strontium-radioisotopes and Myocardial-Infarction

Topics: Angina Pectoris; Animals; Arteriosclerosis; Blood Flow Velocity; Coronary Circulation; Coronary Disease; Diffusion; Dogs; Electrocardiography; Heart; Heart Ventricles; Humans; Ischemia; Male; Middle Aged; Myocardial Infarction; Oxygen; Strontium Radioisotopes

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

Position emission tomography can picture the distribution of flow tracers as well as of metabolic substrates or analogs. Studies of the distribution of these tracers allow to infer information about regional myocardial clearance (flow X extraction) and substrate utilization. In a study of 32 patients after myocardial infarction, we have contrasted flow and substrate utilization to demonstrate ischemic but viable myocardium in the arterial territory of the infarct in a number of patients also specially after fibrinolytic reperfusion. Restoration of blood flow to the ischemic but viable myocardium through coronary bypass or dilatation improves flow from 56.3% to 84.2% of control and restores substrate utilization. In another group of 32 patients studied with the Strontium-82/Rubidium-82 generator, we have demonstrated perfusion changes both in the myocardial infarct area and at a distance. These changes predominate in patients with multiple vessel disease. Combined PET studies of flow and substrate utilization are new tools to study early intervention after myocardial infarction and to document the benefits of revascularization.

Topics: Aged; Coronary Circulation; Deoxyglucose; Female; Fluorodeoxyglucose F18; Heart; Humans; Male; Middle Aged; Myocardial Infarction; Myocardium; Radioisotopes; Rubidium; Strontium Radioisotopes; Tomography, Emission-Computed

Topics: Animals; Cesium Radioisotopes; Coronary Circulation; Digoxin; Disease Models, Animal; Dogs; Electrocardiography; Heart Ventricles; Hemodynamics; Microspheres; Myocardial Contraction; Myocardial Infarction; Strontium Radioisotopes

The external imaging patterns and the kinetics of infiltration of indium-111 labeled polymorphonuclear leukocytes (PMNs) occurring in the course of the inflammatory response associated with myocardial infarction were studied in dogs subjected to closed-chest anterior wall infarction. The effects of infarct age and regional residual myocardial blood flow upon PMN infiltration were investigated and quantified, and the capacity of indium-111 PMNs to image the experimental infarction was evaluated qualitatively. The epicardial accumulation of indium-111 PMNs occurred primarily in infarct zones with residual blood flow of 0.6 times normal and was maximal (14.8 +/- 3.8 times normal) in the lowest blood flow zone (less than 0.1 times normal). PMN accumulation in the endocardial infarct zones occurred in the regions with blood flow less than 0.6 times normal and was maximal (26.8 +/- 4.9 times normal) in the lowest blood flow zone. However, contrary to the maximal epicardial infiltration period, which occurred within the first 24 hours after infarction, the maximal endocardial infiltration occurred at 72 hours after infarction. In both endocardium and epicardium, PMN uptake was minimal at 120 hours after infarction. In vivo cardiac images were abnormal and revealed discrete, anatomically distinct areas of increased myocardial radioactivity uptake in the anterior wall of all dogs studied within 24--96 hours after infarction. All images obtained 120 hours after infarction were negative. Thus, indium-111 PMNs provide a noninvasive means of in vivo imaging of the inflammatory response to myocardial infarction and allow quantification of this response at a tissue level.

Topics: Animals; Chemotaxis, Leukocyte; Coronary Circulation; Dogs; Electrocardiography; Female; Heart; Indium; Male; Myocardial Infarction; Myocardium; Neutrophils; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Time Factors

We studied the early changes in collateral blood flow (CBF) after acute coronary artery occlusion and the relation of these changes to subsequent necrosis. We measured CBF with 7--9 microns radioactive microspheres before and at various times after circumflex artery occlusion in 42 conscious dogs that were killed 48 h later. CBF increased from 20 s postocclusion to later measurements (5 min, 15 min, 1 h, or 6 h) and did so in both necrotic and nonnecrotic areas of the occluded bed. However, the increase in CBF over time was not gradual, but appeared to occur between 20 s and 5 min, with no further changes for up to 6 h. There was a gradation of CBF in the occluded bed, from periphery to center and subepicardium to subendocardium. Central and subendocardial regions with CBF less than 0.40 ml-min-1-g-1 at 5--15 min postocclusion subsequently showed necrosis whereas epicardial and lateral regions with CBF greater than 0.50 ml/min did not. Thus CBF increases very early throughout the occluded coronary bed, and the level of CBF by 5 min appears to determine whether necrosis ultimately occurs.

Topics: Animals; Cesium Radioisotopes; Coronary Circulation; Coronary Disease; Dogs; Iodine Radioisotopes; Microspheres; Myocardial Infarction; Niobium; Radioisotopes; Regional Blood Flow; Scandium; Strontium Radioisotopes

A new rapid method for producing myocardial necrosis in rabbits was developed, using percutaneous intramyocardial injection of vasopressin in peanut oil. The 15-min procedure resulted in a mortality rate of 15% and a success rate among surviving animals of 50%. When the lesions were 24 hr old, strontium-85 and a technetium-99m-tagged agent were injected intravenously simultaneously, and the animals were killed 1,6, and 24 hr later for tissue radioassay. Strontium-85 failed to accumulate appreciably in the lesions. Three bone-seeking technetium complexes (pyrophosphate, methylene diphosphonate, and imidodiphosphonate) produced lesion-to-normal myocardial ratios of 6,5, and 14, respectively, at 1 hr, and 20,30, and 33 at 6 hr. The ratios for 99mTc-glucoheptonate were only 2 at 1 hr and 4 at 6 hr, while the ratios of 99mTc-acetylcysteine and 99mTc-citrate were even lower.

Topics: Animals; Citrates; Cysteine; Diphosphates; Diphosphonates; Disease Models, Animal; Myocardial Infarction; Rabbits; Radionuclide Imaging; Strontium Radioisotopes; Sugar Acids; Technetium; Vasopressins

Strontium-82, produced by spallation reaction with medium-energy proton beams, was used to evaluate Bio-Rex 70 and Chelex-100 ion-exchange resins for use in a compact Rb-82 generator. Adsorption of Sr-82 to the resin column, Rb-82 elution yields, Sr breakthrough, and 82Rb-Sr separation factors were determined for newly prepared columns and for longterm elution conditions. Separation factors of 10(7) to 10(8) were obtained with 2% NaCl elutions from Bio-Rex 70 resin columns while the separation factors was about 5 X 10(4) with the Chelex-100 resin column.

Topics: Evaluation Studies as Topic; Ion Exchange Resins; Myocardial Infarction; Radioisotopes; Radionuclide Imaging; Rubidium; Strontium Radioisotopes

The uptake of liposomes bearing positive, negative, or no net charge on their membrane and containing a radioactive tracer, [99mTc]diethylenetriamine pentaacetic acid, was studied in 12 intact dogs 24 hours after the induction of myocardial infarction, and compared to the relative regional myocardial blood flow determined from radioactive microspheres. Positively charged and neutral liposomes concentrate in infarcted regions against a flow gradient, while negative liposomes are passively distributed according to regional blood flow. Because positively charged and neutral lipisomes concentrate in infarct areas and have the ability to incorporate pharmacologic agents in their aqueous or lipid phase, they may serve as vehicles for drug delivery to infarct zones of low flow.

Topics: Animals; Anions; Coronary Circulation; Dogs; Liposomes; Microspheres; Myocardial Infarction; Myocardium; Strontium Radioisotopes; Technetium

Topics: Acute Disease; Animals; Autoantibodies; Coronary Circulation; Coronary Disease; Diphosphates; Dogs; Gallium Radioisotopes; Myocardial Infarction; Myosins; Oxygen Radioisotopes; Radioisotopes; Radionuclide Imaging; Regional Blood Flow; Rubidium; Strontium Radioisotopes; Tetracyclines

The relationship between regional blood flow and epicardial S-T segment elevation was studied in 26 open-chest anesthetized dogs with left anterior coronary artery ligations. Changes in myocardial blood flow, measured with 15 plus or minus 5mu (diameter) microspheres labeled with 141-Ce, 85-Sr, and 169-Yb, were correlated with summated S-T segment elevations 15 minutes, 1 hour, and 2 hours after coronary artery occlusion. In normal areas, myocardial blood flow was 113 plus or minus 5 ml/min 100 g- minus 1 and summated S-T segment elevation was 0.3 plus or minus 0.2 mv. Fifteen minutes after coronary artery occlusion in 26 dogs, S-T segment elevation was 5.7 plus or minus 0.7 mv over the center of the infarct and myocardial blood flow was 10 plus or minus 1 ml/min 100 g- minus 1; over the border zone, myocardial blood flow was 63 plus or minus 4 ml/min 100 g- minus 1 and S-T segment elevation was 3.1 plus or minus 0.1 mv. One third of the areas with a myocardial blood flow of 10 ml/min 100 g- minus 1 or less had no S-T segment elevation. In the center and border zones of the infarct in 9 dogs, myocardial blood flow increased from 11 plus or minus 2 and 67 plus or minus 8 ml/min 100 g- minus 1 15 minutes after occlusion to 20 plus or minus 4 and 84 plus or minus 12 ml/min 100 g- minus 1, respectively, 2 hours after coronary artery occlusion. These increases were not associated with a significant reduction in summated S-T segment elevation. The results do not suggest a simple quantitative relationship between epicardial S-T segment elevation and myocardial blood flow following acute coronary artery occlusion.

Topics: Animals; Blood Pressure; Cardiac Output; Cerium Radioisotopes; Coronary Circulation; Coronary Vessels; Dogs; Electrocardiography; Endocardium; Heart; Heart Rate; Ligation; Microspheres; Myocardial Infarction; Pericardium; Radioisotope Dilution Technique; Strontium Radioisotopes; Ytterbium

We studied the influence of controlled changes in perfusion pressure and heart rate on the regional distribution of myocardial flow in normal dogs and in dogs with multiple chronic coronary artery occlusions but without infarctions. Local myocardial blood flow was determined with the tracer microsphere technique. By stepwise altering of systemic blood pressure during maximal vasodilation classical pressure flow relations were obtained. One week after complete chronic occlusion a functionally and anatomically well-defined compartmentation of blood flow was found. The dilatory reserve is clearly compromised not only in the collateral-dependent myocardium but also in the apparently normal myocardium which delivers collateral flow. An "arterio-arterial shunting" mechanism is shown to exist. Several months after coronary occlusion, regional mycoardial flow is still nonhomogeneous. Although the coronary dilatory capacity of the collateralized myocardium is nearly normal, that of the normal myocardium is found to be higher than normal. Vessel growth in both areas is discussed as being responsible for this phenomenon. Right ventricular pacing during maximal vasodilation produces a flow decrease to the endocardial muscle layers in normal dogs, while the epicardial flow is unchanged. One week after complete chronic coronary occlusion pacing during maximal vasocilation reduces the dilatory capacity in the collateralized areas to such an extent that the supplementary increase in myocardial oxygen demand will induce ischemia because of the compromised oxygen supply.

Topics: Animals; Blood Pressure; Cerium Isotopes; Chromium Radioisotopes; Collateral Circulation; Coronary Circulation; Coronary Disease; Dogs; Endocardium; Female; Heart Rate; Iodine Radioisotopes; Male; Microspheres; Myocardial Infarction; Myocardium; Niobium; Pacemaker, Artificial; Radioisotopes; Strontium Radioisotopes

The evolution and transmural distribution of coronary collateral blood flow in acute myocardial infarction was determined in 24 trained, unanesthetized dogs by injection of radioactive microspheres into the coronary circulation. Acute coronary artery occlusion resulted in a greater decrease in subendocardial flow than subepicardial flow in both the central and marginal zones of the infarct. Coronary collateral blood flow was distributed primarily to the marginal zone and to the subepicardium of the central zone of the infarct. The greatest increase in collateral flow occured between 12 and 18 hours after coronary artery occlusion. By 24 hours after coronary occlusion, blood flow to all areas of the infarct except the subendocardium of the central zone had returned to near control levels. This dispropotionate distribution of coronary collateral blood flow during the early stages of myocardial ischemic injury helps to explain the apparent lack of protection of the subendocardium by collateral flow.

Topics: Acute Disease; Animals; Blood Pressure; Cardiac Catheterization; Cerium Isotopes; Collateral Circulation; Coronary Circulation; Dogs; Electrocardiography; Heart Rate; Microspheres; Myocardial Infarction; Scandium; Strontium Radioisotopes; Time Factors

The coronary hemodynamic effects of re-establishing blood flow to ischemic myocardium and the regional distribution of myocardial flow during reperfusion were studied in anesthetized open-chest dogs. A large portion of the left ventricular wall was rendered ischemic by occlusion of the left anterior descending coronary artery for 2 hours. During reperfusion of the LAD, coronary resistance in the reperfused vasculature increased progressively for the first 3 hours, while resistance in the intact LC vasculature was unchanged. Minimal resistances in the reperfused vascular bed, calculated from mean aortic pressure and peak coronary reactive hyperemic blood flow following a 90 sec. LAD occlusion, were elevated significantly during reperfusion. The increased minimal resistance values, which reflect the passive physical component of resistance, indicate structural changes in the reperfused vascular bed which were evident shortly after the initiation of reperfusion and persisted throughout the experimental period. Coronary resistances (RH) in the reperfused (LAD) and intact (LC) vasculatures during the reactive hyperemia following 10 sec. coronary occlusions were evaluated. During reperfusion, RH in the reperfused vasculature increased progressively while RH in the intact bed was unchanged. The marked increase in RH in the LAD indicates that the reactive hyperemic flow response to a consistent period of coronary occlusion progressively diminished, and reflects a gradual reduction in the vasodilatory potential of the reperfused coronary circulation. The regional distribution of myocardial blood flow following 5 minutes, 2 hours, and 4 hours of reperfusion was measured with multiple injections of radioactive microspheres. These measurements demonstrated a progressive reduction of blood flow to the reperfused myocardium with no significant change in flow to the control myocardium. In contrast to the uniform transmural distribution of flow in the normal myocardium, the reperfused region showed a distinctly nonuniform distribution of flow after 2 hours and 4 hours of reperfusion, with more severe reduction of flow to the endocardial layer. These studies would suggest that rechannelling blood flow distal to an acute coronary occlusion in human subjects might not in itself be capable of reversing the myocardial injury. It is hoped that additional therapeutic measures might be applied to salvage the injured myocardium.

Topics: Animals; Blood Flow Velocity; Cesium Radioisotopes; Coronary Circulation; Dogs; Female; Male; Myocardial Infarction; Perfusion; Radioisotopes; Scandium; Strontium Radioisotopes; Time Factors; Vascular Resistance

Topics: Animals; Cesium Isotopes; Coronary Circulation; Coronary Vessels; Female; Ligation; Male; Microspheres; Myocardial Infarction; Myocardium; Papio; Radioisotopes; Strontium Radioisotopes; Time Factors; Ventricular Fibrillation; Ytterbium