phosphorus-radioisotopes and Ischemia

Autologous cell therapy (ACT) is a new treatment method for diabetic patients with critical limb ischemia (CLI) not eligible for standard revascularization. After intramuscular injection of bone marrow-derived mononuclear cells local arteriogenesis in the ischemic tissue occurs. Studies assessing visualization of this therapeutic vasculogenesis after ACT by novel imaging techniques are lacking. The aim of our study was to assess the effect of ACT on possible metabolic changes and perfusion of critically ischemic limbs using (31)P magnetic resonance spectroscopy ( (31)P MRS) and its possible correlation with changes of transcutaneous oxygen pressure (TcPO(2)). Twenty-one patients with diabetes and no-option CLI treated by ACT in our foot clinic over 8 years were included in the study. TcPO(2) as well as rest (phosphocreatine, adenosine triphosphate and inorganic phosphate) and dynamic (mitochondrial capacity and phosphocreatine recovery time) (31)P-MRS parameters were evaluated at baseline and 3 months after cell treatment. TcPO(2) increased significantly after 3 months compared with baseline (from 22.4±8.2 to 37.6±13.3 mm Hg, p=0.0002). Rest and dynamic (31)P MRS parameters were not significantly different after ACT in comparison with baseline values. Our study showed a significant increase of TcPO(2) on the dorsum of the foot after ACT. We did not observe any changes of rest or dynamic (31)P MRS parameters in the area of the proximal calf where the cell suspension has been injected into.

Topics: Bone Marrow Transplantation; Follow-Up Studies; Humans; Ischemia; Leg; Magnetic Resonance Spectroscopy; Phosphorus Radioisotopes; Transplantation, Autologous

The assessment of kidney viability before transplantation (with a view of discarding nonviable organs) remains an obstacle to confidently extending organ harvesting to marginal donors. In the present study phosphorus magnetic resonance spectroscopy was used to monitor metabolic changes in (31)P-containing metabolites in isolated porcine kidneys. After various warm ischemia times, the organs were stored at 0 degrees C. Time-dependent changes in the phosphomonoester/inorganic-phosphate ratio were recorded at 0 degrees C were shown to follow a biexponential decay. The first-order kinetic rate constant of the short-time decay was strongly dependent on the warm ischemia time, a result that was discreted in terms of the underlying biochemistry. The metabolic events responsible for the dramatic decrease in phosphomonoester/inorganic phosphate ratio that occur immediately after organ perfusion and storage, suggest that any procedure to minimize organ damage must occur immediately after harvesting.

Topics: Animals; Disease Models, Animal; Ischemia; Kidney; Kinetics; Magnetic Resonance Spectroscopy; Phosphorus; Phosphorus Radioisotopes; Radioisotope Dilution Technique; Renal Circulation; Swine

To evaluate whether the vascular system resulting from an arterial lesion shows differences in permeability to a tracer with respect to the normal vascular system and whether eventual differences are maintained for long periods.. Permanent ischemia was induced in rats with femoral arterial removal, and magnetic resonance (MR) imaging was performed after 1, 7, 14, and 90 days. Gadopentetate dimeglumine was injected, and the kinetics of its penetration in the leg were studied. Phosphorus 31 spectroscopy was performed to determine the bioenergetic characteristics of the gastrocnemius muscle at rest and stimulation. Ischemic muscles were then processed for electron microscopy.. After ischemia induction, a hyperintense area that progressively decreased was present on T2-weighted images. Gadopentetate dimeglumine improved the signal intensity of the area. Three months after arterial occlusion, the contrast-enhanced images still showed microvessels highly permeable to the tracers. Spectroscopic data revealed that 3 months after arterial removal, the bioenergetic reserve of the gastrocnemius muscle was reduced, suggesting that the contrast-enhanced MR imaging-visible area is functionally relevant. Ultrastructural examination revealed persistent muscle damage and signs of chronic microangiopathy.. After ischemia induction, the restitutio ad integrum is not complete, and delayed muscle injuries can result from arterial insufficiency.

Topics: Animals; Arteries; Contrast Media; Gadolinium DTPA; Ischemia; Leg; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Muscle, Skeletal; Muscles; Phosphorus Radioisotopes; Rats; Rats, Wistar

The effects of prostaglandin E1 (PGE1) and tyrosine kinase inhibitors on hepatic energy status and protein synthesis in ischemic livers were studied using 31P-magnetic resonance spectroscopy in a rat model. The continuous administration of PGE1 significantly increased the beta-adenosine triphosphate/inorganic phosphate (beta-ATP/Pi) ratio and hepatic protein synthesis rate (HPS) after ischemia-reperfusion injury. Microscopic examination showed that the continuous administration of PGE1 inhibited the development of sinusoidal hemorrhage and edema. Thus, it was concluded that PGE1 has a beneficial effect on ischemia-reperfusion injury in the liver. Pretreatment with tyrosine kinase inhibitor also increased the beta-ATP/Pi ratio; however, when tyrosine kinase inhibitor was injected before ischemia, the HPS became significantly reduced. Based on these data, the protective effect of tyrosine kinase inhibitor is unconvincing.

Topics: Alprostadil; Animals; Energy Metabolism; Ischemia; Liver; Magnetic Resonance Spectroscopy; Male; Phosphorus Radioisotopes; Protein Synthesis Inhibitors; Protein-Tyrosine Kinases; Rats; Rats, Wistar; Reperfusion Injury

Using 31P nuclear magnetic resonance spectroscopy of the calf muscle, the authors studied patients with peripheral arterial occlusive disease. They studied PCr depletion and intracellular pH during aerobic exercise in patients and controls. The phosphocreatine (PCr) index ([PCr]/([PCr] + [Pi])) at rest was correlated with blood flow measured by plethysmography. During aerobic exercise a greater decrease in pH was obtained in patients (p < 0.03). They also studied the work necessary to reach a PCr index = 0.5 during ischemic exercise. This workload was lower in patients than in controls: 32.99 +/- 3.04 J vs 58.89 +/- 8.55 J, p < 0.05. After vasodilator therapy the workload was improved in patients: 32.99 +/- 3.04 J vs 38.85 +/- 3.54 J, p < 0.05. These results suggest that therapy resulted in improved tissue perfusion in patients.

Topics: Arterial Occlusive Diseases; Exercise; Humans; Hydrogen-Ion Concentration; Intermittent Claudication; Ischemia; Leg; Magnetic Resonance Spectroscopy; Middle Aged; Oxidative Phosphorylation; Phosphocreatine; Phosphorus Radioisotopes; Vasodilator Agents

Topics: Adult; Humans; Ischemia; Magnetic Resonance Spectroscopy; Middle Aged; Muscles; Phosphorus Radioisotopes; Risk Factors; Time Factors; Tourniquets

The possible direct attenuating modification by diltiazem (DZ) 10(-6) M of ischaemia-induced metabolic damage was studied by 31P NMR spectroscopy (at 101.3 MHz) on retrogradely perfused rat hearts submitted to a 24 min, normothermic (37 degrees C), global low-flow ischaemia (1% of the pre-ischaemic spontaneous coronary flow), followed by a 30 min reperfusion. The presence of DZ 10(-6) M altered neither the heart rate and the left intraventricular pressure under normoxic conditions, nor the extent of ATP and CP depletion during ischaemia, whilst the intramyocardial Pi accumulation during ischaemia was significantly reduced (by about 30%). The intracellular acidification induced by ischaemia was initially less in the presence of DZ, but the pH values reached by the end of ischaemia were somewhat lower than in control (albeit not significantly so): 5.85 +/- 0.07 v. 6.00 +/- 0.07 (Means +/- S.E.M.). On reperfusion, DZ-treated hearts exhibited a greater oxidative phosphorylation capacity than did control hearts. Indeed, NMR spectroscopy revealed a prompter, greater and durable rephosphorylation of creatine together with a simultaneous more rapid and furthermore sharp drop in Pi content in DZ-treated hearts. Moreover, although NMR spectroscopy did not reveal any significant difference in ATP alteration on reperfusion in DZ-treated hearts as compared with controls, biochemical measurements indicated slightly higher ATP content at the end of reperfusion and, more particularly, a better recovery of the adenylate charge: 0.81 +/- 0.03 v. 0.72 +/- 0.03, means +/- S.E.M. (Pre-ischaemic value 0.90-0.91). The intracellular pH differed insignificantly from its pre-ischaemic value at the end of reperfusion in DZ-treated hearts (7.08), while remaining below initial values in controls (7.00). From these results, it is inferred that, at relatively low concentration (10(-6) M), DZ exerts a direct beneficial effect on the energy metabolism of the ischaemic heart without preserving high-energy phosphate compounds during ischaemia and, most importantly, without reducing the extent of the concomitant intracellular acidification.

Topics: Adenosine Triphosphate; Animals; Diltiazem; Energy Metabolism; Heart; Heart Rate; Hydrogen-Ion Concentration; Ischemia; Magnetic Resonance Spectroscopy; Male; Myocardium; Oxidative Phosphorylation; Phosphocreatine; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains; Stroke Volume

Hepatic metabolism in intact livers has been studied by 31P nuclear magnetic resonance (NMR) spectroscopy. 31P NMR spectroscopy of normal liver detects little ADP and much lower amounts of inorganic phosphate than are found by enzymatic or chemical analysis. Ischaemia of 30 min duration provokes a rapid fall in ATP to undetectable levels; reflow restores the ATP concentration to 70% of its former level. Intracellular pH changes are qualitatively similar. Fructose and glycerol both cause rapid falls in ATP and inorganic phosphate; these original concentrations are almost restored after 30 min in the case of fructose but not with glycerol where they remain depressed.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Ischemia; Liver; Magnetic Resonance Spectroscopy; Phosphates; Phosphorus Radioisotopes; Rats; Rats, Inbred Strains

Topics: Adenosine Triphosphate; Animals; Brain; Electroencephalography; Ischemia; Microscopy, Electron; Mitochondria; Osmolar Concentration; Phosphates; Phosphorus Radioisotopes; Rabbits; Sucrose; Synaptosomes; Time Factors

Topics: Blood Platelets; Fingers; Gangrene; Humans; Ischemia; Neuritis; Phosphorus; Phosphorus Radioisotopes; Thrombocytosis