Role of gender upon basal and postprandial systemic and splanchnic haemodynamics in humans

BACKGROUND: Food intake, accompanied by systemic and splanchnic haemodynamic changes, has only been studied in males. The extent to which splanchnic postprandial hyperaemia shows gender differences is unknown. METHODS: We tested 1) the splanchnic hyperaemic response to food in females and 2) whether postprandial haemodynamic changes show gender differences. Twenty-four healthy women (aged 20-35 years) and 20 healthy men (aged 21-34 years) participated in the study. A liquid test meal (Ensure plus, 1.5 kcal/ml) was perfused intraduodenally for 75 min through an enteral feeding tube at a rate of 3 ml/min after a 45-min basal period. Blood flow parameters were measured using Echo-Doppler technology. RESULTS: Basal diastolic arterial blood pressure was significantly (P < 0.05) lower in females (66+/-2 versus 72+/-2 mmHg), whereas heart rate was the same (58+/-2 b/min, ns). Postprandially, diastolic blood pressure fell, but reached significance only in males (-10+/-3 mmHg; P < 0.05). Mean velocity in the superior mesenteric artery (SMA) was significantly (P < 0.05) higher in females compared to males at baseline (47+/-3 versus 39+/-2 cm/s), whereas maximal postprandial changes were similar (64+/-6 versus 56+/-6 cm/s, ns). Volume flow in the portal vein (PV) at baseline was 656+/-29 and 716+/-35 ml/min females and males, respectively (ns between gender). Maximal postprandial changes amounted to 808+/-86 and 884+/-107 ml/min, respectively (ns). CONCLUSIONS: 1) Perfusion of a liquid test meal induces significant increases in flow parameters in the SMA and PV in both genders. 2) These changes are partly paralleled by alterations in systemic haemodynamics. 3) Postprandial splanchnic flow parameters are qualitatively and quantitatively not different between genders.     

Different haemodynamic effects of a single dose of long-acting isosorbide-5-mononitrate in healthy subjects and patients with cirrhotic portal hypertension

BACKGROUND: The action pathways of nitrates are hypothesised to be deranged in cirrhosis. AIM: In order to confirm it, the acute haemodynamic effects of isosorbide-5-mononitrate in cirrhotic patients and controls was investigated. PATIENT: Nine cirrhotics and nine healthy controls. METHODS: Evaluation in the fasting state, 90 min after isosorbide-5-mononitrate or placebo (double-blind on two different days) and then 30 and 120 min after eating a standard meal. Various systemic and splanchnic haemodynamic parameters, including arterial impedance, assessed as Doppler pulsatility index, were measured. RESULTS: isosorbide-5-mononitrate reduced arterial pressure and increased heart rate and mesenteric pulsatility index both in controls and in cirrhotics, whereas the following parameters behaved differently in the two groups (P < 0.05): hepatic pulsatility index decreased (-9%) and the portal velocity increased (+13%) in controls, whereas hepatic pulsatility increased (+18%) and portal velocity decreased (-18%) in cirrhotics. The two groups presented a similar pattern of changes in most variables under placebo after a meal. In controls, the administration of isosorbide-5-mononitrate blunted the postprandial mesenteric vasodilation and related changes in splanchnic and systemic circulation, expected at 30 min, in comparison to those observed under placebo. In cirrhotics, instead, the postprandial pattern was similar under placebo and isosorbide-5-mononitrate. CONCLUSIONS: The acute administration of isosorbide-5-mononitrate produces different haemodynamic effects in healthy and diseased livers, both in the fasting state and after a meal, consistent with the hypothesis of a deranged response of the intrahepatic microcirculation to nitrates in cirrhosis.     

Effect of the somatostatin analogue lanreotide on meal-stimulated portal blood flow in patients with liver cirrhosis

BACKGROUND: Lanreotide, a new long-acting somatostatin analogue, has been shown to inhibit the meal-stimulated increase of splanchnic blood flow in healthy volunteers. To date, similar data in patients with liver cirrhosis have not been available. We have examined the effect of lanreotide compared with placebo on meal-stimulated portal blood flow in patients with liver cirrhosis using Doppler ultrasound. METHODS: 20 cirrhotic patients (placebo n = 12, lanreotide n = 8) with proven portal hypertension were studied after an overnight fast. Lanreotide, at a dose of 100 microg/h, was infused intravenously over 7 h after a 1-hour basal period. In parallel to the intravenous infusion, a liquid test meal (Ensure plus, 1.5 kcal/min) was perfused for 7 h through an intraduodenal tube at a rate of 3 ml/min. Blood pressure, heart rate and portal vein blood flow (PVF, ml/min, Doppler technique) were determined at regular intervals. RESULTS: Baseline PVF amounted to 725 +/- 182 ml/min in the placebo and to 917 +/- 252 ml/min in the lanreotide group (n.s.). The meal-stimulated increase in PVF was blunted by lanreotide (AUC, % x min): 62,709.6 +/- 6,817 (placebo) vs. 45,237 +/- 2,507 (lanreotide), p < 0.05. Lanreotide also blunted the postprandial increase in heart rate for the first 2 h of meal perfusion. CONCLUSIONS: Because of potent inhibition of postprandial splanchnic hyperemia in patients with liver cirrhosis, lanreotide may be useful in the treatment of complications of portal hypertension.     

Prevalence of and risk factors for postprandial hypotension in older Chinese men

Objective To assess the prevalence of and risk factors for postprandial hypotension (PPH) among old and very old Chinese men. Methods The study included 349 Chinese men aged 65 and older, grouped into two age categories: group 1 (old) included 163 men aged 65 to 80 years; group 2 (very old) included 186 men aged over 80 years. Blood pressure changes after meals were assessed every 15 min by ambulatory blood pressure monitoring. Symptoms after meal ingestion and after standing up and changes in the baseline condition relative to blood pressure changes were observed continuously. Additional baseline data included body mass index, medical history, and medication use. Results The prevalence of PPH was 59.3% overall and was significantly higher in group 2 than group 1 (63.4% vs. 54.6%, P < 0.05). In group 2, the prevalence of PPH after breakfast (33.8%) and lunch (32.1%) were higher than that after supper (20.9%), P < 0.05. Hypertension and age were significant risk factors for PPH (OR = 2.188, 95% CI: 1.134?4.223, P = 0.02; OR = 1.86, 95% CI: 1.112?3.11, P = 0.018, respectively). In contrast, acarbose use was protective against PPH (OR = 0.4, 95% CI: 0.189?0.847, P = 0.017). The decrease in blood pressure during PPH was 20?40 mmHg and the maximum was 90 mmHg. PPH usually occurred at 30?60 min after a meal and lasted 30?120 min. Conclusions These findings demonstrate that the prevalence of PPH in men aged over 80 years is significantly higher than those in men aged 65 to 80 years, and the blood pressure decline is also higher for men aged over 80 years. In addition, hypertension and age were main risk factors for PPH in the older men, which suggest that preventing and treating PPH is worthwhile.     

Meal-induced changes in splanchnic blood flow and oxygen uptake in middle-aged healthy humans

Objective. For decades, the determination of changes in splanchnic blood flow and oxygen uptake after a meal has been used in the management of patients with suspected chronic intestinal ischaemia. However, little is known about the normal meal-induced responses. The aim of the present study was therefore to measure the splanchnic blood flow and oxygen uptake before and after a standardized meal in a group of middle-aged normal volunteers. Material and methods. Splanchnic blood flow and oxygen uptake were determined at baseline and after a 3600-kJ mixed meal in 8 healthy women (50–70 years) and 10 healthy men (52–76 years). Splanchnic blood flow was measured during hepatic vein catheterization by indirect Fick principle with indocyanine green as the indicator. Splanchnic oxygen uptake was calculated from splanchnic blood flow and the arteriovenous oxygen difference. Results. The meal induced a significant peak increase in splanchnic blood flow of 0.60 (0.26–1.07) l×min^?1 (mean, range) from a baseline level of 1.05 (0.66–1.33) l×min^?1. Splanchnic oxygen uptake showed a significant peak increase of 1.40 (0.44–4.13) mmol×min^?1 from a baseline level of 2.18 (1.41–3.31) mmol×min^?1. A close association was found between the meal-induced peak increases in splanchnic blood flow and oxygen uptake, but the variables were not related to gender or body surface area of the subjects. Conclusions. A 3600-kJ mixed meal induces a significant increase in splanchnic blood flow and oxygen uptake in middle-aged healthy humans. Our data may be relevant for the evaluation of corresponding data from patients with suspected chronic intestinal ischaemia.     

Postprandial splanchnic haemodynamic changes in patients with liver cirrhosis and patent paraumbilical vein

OBJECTIVE: The haemodynamic changes induced by a meal on collateral vessels in portal hypertensive cirrhotic patients are not well characterized. We aimed to study the postprandial modifications of splanchnic circulation in patients with a patent paraumbilical vein (PUV). METHODS: We studied 10 cirrhotic patients with patent PUV and 10 matched cirrhotic patients without PUV, by using echo colour Doppler at baseline and 15, 30 and 45 min after a standard mixed liquid meal (400 ml; 600 kcal). Calibre and blood flow velocities of the superior mesenteric artery, portal vein and PUV were obtained; congestion index of portal vein, portal blood flow, paraumbilical blood flow and effective portal liver perfusion were calculated; intrahepatic and intrasplenic arterial resistance and pulsatility indexes were recorded. RESULTS: We observed a postprandial splanchnic hyperaemia (superior mesenteric artery and portal vein blood flow increased after the meal in both groups; ANOVA P < 0.05), with no changes of hepatic impedance. In PUV patients, PUV constricted significantly postprandially, maximally at 30 min (calibre -17.5 +/- 7.0%; P = 0.003). Intrasplenic impedance, which may reflect portal pressure, increased, maximally at 30 min (pulsatility index +22.6 +/- 27.0%; P = 0.01), and inversely correlated with PUV vasoconstriction (R = 0.75, P = 0.01). In non-PUV patients intrasplenic impedance did not change. Portal liver perfusion increased similarly in both groups. CONCLUSIONS: PUV constricts after the meal, and this vasoconstriction is associated with an increase of splenic impedance which may indicate the postprandial increase of portal pressure observed in cirrhosis. The increase in postprandial portal liver perfusion in the PUV group is allowed by a paradox constriction of the collateral vessel.     

Gastric Relaxation in Response to a Soup Meal in Healthy Subjects A Study Using a Barostat in the Proximal Stomach

Background: Meal-induced relaxation of the proximal stomach can be investigated by means of a barostat. Using a standard liquid meat soup that elicits symptoms and a wide antrum in patients with functional dyspepsia, we aimed at finding the best meal size and fat load for studying gastric relaxation. Method: In the first trial 200ml and 500 ml meat soup (1 g fat/200 ml) was given to six healthy individuals. In the second trial a constant volume of soup (200ml) containing graded amounts of fat (1, 10, and 20g/200ml) was given to seven healthy individuals. Gastric relaxation was investigated for 1 h after consumption of the soup. A sagittal cross-sectional antral area was assessed ultrasonographically every 10min, and abdominal discomfort was scored. Results: Overall, a positive response (volume increase of 30 ml or more within 5 min after consumption of the meal) was found in 26 of 30 (87%) investigations. Individual maximal responses ranged from 38 to 482 ml (mean, 180 ml ± 128). Area under the time-volume curve (AUC) was similar after 200 and 500 ml soup (mean, 100 ml/30 min and 107 ml/ 30 min, respectively). AUC increased with increasing fat content, with a significant difference between the low-fat and high-fat meal (p < 0.05). The barostat bag induced fed-state antral contractions in most individuals (p < 0.001). There was a negative correlation between AUC and postprandial abdominal discomfort (p = 0.04). Conclusions: The barostat is a sensitive technique for detecting gastric relaxation, also in response to our standard meat soup meal. The postprandial relaxation response in healthy individuals is dependent on the fat content of the meal. The barostat bag may alter gastric motor activity. Abdominal discomfort after soup ingestion may be related to poor gastric relaxation.     

Effects of glucagon on systemic and splanchnic circulation in conscious rats with biliary cirrhosis

To elucidate the relationship between the haemodynamic changes and glucagon in cirrhosis, we infused physiologic and supraphysiologic doses of this hormone in conscious rats with portal hypertension due to biliary cirrhosis. Cardiac output and splanchnic organ blood flows were measured by the radioactive microsphere method before and 30 min after glucagon infusion at doses of 2, 5 and 10 ng/min. Serum glucagon increased from a basal level of 92 +/- 17 pg/ml (mean +/- S.E.) to 399 +/- 89, 1151 +/- 136 and 2064 +/- 328 pg/ml, respectively, in sham-operated rats, and from 743 +/- 75 pg/ml to 1497 +/- 197, 1583 +/- 356 and 2957 +/- 649 pg/ml, respectively, in cirrhotic animals at 2, 5 and 10 ng/min doses. In both groups, cardiac output did not change after glucagon infusion at 2 and 5 ng/min doses, suggesting that factors other than glucagon are primarily responsible for the systemic hyperdynamic circulation in cirrhosis. Portal tributary blood flow increased significantly after glucagon infusion in sham-operated rats by 34 and 65% at doses of 5 ng/ml and 10 ng/ml, respectively, and in cirrhotic rats by 29% at a dose of 10 ng/ml. However, portal tributary blood flow did not change after glucagon infusion at the physiologic dose of 2 ng/min. This study shows that glucagon infused at a physiologic dose does not increase splanchnic blood flow, although it increases portal tributary blood flow at supraphysiologic doses. The discrepancy between blood glucagon levels and splanchnic haemodynamic responses suggests that glucagon plays only a minor role and that other factors are primarily responsible for the hyperdynamic state of the splanchnic circulation in rats with biliary cirrhosis.     

Effects of lipase inhibition on gastric emptying of,and on the glycaemic,insulin and cardiovascular responses to,a high-fat/carbohydrate meal in type 2 diabetes

Aims/hypotheses We examined the effects of lipase inhibition with orlistat on (i) gastric emptying of, and (ii) the glycaemic, glucagon-like peptide-1 (GLP-1) and cardiovascular responses to, a high-fat/carbohydrate meal in type 2 diabetic patients.Methods Eight type 2 diabetic patients, who were aged 62 years (median range: 49–68 years) and managed by diet alone, consumed a meal containing 65 g powdered potato, 20 g glucose reconstituted with 200 ml water (labelled with 20 MBq ^99mTc-sulphur-colloid) and 45 g margarine. They did this on two separate occasions, with and without 120 mg orlistat, and while in the seated position with their back against a gamma camera. Venous blood samples for measurement of blood glucose, plasma insulin and GLP-1 were obtained immediately before the meal and at regular intervals afterwards. Blood pressure (systolic and diastolic) and heart rate were measured using an automated device.Results Gastric emptying of the meal was faster after orlistat than without orlistat (50% emptying time [mean ± SEM], 61±8 min vs 98±5 min; p=0.0001). In the first 60 min after the meal blood glucose (p=0.001) and plasma insulin (p=0.01) concentrations were higher in patients who had taken orlistat; between 60 and 180 min plasma GLP-1 (p=0.02) concentrations were lower after orlistat than without orlistat. Between 0 and 30 min systolic blood pressure (p=0.003) was lower, and heart rate (p=0.03) greater in subjects who had taken orlistat than in those who had not.Conclusions/interpretation Inhibition of fat digestion by orlistat may—as a result of more rapid gastric emptying—exacerbate postprandial glycaemia and the postprandial fall in blood pressure in patients with type 2 diabetes after ingestion of meals containing fat and carbohydrate.Conflict of Interest: None of the authors have a conflict of interest in relation to this study.     

Effect of Beta-adrenergic Blockade on Elevated Arterial Compliance and Low Systemic Vascular Resistance in Cirrhosis

Background: Patients with cirrhosis exhibit a characteristic hyperdynamic circulation with increased cardiac output and heart rate and reduced systemic vascular resistance. The compliance of the arterial tree has recently been reported to be increased in these patients, who are often treated with beta-blockers, but the effect of this treatment on arterial compliance has not been investigated. The aim of the present study was therefore to assess the effects of propranolol on the arterial compliance of patients with cirrhosis. Methods: Twenty patients with cirrhosis underwent a haemodynamic investigation with determination of splanchnic and systemic haemodynamics. Arterial compliance was determined as the ratio of the stroke volume to the pulse pressure and compared to normal values. Results: All the patients had significant portal hypertension, with a mean hepatic venous pressure gradient (HVPG) of 17.8 mmHg, and responded to beta-blocker treatment with a significant reduction in the HVPG (-16%; P &lt; 0.001). Arterial compliance was elevated (1.27 versus controls 1.01 ml/mmHg; P     

Postprandial hypotension in elderly subjects: spectral analysis of heart rate variability and electrogastrograms

Background. In order to clarify the mechanism of postprandial hypotension in the elderly, the influence of gastric motility and autonomic nervous activity on hypotensive reactions after meals was investigated, using electrogastrograms (EGGs) and spectral analysis of heart rate variability. Methods. EGGs, heart rate variability, blood pressure, and blood catecholamine levels before and after a meal were measured in 20 healthy young subjects (mean age, 25.6 ± 5.6 years; young group) and in 20 healthy elderly subjects (mean age, 78.3 ± 5.6 years; elderly group). Results. In the analy-sis of heart rate variability, no significant changes were observed in the low-frequency component (LF power), high-frequency component (HF power), or LF/HF ratio after the meal in the young group. In the other hand, the LF/HF ratio was significantly increased after the meal in the elderly group. In the EGG analysis, the peak power amplitudes after the meal were significantly increased compared with those before the meal in both groups. After the meal, the peak power amplitudes in the young group were significantly greater than those in the elderly group. The baseline blood noradrenaline level (before the meal) was higher in the elderly group than in the younger group, but the level of this catecholamine in the elderly group did not increase significantly after the meal. Conclusions. It is suggested that the down-regulation of catecholamine may be one of the causes of postprandial hypotension in the elderly. The response to secreted catecholamine and the compensatory response to decreased blood flow in the systemic circulation were impaired in the elderly group, which finding may explain the high incidence of postprandial hypotension in the elderly subjects. Received: January 9, 2001 / Accepted: August 10, 2001     

Variations in postprandial ghrelin status following ingestion of high-carbohydrate, high-fat, and high-protein meals in males

AIM: The purpose of this study was to investigate the response of postprandial acylated ghrelin to changes in macronutrient composition of meals in healthy adult males. METHODS: A randomized crossover study was performed. Ten healthy adult males were recruited. All subjects received, on separate occasions, a high-carbohydrate (HC), a high-fat (HF), and a high-protein (HP) meal. Blood samples were collected before and 15, 30, 60, 120, and 180 min following the ingestion of each meal. Plasma acylated ghrelin as well as serum insulin, glucose, and triglycerides were measured. RESULTS: The levels of acylated ghrelin fell significantly following the three meals. The HC meal induced the most significant decrease in postprandial ghrelin secretion (-15.5 +/- 2.53 pg/ml) as compared with HF (-8.4 +/- 2.17 pg/ml) and HP (-10.0 +/- 1.79 pg/ml) meals (p < 0.05). However, at 180 min, the HP meal maintained significantly lower mean ghrelin levels (29.7 +/- 3.56 pg/ml) than both HC (58.4 +/- 5.75 pg/ml) and HF (45.7 +/- 5.89 pg/ml) meals and lower levels than baseline (43.4 +/- 5.34 pg/ml) (p <0.01). The postprandial insulin levels increased to significantly higher levels following the HC meal (+80.6 +/- 11.14 microU/ml) than following both HF (37.3 +/- 4.82 microU/ml) and HP (51.4 +/- 6.00 microU/ml) meals (p < 0.001). However, at 180 min, the mean insulin levels were found to be significantly higher following the HP meal (56.4 +/- 10.80 microU/ml) as compared with both HC (30.9 +/- 4.31 microU/ml) and HF (33.7 +/- 4.42 microU/ml) meals (p < 0.05). Acylated ghrelin was also found to be negatively correlated with circulating insulin levels, across all meals. CONCLUSIONS: These results indicate that the nutrient composition of meals affects the extent of suppression of postprandial ghrelin levels and that partial substitution of dietary protein for carbohydrate or fat may promote longer-term postprandial ghrelin suppression and satiety. Our results also support the possible role of insulin in meal-induced ghrelin suppression.     

Influence of gender on proximal gastric motor and sensory function

OBJECTIVE: Gender-related differences have been demonstrated with regard to GI motility: gallbladder contraction, colonic transit, and gastric emptying are delayed in women. It is not known whether gender influences proximal gastric motility and perception. METHODS: We have studied the influence of gender on proximal gastric motility and perception under fasting and postprandial conditions by retrospective analysis of data obtained in 99 healthy volunteers (42 men, 57 women) who participated in barostat studies performed according to standardized protocols at the Leiden University Medical Center (Leiden, The Netherlands) between 1996 and 2000. RESULTS: Minimal distending pressure (MDP) was significantly higher in women than in men (respectively, 6.8+/-0.2 vs 5.5+/-0.2 mm Hg; p < 0.001). During stepwise pressure distensions pressure-volume curves were similar in both sexes after correction for MDP, whereas perception of fullness and abdominal pressure increased significantly (p < 0.05) more rapidly in women. Before the meal intragastric volumes (at MDP + 2 mm Hg) did not differ between sexes. After the meal gastric relaxation in the first 30 min did not differ in women and men (respectively, 186+/-23 ml and 140+/-32 ml). However, from 30 until 90 min after the meal a significantly (p < 0.05) delayed return of intragastric volume to basal was seen in women. Perception of postprandial nausea was significantly (p < 0.01) increased in women. Perception of postprandial fullness remained increased for a longer period of time in women. CONCLUSIONS: Proximal gastric motility and perception are influenced by gender. Gender-related differences in postprandial proximal gastric motility and perception should be taken into account in barostat studies comparing patients with controls.     

The Splanchnic Circulation and Postural Hypotension in Diabetic Autonomic Neuropathy

Postural hypotension results from sympathetic failure to cause superior peripheral vasoconstriction. The importance of the splanchnic circulation was studied by measuring mesenteric artery blood flow with duplex Doppler scanning. Nine normal and 9 Type 1 diabetic controls were compared to 8 Type 1 patients with autonomic neuropathy whose pressure fell 40–113 mmHg (range) on tilting. Measurements were made supine and after vertical tilt, fasting without insulin and after a 550 kcal meal. Superior mesenteric artery diameter decreased on tilting in normal controls but not in diabetic control or neuropathy groups (supine vs tilted: controls. 6.3 ± 0.9 to 5 ± 0.9 mm, p = 0.004, diabetic controls: 6.0 ± 0.6 to 6.0 ± 1.0 mm, and neuropathy group: 6.4 ± 0.9 to 5.6 ± 0.9 mm), but proportional blood flow changes were similar in all subjects (controls: 407 ± 154 to 255 ± 67 ml min^?1 (-31%, p = 0.03), diabetic controls: 379 ± 140 to 306 ± 149 ml min^?1 (-8%, p = 0.28), neuropathy group: 639 ± 371 to 435 ± 142 ml min^?1 (-23%, p = 0.10). Postprandially supine superior mesenteric artery flow increased in all subjects but this did not affect the degree of systolic blood pressure drop on tilting (fasting vs postprandial blood flow: controls: 407 ± 154 to 775 ± 400 ml min^?1 (p = 0.04), diabetic controls: 379 ± 140 to 691 ± 262 ml min^?1 (p = 0.01), neuropathy group: 639 ± 371 to 943 ± 468 ml min^?1 (p < 0.06)). The similarity of superior mesenteric artery responses to tilting in the three groups, and the lack of exacerbation of postural hypotension in the presence of postprandial hyperaemia indicates that control of splanchnic blood flow is less important in the aetiology of diabetic autonomic postural hypotension than previously thought.     

Effects of ursodeoxycholic acid on splanchnic and systemic hemodynamics. A double-blind, cross-over, placebo-controlled study in healthy volunteers

BACKGROUND: Recently, the beneficial effects of ursodeoxycholic acid (UDCA) on the portal hypertensive state have been demonstrated in patients with primary biliary cirrhosis. However, it is not known whether UDCA has direct or indirect effects on the vascular smooth muscles in humans, thereby leading to a change in splanchnic or systemic hemodynamics. AIMS: We therefore evaluated the hemodynamic effects of UDCA as to its established effect on gallbladder motility under fasting and postprandial conditions in healthy volunteers. METHODS: In a double-blind, cross-over study of 20 healthy volunteers, placebo or UDCA (750 mg/d) were randomly administered over 4 weeks with an interim 4-week washout period. Portal blood flow, cardiac output and gallbladder motility were measured using echo-Doppler and b-mode sonography before and after placebo and verum, respectively. ECG, blood pressure, heart rate and blood chemistry were also measured. RESULTS: UDCA did not significantly change fasting portal flow or meal-induced portal hyperemia. Both fasting and postprandial gallbladder volumes increased (26.5 +/- 6.0 vs. 40.7 +/- 13.8 ml, p < 0.05, and 11.2 +/- 6.2 vs. 14.8 +/- 6.7 ml, p < 0.05). Diastolic blood pressure decreased under UDCA (71.2 +/- 8.7 vs. 66.5 +/- 6.5 mm Hg, p < 0.05). Serum levels of chloride and gamma-glutamyltransferase decreased slightly, while alkaline phosphatase increased. CONCLUSIONS: UDCA affected systemic but not portal hemodynamics. The increase in gallbladder volume is obviously mediated by factors that do not influence the splanchnic vascular bed.     

The cardiovascular risk profile of atherosclerotic gastrointestinal ischemia is different from other vascular beds

BackgroundThe distribution of cardiovascular risk factors in patients with chronic gastrointestinal ischemia due to atherosclerosis of the splanchnic vessels (chronic splanchnic syndrome) is not well studied. The aim of this study was to determine the cardiovascular risk factor pattern in patients with chronic splanchnic syndrome.MethodsFrom April 2003 to September 2007, atherosclerotic risk factors in consecutive patients with chronic splanchnic syndrome were compared prospectively with the general atherosclerotic risk profile in Western Europe and worldwide risk profile of coronary heart disease, peripheral artery disease, and cerebral vascular disease.ResultsOf 376 analyzed patients, 97 were diagnosed with chronic splanchnic syndrome. Data from 90 patients were available for analysis (7 were excluded because of incomplete data). Mean age was 63 years (range 28-86 years), and 74% were female. Fifty-nine percent of the patients had atherosclerotic disease in other vascular beds. Smoking was reported in 57%, and increased bodyweight in 21%. Hypercholesterolemia was present in 53%, hypertension in 62%, and diabetes in 21%.ConclusionsThe atherosclerotic risk profile in patients with chronic splanchnic syndrome differed from other atherosclerotic diseases with a female preponderance, lower incidence of obesity/increased bodyweight, diabetes, hypertension, and hypercholesterolemia. Reduced caloric intake, related to the postprandial pain, may explain the observed differences.     

Increased splanchnic arterial vascular resistance in oldest old patients

OBJECTIVES: The aim of this study was to evaluate possible age-related changes in mesenteric artery and portal venous blood flow dynamics in relation to systemic haemodynamics in order to delineate putative haemodynamic changes relevant for postprandial hypotension in the elderly. Studies were performed over a wide age-range and for the first time in over 85-year-old patients. DESIGN: Superior mesenteric artery (SMA) parameters (diameter, peak systolic velocity, end diastolic velocity, pulsatility index, volume flow) and portal vein (PV) parameters (diameter, portal vein velocity, volume flow) were measured by duplex ultrasound (General Electrics, Vivid 3) in 98 fasting subjects aged from 21 to 96 years. Systemic vascular parameters such as blood pressure, heart rate and cardiac output (echocardiography) were also determined. Excluded were patients with severe heart failure, liver cirrhosis, sepsis and those with mesenteric artery stenosis. RESULTS: Pulsatility index (PI) was positively correlated with age (r=0.33, p=0.015). In patients over 85 years, PI was significantly increased (p=0.002) as compared to younger controls. Cardiac output was negatively correlated with age (r=-0.247, p=0.005). The other haemodynamic parameters did not show age-dependent alterations. CONCLUSION: The increase of PI in the SMA in patients over 85 years represents an increase of vascular resistance in the splanchnic area, because PI is sensitive to resistance changes of small arterial vessels. The pulsatility index in the splanchnic area seems to rise steeply in oldest old patients, probably as an attempt to compensate diminutions in cardiac output seen in this age group. These findings indicate that the splanchnic vascular bed is already used in the fasting state to guarantee systemic haemodynamics. Vasodilatation of this vascular bed as physiologically seen postprandially may therefore easily induce postprandial hypotension in the oldest old.     

Insulin-induced hypoglycaemia increases plasma concentrations of angiotensin II and does not modify atrial natriuretic polypeptide secretion in man

Summary Insulin-induced hypoglycaemia causes profound haemodynamic changes, commonly ascribed to catecholamine increase. The aim of the present study was to investigate the influence of insulin-induced hypoglycaemia on nonadrenergic factors potentially involved in haemodynamic regulation: angiotensin II and alpha-human atrial natriuretic polypeptide. Fourteen healthy male subjects, aged 25.5±0.74 years, body mass index 23.81±0.68 kg/m², received (after an overnight fast and at least 60 min rest in a supine position) an i.v. bolus injection of human regular insulin (Actrapid HM, Novo, Bagsvaerd, Denmark: 3.84 U/m²). Serial venous blood samples were drawn in the following 150 min, to measure plasma glucose, angiotensin II, alpha-human natriuretic polypeptide, and factors potentially involved in the regulation of the renin-angiotensin-aldosterone system. During the study, we observed a plasma glucose fall, reaching a nadir of 1.95±0.11 mmol/l between 25 and 30 min, and an increase of angiotensin II (from 7.6±0.8 to 13.5±1.1 pg/ml, p = 0.01, quadratic model evaluated by an analysis of the variance for repeated measures), whereas atrial natriuretic polypeptide remained unchanged. As far as the regulation of the renin-arigiotensin-aldosterone system is concerned, the increase of angiotensin II is attributable to the increased plasma renin activity, whereas angiotensin converting enzyme was not modified. The increase of plasma renin activity, in turn, is attributable both to the increased catecholamine concentrations and to the decreased potassium levels. Both adrenocorticotropic hormone and angiotensin II are potentially involved in the hypoglycaemia-induced increase of aldosterone concentrations.     

Circulating nitric oxide products do not solely reflect nitric oxide release in cirrhosis and portal hypertension

Background: Patients with cirrhosis often develop a systemic vasodilatation and a hyperdynamic circulation with activation of vasoconstrictor systems such as the renin–angiotensin–aldosterone system (RAAS), and vasopressin. Increased nitric oxide (NO) synthesis has been implicated in the development of this state of vasodilation and pulmonary dysfunction including increased exhaled NO concentrations. Circulating metabolites (NO_x) may affect the systemic and pulmonary NO‐generation. However, the relations of these abnormalities to the haemodynamic changes remain unclear. Aims: The aims of the present study were to measure changes in exhaled NO in relation to circulating NO_x, RAAS, and haemodynamics. Methods: Twenty patients (eight child class A and 12 class B patients) underwent a liver vein catheterization with determination of splanchnic and systemic haemodynamics. Circulating NO_x and exhaled NO were determined in the supine and sitting positions and related to haemodynamics, RAAS and lung diffusing capacity (D_LCO). Eight matched healthy individuals served as controls. Results: All patients with cirrhosis had portal hypertension. We found no significant difference in exhaled NO between patients and controls and no changes from the supine to the sitting position. Exhaled NO in the patients correlated significantly with plasma volume, heart rate and D_LCO. NO_x concentrations were not significantly increased in the patients. NO_x correlated with portal pressure and haemodynamic indicators of vasodilatation, but not with exhaled NO concentrations. Conclusion: In patients with moderate cirrhosis, exhaled NO is normal. Circulating NO_x do not seem to reflect pulmonary and systemic NO release, but NO_x seems to reflect systemic and splanchnic haemodynamic changes in cirrhosis.     

Subtotal hepatectomy in swine for studying small-for-size syndrome and portal inflow modulation: is it reliable?

BackgroundSmall-for-size syndrome (SFSS) is a feared complication of extended liver resection and partial liver transplantation. Swine models of extended hepatectomy have been developed for studying SFSS and its different treatment options. Although portal inflow modulation (PIM) by splenectomy or splenic artery ligation (SAL) has been proposed in humans to prevent SFSS, such procedures have not yet been evaluated in swine.ObjectivesThe present study was designed to evaluate modifications in splanchnic haemodynamics yielded by extended hepatectomy with and without PIM in swine.MethodsNineteen animals underwent 70% hepatectomy (H70, n = 7), 90% hepatectomy (H90, n = 7) or sham laparotomy (H0, n = 5). Haemodynamic measurements were performed at baseline, after hepatectomy and after PIM by SAL and splenectomy.ResultsPortal vein flow increased after both H70 (273 ml/min/100 g versus 123 ml/min/100 g; P = 0.016) and H90 (543 ml/min/100 g versus 124 ml/min/100 g; P = 0.031), but the hepatic venous pressure gradient (HVPG) increased only after H90 (10.0 mmHg versus 3.7 mmHg; P = 0.016). Hepatic artery flow did not significantly decrease after either H70 or H90. In all three groups, neither splenectomy nor SAL induced any changes in splanchnic haemodynamics.ConclusionsSubtotal hepatectomy of 90% in swine is a reliable model for SFSS inducing a significant increase in HVPG. However, in view of the relevant differences between swine and human splanchnic anatomy, this model is inadequate for studying the effects of PIM by SAL and splenectomy.