baseline blood sampling, the control patients and the patients in the magnesium group received intravenous infusion of saline or magnesium sulphate (10 mmol). All patients were then subjected to 3 min of handgrip exercise stress test to augment sympathetic efferent neuronal activity, and the blood sampling was repeated. RESULTS: Although blood pressure was increased by the handgrip stress test, there were no differences in heart rate and blood pressure between the two groups, both at baseline and during the handgrip stress test. The plasma noradrenaline and adrenaline concentrations and noradrenaline or adrenaline release from the heart did not differ between the two groups in the baseline condition. However, the handgrip stress increased plasma noradrenaline concentrations and the cardiac noradrenaline release was increased in the control group, whereas the cardiac noradrenaline release was not increased by the handgrip stress in the magnesium group (P<0.02). CONCLUSIONS: These data indicate that magnesium sulphate infusion suppresses the release of catecholamines by the heart, which is an indirect index of sympathetic efferent neuronal activity.     

Plasma endotoxin concentrations in patients with alcoholic and non-alcoholic liver disease: reevaluation with an improved chromogenic assay

Plasma endotoxin concentration was measured in 85 patients with alcoholic liver disease (alcoholic cirrhosis (n = 64), alcoholic hepatitis without cirrhosis (n = 11), fatty liver (n = 10), and in patients with non-alcoholic cirrhosis (n = 15]. Endotoxin concentration was determined with an improved chromogenic substrate assay, using individual standard curves for each plasma sample. In patients with alcoholic cirrhosis the mean endotoxin concentration was significantly higher than in patients with non-alcoholic cirrhosis (p less than 0.05). In addition, distinctly higher endotoxin concentrations (greater than 20 pg/ml) were more frequently observed in patients with alcoholic cirrhosis than in non-alcoholic cirrhosis (34.4 vs. 14.3%, p less than 0.05). Mean endotoxin concentration was not significantly higher in cirrhotics with ascites or esophageal varices as compared with the subgroup without ascites or esophageal varices. The endotoxin concentration did not correlate with serum bilirubin, prothrombin concentration or serum enzyme activities. In patients with alcoholic liver disease, however, endotoxin concentration revealed a negative correlation (p less than 0.05) with the concentration of high density lipoprotein cholesterol. On admission endotoxin concentrations in alcoholics with fatty liver were similarly elevated as observed in alcoholic cirrhosis. In six out of 12 patients with fatty liver or alcoholic hepatitis, in whom a second sample of plasma was investigated after 6 to 8 days, endotoxemia was no longer detectable; in the remaining patients, the endotoxin concentration decreased markedly. The results indicate that, irrespective of the stage of liver disease, alcohol abuse favours the development of endotoxemia. They support the hypothesis that gut-derived endotoxins might play a role in the initiation and aggravation of alcohol-induced liver disease.     

Raised concentrations of glucose and adrenaline and increased in vivo platelet activation after myocardial infarction

Plasma concentration of beta thromboglobulin was used as an index of in vivo platelet activation in 36 patients after acute myocardial infarction. Twelve patients had diabetes, seven had pulmonary oedema or cardiogenic shock (pump failure) or both, and 17 had uncomplicated infarcts. On the first day of admission, concentrations of beta thromboglobulin were higher in the patients with diabetes and those with pump failure than in those with uncomplicated infarcts. Concentrations of beta thromboglobulin in the non-diabetic patients were studied by multiple regression analysis and were significantly associated with plasma concentrations of adrenaline, pump failure, and glucose but not with noradrenaline or infarct size. When all subjects were considered together, glucose, adrenaline, and pump failure were associated with the beta thromboglobulin concentration but diabetes was without significant effect. Hyperglycaemia and raised plasma adrenaline concentration after myocardial infarction may activate platelets, and this could contribute to poor outcome in such patients.