strontium-radioisotopes and Coronary-Disease

Restenosis after PTCA is still an unresolved problem and occurs in approximately 30% of our patients despite a stent implantation rate of up to 63%. Intracoronary brachytherapy has the potential to counteract the proliferative component of restenosis as well as to prevent shrinking of the coronary artery. Two years ago, we applied for the license to use the Novoste Beta-Cath system. This is the first report of its use in Germany. Attaining the license was complicated by the facts that this device did not yet have CE-certification (MPG section 17), that brachytherapy is not yet an approved method of treatment (StrSchV section 41), the report of the BfS and the approval by an accredited ethical committee. The application becomes even more complicated by the amount demanded by the LfU for insurance: 1 Million DM for each individual patient (AtDeckV section 15). The final local inspection needs to be performed by an expert from the LfAS (StrSchV section 76). Strontium-90 decays into Yttrium-90 with a half-life time of approximately 28 years. Yttrium-90, too, is a pure beta-emitter with a shorter half-life time of approximately 64 hours and a considerably higher electron energy of maximum 2.27 MeV. Yttrium-90 is the therapeutic agent. The radiation source of the Beta-Cath system consists of 12 single, separate cylinders (pellets, seeds) with a total length of 3 cm. The activity of the total train is approximately 1.3 to 1.5 GBq (35 to 40 mCi). For verification of the dose rate provided by the manufacturer, we performed a check using the GafChromic film. The test dose (exactly 2 mm from the center of the long axis of the activity train) was 150 Gy. We obtained the following results for the optical density: reference source: 0.29 +/- 0.01, source C: 0.318 +/- 0.013 and source D: 0.317 +/- 0.028. For a dose rate of e.g. 0.083 Gy/s, the radiation times are 169 s for a dose of 14 Gy (vessel diameter 2.7 to 3.35 mm) or 217 s for 18 Gy (vessel diameter 3.36 to 4.0 mm), respectively. In our cath lab, the following dose rates were measured: at the lead container: 20 microSv/h, surface of the transfer device: 400 microSv/h, surface of the phantom: 20 microSv/h and surface of the bail out box: 100 microSv/h. Because moving the source train to the tip of the catheter takes only approximately 1 s, the exposure to other tissues or organs is negligible. However, inappropriate handling of the device could cause significant radiation of other organs. Therefore, the importance

Topics: Angioplasty, Balloon, Coronary; Brachytherapy; Coronary Disease; Equipment Design; Germany; Half-Life; Humans; Multicenter Studies as Topic; Recurrence; Retreatment; Stents; Strontium Radioisotopes; Treatment Outcome; Yttrium Radioisotopes

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

We report a double-blind, randomized clinical trial of intracoronary beta-radiation for prevention of restenosis after stent implantation in native coronary de novo lesions in diabetic patients.. After successful stent implantation in native coronary de novo lesions, 106 lesions in 89 diabetic patients were randomly allocated to treatment with beta-radiation with 18 Gy at 1 mm vessel depth (n = 53) or placebo treatment (n = 53).. Angiographic analysis at 9 month follow-up revealed a late lumen loss of 0.7+/-0.9 mm in the radiotherapy group versus 1.2+/-0.8 mm in the control group at the injured segment (P = 0.006), 0.9+/-1.0 versus 1.3+/-0.7 mm at the radiated segment (P = 0.02), and 0.9+/-1.0 versus 1.3+/-0.7 mm at the target segment (P = 0.04) (defined as active source length plus 5mm on proximal and distal sites). Binary restenosis rates were significantly lower in the radiation group in all subsegments (injured segment: 10.9 versus 37.3%, P = 0.003; radiated segment: 21.7 versus 49.0%, P = 0.005; target segment: 23.9 versus 49.0%, P = 0.01). Target lesion revascularization for restenosis was required in nine lesions (17.6%) in the radiotherapy group versus 18 (34.0%) in the placebo group (P = 0.05). Late thrombosis occurred in four radiated patients (after premature discontinuation of antiplatelet therapy in all), resulting in a major adverse clinical event rate of 37.2% in the brachytherapy group versus 38.6% in the placebo group (P = ns).. In diabetic patients with de novo coronary lesions, intracoronary radiation after stent implantation significantly reduced restenosis. However, this clinical benefit was reduced by the frequent occurrence of late thrombosis.

Topics: Aged; Angioplasty, Balloon, Coronary; Beta Particles; Brachytherapy; Coronary Disease; Coronary Restenosis; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Membrane Glycoprotein IIb; Prospective Studies; Regression Analysis; Stents; Strontium Radioisotopes; Treatment Outcome; Yttrium

It is an ongoing concern that intracoronary brachytherapy may possibly just delay the problem of in-stent restenosis ("late catch up"). For gamma-radiation, 3 placebo-controlled studies have shown the maintenance of the initially positive effect after 2 years, but similar data do not exist for beta-radiation. STents And Restenosis Trial (START) was the first placebo-controlled randomized trial for in-stent restenosis with beta-radiation; herein, we report the 2-year clinical follow-up.. Two hundred and forty-four patients were randomized to active treatment, 232 patients to placebo (nonactive source train) treatment. The primary end point of efficacy was target vessel revascularization (TVR); primary safety end point was any major adverse cardiac event (MACE) at 8 months and 2 years. Two-year clinical outcome in patients receiving brachytherapy was based on 195 of 244 original patients (79.9%) and in the placebo arm on 183 of 232 original patients (78.9%). TVR was significantly reduced by 25%; from 36.6% (placebo) to 27.5% (brachytherapy) remained significant after 2 years (RR .7 [.57-.98], 95% CI -9.2 [-17.5-0.8]). The Kaplan-Meier analysis for TVR and MACE showed improvement beginning approximately 90 days after radiation and remained almost constant for the 2 following years. Freedom from TVR was significantly increased from 62.4% +/- 3.8% to 71.6% +/- 3.3% (P = .027) and freedom from MACE from 58.9% +/- 3.7% to 68.0% +/- 3.4% (P = .035).. The START trial shows for the first time that the initial beneficial effects of intracoronary brachytherapy with beta-radiation using 90 Sr/ 90 Y are maintained at 2-year clinical follow-up period.

Topics: Aged; Angioplasty, Balloon, Coronary; Anticoagulants; Beta Particles; Brachytherapy; Coronary Angiography; Coronary Disease; Coronary Restenosis; Diabetes Complications; Disease-Free Survival; Female; Follow-Up Studies; Humans; Life Tables; Male; Middle Aged; Prognosis; Stents; Strontium Radioisotopes; Thrombophilia; Treatment Outcome; Yttrium Radioisotopes

Recently, it has been reported that brachytherapy catheters ruptured in vivo. Localization of lost beta-radiation-emitting seeds is a problem because no appropriate technique is available that is rapid and precise. We developed a technique to localize beta-emitting seeds utilizing the effect that beta-radiation induces bremsstrahlung. The loss of a single radioactive source was simulated in an Alderson Phantom representing a human body. The beta-induced bremsstrahlung could be detected selectively by a gamma-camera. The position of the radioactive seed could be located within 5 min with an accuracy of +/- 0.5 cm. The result of this study suggests that in an emergency case of loss of a brachytherapy source, a commercially available gamma-camera can be a valuable tool to detect lost beta-radiation-emitting seeds rapidly and precisely. In addition, the technique minimizes the patient's as well as the surgeon's exposure to radiation and reduces the extent of surgical trauma.

Topics: Beta Particles; Brachytherapy; Cardiac Catheterization; Coronary Disease; Emergency Medical Services; Equipment Failure; Gamma Cameras; Humans; Phantoms, Imaging; Radiation Injuries; Radiographic Image Interpretation, Computer-Assisted; Strontium Radioisotopes; Time Factors; Yttrium Radioisotopes

Although randomized clinical trials have demonstrated efficacy of coronary irradiation versus placebo for the treatment of in-stent restenosis (ISR), durable long-term benefit in community practice is less well defined. From January 1, 2001, through June 30, 2002, consecutive percutaneous coronary intervention (n = 3,869) were analyzed at our center with a total of 330 patients undergoing coronary irradiation for ISR (53, Ir192; 12, P32; 265 Novoste Sr90). Novoste Sr90 was successfully performed in 265 of 270 (98%) of patients attempted by 10 operators. The mean patient age was 63 years (range 35 90) with 55% male (145/265) and 45% female (120/265). ISR anatomic subsets included multi-lesion (45/265; 17%), multi-vessel (27/265; 10.0%) and saphenous vein graft (16/265; 6.0%) interventions. At a mean follow-up of 10.5 2.8 (SD) months, fifty-three (20%) of the Novoste Sr90 treated patients had returned for symptoms requiring repeat angiography. Of these, 23 patients had repeat percutaneous coronary intervention (PCI) including 2 target site revascularizations (TSR), twelve non-TSR (distinct from the radiated segment of the target vessel), and 9 non-target vessel revascularizations (TVR). Coronary artery bypass surgery was performed in 11 total patients, 4 due to TSR, and 7 due to non-TVR. Clinical TSR was 2.3% (6/265) and TVR was 6.8% (18/265). In conclusion, the Novoste SR90 Beta-Cath System for the treatment of ISR is associated with a high procedural success rate and low TSR and TVR. Revascularization in follow-up is predominantly due to progressive disease outside the radiated segment and aggressive secondary prevention, especially prolonged anti-platelet therapy, appear critical to long-term procedural success.

Topics: Adult; Aged; Aged, 80 and over; Angioplasty, Balloon, Coronary; Beta Particles; Community Health Services; Coronary Disease; Coronary Restenosis; Female; Follow-Up Studies; Humans; Male; Middle Aged; Ohio; Radiography; Stents; Strontium Radioisotopes; Treatment Outcome

The dose parameters for the beta-particle emitting 90Sr/90Y source for intravascular brachytherapy (IVBT) have been calculated by different investigators. At a distant distance from the source, noticeable differences are seen in these parameters calculated using different Monte Carlo codes. The purpose of this work is to quantify as well as to understand these differences. We have compared a series of calculations using an EGS4, an EGSnrc, and the MCNP Monte Carlo codes. Data calculated and compared include the depth dose curve for a broad parallel beam of electrons, and radial dose distributions for point electron sources (monoenergetic or polyenergetic) and for a real 90Sr/90Y source. For the 90Sr/90Y source, the doses at the reference position (2 mm radial distance) calculated by the three code agree within 2%. However, the differences between the dose calculated by the three codes can be over 20% in the radial distance range interested in IVBT. The difference increases with radial distance from source, and reaches 30% at the tail of dose curve. These differences may be partially attributed to the different multiple scattering theories and Monte Carlo models for electron transport adopted in these three codes. Doses calculated by the EGSnrc code are more accurate than those by the EGS4. The two calculations agree within 5% for radial distance <6 mm.

Topics: Beta Particles; Biophysical Phenomena; Biophysics; Brachytherapy; Coronary Disease; Humans; Monte Carlo Method; Radiotherapy Planning, Computer-Assisted; Scattering, Radiation; Strontium Radioisotopes; Yttrium Radioisotopes

Intracoronary irradiation is currently the most promising approach to reduce restenosis after percutaneous transluminal coronary angioplasty. Meanwhile numerous data are available concerning efficacy and safety of this novel method. These data confirm the results of preclinical studies that reported a dramatic reduction of neo-intima proliferation and negative remodeling. However, the number of reports on an elevated incidence of late stent thrombosis (> 30 days post intervention) are increasing. It is commonly suggested that the delayed neo-intima formation within vascular stents is responsible for this new phenomenon. We report the case of a 48-year-old man who underwent coronary irradiation therapy after stent placement in a de-novo/restenotic lesion. Despite an explicit recommendation of a combined anti-aggregatory therapy consisting of ticlopidine and acetysalicylic acid for at least 6 months, ticlopidine was withdrawn after 4 weeks. Two weeks later, the patient was readmitted to an external hospital with an acute myocardial infarction and successfully treated with thrombolysis. The angiographic and intravascular control, which was conducted after another two weeks, showed absolutely no neointima formation within the implanted stent. Thus, a late thrombotic occlusion of the implanted stent appears most likely to be the cause underlying the myocardial infarction. This case underlines, together with other existing reports, the importance of a prolonged, combined anti-aggregatory therapy after stent placement and subsequent intracoronary irradiation.

Topics: Angina Pectoris; Angioplasty, Balloon, Coronary; Aspirin; Brachytherapy; Clinical Trials as Topic; Coronary Angiography; Coronary Disease; Electrocardiography; Fibrinolytic Agents; Follow-Up Studies; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Recurrence; Stents; Strontium Radioisotopes; Thrombosis; Ticlopidine; Time Factors; Ultrasonography, Interventional; Yttrium Radioisotopes

Both beta and gamma emitters are currently used in the catheter-based intravascular brachytherapy. The dosimetric effects due to the presence of metallic stents and calcified plaques have not been fully addressed. This work compares these effects for two most commonly used beta and gamma sources ( (90)Sr and (192)Ir).. An EGS4 Monte Carlo package was used to calculate dose in water for a (90)Sr (supplied by NOVOSTE) and an (192)Ir (Supplied by BEST) source, with or without the presence of a calcified plaque or a metallic stent. Plaques of different shape (shell and disk), size and density, and two types of stainless-steel stents (ring or mesh stent) were studied. The ring stent consists of identical rings stacked along the long axis of the sources. The gap between two rings is 0.3 mm. The mesh stents are made of identical square (0.1 x 0.1 or 0.2 x 0.2 mm(2)) holes separated from each other by stainless-steel wire. The cross section of wire for both ring and mesh stents is 0.1 x 0.1 mm(2). A dose perturbation factor (DPF), defined as the ratio of the doses with and without the presence of a plaque or a stent, was introduced to quantify the effects. A carefully chosen set of EGS4 transport parameters for the small geometry in question was used in the calculation.. The radial and axial dose distributions calculated in water were found to agree with the published measurements to within 3%. The dose perturbations due to the presence of calcified plaques or metallic stents were found far more significant for the (90)Sr source than those for the (192)Ir source. Up to 30% dose reduction behind a plaque were observed for the (90)Sr source, while the dose reduction for the (192)Ir source was found to be negligible. The dose enhancement inside a plaque was as high as 10% for the beta source or 6% for the gamma source. In the presence of a stent, the DPF was in the range of 1.15-0.75 for the beta source, while it was almost equal to 1.0 for the gamma source.. The dose perturbation due to the presence of a calcified plaque or a metallic stent is significant for the beta source. The dose reduction in the region beyond a plaque or a stent could be more than 20%. For the gamma source, the dose effect behind a plaque or a stent is practically negligible. These dosimetric differences between the beta and gamma sources in the presence of a calcified plaque or metallic stent should be considered in the dose prescription of intravascular brachytherapy.

Topics: Beta Particles; Brachytherapy; Calcinosis; Coronary Disease; Gamma Rays; Iridium Radioisotopes; Monte Carlo Method; Physical Phenomena; Physics; Prosthesis Design; Radiotherapy Dosage; Stents; Strontium Radioisotopes

We describe a protocol to manufacture 82Sr/82Rb generators and 82RbCl for myocardial imaging with PET. The generators are manufactured in 3 stages: (1) preparation of a tin oxide column, (2) leak test of the generator column and (3) loading of the generator with 82Sr. The generators produced sterile and non-pyrogenic 82RbCl for i.v. injection. No significant 82Sr/85Sr breakthroughs were observed after elution with 20 1 of saline. The automated system delivered human doses of 82RbCl accurately.

Topics: Chlorides; Coronary Disease; Heart; Humans; Quality Control; Radiation Protection; Radionuclide Generators; Rubidium; Rubidium Radioisotopes; Strontium Radioisotopes; Tomography, Emission-Computed

Recent data indicate that intraluminal irradiation of coronary arteries following balloon angioplasty reduces proliferation of smooth muscle cells, neointima formation, and restenosis. We present calculations for various isotopes and geometries in an attempt to identify suitable source designs for such treatments.. Analytical calculations of dose distributions and dose rates are presented for 192Ir, 125I, 103Pd, 32P, and 90Sr for use in intracoronary irradiation. The effects of source geometry and positioning accuracy are studied.. Accurate source centering, high dose rate, well-defined treatment volume, and radiation safety are all of concern; 15-20 Gy are required to a length of 2-3 cm of vessel wall (2-4 mm diameter). Dose must be confined to the region of the angioplasty, with reduced doses to normal tissues. Beta emitters have radiation safety advantages, but may not have suitable ranges for treating large diameter vessels. Gamma emitters deliver larger doses to normal tissues and to staff. Low energy x-ray emitters such as 125I and 103Pd reduce these risks but are not available at high enough activities. The feasibility of injecting a radioactive liquid directly into the angioplasty balloon is also explored.. Accurate source centering is found to be of great importance. If this can be accomplished, then high energy beta emitters such as 90Sr would be ideal sources. Otherwise, gamma emitters such as 192Ir may be optimal. A liquid beta source would have optimal geometry and dose distribution, but available sources, such as 32P are unsafe for use with available balloon catheters.

Topics: Brachytherapy; Coronary Disease; Humans; Iodine Radioisotopes; Iridium Radioisotopes; Models, Cardiovascular; Palladium; Phosphorus Radioisotopes; Radioisotopes; Radiotherapy Dosage; Recurrence; Strontium Radioisotopes

Neointima formation contributing to recurrent stenosis remains a major limitation of percutaneous transluminal angioplasty. Endovascular low-dose gamma-irradiation has been shown to reduce intimal thickening (hyperplasia) after balloon overstretch injury in pig coronary arteries, a model of restenosis. The objective of this study was to determine whether the use of a beta-emitting radioisotope for this application would have similar effects and to examine the dose-response relations with this approach.. Normal domestic pigs underwent balloon overstretch injury in the left anterior descending and left circumflex and coronary arteries. A flexible catheter was introduced by random assignment into one of these arteries and was afterloaded with a 2.5-cm ribbon of encapsulated 90Strontium/90Yttrium sources (90Sr/Y, a pure beta-emitter). It was left in place for a period of time sufficient to deliver one of four doses: 7, 14, 28, or 56 Gy, to a depth of 2 mm. Animals were killed 14 days after balloon injury, the coronary vasculature was pressure-perfusion fixed, and histomorphometric analysis of arterial cross sections was performed. All arteries treated with radiation demonstrated significantly decreased neointima formation compared with control arteries. The ratio of intimal area to medial fracture length was inversely correlated with increasing radiation dose: control (no radiation), 0.47; 7 Gy, 0.34; 14 Gy, 0.20; 28 Gy, 0.08; and 56 Gy, 0.02 (r = -.78, P < .000001). Scanning electron microscopy demonstrated a confluent layer of endothelium-like cells both in control and in 14 Gy-irradiated arteries. There was neither evidence of significant necrosis nor excess fibrosis in the media, adventitia, or perivascular space of the coronary arteries or adjacent myocardium in the irradiated groups. Furthermore, the exposure to the staff and the total body exposure to the pig with the beta source was a small fraction of the dose previously measured and calculated with 192Ir, a gamma-emitting radioisotope.. Administration of endovascular beta-radiation to the site of coronary arterial overstretch balloon injury in pigs with 90Sr/Y is technically feasible and safe. Radiation doses between 7 and 56 Gy showed evidence of inhibition of neointima formation. A dose-response relation was demonstrated, but no further inhibitory effect was seen beyond 28 Gy. These data suggest that intracoronary beta-irradiation is practical and feasible and may aid in preventing clinical restenosis.

Topics: Angioplasty, Balloon, Coronary; Animals; Beta Particles; Brachytherapy; Coronary Disease; Coronary Vessels; Dose-Response Relationship, Radiation; Female; Microscopy, Electron, Scanning; Radiotherapy Dosage; Recurrence; Strontium Radioisotopes; Swine; Tunica Intima; Yttrium Radioisotopes

Verapamil may protect ischemic myocardium by several mechanisms: prevention of Ca overload as a direct effect of blocking Ca influx through slow channels, coronary vasodilatation, decreased contractility, or cardioplegia produced by high doses. We manipulated the experimental situation to ask whether the first mechanism alone could be protective. We studied isovolumically contracting rabbit hearts perfused at 37 degrees C, paced at 150/min, and maximally vasodilated by dipyridamole. Hearts were subjected to 60 min of low flow ischemia followed by 60 min reperfusion. Two groups were exposed to verapamil 0.5 microM beginning either 2 to 4 min before ischemia or 10 min after the onset of ischemia (when pressure development had ceased) and continuing until reperfusion. Developed pressure recovered during reperfusion to 70 +/- 4% of its initial value in hearts treated with verapamil before ischemia compared to 40 +/- 5% for control hearts and 35 +/- 11% for hearts treated with verapamil 10 min after the onset of ischemia. There was significant preservation of phosphocreatine at 10 min of ischemia and of ATP at 60 min in the early verapamil group compared to the other two. When verapamil was present before ischemia, pressure development during early ischemia was reduced to about 50% of control. Consequently there was substantial sparing of high energy phosphates and enhanced recovery of mechanical function. If verapamil was added 10 min after the onset of ischemia, when it no longer could affect cardiac work, there was no protection. Therefore, in the isolated rabbit heart, verapamil had an important protective effect only by reducing contractility of ischemic myocardium.

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Calcium; Coronary Disease; Creatine; In Vitro Techniques; Ion Channels; Male; Myocardial Contraction; Phosphocreatine; Rabbits; Strontium Radioisotopes; Vasodilation; Verapamil

The cardiac lymph from conscious animals was monitored for the presence or absence of radiolabelled 15 micrometer microspheres during: 1) control periods after left atrial injection of microspheres and b) after circumflex coronary artery (CFX) occlusions (10--20 min total or less than 40 mins 50% of control flow) followed by full reperfusions. Microspheres (15 mu) numbering 7--150 were present in the lymph within 2 hrs after the occlusions; and in three experiments, the presence of a small number in the lymph on the following day implied continual release overnight. No microspheres were present in 8--48 hr lymph samples prior to occlusions. This study suggests that some microspheres escape from the intravascular space of the myocardium and are channeled into the cardiac lymphatics; this is apparent even after short-term ischemic events.

Topics: Animals; Catheters, Indwelling; Cerium Radioisotopes; Coronary Disease; Dogs; Heart; Lymph; Lymphatic System; Microspheres; Radioisotopes; Ruthenium; Strontium Radioisotopes

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

Myocardial perfusion imaging after administration of the potent coronary vasodilator ethyl adenosine-5'-carboxylate, which increases flow to normal areas in excess of that to areas supplied by subcritically stenosed vessels, was investigated as a nonischemia-producing stimulus for detecting subcritical coronary stenosis. Preliminary studies in 10 dogs with reactive hyperemia were performed with thallium-201 and potassium-43 to determine which tracer was a better indicator of increased flow. Neither agent was a linear indicator of increased flow caused by reactive hyperemia but thallium-201, because of its imaging characteristics, was selected as a flow indicator after administration of ethyl adenosine. Five dogs were studied after placement of a subcritical stenosis on the left circumflex coronary artery. Strontium-85 microspheres were injected into the left atrium after placement of the stenosis to verify that changes in resting blood flow were only minimal. Thereafter, intravenous administration of ethyl adenosine was followed by injection of chromium-51-labeled microspheres into the left atrium and intravenous administration of thallium-201. The mean ratio of left circumflex to left anterior descending coronary arterial flow was 0.96 +/- 0.16 for the control experiment after subcritical stenosis; after administration of the vasodilator the ratio of activity levels in the two arteries was 0.43 +/- 0.09 with the chromium-51 microspheres and 0.56 +/- 0.07 with thallium-201. Imaging performed in three additional dogs after injection of microspheres in the presence of subcritical stenosis revealed a normal pattern, whereas imaging after administration of the vasodilator and thallium-201 revealed a perfusion deficit. In two additional dogs without subcritical stenosis, thallium was administered after injection of ethyl adenosine to determine that the drug alone did not cause perfusion deficits. The perfusion scans in these two dogs were normal. These studies suggest that a coronary vasodilator and thallium-201 myocardial imaging can be used to detect subcritical coronary stenosis.

Topics: Adenosine; Animals; Blood Pressure; Coronary Circulation; Coronary Disease; Dogs; Heart Rate; Hyperemia; Potassium Radioisotopes; Radioisotopes; Radionuclide Imaging; Strontium Radioisotopes; Thallium; Vasodilator Agents

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

We investigated the effect that mild coronary stenosis exerts on the ability of the coronary circulation to compensate for the increased extravascular compression that occurs in the subendocardium during tachycardia. An electromagnetic flowmeter transducer and balloon cuff occluder were implanted on the left circumflex coronary artery in seven dogs, and experiments were performed 1 week later with the dogs under sedation but conscious. Stenosis of the left circumflex artery was produced by partial inflation of the cuff occluder. We determined coronary blood flow distribution by the radioactive microsphere technique, injection 200,000 15mu spheres into the left ventricular cavity during (1) a control period, (2) stenosis of the left circumflex artery and a normal heart rate, and (3) stenosis of the left circumflex artery and tachycardia. When the heart rate was normal, the degree of stenosis used caused no change in myocardial microsphere distribution but eliminated postocclusion reactive hyperemia. Thus, reserve coronary vasodilation compensated for the stenosis. With the degree of stenosis kept constant, an increase in heart rate to 196 beats/min caused a marked transmural shift in distribution of microspheres from subendocardium into subepicardium within the region of the left ventricle supplied by the left circumflex artery. There was no significant transmural shift in the region supplied by the uninvolved left anterior descending coronary artery. Myocardial lactate extraction decreased. These results suggest that when reserve coronary vasodilation has already been utilized to compensate for coronary stenosis, the increased extravascular coronary compression from tachycardia causes subendocardial ischemia and hypoxia.

Topics: Animals; Atropine; Blood Flow Velocity; Cesium; Coronary Circulation; Coronary Disease; Dogs; Heart Ventricles; Lactates; Microspheres; Myocardium; Niobium; Radioisotopes; Statistics as Topic; Strontium Radioisotopes; Tachycardia; Transducers

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

Following intravenous administration, the myocardial concentration of tracer thallium-201, potassium-43, and rubidium-81 were determined in mice; thallium was present in the greatest concentration in the myocardium (2.08% compared 1.25% for potassium and 1.15% for rubidium at 10 minutes). The regional myocardial distribution of thallium-201 was determined in dogs under conditions of normal flow, and total occlusion, and compared with potassium-43 (r=0.97). The regional distribution of thallium-201 was compared to microspheres under conditions of partial occlusion and reactive hyperemia (r=0.97). Thallium-201 was evaluated in a series of phantom scans, which demonstrated that the low energy X-ray of thallium was suitable for imaging. These results suggest that thallium-201 can be used for the evaluation of the distribution of regional myocardial perfusion.

Topics: Animals; Coronary Circulation; Coronary Disease; Dogs; Mice; Microspheres; Myocardium; Potassium Isotopes; Radionuclide Imaging; Rubidium; Strontium Radioisotopes; Thallium

In this study, we have tried to determine the magnitude of the inaccuracy of the radioactive microsphere method - due to variations in the diameter distribution of the spheres - for measuring regional myocardial blood flow after coronary artery occlusion. In 5 mongrel dogs, three types of 15 mum microspheres, labelled with 125I, 141Ce or 85Sr, were injected simultaneously after the descending branch of the left coronary artery had been ligated. Myocardial samples wert taken from the left ventricle and divided into four groups according to the number of spheres per sample. The radioactivity of the various isotopes per gram tissue was expressed as percentage of their activity per milliliter of the reference sample. The diameter distribution of microspheres, labelled with each of the isotopes, was determined light-microscopically in suspensions belonging to three different batches. The relative error, as determined from the difference in relative radioactivity of the various types of microspheres in the tissue samples, was higher than the theoretical error for each of the number of spheres per sample. It is very likely that this discrepancy is caused by the differences in diameter distribution of the various types of microspheres, resulting in non-random error. The smaller spheres tended to go to low flow areas and the larger ones to high flow areas. Because of the non-randomness, the error due to diameter variations in the spheres can be diminished by randomizing the order of injection of the various isotopes. The present study indicates that the relatively high degree of accuracy of the microsphere method for the determination of blood flow to large parts of the myocardium with an unimpeded coronary circulation, as was described in literature, cannot be extrapolated to the determination of regional myocardial blood flow after coronary artery occlusion, when the combination of small tissue samples, variations in the diameter distribution of the spheres and an unevenly distributed myocardial blood flow unfavourably affect the accuracy of the method.

Topics: Animals; Cerium Isotopes; Coronary Disease; Coronary Vessels; Diagnostic Errors; Dogs; Evaluation Studies as Topic; Female; Iodine Radioisotopes; Male; Microspheres; Radiometry; Radionuclide Imaging; Regional Blood Flow; Strontium Radioisotopes

Topics: Animals; Blood Flow Velocity; Cardiopulmonary Bypass; Cerium Isotopes; Coronary Circulation; Coronary Disease; Dogs; Electric Stimulation; Heart Ventricles; Hydrogen-Ion Concentration; Hyperemia; Lactates; Myocardium; Oxygen Consumption; Potassium; Radioisotopes; Rheology; Scandium; Strontium Radioisotopes; Time Factors; Vascular Resistance; Ventricular Fibrillation

This study was designed to determine whether coronary vasodilation distal to a flow-limiting coronary artery stenosis could result in redistribution of myocardial blood flow to produce subendocardial underperfusion. Studies were performed in 10 awake dogs chronically prepared with electromagnetic flow-meters and hydraulic occluders on the left circumflex coronary artery. Regional myocardial blood flow was measured using radionuclide-labeled microspheres, 7-10 mum in diameter, injected into the left atrium. A 5(-s) coronary artery occlusion was followed by reactive hyperemia with excess inflow of arterial blood effecting 375+/-20% repayment of the blood flow debt incurred during occlusion. When, after a 5(-s) occlusion, the occluder was only partially released to hold arterial inflow to the preocclusion level for 20 s before complete release, the delayed reactive hyperemia was augmented (mean blood flow repayment = 610+/-45%, P < 0.01). This augmentation of the reactive hyperemia suggested that ischemia was continuing during the interval of coronary vasodilation when coronary inflow was at the preocclusion level. Measurements of regional myocardial blood flow demonstrated that endocardial flow slightly exceeded epicardial flow during control conditions. When arterial inflow was limited to the preocclusion rate during vasodilation after a 5(-s) total coronary artery occlusion, however, flow to the subepicardial myocardium was increased at the expense of underperfusion of the subendocardial myocardium. Thus, in the presence of a flow-limiting proximal coronary artery stenosis, ischemia-induced coronary vasodilation resulted in redistribution of myocardial blood flow with production of subendocardial ischemia in the presence of a net volume of arterial inflow which, if properly distributed, would have been adequate to prevent myocardial ischemia.

Topics: Animals; Cerium Isotopes; Computers; Coronary Circulation; Coronary Disease; Coronary Vessels; Dogs; Electromagnetic Phenomena; Endocardium; Heart Rate; Hemodynamics; Hyperemia; Ischemia; Radioisotopes; Rheology; Scandium; Spectrometry, Gamma; Strontium Radioisotopes

Topics: Animals; Blood; Blood Flow Velocity; Cardiopulmonary Bypass; Cerium Isotopes; Coronary Circulation; Coronary Disease; Dogs; Electric Stimulation; Heart Ventricles; Hydrogen-Ion Concentration; Hyperemia; Lactates; Myocardium; Oxygen Consumption; Potassium; Radioisotopes; Scandium; Strontium Radioisotopes; Ventricular Fibrillation

Topics: Animals; Aorta; Cardiac Output; Cerium Isotopes; Consciousness; Coronary Circulation; Coronary Disease; Dogs; Heart Atria; Heart Rate; Heart Ventricles; Microspheres; Radioisotopes; Regional Blood Flow; Strontium Radioisotopes; Vascular Resistance

Topics: Animals; Coronary Circulation; Coronary Disease; Dogs; Male; Microspheres; Rubidium; Strontium Radioisotopes

Topics: Animals; Blood Pressure; Cesium Isotopes; Coronary Circulation; Coronary Disease; Dogs; Electrocardiography; Heart; Heart Rate; Male; Microspheres; Radioisotopes; Strontium Radioisotopes

Topics: Albumins; Animals; Coronary Circulation; Coronary Disease; Dogs; Electric Stimulation; Hyperemia; Microspheres; Potassium Isotopes; Radioisotopes; Radionuclide Imaging; Regional Blood Flow; Rest; Strontium Radioisotopes; Technetium

Topics: Animals; Assisted Circulation; Cesium Isotopes; Chromium Radioisotopes; Coronary Circulation; Coronary Disease; Dogs; Female; Ischemia; Male; Methods; Microspheres; Radioisotopes; Strontium Radioisotopes; Time Factors

Topics: Animals; Blood Flow Velocity; Blood Pressure; Cardiac Output; Cesium Isotopes; Coronary Circulation; Coronary Disease; Coronary Vessels; Dogs; Electrocardiography; Heart Ventricles; Hemoglobins; Ischemia; Ligation; Microspheres; Oxygen; Oxygen Consumption; Radioisotopes; Strontium Radioisotopes