technetium-tc-99m-mebrofenin and Ischemia

A redundant collateral network between the intestinal arteries is present at all times. In case of ischaemia in the gastrointestinal tract, the collateral blood supply can develop further, thus accommodating the demand for oxygen even in the presence of significant stenosis or occlusion of the intestinal arteries without clinical symptoms of intestinal ischaemia. Symptoms of ischemia develop when the genuine and collateral blood supply no longer can accommodate the need for oxygen. Atherosclerosis is the most common cause of obliteration in the intestinal arteries. In chronic intestinal ischaemia (CII), the fasting splanchnic blood flow (SBF) is sufficient, but the postprandial increase in SBF is inadequate and abdominal pain will therefore develop in relation to food intake causing the patient to eat smaller meals at larger intervals with a resulting weight loss. Traditionally, the CII-diagnosis has exclusively been based upon morphology (angiography) of the intestinal arteries; however, substantial discrepancies between CII-symptoms and the presence of atherosclerosis/stenosis in the intestinal arteries have been described repeatedly in the literature impeding the diagnosis of CII. This PhD thesis explores a method to determine the total SBF and its potential use as a diagnostic tool in patients suspected to suffer from CII. The SBF can be measured using a continuous infusion of a tracer and catheterisation of a hepatic vein and an artery. By measuring the SBF before and after a standard meal it is possible to assess the ability or inability to enhance the SBF and thereby diagnosing CII. In Study I, measurement of SBF was tested against angiography in a group of patients suspected to suffer from CII due to pain and weight loss. A very good agreement between the postprandial increase in SBF and angiography was found. The method was validated against a well-established method independent of the hepatic extraction of tracer using pAH in a porcine model (study II). An excellent agreement was found between the two methods for the measurement of SBF. In the same set-up metabolism and recirculation in the intestines of the 99mTechnetium labelled tracer was rejected based on the consistency between the portal and arterial contents of tracer. Based on this study we concluded that an arterial blood sample can be used instead of a portal blood sample, making the method applicable to patients. In study III, 20 healthy volunteers and 29 patients with weight loss and

Topics: Angiography; Aniline Compounds; Animals; Anthropometry; Chronic Disease; Fasting; Glycine; Humans; Imino Acids; Intestinal Diseases; Ischemia; Organotechnetium Compounds; Oxygen Consumption; p-Aminohippuric Acid; Postprandial Period; Radiopharmaceuticals; Splanchnic Circulation; Swine

The diagnosis chronic intestinal ischaemia (CII) is based on the clinical symptoms postprandial pain and weight loss combined with abnormal findings during angiography. Despite the well-known poor correlation between symptoms and morphology, physiological tests are rarely performed.. It is possible to measure the total splanchnic blood flow (SBF) before and after a test meal, and the results supply additional information to the morphologic investigations. To date, no papers have addressed the impact of morphologic changes of the mesenteric arteries on the SBF.. Forty-six consecutive patients suspected of CII were investigated. The routine investigation included angiography and measurements of the SBF before and after a test meal. Measurements of the total SBF were performed using the 'Fick principle'. (99m)Technetium-labelled Mebrofenin was used as a tracer. Digital subtraction angiography was performed.. Agreement between SBF and angiography was found in 44 of 46 patients. Mean baseline SBF for all patients was 985 ml/min, total range (525-1932) and within the reported normal range. The mean postprandial increase in SBF was 480 mL min(-1) (-130 to 1353), thus 36 patients were categorized as normal by both angiography and SBF, eight patients were abnormal by both methods and two patients had abnormal SBF but normal angiography.. In this cohort, SBF detects CII with sensitivity of 1.0, and specificity of 0.95. SBF supplies additional information in patients with convincing symptoms and normal angiography. In these patients, the affection of the intestinal arteries may be too distant or too subtle to be visualized on angiography.

Topics: Adult; Aged; Aged, 80 and over; Angiography; Aniline Compounds; Blood Flow Velocity; Chronic Disease; Cohort Studies; Female; Follow-Up Studies; Glycine; Humans; Imino Acids; Intestines; Ischemia; Male; Mesenteric Arteries; Middle Aged; Organotechnetium Compounds; Oxygen Consumption; Radionuclide Imaging; Sensitivity and Specificity; Splanchnic Circulation

To determine the splanchnic blood flow and oxygen uptake in healthy-subjects and patients and to relate the findings to body-composition.. The total splanchnic blood flow (SBF) and oxygen uptake (SO₂U) were measured in 20 healthy volunteers (10 women) and 29 patients with suspected chronic intestinal ischemia (15 women), age 40-85 years, prior to and after a standard meal. The method is based on the Fick principle using the continuous infusion of an indicator (99mTechnetium-labelled mebrofenin) and catheterization of an artery and the hepatic vein. An angiography of the intestinal arteries was performed during the same investigation. A whole-body dual-energy x-ray absorptiometry scan was performed in healthy volunteers to determine body composition.. Angiography revealed no atherosclerotic lesions in the intestinal arteries. The mean baseline SBF was 1087 mL/min (731-1390), and this value increased significantly to 1787 mL/min after the meal in healthy volunteers (P < 0.001). The baseline SBF in patients was 1080 mL/min, which increased to 1718 mL/min postprandially (P < 0.001). The baseline SBF was independent of age, sex, lean body mass and percentage of body fat. The mean meal-induced increase in SBF was equal to 282 mL/min + 5.4 mL/min × bodyweight, (P = 0.025). The SO₂U in healthy volunteers and patients was 50.7 mL/min and 48.0 mL/min, respectively, and these values increased to 77.5 mL/min and 75 mL/min postprandially, respectively. Both baseline and postprandial SO₂U were directly related to lean body mass. Age and sex exerted no impact on SO₂U.. A direct correlation between body weight and the postprandial increase in SBF was observed. The effect of body weight should be considered in the diagnosis of chronic intestinal ischemia.

Topics: Absorptiometry, Photon; Adult; Aged; Aged, 80 and over; Aniline Compounds; Body Composition; Body Weight; Case-Control Studies; Female; Glycine; Humans; Imino Acids; Ischemia; Linear Models; Male; Mesenteric Arteries; Mesenteric Ischemia; Mesenteric Vascular Occlusion; Middle Aged; Organotechnetium Compounds; Oxygen Consumption; Postprandial Period; Predictive Value of Tests; Radiopharmaceuticals; Reference Values; Regional Blood Flow; Splanchnic Circulation; Vascular Diseases

The kinetics of 99mTc-Trimethyl-Br-IDA blood clearance was analysed in the rat 24 h after warm ischaemia and reperfusion of the liver. There were changes in the elimination of 99mTc-Trimethyl-Br-IDA depending on the length of the ischaemic period and the dose given. Statistically significant differences were found between the various periods of ischaemia when higher doses of the radionuclide were utilised. At lower doses, the clearance was not capable to discriminate between control rats and rats submitted to 45 min of ischaemia, but it did discriminate more severe degrees of ischaemic liver injury. Instead, galactose elimination capacity discriminated between ischaemic and control rats, but not between 45 and 90 min or between 90 and 120 min of ischaemia. Alanine aminotransferase was able to discriminate between control and ischaemic rats and between 45 and 90 min of ischaemia, but not between 90 and 120 min of ischaemia. The response of 99mTc-Trimethyl-Br-IDA clearance under extreme conditions of ischaemia and reperfusion is consistent and opens a possible window for the application of this test in the quantification of liver function in severely damaged livers and in decision making and prognosis in liver disease.

Topics: Alanine Transaminase; Aniline Compounds; Animals; Galactosemias; Glycine; Imino Acids; Ischemia; Liver; Liver Circulation; Male; Organotechnetium Compounds; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Severity of Illness Index; Time Factors