82Rb and [15O]H2O myocardial perfusion PET imaging: a prospective head to head comparison.

BACKGROUND: 82Rb PET and [15O]H2O PET are both validated tracers for myocardical perfusion imaging but have not previously been compared clinically. During our site's transition from 82Rb to [15O]H2O PET, we performed a head-to-head comparison in a mixed population with suspected ischemic heart disease. METHODS: A total of 37 patients referred for perfusion imaging due to suspicion of coronary stenosis were examined with both 82Rb and [15O]H2O PET on the same day in rest and during adenosine-induced stress. The exams were rated by two blinded readers as normal, regional ischemia, globally reduced myocardial perfusion, or myocardial scarring. For [15O]H2O PET, regional ischemia was defined as two neighboring segments with average stress perfusion ≤ 2.3 mL/(min·g). Further, we evaluated a total perfusion deficit (TPD) of ≥ 10% as a more conservative marker of ischemia. RESULTS: [15O]H2O PET identified more patients with regional ischemia: 17(46%) vs 9(24%), agreement: 59% corresponding to a Cohen's kappa of .31 [95%CI .08-.53], (P < .001). Using the more conservative TPD ≥ 10%, the agreement increased to 86% corresponding to a kappa of .62 [95%CI .33-.92], (P = .001). For the subgroup of patients with no known heart disease (n = 18), the agreement was 94%. Interrater agreement was 95% corresponding to a kappa of .89 [95%CI .74-1.00] (P < .001). CONCLUSIONS: In clinical transition from 82Rb to [15O]H2O PET, it is important to take into account the higher frequency of patients with regional ischemia detected by [15O]H2O PET.

Gastric Emptying Is Not Delayed and Does Not Correlate With Attenuated Postprandial Blood Flow Increase in Medicated Patients With Early Parkinson's Disease.

Background: We have recently used phase-contrast magnetic resonance imaging (PC-MRI) to demonstrate an attenuated postprandial blood flow response in the superior mesenteric artery (SMA) in 23 medicated patients with Parkinson's disease (PD) compared to 23 age- and sex-matched healthy controls. Objective: To investigate in a sub-sample of the original cohort whether the observed blood flow response in SMA after oral food intake is related to a delay in gastric emptying. Methods: We studied 15 patients with PD in an "ON-medication" state with a mean disease duration of 3.9 ± 2.2 years and 15 healthy age- and sex-matched individuals. Participants underwent dynamic gastric scintigraphy 0, 30, 60, 120, 180 and 240 minutes after the intake of a standardized radiolabeled test meal. Gastric emptying was compared between groups. 14 of the 15 PD patients and 12 of the 15 healthy control subjects had previously undergone serial postprandial PC-MRI measurements. In these individuals, we tested for a relationship between gastric emptying and postprandial blood flow response in the SMA. Results: The dynamics of gastric emptying did not differ between groups (p = 0.68). There was substantial inter-subject variability of gastric emptying in PD patients and healthy participants. Only a single PD patient had delayed gastric emptying. In those participants who had undergone PC-MRI, postprandial increase in SMA blood flow was attenuated in PD compared to healthy controls as reported previously (p = 0.006). Gastric emptying did not correlate with the timing and amplitude of postprandial blood flow increase in SMA. Conclusion: Our preliminary results, obtained in a small group of early-stage PD patients who continued their usual dopamine replacement therapy, suggest that variations in gastric emptying after solid meal intake is within the normal range in the majority of cases. There is also no evidence for a tight relationship between the attenuated postprandial blood flow response in the SMA and normal variations in gastric emptying.

Bilio-enteric flow and plasma concentrations of bile acids after gastric bypass and sleeve gastrectomy.

BACKGROUND/OBJECTIVES: Bile acids in plasma are elevated after bariatric surgery and may contribute to metabolic improvements, but underlying changes in bile flow are poorly understood. We assessed bilio-enteric flow of bile and plasma bile concentrations in individuals with Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with matched non-surgical controls (CON). SUBJECTS/METHODS: Fifteen RYGB, 10 SG and 15 CON underwent 99Tc-mebrofenin cholescintigraphy combined with intake of a high-fat 111In-DTPA-labelled meal and frequent blood sampling. A 75Se-HCAT test was used to assess bile acid retention. RESULTS: After RYGB, gallbladder filling was decreased (p = 0.045 versus CON), basal flow of bile into the small intestine increased (p = 0.005), bile acid retention augmented (p = 0.021) and basal bile acid plasma concentrations elevated (p = 0.009). During the meal, foods passed unimpeded through the gastric pouch resulting in almost instant postprandial mixing of bile and foods, but the postprandial rise in plasma bile acids was brief and associated with decreased overall release of fibroblast growth factor-19 (FGF-19) compared with CON (p = 0.033). After SG, bile flow and retention were largely unaltered (p > 0.05 versus CON), but gastric emptying was accelerated (p < 0.001) causing earlier mixture of bile and foods also in this group. Neither basal nor postprandial bile acid concentrations differed between SG and CON. CONCLUSIONS: Bilio-enteric bile flow is markedly altered after RYGB resulting in changes in plasma concentrations of bile acids and FGF-19, whereas bile flow and plasma concentrations are largely unaltered after SG.

Effect of Glepaglutide, a Long-Acting Glucagon-Like Peptide-2 Analog, on Gastrointestinal Transit Time and Motility in Patients With Short Bowel Syndrome: Findings From a Randomized Trial.

BACKGROUND: Patients with short bowel syndrome (SBS) and distal-bowel resections lack neuroendocrine feedback regulations, potentially resulting in rapid gastrointestinal (GI) transit. The objective was to assess the efficacy of glepaglutide, a long-acting glucagon-like peptide-2 analog, on GI transit in patients with SBS. METHODS: In this single-center, double-blind, dose-finding, phase 2 trial, patients with SBS were randomly assigned to 3 treatments (0.1, 1, and 10 mg) in a 2-period crossover design. Each treatment period included 3 weeks of daily, subcutaneous glepaglutide injections separated by a washout period of 4-8 weeks. Endpoints were changes from baseline and included scintigraphy, wireless motility capsule (WMC, SmartPill Given Imaging, Ltd, Yokneam, Israel), and paracetamol absorption test. RESULTS: A total of 18 patients were randomized. In the 10-mg dose group (n = 9), glepaglutide significantly increased time to 10% gastric emptying (GE) of solids by 27 (4-50) minutes (adjusted mean [95% CI]), time to 50%GE of fluids by 40 (1-80) minutes, and time to 10% small bowel-emptying of solids by 21 (1-41) minutes. The WMC transit did not significantly change in any of the dose groups. The maximum paracetamol concentration significantly increased in the 10-mg dose group; however, the area under the curve remained the same. CONCLUSION: The prolonged GI transit after glepaglutide treatment, along with demonstrated positive effects on intestinal mucosal growth and potential effects on GI hypersecretions, is believed to contribute to the observed beneficial effects on fecal output (primary endpoint) and associated improvement in intestinal absorption.

Glepaglutide, a novel long-acting glucagon-like peptide-2 analogue, for patients with short bowel syndrome: a randomised phase 2 trial.

BACKGROUND: Patients with short bowel syndrome might have impaired postprandial endogenous glucagon-like peptide-2 (GLP-2) secretion, which is required for optimal intestinal adaptation. We aimed to assess the therapeutic potential of glepaglutide, a novel long-acting GLP-2 analogue, for reducing faecal output and increasing intestinal absorption in patients with short bowel syndrome. METHODS: In this single-centre, double-blind, crossover, randomised phase 2 trial, adults (aged ≥18 to ≤90 years) with short bowel syndrome and with a faecal wet weight output of 1500 g/day or more were randomly assigned to receive one of six dose sequences of glepaglutide (10 mg, 1 mg; 10 mg, 0·1 mg; 1 mg, 10 mg; 1 mg, 0·1 mg; 0·1 mg, 10 mg; or 0·1 mg, 1 mg). Patients received daily subcutaneous injections of the first assigned dose of glepaglutide for 3 weeks, followed by a washout period of 4-8 weeks, and then the second dose of glepaglutide for 3 weeks. An unmasked statistician generated the randomisation list, and the trial investigator enrolled patients and assigned them their patient numbers. Trial investigators, patients, and other care providers were masked throughout the trial. The primary endpoint was the absolute change from baseline in faecal wet weight output, measured separately over the two treatment periods. Metabolic balance studies were done before and after each treatment period to assess the primary endpoint. Per-protocol analysis was used to assess the efficacy. Safety analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT02690025, and has completed. FINDINGS: Of the 22 patients screened between Feb 5, 2016, and Jan 25, 2017, 18 patients were randomly assigned and treated with glepaglutide; 16 patients completed the trial. Treatment with 1 mg and 10 mg glepaglutide changed the adjusted mean faecal output by -592 g/day (95% CI -913 to -272; p=0·002) and -833 g/day (-1152 to -515; p=0·0002) from baseline, respectively. No changes were observed with 0·1 mg glepaglutide. Of the 18 patients who were randomly assigned to treatment, common treatment-related adverse events were stoma complications (13 [72%] patients), injection site reactions (11 [61%]), peripheral oedema (ten [56%]), nausea and abdominal pain (eight [44%] each), polyuria and fatigue (six [33%] each), abdominal distention, vomiting, and dizziness (five [28%] each); and cough and decreased appetite (four [22%] each). Related or possibly related serious adverse events were reported in two patients in the 0·1 mg dose group and two patients in the 10 mg dose group. These events included abdominal pain, stoma obstruction, catheter-related sepsis, and infection of unknown origin. No patients died during the trial. INTERPRETATION: Glepaglutide was well tolerated, and was associated with improved intestinal absorption in patients with short bowel syndrome with 1 mg and 10 mg glepaglutide, but not with 0·1 mg glepaglutide. Larger phase 3 clinical trials of longer durations have been initiated to fully assess the safety and efficacy of glepaglutide. FUNDING: Zealand Pharma.

Gastrointestinal motility in patients with end-stage renal disease on chronic hemodialysis.

BACKGROUND: Previous studies indicated delayed gastric emptying in patients with end-stage renal disease (ESRD) using indirect methods. The objective of the current study was to examine gastrointestinal motility using a direct method as well as the role of the incretin hormones and glucagon. METHODS: Patients on chronic hemodialysis and with either normal glucose tolerance, impaired glucose tolerance or type 2 diabetes, and healthy control subjects (N = 8, respectively) were studied. Gastric emptying time was measured by repeated gamma camera imaging for 6 hours after intake of a radioactive labeled standardized mixed solid and liquid meal. Glucagon, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) levels were measured. KEY RESULTS: Patients were age, gender and BMI matched with controls. We found significantly higher gastric retention at 15 minutes, prolonged gastric mean emptying time, and gastric half-emptying time of the solid marker in all three groups of ESRD patients compared to controls. Significant differences in mean total area under the concentration curve (AUC) values across the four groups for GIP (P = 0.001), but not for GLP-1 and glucagon. The ESRD group had significant higher total AUC of GIP and glucagon compared to controls (P < 0.001 and P < 0.04) but not for GLP-1 (P = 0.4). No difference in incremental AUC was found. CONCLUSIONS AND INFERENCES: We found altered gastrointestinal motility in dialysis patients, with higher gastric retention and prolonged gastric emptying, and higher total AUC of GIP and glucagon independent of the presence of diabetes or prediabetes.

Gastrointestinal motility, gut hormone secretion, and energy intake after oral loads of free fatty acid or triglyceride in older and middle-aged men.

In young individuals, oral free fatty acid delays gastric emptying, promotes gut hormone release, and reduces energy intake more than an isocaloric load of triglyceride does. The objective of this study was to compare the effects of the free fatty acid oleic acid (OA) and the triglyceride olive oil (OO) on gastrointestinal motility, gut hormone secretion, and energy intake in older and middle-aged healthy volunteers. In a double-blind, randomized, cross-over, study 10 older (age 83.0 ±â€¯3.4 (mean ±â€¯SD) years) and 10 middle-aged (age 43.1 ±â€¯8.9 years) men were examined on two occasions to evaluate the effect of isocaloric and isovolaemic loads of radiolabelled OA or OO on gastric emptying, oro-caecal transit, glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) secretions, and energy intake. Gastric emptying was slower in older than in middle-aged men (lipid p < 0.001, water p = 0.010), while no difference between these groups was found for oro-caecal transit. In comparison with OO, OA caused slower gastric emptying (lipid p < 0.001, water p = 0.020) and faster oro-caecal transit (p = 0.025). Postprandial secretion of GLP-1 and PYY was comparable for older and middle-aged men, as well as for OA and OO. Older men ingested less energy than middle-aged men did (p < 0.001) and their energy intake was lower after OA than OO (p = 0.002). Thus, gastric emptying of an oral lipid load is slower in older than in middle-aged men; gastric emptying is slower and oro-caecal transit faster after OA than OO in both age groups; and older men ingest less energy than middle-aged men and less energy after OA than OO.

Energy intake, gastrointestinal transit, and gut hormone release in response to oral triglycerides and fatty acids in men with and without severe obesity.

Dietary fat, and particularly fatty acids (FAs) from hydrolyzed triglycerides (TGs), reduces appetite, whereas paradoxically, a high-fat diet leads to excess calorie intake. We therefore hypothesized that the appetite-regulating effects of FAs are perturbed in obesity. Ten men with severe obesity [median body mass index (BMI) of 51.0 kg/m2 (range of 47.9-69.0)] and 10 men without obesity [BMI of 24.6 kg/m2 (range of 21.7-26.8)] were recruited for a double-blind randomized crossover study. On two occasions, participants were given isocaloric (2,660 kJ) and isovolemic (80 ml) loads of either oleic acid (long-chain FA) or olive oil (TG) containing radiolabeled lipid and water markers. Postload scintigraphy, blood sampling, and assessment of appetite were performed for 10 h, after which an ad libitum meal was served. Compared with olive oil, oleic acid slowed gastric mean emptying time (GMET) for lipids ( P < 0.001), accelerated orocoecal transit time (OCTT; P = 0.005), increased postload cholecystokinin section ( P < 0.001), and suppressed ad libitum energy intake ( P = 0.028) in men with severe obesity, and similar effects were seen in the nonobese group (no group × lipid interactions). However, independent of lipid loads, GMET and OCTT were slower (GMETlipid P = 0.046; GMETwater P = 0.003; OCTT P = 0.001), and basal and postload secretion of glucagon-like peptide-1 (GLP-1) was attenuated ( P = 0.045 and P = 0.048, respectively) in men with severe obesity compared with men without obesity. We conclude that the more potent appetite-regulating effects of oleic acid versus olive oil are unimpaired in men with severe obesity. However, regardless of lipid formulations, severe obesity is associated with slowed gastrointestinal transit and attenuated GLP-1 secretion. NEW & NOTEWORTHY Orally ingested fatty acids more efficiently reduce appetite and energy intake than triglycerides also in men with severe obesity. Men with severe obesity have delayed gastrointestinal transit and attenuated early gut hormone responses after an oral lipid load compared with men without obesity.

Comparison of analytical methods of brain [18F]FDG-PET after severe traumatic brain injury.

BACKGROUND: Loss of consciousness has been shown to reduce cerebral metabolic rates of glucose (CMRglc) measured by brain [18F]FDG-PET. Measurements of regional metabolic patterns by normalization to global cerebral metabolism or cerebellum may underestimate widespread reductions. NEW METHOD: The aim of this study was to compare quantification methods of whole brain glucose metabolism, including whole brain [18F]FDG uptake normalized to uptake in cerebellum, normalized to injected activity, normalized to plasma tracer concentration, and two methods for estimating CMRglc. Six patients suffering from severe traumatic brain injury (TBI) and ten healthy controls (HC) underwent a 10min static [18F]FDG-PET scan and venous blood sampling. RESULTS: Except from normalizing to cerebellum, all quantification methods found significant lower level of whole brain glucose metabolism of 25-33% in TBI patients compared to HC. In accordance these measurements correlated to level of consciousness. COMPARISON WITH EXISTING METHODS: Our study demonstrates that the analysis method of the [18F]FDG PET data has a substantial impact on the estimated whole brain cerebral glucose metabolism in patients with severe TBI. Importantly, the SUVR method which is often used in a clinical setting was not able to distinguish patients with severe TBI from HC at the whole-brain level. CONCLUSION: We recommend supplementing a static [18F]FDG scan with a single venous blood sample in future studies of patients with severe TBI or reduced level of consciousness. This can be used for simple semi-quantitative uptake values by normalizing brain activity uptake to plasma tracer concentration, or quantitative estimates of CMRglc.

Effects of transjugular intrahepatic portosystemic shunt (TIPS) on blood volume distribution in patients with cirrhosis.

BACKGROUND: Cirrhosis is accompanied by portal hypertension with splanchnic and systemic arterial vasodilation, and central hypovolaemia. A transjugular intrahepatic portosystemic shunt (TIPS) alleviates portal hypertension, but also causes major haemodynamic changes. AIMS: To investigate effects of TIPS on regional blood volume distribution, and systemic haemodynamics. METHODS: Thirteen cirrhotic patients had their regional blood volume distribution determined with gamma-camera technique before and after TIPS. Additionally, we measured systemic haemodynamics during liver vein and right heart catheterization. Central and arterial blood volume (CBV) and cardiac output (CO) were determined with indicator dilution technique. RESULTS: After TIPS, the thoracic blood volume increased (+10.4% of total blood volume (TBV), p<0.01), whereas the splanchnic blood volume decreased (-11.9% of TBV, p<0.001). CO increased (+22%, p<0.0001), and systemic vascular resistance decreased (-26%, p<0.001), whereas CBV did not change. Finally, right atrial pressure and mean pulmonary artery pressure increased after TIPS (+50%, p<0.005; +40%, p<0.05, respectively). CONCLUSIONS: TIPS restores central hypovolaemia by an increase in thoracic blood volume and alleviates splanchnic vascular congestion. In contrast, CBV seems unaltered. The improvement in central hypovolaemia is therefore based on an increase in thoracic blood volume that includes both the central venous and arterial blood volume. This is supported by an increase in preload, combined with a decrease in afterload.

Gamma-variate plasma clearance versus urinary plasma clearance of 51 Cr-EDTA in patients with cirrhosis with and without fluid retention.

In patients with fluid retention, the plasma clearance of 51 Cr-EDTA (Clexp obtained by multiexponential fit) may overestimate the glomerular filtration rate (GFR). The present study was undertaken to compare a gamma-variate plasma clearance (Clgv) with the urinary plasma clearance of 51 Cr-EDTA (Clu ) in patients with cirrhosis with and without fluid retention. A total of 81 patients with cirrhosis (22 without fluid retention, 59 with ascites) received a quantitative intravenous injection of 51 Cr-EDTA followed by plasma and quantitative urinary samples for 5 h. Clgv was determined from the injected dose relative to the plasma concentration-time area, obtained by a gamma-variate iterative fit. Clexp and Clu were determined by standard technique. In patients without fluid retention, Clgv , Clexp and Clu were closely similar. The difference between Clgv and Clu (Clgv - Clu  = ΔCl) was mean -0·6 ml min-1  1·73 m-2 . In patients with ascites, ΔCl was significantly higher (11·8 ml min-1  1·73 m-2 , P<0·0001), but this value was lower than Clexp - Clu (17·5 mL min-1  1·73 m-2 , P<0·01). ΔCl increased with lower values of GFR (P<0·001). In conclusion, in patients with fluid retention and ascites Clgv and Clexp overestimates GFR substantially, but the overestimation is smaller with Clgv . Although Clu may underestimate GFR slightly, patients with ascites should collect urine quantitatively to obtain a reliable measurement of GFR.

Absorption and initial metabolism of 75Se-l-selenomethionine: a kinetic model based on dynamic scintigraphic data.

Selenomethionine (SeMet) is an important organic nutritional source of Se, but the uptake and metabolism of SeMet are poorly characterised in humans. Dynamic gamma camera images of the abdominal region were acquired from eight healthy young men after the ingestion of radioactive 75Se-l-SeMet (75Se-SeMet). Scanning started simultaneously to the ingestion of 75Se-SeMet and lasted 120 min. We generated time-activity curves from two-dimensional regions of interest in the stomach, small intestine and liver. During scanning, blood samples were collected at 10-min intervals to generate plasma time-activity curves. A four-compartment model, augmented with a delay between the liver and plasma, was fitted to individual participants' data. The mean rate constant for 75Se-SeMet transport was 2·63 h-1 from the stomach to the small intestine, 13·2 h-1 from the small intestine to the liver, 0·261 h-1 from the liver to the plasma and 0·267 h-1 from the stomach to the plasma. The delay in the liver was 0·714 h. Gamma camera imaging provides data for use in compartmental modelling of 75Se-SeMet absorption and metabolism in humans. In clinical settings, the obtained rate constants and the delay in the liver may be useful variables for quantifying reduced intestinal absorption capacity or liver function.

Gamma camera imaging for studying intestinal absorption and whole-body distribution of selenomethionine.

Se metabolism in humans is not well characterised. Currently, the estimates of Se absorption, whole-body retention and excretion are being obtained from balance and tracer studies. In the present study, we used gamma camera imaging to evaluate the whole-body retention and distribution of radiolabelled selenomethionine (SeMet), the predominant form of Se present in foods. A total of eight healthy young men participated in the study. After consumption of a meal containing 4 MBq [75Se]L-SeMet ([75Se]SeMet), whole-body gamma camera scanning was performed for 45 min every hour over a 6 h period, every second hour for the next 18 h and once on each of the subsequent 6 d. Blood, urine and faecal samples were collected to determine the plasma content of [75Se]SeMet as well as its excretion in urine and faeces. Imaging showed that 87·9 (sd 3·3)% of the administered activity of [75Se]SeMet was retained within the body after 7 d. In contrast, the measured excretion in urine and faeces for the 7 d period was 8·2 (sd 1·1)% of the activity. Time-activity curves were generated for the whole body, stomach, liver, abdomen (other than the stomach and the liver), brain and femoral muscles. Gamma camera imaging allows for the assessment of the postprandial absorption of SeMet. This technique may also permit concurrent studies of organ turnover of SeMet.

A kinetic compartment model for evaluating salivary gland scintigraphies.

PURPOSE: The semi-quantitative analysis of salivary gland scintigraphy with (99m) Tc-pertechnetate has been used to evaluate salivary gland function. However, no objective parameters distinguishing abnormal from normal functions have been established thus far. We propose using a simple kinetic model applied to the four major salivary glands. This kinetic model is based on a two-compartment model and the assumption of first-order kinetics to characterize normal salivary gland function and other selected parameters to evaluate the normal function of salivary glands. METHODS: Thirty patients referred for (99m) Tc-pertechnetate thyroid scintigraphy were studied. Dynamic imaging of the head in a fixed anterior projection was performed after an intravenous bolus injection of 150 MBq (99m) Tc-pertechnetate using a gamma scintillation camera. After 30 min, lemon juice was orally administered through a syringe. Time activity curves were generated for each of the four major salivary glands (i.e. the right and left submandibular and right and left parotid glands). Excretion fractions (the fraction of mobilizable radioactivity after administering lemon juice) and the gland activity-to-thyroid activity ratio were calculated. The data were fitted to both a one- and two-phase uptake model. RESULTS: The median uptake slope and maximal activity were significantly higher in the parotid glands than the submandibular glands (P<0·0001). The gland-to-thyroid ratio was higher in the parotid glands than the submandibular glands (P<0·0001), and the ejection fractions were higher in the parotid glands (P<0·0001). No difference was found in functional contributions of the parotid and submandibular glands. CONCLUSIONS: Tracer accumulation can be represented by a one-phase simple uptake model. The background regions that have been previously recommended in the literature are acceptable.

Arterial pressure profile in patients with cirrhosis: Fourier analysis of arterial pulse in relation to pressure level, stroke volume, and severity of disease: on the reduction of afterload in the hyperdynamic syndrome.

OBJECTIVE: Patients with cirrhosis have cardiovascular dysfunction and altered mechanical properties of large and small arteries. This study was undertaken in order to analyze the arterial pressure curve in relation to mean arterial pressure level, stroke volume, and severity of liver disease. MATERIALS AND METHODS: Forty-one patients with cirrhosis (Child-Turcotte classes A/B/C = 13/15/13) were studied during a hemodynamic investigation of portal hypertension. Fifteen patients without liver disease served as controls. We applied fast Fourier analysis to quantify the pressure components of the arterial curve, the harmonic Fourier coefficients (HFC). RESULTS: Mean arterial pressure was significantly reduced (91 vs. 98 mmHg, p < 0.001) and stroke volume was significantly increased (94 vs. 78 ml, p < 0.001) in patients with cirrhosis versus controls. The HFC were significantly lower in patients with cirrhosis than in controls (-15 to -24%, p < 0.002), except for the fourth HFC, which was significantly increased (+28%, p < 0.02). In contrast to controls, which showed a highly significant effect of the level of arterial pressure on their HFC (p < 0.001), patients with cirrhosis did not show pressure or stroke volume dependence on their HFC, indicating an overall compliant and slow reflective arterial vascular bed. The initial rise in pulse pressure (dP/dt) was inversely related to the Child-Turcotte score (p < 0.05), and the HFC were borderline significantly related to this score (p = 0.07). CONCLUSIONS: The arterial pulsation in cirrhosis is qualitatively changed with reduced pulse reflections, which may protect against manifest cardiac failure in patients with advanced cirrhosis.

Single photon emission computed tomography for gastric volume assessment: a method with observer-defined regions of interest.

AIM: Single photon emission computed tomography (SPECT) imaging allows non-invasive measurement of gastric volume. In previous studies, the processing of the SPECT data involved global threshold algorithms that do not take into account the non-uniform distribution of radioactivity in the gastric wall. The aim of this study was to develop a simple alternative method based on observer-defined regions of interest. METHODS: A phantom study was performed to standardize volume calculations from SPECT derived cross-sectional areas. In 12 healthy volunteers, the principle was then used to determine gastric volume before and after a 600 ml liquid meal. Furthermore, gastric emptying of the meal was followed with planar scintigraphy. RESULTS: The median volume of the stomach was 86 ml (range 62-130 ml) at baseline, 642 ml (536-748 ml) immediately after the meal, and 370 ml (221-481 ml) 1 h after the meal. The coefficient of variation for the calculations was 9%, 2% and 4%, respectively. The median increase in gastric volume was 562 ml (501-628 ml) immediately after the meal and 294 ml (159-370 ml) after 1 h. Gastric retention of the meal was 68% (50-73%) after 0.5 h and 51% (39-57%) after 1 h. CONCLUSIONS: The present manual technique may be a reliable alternative to the automated SPECT methods for assessing gastric volume. The liquid meal that was used in our study did not seem to cause an increase in gastric volume that differed from the volume of the meal.

Prolonged Q-T(c) interval in mild portal hypertensive cirrhosis.

BACKGROUND/AIMS: The Q-T(c) interval is prolonged in a substantial fraction of patients with cirrhosis, thus indicating delayed repolarisation. However, no information is available in mild portal hypertensive patients. We therefore determined the Q-T(c) interval in cirrhotic patients with hepatic venous pressure gradient (HVPG) < 12 mmHg. METHODS: Forty-four patients with cirrhosis and HVPG < 12 mmHg underwent a haemodynamic study. They were compared with 36 cirrhotic patients with clinically significant portal hypertension (HVPG> or = 12 mmHg) and controls without liver disease. RESULTS: The fraction with prolonged Q-T(c) interval (> 0.440 s(1/2)) was similar in the two cirrhotic groups (49 vs 50%, ns) and significantly above that of the controls (5%, P < 0.005). Q-T(c) was normal in patients with normal HVPG. Likewise, mean Q-T(c) was 0.449 and 0.447 s(1/2) in the two cirrhotic groups (ns), values which are significantly above that of the controls (0.410 s(1/2), P < 0.01). In the mild portal hypertensive group, the Q-T(c) interval was inversely related to indicators of liver function, such as indocyanine green clearance (r = -0.34, P < 0.02). CONCLUSIONS: Delayed repolarisation of the myocardium already occurs in a substantial fraction of patients with cirrhosis with only a mild increase in portal pressure. The prolonged Q-T(c) interval may be related to liver dysfunction and to the presence of portal hypertension.

Detection of early central circulatory transits in patients with cirrhosis by gamma variate fit of indicator dilution profiles.

Patients with cirrhosis have hyperdynamic circulation with abnormally distributed blood volume and widespread arteriovenous communications. We aimed to detect possible very early (i.e., before 4 s) and early (i.e., after 4 s) central circulatory transits and their potential influence on determination of central and arterial blood volume (CBV). Thirty-six cirrhotic patients and nineteen controls without liver disease undergoing hemodynamic catheterization were given central bolus injections of albumin with different labels. Exponential and gamma variate fits were applied to the indicator dilution curves, and the relations between flow, circulation times, and volumes were established according to kinetic principles. No significant very early central circulatory transits were identified. In contrast, early (i.e., 4 s to maximal) transits corresponding to a mean of 5.1% (vs. 0.8% in controls; P < 0.005) of cardiac output (equivalent to 0.36 vs. 0.05 l/min; P < 0.01) were found in cirrhotic patients. These early transits averaged 7.7 vs. 12.7 and 17.2 s of ordinary central transits of cirrhotic patients and controls, respectively (P < 0.001). Early transits were directly correlated to the alveolar-arterial oxygen difference in the cirrhotic patients (r = 0.46, P < 0.01) but not in controls (r = 0.04; not significant). There was good agreement between the CBV determined by the conventional indicator dilution method and that determined by separation of early and ordinary transits by the gamma variate fit method (1.51 vs. 1.53 liter; not significant). In conclusion, no very early central circulatory transits were identified in cirrhotic patients. A significant part of the cardiac output undergoes an early transit, probably through pulmonary shunts or areas with low ventilation-perfusion ratios in cirrhotic patients. Composite determination of CBV by the gamma variate fit method is in close agreement with established kinetic methods. The study provides further evidence of abnormal central circulation in cirrhosis.