A woman in her fifties with abdominal pain and severe lactic acidosis. / En kvinne i 50-årene med magesmerter og alvorlig laktacidose.

BACKGROUND: Pheochromocytoma is referred to as 'the great mimic' with a broad spectrum of presenting symptoms. In the following case, the diagnosis had an unusual presentation as a medical emergency - pheochromocytoma crisis. CASE PRESENTATION: A previously healthy woman in her fifties was admitted due to abdominal pain and dyspnoea. At admission she was haemodynamically stable, with stable respiration, but arterial blood gas showed serious lactic acidosis with pH 6.8 (7.35-7.45), HCO3 3 mmol/l (22-26) and lactate 28 mmol/L (0.4-1.8). Her haemoglobin level was 12 g/dl (11,7-17,0). Further examination with CT and gastroscopy confirmed a duodenal bleeding. The lactic acidosis was corrected quickly, but the patient developed acute kidney injury, rhabdomyolysis and increased liver enzymes. The complex composition of organ manifestations could not be explained by the duodenal bleeding alone. An adrenal mass with high density was identified through re-evaluation of the CT scans. In the following case, a duodenal bleeding provoked catecholamine-induced haemodynamic instability and end-organ damage in a patient with an undiagnosed pheochromocytoma. INTERPRETATION: Endocrine emergencies are important differential diagnoses in critically ill patients. Pheochromocytoma crisis most commonly presents as hypertensive crisis or catecholamine cardiomyopathy but can also lead to lactic acidosis and multi-organ failure.

MnDPDP: Contrast Agent for Imaging and Protection of Viable Tissue.

The semistable chelate manganese (Mn) dipyridoxyl diphosphate (MnDPDP, mangafodipir), previously used as an intravenous (i.v.) contrast agent (Teslascan™, GE Healthcare) for Mn-ion-enhanced MRI (MEMRI), should be reappraised for clinical use but now as a diagnostic drug with cytoprotective properties. Approved for imaging of the liver and pancreas, MnDPDP enhances contrast also in other targets such as the heart, kidney, glandular tissue, and potentially retina and brain. Transmetallation releases paramagnetic Mn2+ for cellular uptake in competition with calcium (Ca2+), and intracellular (IC) macromolecular Mn2+ adducts lower myocardial T 1 to midway between native values and values obtained with gadolinium (Gd3+). What is essential is that T 1 mapping and, to a lesser degree, T 1 weighted imaging enable quantification of viability at a cellular or even molecular level. IC Mn2+ retention for hours provides delayed imaging as another advantage. Examples in humans include quantitative imaging of cardiomyocyte remodeling and of Ca2+ channel activity, capabilities beyond the scope of Gd3+ based or native MRI. In addition, MnDPDP and the metabolite Mn dipyridoxyl diethyl-diamine (MnPLED) act as catalytic antioxidants enabling prevention and treatment of oxidative stress caused by tissue injury and inflammation. Tested applications in humans include protection of normal cells during chemotherapy of cancer and, potentially, of ischemic tissues during reperfusion. Theragnostic use combining therapy with delayed imaging remains to be explored. This review updates MnDPDP and its clinical potential with emphasis on the working mode of an exquisite chelate in the diagnosis of heart disease and in the treatment of oxidative stress.

Manganese dipyridoxyl-diphosphate (MnDPDP) as a viability marker in patients with myocardial infarction.

PURPOSE: To evaluate contrast accumulation in left ventricular (LV) myocardium after manganese dipyridoxyl-diphosphate (MnDPDP) administration in patients with recent first time myocardial infarction. MATERIALS AND METHODS: MnDPDP (5 micromol/kg) was administered to 10 patients with recent myocardial infarction (three to 12 weeks). One slice of interest (SOI) likely to traverse the infarction was chosen, and sectorial pre- and postcontrast longitudinal relaxivity rates (R(1)) and signal changes during infusion were estimated with a fast gradient echo sequence. LV volume and wall thickening were measured in short-axis cine recordings. Infarct localization from R(1) and wall thickening data were compared by vector analyses. RESULTS: Reduced wall thickening was associated with reduced precontrast R(1) and reduced contrast enhancement. Both remote and infarcted regions showed rapid initial contrast accumulation. In remote regions, this was followed by a continuing slow increase. Mean precontrast R(1) was 0.87 +/- 0.06 second(-1) in infarcted regions and 0.96 +/- 0.03 second(-1) in remote regions (P < 0.001). Mean R(1) change over one hour was 0.24 +/- 0.07 second(-1) in infarcted regions and 0.38 +/- 0.03 second(-1) in remote regions (P < 0.0001). CONCLUSION: Remote regions showed larger increases in R(1) than infarcted regions. This is most likely due to selective and slow Mn accumulation in viable myocytes.

An apparent unidirectional influx constant for manganese as a measure of myocardial calcium channel activity.

PURPOSE: To develop an in vivo MR method for evaluation of myocardial calcium channel activity through quantification of apparent unidirectional manganese influx constants following manganese dipyridoxyl-diphosphate (MnDPDP) infusions. MATERIALS AND METHODS: A total of 10 healthy volunteers were divided in two groups, and received 5 micromol of MnDPDP per kg of body weight intravenously in a 1.5 Tesla scanner over five or 30 minutes, respectively. A fast inversion recovery gradient echo sequence was used to estimate pre- and postcontrast R1 values and to measure signal changes following infusions. By assuming equal longitudinal relaxivity (r1) of the contrast in all tissue compartments, signal changes in blood and myocardial tissue yielded temporal input and tissue contrast concentrations respectively. Through a two-tissue compartment model, apparent unidirectional influx constants (Ki) for myocardial manganese accumulation were estimated. RESULTS: Consistent values for Ki in left ventricular wall were found, with a mean value of 5.96 mL/100 g/minute (SD=0.49; N=10). No statistical significant differences in Ki were found between the two infusion groups. CONCLUSION: Since unidirectional manganese accumulation depends upon intact myocyte membranes with functioning calcium channels, the use of unidirectional manganese influx rates may be a valuable research tool for in vivo studies of myocyte functioning in myocardial disease.

Relaxation enhancing properties of MnDPDP in human myocardium.

PURPOSE: To assess magnitude and duration of changes in myocardial longitudinal relaxation rate (R1) in humans following infusion of the manganese (Mn) releasing contrast agent MnDPDP (Mn-dipyridoxyl-diphosphate). MATERIALS AND METHODS: Fifteen healthy volunteers were divided into three groups. After initial myocardial and liver R1 measurements using an inversion recovery (IR) turbo fast low-angle shot (FLASH) sequence at 1.5 Tesla, the groups were given different doses of intravenous MnDPDP: 5, 10 and 15 micromol/kg body weight, respectively, over 30 minutes. R1 measurements were then repeated at 1, 2, 4, 8, and 24 hours after the infusion ended. RESULTS: The left ventricular wall R1 prevalue was 0.98 second(-1) (+/-0.04). R1 increased on average (all 15 subjects) 0.41 second(-1) (+/-0.09). The increase was present one hour after the end of the infusion, remained relatively constant the next two hours, and then declined gradually. After 24 hours, there was still a moderate R1 elevation present, with an average R1-value of 1.16 (+/-0.05). There were only small differences in myocardial R1 responses between the three doses investigated, which was contrasted by a marked dose-response in liver tissue. CONCLUSION: MnDPDP gave a significant and prolonged rise in myocardial R1 even at a dose of 5 micromol/kg. The R1-values in the myocardium did not increase linearly with higher doses.