phosphorus-radioisotopes and Myocardial-Infarction

During the past several years, the production of high resolution images of organs in intact animals and human beings using nuclear magnetic resonance (nmr) has generated much interest and raised the possibility that the technique could be usefully applied to clinical problems. Because the images are derived from biochemical as well as structural information, valuable data relating to the metabolic status of the tissues and organs may be obtained. Furthermore, nuclear magnetic resonance imaging involves no potentially hazardous ionizing radiation. The technology of the technique is complex and much work remains to be done defining the biochemical and physiologic basis of such images, but the potential rewards of defining the metabolic state of organs such as heart and brain in the intact animal and human justify continued research.

Topics: Animals; Coronary Disease; Heart; Humans; Magnetic Resonance Spectroscopy; Myocardial Infarction; Phosphorus Radioisotopes; Rabbits; Radionuclide Imaging; Spectrum Analysis

Increased major adverse cardiac events (MACE) beyond six months after intracoronary β radiation brachytherapy (IRBT) are a major concern. The aim of this study was to evaluate the 10-year clinical outcome after IRBT.. From 1997 to 2002, 301 consecutive patients treated with IRBT were included prospectively, whereafter 602 control patients treated with conventional percutaneous coronary intervention (PCI) were matched by propensity score methodology. MACE was defined as all-cause death, any myocardial infarction or any revascularisation. Median follow-up duration was 9.7 years. Mortality rates in both groups were similar. Cumulative 5-month, 2-, and 10- year MACE-free survival rates of IRBT patients were 89%, 56% and 29%, respectively, while those of the control patients were 90%, 76% and 52%, respectively (p < 0.001). The difference in the MACE rate was mainly driven by target vessel revascularisation (TVR) (p < 0.001). Furthermore, two or more repeat TVRs were needed in 12% of IRBT patients and in only 6% of control patients (p < 0.01). Adjusted hazard ratios for IRBT-associated all-cause mortality and MACE were 1.0 (95% CI 0.7-1.5) and 1.8 (95% CI 1.5-2.2), respectively.. IRBT was associated with increased MACE between five months and two years of follow-up, mainly driven by repeat revascularisations. Similar event rate after two years indicate that there were no very late adverse effects related to IRBT.

Topics: Angioplasty, Balloon, Coronary; Brachytherapy; Case-Control Studies; Chi-Square Distribution; Coronary Artery Disease; Disease-Free Survival; Follow-Up Studies; Humans; Kaplan-Meier Estimate; Logistic Models; Myocardial Infarction; Netherlands; Phosphorus Radioisotopes; Propensity Score; Proportional Hazards Models; Prospective Studies; Risk Assessment; Risk Factors; Strontium Radioisotopes; Survival Rate; Time Factors; Treatment Outcome; Yttrium Radioisotopes

Treatment of in-stent restenosis after implantation of a drug-eluting stent is a critical issue. We provide the first report of the use of intravascular radiation therapy for this purpose in a 73-year-old diabetic patient stented for small-vessel bifurcation; treatment of Cypher diffuse in-stent restenosis with (32)P brachytherapy proved successful at clinical and angiographic follow-up at 7 months. This finding should encourage systematic studies on the safety and efficacy of IRT in this problematic setting.

Topics: Aged; Blood Vessel Prosthesis Implantation; Brachytherapy; Coronary Angiography; Coronary Restenosis; Coronary Vessels; Follow-Up Studies; Humans; Male; Myocardial Infarction; Phosphorus Radioisotopes; Prosthesis Failure; Stents

We report a case of obstructive in-stent restenosis in a diffusely diseased saphenous vein graft complicated by a non-ST-elevation myocardial infarction. With tirofiban infusion, the extensively occluded saphenous bypass was reperfused, establishing a TIMI flow 3, and then entirely irradiated with a beta source (32P) without any complication. At 7 months the patient was asymptomatic and the control angiogram did not reveal any restenosis. In conclusion, 32P beta brachytherapy may be extremely effective not only in case of native vessel in-stent restenosis but also in cases of high-risk vein graft in-stent restenosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Aspirin; Beta Particles; Blood Vessel Prosthesis; Brachytherapy; Coronary Angiography; Coronary Artery Bypass; Coronary Artery Disease; Female; Fibrinolytic Agents; Graft Occlusion, Vascular; Humans; Myocardial Infarction; Phosphorus Radioisotopes; Reoperation; Saphenous Vein; Stents; Ticlopidine; Tirofiban; Tyrosine

Acute myocardial infarction, which occurs because of the occlusion of one or more coronary arteries, is the most common form of cardiovascular disease. Balloon angioplasty is often used to treat coronary artery occlusion and is less invasive than surgery involving revascularisation of the myocardium, thus promising a better quality of life for patients. Unfortunately, the rate of re-stenosis after balloon angioplasty is high (approximately 30-50% within the first year after treatment). Intravascular radiation therapy has been used with several types of radiation source, and researchers have observed some success in decreasing the rate of re-stenosis. In this paper theoretical radiation dose distributions for monoenergetic electrons (with discrete energies) and photons are calculated for blood vessels of diameter 1.5, 3.0 and 4.5 mm with balloon and wire sources using the radiation transport code MCNP4B. Stent sources employing 32P are also simulated. Advantages and disadvantages of the radionuclides and source geometries are discussed, as well as issues regarding possible benefits to the patients.

Topics: Angioplasty, Balloon, Coronary; Coronary Stenosis; Coronary Vessels; Humans; Myocardial Infarction; Phosphorus Radioisotopes; Radioisotopes; Radiotherapy; Radiotherapy Dosage; Reproducibility of Results; Rhenium; Stents

This study is the contribution by the Thoraxcenter, Rotterdam, to the European(32)P Dose Response Trial, a non-randomized multicentre trial to evaluate the safety and efficacy of the radioactive Isostent in patients with single coronary artery disease.. The radioactivity of the stent at implantation was 6--12 microCi. All patients received aspirin indefinitely and either ticlopidine or clopidogrel for 3 months. Quantitative coronary angiography measurements of both the stent area and the target lesion (stent area and up to 5 mm proximal and distal to the stent edges) were performed pre- and post-procedure and at the 5-month follow-up. Forty-two radioactive stents were implanted in 40 patients. Treated vessels were the left anterior descending coronary artery (n=20), right coronary artery (n=10) or left circumflex artery (n=10). Eight patients received additional non-radioactive stents. Lesion length measured 10+/-3 mm with a reference diameter of 3.07+/-0.69 mm. Minimal lumen diameter increased from 0.98+/-0.53 mm pre-procedure to 2.29+/-0.52 mm (target lesion) and 2.57+/-0.44 mm (stent area) post-procedure. There was one procedural non-Q wave myocardial infarction, due to transient thrombotic closure. Thirty-six patients returned for angiographical follow-up. Two patients had a total occlusion proximal to the radioactive stent. Of the patent vessels, none had in-stent restenosis. Edge restenosis was observed in 44%, occurring predominantly at the proximal edge. Target lesion revascularization was performed in 10 patients and target vessel revascularization in one patient. No additional clinical end-points occurred during follow-up. The minimal lumen diameter at follow-up averaged 1.66+/-0.71 mm (target lesion) and 2.12+/-0.72 (stent area); therefore late loss was 0.63+/-0.69 (target lesion) and 0.46+/-0.76 (stent area), resulting in a late loss index of 0.65+/-1.15 (target lesion) and 0.30+/-0.53 (stent area).. These results indicate that the use of radioactive stents is safe and feasible, however, the high incidence of edge restenosis makes this technique currently clinically non-applicable.

Topics: Adult; Aged; Angioplasty, Balloon, Coronary; Brachytherapy; Coronary Angiography; Feasibility Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Myocardial Infarction; Phosphorus Radioisotopes; Radiation Dosage; Recurrence; Risk Factors; Safety; Severity of Illness Index; Stents; Treatment Outcome

In this study we evaluated whether storing non-deparaffinized sections can affect the detection of specific mRNAs by radioactive in situ hybridization (ISH). Using a standard ISH protocol, we hybridized serial sections of paraffin blocks stored for different periods of time with (33)P-labeled riboprobes specific for rat Type III collagen and matrix metalloproteinase-2 (MMP-2). Signal intensities were evaluated using a phosphorimager and by blinded microscopic examination. For slides hybridized with the Type III collagen riboprobe, signal intensities measured with the phosphorimager or evaluated by microscopic examination were negatively correlated with the storage period of the sections. For slides hybridized with the MMP-2 riboprobe, differences in signal intensity could be detected, albeit inconsistently, with the phosphorimager, although microscopic examination consistently indicated stronger signals in freshly sectioned slides compared to slides stored for 2 weeks or more. We concluded that it was preferable to use recently prepared sections for trying to locate mRNAs in paraffin-embedded tissues by ISH. In addition, our results suggest that quantifying signal intensity using a phosphorimager is feasible for abundant mRNAs or when large differences in expression are anticipated.(J Histochem Cytochem 49:927-928, 2001)

Topics: Animals; Bleomycin; Collagen; In Situ Hybridization; Lung; Matrix Metalloproteinase 2; Myocardial Infarction; Paraffin Embedding; Phosphorus Radioisotopes; Pulmonary Fibrosis; Rats; RNA, Messenger; Skin; Time Factors

Postmortem angiography and histologic analysis of a fatal coronary thrombosis 4 months after implantation of a radioactive stent are described. Histologic findings suggested incomplete re-endothelialization in the segment with the stent. Ionizing radiation may delay re-endothelialization after revascularization, thus maintaining the thrombogenicity of the irradiated vessel segment. Thus, prolonged antiplatelet therapy should be considered after intravascular radiation therapy.

Topics: Aged; Autopsy; Biopsy, Needle; Cardiac Catheterization; Coronary Angiography; Coronary Vessels; Fatal Outcome; Humans; Male; Myocardial Infarction; Phosphorus Radioisotopes; Radioisotopes; Recurrence; Risk Assessment; Sensitivity and Specificity; Stents

P 31 NMR spectroscopy is a recent technique which allows a non-invasive and direct analysis of oxidative metabolism and pH changes, an indicator of acidosis due to lactic acid accumulation in the skeletal muscles. The authors investigated oxidative muscular metabolism of the sural triceps in 10 patients after myocardial infarction by performing a study after the acute phase and repeating the study after a programme of physical training. At rest, there were no significant differences. On the other hand, for the same level of maximal effort, the depletion in phosphocreatinine (PCr) and the accumulation of inorganic phosphate (Pi) were significantly lower after physical training: the PCr/PCr + Pi increased from 0.467 +/- 0.179 to 0.538 +/- 0.20 (p < 0.02) and the Pi/PCr ratio decreased from 1.570 +/- 1.440 to 1.181 +/- 1.069 (p < 0.05). The pH at the same level of maximal exercise did not change significantly between the two periods: 6.85 +/- 0.16 vs 6.88 +/- 0.15 (NS). The peak oxygen consumption (VO2) measured during bicycle ergometry increased significantly from 23.4 +/- 10.5 to 28.3 +/- 12.14 ml/min/kg after exercise training (p < 0.01). In addition, a correlation was observed between the improvement of the peripheral parameters (PCr/PCr + Pi) and the increase in VO2 max (r = 0.757, p < 0.01). The authors results confirm the effects of physical training on oxidative metabolisms of the peripheral muscles and its influence on improvement of global performance of coronary patients.

Topics: Adult; Aged; Energy Metabolism; Exercise Test; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle Fibers, Skeletal; Myocardial Infarction; Phosphorus Radioisotopes

31P-magnetic resonance (MR) spectra of the heart can be obtained from well-defined myocardial regions by combined MR imaging and variable selected volumes for spectroscopy. 31P-spectra of 33 volunteers and of 43 patients with dilated and hypertrophic cardiomyopathy and with coronary artery disease were quantified using a curve-fitting routine. To optimize our technique, we recorded unsaturated and partially saturated spectra in several volunteers. Relative peak areas and signal-to-noise ratios showed significant changes with varying pulse repetition times. Saturation factors were applied to correct spectra from volunteers and patients for the effects of partial saturation. Under resting conditions, peak areas of volunteers and patients from the various groups were statistically indistinct.

Topics: Adult; Cardiomyopathy, Dilated; Cardiomyopathy, Hypertrophic; Female; Glycogen Storage Disease Type V; Humans; Magnetic Resonance Spectroscopy; Male; Myocardial Infarction; Myocarditis; Myocardium; Phosphorus Radioisotopes

Thrombolytic therapy has increased the need for a technique to assess the viability of recently reperfused myocardium. This study examined the ability of in vivo phosphorus-31 (P-31) nuclear magnetic resonance (NMR) spectroscopy to distinguish reperfused-viable (stunned) from reperfused-infarcted myocardium at 6, 30, and 54 hours following coronary artery occlusion in a canine model. A 15-minute occlusion produced reperfused-viable myocardium in five animals and a 360-minute occlusion produced reperfused-infarcted myocardium in six animals. Postreperfusion risk zone myocardial phosphocreatine (PCr) concentration measured by P-31 NMR spectroscopy was significantly depressed throughout the 3-day study period in infarcted but not in viable myocardium (p less than 0.01 between groups, all time points). The postreperfusion ratio of inorganic phosphate (Pi) to PCr concentration, as determined by NMR spectroscopy, was elevated throughout the study period in infarcted but not in viable reperfused myocardium (p less than 0.01 between groups, all time points). Postreperfusion Pi concentration was elevated at 6 hours but not subsequently in reperfused-infarcted myocardium, and was not elevated in reperfused-viable myocardium. Logistic regression models selected PCr concentration and the Pi/PCr ratio as providing the best discrimination between reperfused-viable and reperfused-infarcted myocardium. The accuracy of P-31 NMR variables selected by logistic regression analysis for determining myocardial viability ranged from 97% to 100%.

Topics: Animals; Coronary Circulation; Coronary Disease; Diagnosis, Differential; Disease Models, Animal; Dogs; Magnetic Resonance Spectroscopy; Myocardial Infarction; Myocardial Reperfusion; Phosphorus Radioisotopes; Regression Analysis; Time Factors

The effects of nisoldipine (0.1 micrograms/kg/min; n = 9) or its solvent (n = 9) were studied in pigs, in which left anterior descending coronary artery (LADCA) blood flow in both groups was reduced to 20% of baseline for 60 min and reperfused for 2 hr. Infusions were started at 30 min of ischaemia and lasted throughout reperfusion. In both groups, flow reduction abolished regional contractile function and caused similar decreases in the level of creatine phosphate (CP; by 70%) and the energy charge (from 0.91 to 0.69), mean arterial blood pressure (by 25%), LVdP/dtmax (by 30%) and cardiac output (by 30%). During ischaemia LADCA blood flow slightly increased (from 14 +/- 8 to 24 +/- 6 mL/min/100 g; P less than 0.05) in the nisoldipine-treated animals, resulting in an increase in CP to 91 +/- 24% of baseline and preventing further decreases in energy charge, as observed in the solvent-treated animals. After 2 hr of reperfusion in neither group return of contractile function of the post-ischaemic myocardium was observed. Post-ischaemic blood flow in the nisoldipine-treated pigs increased from 24 +/- 6 mL/min/100 g to 76 +/- 14 mL/min/100 g and from 19 +/- 6 mL/min/100 g to 41 +/- 6 ml/min/100 g in the solvent-treated animals (P less than 0.05) after 2 hr of reperfusion. Myocardial work was significantly higher in the nisoldipine-treated animals (111 +/- 15 mmHg.L/min as compared to 69 +/- 14 mmHg.L/min in the solvent-treated pigs after 2 hr of ischaemia). The energy charge of the post-ischaemic myocardium was similar for both groups (0.84 +/- 0.02 for the nisoldipine-treated and 0.83 +/- 0.03 for the solvent-treated animals). The rate of sarcoplasmic reticular Ca2+ uptake of the non-ischaemic segment of the nisoldipine-treated animals was 61% higher (P less than 0.05) than that of the solvent-treated animals. In the post-ischaemic myocardium similar rates of Ca2+ uptake were found in both groups, but the activities were markedly lower as compared to the non-ischaemic myocardium. It is concluded that nisoldipine increases blood flow during reperfusion, which may have been caused by coronary vasodilatation. However, attenuation of the "no-reflow" phenomenon also contributed, since more rapid rephosphorylation of ADP leading to an increase in CP during ischaemia may have preserved jeopardized cells. Moreover, nisoldipine increases the sarcoplasmic reticular Ca2+ pump activity independent of ischaemia, which may have contributed in reducing the Ca2+ overload.

Topics: Animals; Calcium; Calcium-Binding Proteins; Coronary Circulation; Coronary Vessels; Heart; Hemodynamics; In Vitro Techniques; Myocardial Contraction; Myocardial Infarction; Myocardial Reperfusion; Nisoldipine; Phosphocreatine; Phosphorus Radioisotopes; Sarcoplasmic Reticulum; Swine

The high-energy myocardial phosphate metabolism of four patients with acute anterior myocardial infarction after coronary angioplasty and drug therapy was evaluated with cardiac-gated phosphorus magnetic resonance (MR) depth-resolved surface coil spectroscopy (DRESS) 5-9 days after the onset of symptoms. Significant reductions (about threefold) in the phosphocreatine (PCr) to inorganic phosphate (Pi) ratio and elevations in the Pi to adenosine triphosphate (ATP) ratio were observed in endocardially or transmurally derived MR spectra when compared with values from epicardially displaced spectra and values from seven healthy volunteers (P less than .05). High-energy phosphate metabolites and Pi ratios did not vary significantly during the cardiac cycle in healthy volunteers. However, contamination of Pi resonances by phosphomonoester components, including blood 2,3-diphosphoglycerate, precluded accurate spectral quantification of Pi and pH. The results indicate that localized P-31 MR spectroscopy may be used to directly assess cellular energy reserve in clinical myocardial infarction and to evaluate metabolic response to interventions.

Topics: Adult; Aged; Angioplasty, Balloon; Cardiac Catheterization; Coronary Vessels; Energy Metabolism; Female; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Myocardial Infarction; Myocardium; Phosphates; Phosphorus Radioisotopes

Topics: Diphosphates; Heart; Humans; Myocardial Infarction; Phosphorus Radioisotopes; Radionuclide Imaging