technetium-tc-99m-pyrophosphate and Disease-Models--Animal

The effect of hyperbaric oxygen treatment on skeletal muscle submitted to 3 or 4 hours of ischemia was studied in a rat hindlimb model after 48 hours of reperfusion. Forty-eight male Sprague-Dawley rats were allocated to four groups. In the two treatment groups, hyperbaric oxygen was given for 45 minutes at 2.2 atm immediately and 4,8,16,24,32, and 40 hours after release of the ischemia-inducing tourniquet. The injury to skeletal muscle was quantified from the uptake of 99mtechnetium-pyrophosphate (injected intravenously after 45 hours of reperfusion) in anterior tibial muscle harvested 3 hours later. The uptake was significantly lower in hyperbaric oxygen-treated rats than in untreated rats with 3 or 4 hours of ischemia (p < 0.01 and P < 0.05). After 4 hours of ischemia, the changes in levels of the intracellular muscle compounds adenosine triphosphate, phosphocreatine, and lactate were less in the hyperbaric oxygen-treated rats than in the untreated animals.

Topics: Animals; Biopsy; Disease Models, Animal; Hyperbaric Oxygenation; Ischemia; Male; Muscle, Skeletal; Radionuclide Imaging; Random Allocation; Rats; Rats, Sprague-Dawley; Technetium Tc 99m Pyrophosphate; Time Factors

Taking an overdose of AMT, a commonly prescribed tricyclic antidepressant drug, has an increased risk of sudden cardiac death. The cardiotoxicity of amitriptyline (AMT) is a commonly observed toxicity with high morbidity and mortality rates in emergency departments (ED). Nevertheless, there are still no effective treatment options for AMT-induced cardiotoxicity. The aim of the present study was to evaluate the effects of paricalcitol (PRC), a Vitamin D receptor agonist, using electrocardiographic (ECG), biochemical, and scintigraphic methods. Twenty-eight male Wistar rats were randomly divided into four groups: untreated control (CON), amitriptyline-induced cardiotoxicity (AMT), paricalcitol (PRC), and amitriptyline + paricalcitol (AMT + PRC). Cardiotoxicity was induced by intraperitoneal (i.p) injection of a single-dose AMT (100 mg/kg). PRC was administered as 10 μg/kg (i.p.) after the injection of AMT. We examined ECG, biochemical, and scintigraphic results of PRC administration on AMT-induced changes. Cardiotoxicity of AMT was characterized by conduction abnormalities (increased QRS complex, T wave, and QT interval duration and elevation of ST segment amplitude), elevated

Topics: Action Potentials; Amitriptyline; Animals; Antidepressive Agents, Tricyclic; Biomarkers; Cardiotoxicity; Disease Models, Animal; Electrocardiography; Ergocalciferols; Heart; Heart Diseases; Heart Rate; Male; Positron Emission Tomography Computed Tomography; Predictive Value of Tests; Radiopharmaceuticals; Rats, Wistar; Technetium Tc 99m Pyrophosphate; Troponin T

To develop a model that compares 2 different routes of antivenom administration (standard intravenous [IV] administration vs regional administration below a tourniquet) to assess their ability to limit muscle necrosis in a rabbit model of rattlesnake venom poisoning.. New Zealand white rabbits were randomly assigned to 4 groups. All animals underwent general anesthesia and were then injected intramuscularly (IM) with a sublethal dose of western diamond-back rattlesnake (Crotalus atrox) venom in the right thigh and a similar volume of normal saline (NS) control in the left thigh. Thirty minutes later, standard treatment group animals (n = 4) received 1 vial of reconstituted Antivenin (Crotalidae) Polyvalent (ACP) and 10 mL of NS through an ear vein. Experimental treatment group animals (n = 4) had their lower extremities exsanguinated and isolated by arterial tourniquets. One vial of ACP was then given through a distal IV in the envenomed extremity, and 10 mL of NS was given through an IV in the sham extremity. Tourniquets were removed 30 minutes later. Positive control group animals (n = 2) similarly had their lower extremities exsanguinated and isolated by tourniquets. They then received 10 mL of NS through distal IVs in each lower extremity. Tourniquets were again removed after 30 minutes. Negative control group animals (n = 2) received 2 doses of NS only (10 mL each) through an ear vein. Serum creatinine phosphokinase (CPK) levels were drawn at baseline and 48 hours following venom injection. At 48 hours, the animals were injected with technetium pyrophosphate. Two hours later, they were euthanized, and the lower extremities were scanned to determine levels of radionucleotide uptake in envenomed muscles compared to contralateral sham-injected muscles. The anterior thigh muscle groups were then removed, fixed, stained, sectioned, and analyzed in a blinded fashion by a veterinary pathologist for muscle necrosis grading.. There was no evidence of statistically significant differences in changes in serum CPK levels (from baseline to 48 hours), technetium pyrophosphate uptake ratios (right leg/left leg), or muscle necrosis indices in any 2-group analysis.. Results of this pilot study do not suggest any beneficial effect of ACP, in the dose and routes used, in limiting local muscle necrosis following IM rattlesnake venom poisoning in the rabbit model.

Topics: Animals; Antivenins; Creatinine; Crotalid Venoms; Crotalus; Disease Models, Animal; Hindlimb; Infusions, Intravenous; Injections, Intramuscular; Muscle, Skeletal; Necrosis; Rabbits; Radionuclide Imaging; Random Allocation; Technetium Tc 99m Pyrophosphate

The mechanism of testicular ischemia-reperfusion injury has not been well delineated. We determined the efficacy of a biocompatible surfactant (tetronic 1107) to reduce tissue injury and evaluated cell membrane integrity as reflected by calcium ion permeability in an in vivo animal model of testicular ischemia-reperfusion.. Three groups of male Sprague-Dawley rats (6 per group) were studied. Group 1 was the nonoperative control, and groups 2 and 3 underwent 4 hours of unilateral testicular ischemia followed by 4 hours of reperfusion. Ten minutes after reperfusion 0.4 ml. saline was administered intravenously to group 2 and 180 mg./kg. surfactant tetronic 1107 to group 3. 99mTechnetium pyrophosphate was used to monitor calcium ion uptake by the ipsilateral and contralateral testicles. Both testicles were also examined histologically.. The surfactant treated animals had markedly diminished hemorrhagic discoloration and vascular congestion compared to saline treated animals. These results were confirmed microscopically with improved nuclear chromicity and disarray of germ cell layers of the seminiferous tubules. The surfactant treated group also had a statistically significant (p <0.05) reduction in radiotracer uptake compared to the saline treated animals, confirming a reduction in calcium ion permeability.. The results of this study suggest that tetronic 1107 is effective in reducing tissue damage in a testicular ischemia-reperfusion animal model.

Topics: Animals; Calcium; Disease Models, Animal; Ethylenediamines; Male; Radiopharmaceuticals; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Seminiferous Tubules; Spermatic Cord Torsion; Surface-Active Agents; Technetium Tc 99m Pyrophosphate; Testis

To study the relationship between ischaemia-reperfusion and multiple organ dysfunction syndrome (MODS), a new anaesthesia method was required to be applied to C57BL/6 mice. These mice are also used in a well accepted, standardized model for MODS using intraperitoneally administered zymosan (zymosan induced general inflammation, ZIGI). The aim was to develop a new model for ischaemia-reperfusion with 6 h of anaesthesia. This and further specific requirements for the combination of ischaemia-reperfusion and the ZIGI method, made us select inhalational anaesthesia using isoflurane in oxygen. This study evaluates whether long-term anaesthesia confounds the results of ischaemia-reperfusion and the ZIGI model. In addition the benefits of using the analgesic buprenorphine were evaluated. Ischaemia was induced with a tourniquet around the hindlimb. Ischaemia and reperfusion were verified by imaging a radioactive tracer with a gamma-camera. It was established that anaesthesia with isoflurane in oxygen caused little perturbation of body temperature and respiratory rate. A survival rate of 89% without noteworthy influence on organs was obtained. Buprenorphine proved to provide adequate analgesia and had no influence on measured parameters. In our experimental setting, this model with long duration anaesthesia allowed us to induce ischaemia and reperfusion of the hindlimb without perturbation of measurements. It also allowed good exposure of the abdomen and facilitated combination with the ZIGI model.

Topics: Analgesics, Opioid; Anesthesia; Anesthetics, Inhalation; Animals; Body Temperature; Buprenorphine; Disease Models, Animal; Isoflurane; Male; Mice; Mice, Inbred C57BL; Organ Size; Radionuclide Imaging; Radiopharmaceuticals; Reperfusion Injury; Respiration; Technetium Tc 99m Pyrophosphate

Due to the fact that there were difficulties in interpreting the cardiac scintigrams after 99mTC pyrophosphate had been given to patients with coronary heart disease without acute myocardial infarction, an experimental study was undertaken. The scintigraphic characteristics were examined in 10 cats following ligation of the interventricular artery at its middle third for more than 20 min, followed by myocardial reperfusion, histochemical and electron microscopic studies. Cat interventricular artery occlusion for a more than 20 min was found to be followed by specific ischemic changes in ECG and myocardial accumulation of 99mTc pyrophosphate. The histochemical and electron microscopic studies indicated that there were both reversible and irreversible cardiomyocyte lesions. Reversible myocardial changes were detected not only in the ischemic area, but in the other myocardial regions away from the basin of the ligated artery. If occlusion was short, the rate of myocardial tracer accumulation rapidly became lower; with long-term occlusion or profound myocardial damage caused by reperfusion, tracer accumulation became higher. There is experimental evidence for applying 99mTc-pyrophosphate scintigraphy in the clinical setting to reveal reversible myocardial changes that are most common in chronic coronary heart disease.

Topics: Animals; Cats; Coronary Disease; Diphosphates; Disease Models, Animal; Heart; Microscopy, Electron; Myocardium; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

Limiting the rate of reperfusion blood flow has been shown to be beneficial locally in models of ischemia-reperfusion injury. We investigated the effects of this on eicosanoids (thromboxane B2, 6-keto-PGF1 alpha, and leukotriene B4), white blood cell activation, and skeletal muscle injury as quantitated by triphenyltetrazolium chloride and technetium-99m pyrophosphate after ischemia-reperfusion injury in an isolated gracilis muscle model in 16 anesthetized dogs. One gracilis muscle in each dog was subjected to 6 hours of ischemia followed by 1 hour of limited reperfusion and then by a second hour of normal reperfusion. The other muscle was subjected to 6 hours of ischemia followed by 2 hours of normal reperfusion. Six dogs each were used as normal reperfusion controls (NR) and limited reperfusion controls (LR), with 5 dogs being treated with a thromboxane synthetase inhibitor (LR/TSI) and another five with a leukotriene inhibitor (LR/LI). LR in all three groups (LR, LR/TSI, and LR/LI) showed a benefit in skeletal muscle injury as measured by triphenyltetrazolim chloride and technetium-99m pyrophosphate when compared with NR. However, there was no significant difference between the groups with LR regarding eicosanoid levels and white blood cell activation when compared with NR. These results demonstrate that LR produces benefits by mechanisms other than those dependent upon thromboxane A2, prostacyclin, or white blood cell activation.

Topics: Animals; Blood Flow Velocity; Diphosphates; Disease Models, Animal; Dogs; Eicosanoids; Leukocytes; Muscles; Reperfusion Injury; Technetium; Technetium Tc 99m Pyrophosphate; Tetrazolium Salts; Time Factors

The susceptibility of the cardiovascular system to exposure to a high-boiling coal liquid (heavy distillate, HD) was studied in the rat using an isoproterenol (ISO) myocardial infarction model. Male Fischer rats were exposed to HD by inhalation (0.7 mg/l), 6 h/day, 5 days/week, for 6 weeks. After a 10-day recovery period, sham-exposed and HD-exposed rats were injected subcutaneously with 0, 20, 40 or 60 mg ISO/kg body weight. Blood pressure, heart rate, electrocardiogram and 99mTc uptake by the heart were measured 1 day later. A dose-related increase was observed in the uptake of 99mTc by the hearts of both sham-exposed and HD-exposed animals after ISO injection; however, uptake by the sham-exposed group was significantly greater than that of exposed groups. The most striking observation was a 20% elevation in arterial blood pressure of HD-exposed rats over that of sham-exposed animals when no ISO was injected. These results suggest that the cardiovascular system could be detrimentally affected by exposure to coal-derived complex mixtures and, possibly, to other complex organic mixtures.

Topics: Administration, Inhalation; Animals; Blood Pressure; Coal Tar; Diphosphates; Disease Models, Animal; Dose-Response Relationship, Drug; Electrocardiography; Heart Rate; Isoproterenol; Male; Myocardial Infarction; Rats; Rats, Inbred F344; Technetium; Technetium Tc 99m Pyrophosphate; Time Factors

The relationship between myocardial lactate metabolism and the energy dose of direct countershock was studied in 15 dogs anesthetized with halothane. Five dogs received two shocks of 5 joules delivered energy each, five animals received two shocks of 10 joules delivered energy each, and five dogs received two shocks of 20 joules delivered energy each. All animals had positive myocardial lactate extraction in the baseline state (5 joules, 38% +/- 23.7 (SD); 10 joules, 59.6% +/- 11.4; 20 joules, 38% +/- 11.1). Lactate extraction after countershock progressively decreased with increasing energy dose and then returned to baseline. The maximal reduction in percent lactate extraction increased with increasing energy dose (5 joules, 13.9% +/- 16.1; 10 joules, 33% +/- 37; 20 joules, 30.5% +/- 37.5) and seemed to reach a threshold below which no further decrease occurred. Myocardial damage, as measured by a damage index derived from myocardial uptake of technetium-99 pyrophosphate, increased steadily with increasing energy dose (2.0 +/- 2.5 with 5-joule shocks; 38 +/- 32 with 10 joules; and 99 +/- 70 with 20 joules). These results show a consistent reduction in aerobic metabolism immediately following electric countershock. Even at low-energy doses, myocardial lactate extraction showed a detectable decrease and at higher energies approached net lactate production. Reductions of global lactate extraction did not completely predict the amount of myocardial damage. Localized measures of anaerobic metabolism or mitochondrial function might provide a better correlation with localized damage.

Topics: Anesthetics, Inhalation; Animals; Cardiomyopathies; Differential Threshold; Disease Models, Animal; Dogs; Electric Countershock; Halothane; Lactic Acid; Myocardium; Technetium Tc 99m Pyrophosphate; Time Factors

Abnormal loculated or diffuse blood pools adjacent to the heart have been observed in patients with pericardial bleeding who have been imaged by gated equilibrium radionuclide ventriculography (RNV). To study the scintigraphic appearance of fresh pericardial blood, we performed equilibrium RNV in six dogs with measured volumes (10, 30, or 50 ml) of intrapericardial blood. Loculated and diffuse pericardial blood was simulated by injecting the blood either into an intrapericardial balloon, or freely into the pericardial space. Ability to detect pericardial blood was determined by blinded review, and blood volume analysis was attempted by measuring its scintigraphic thickness, brightness (relative to the left ventricle), extent, and background-subtracted count rate and a peak count index. Detection rates for 10, 30, and 50 ml were all 100% for loculated pericardial blood, and 67%, 100% and 100% for free pericardial blood, with the use of three scintigraphic views. Visually determined "extent" of the abnormal blood pool was the most reliable indicator of pericardial blood volume. When the volume was 30 ml or more, at least 40% of the heart was surrounded in 26 of 27 cases (96%); the specificity of this finding was 90%. We conclude from this animal study that RNV should be a sensitive method for detecting pericardial bleeding; visual appearance permits qualitative assessment of the volume of accumulated labeled blood.

Topics: Animals; Blood Volume; Diphosphates; Disease Models, Animal; Dogs; Erythrocytes; Heart Ventricles; Hemorrhage; Pericardium; Radionuclide Imaging; Technetium; Technetium Tc 99m Pyrophosphate

To determine the validity of a method for induction of experimental hemarthrosis in dogs and for the nuclear imaging of hemarthrosis, serial technetium-99m pyrophosphate [( 99mTc]PYP) flow and blood-pool scans were performed monthly in eight dogs who received bi-weekly injections of autologous blood into their femoro-tibial joints (also called stifle joint). In four control dogs, one joint was injected with saline while the other joint received only a sham injection. In addition, two dogs received intra-articular injections of autologous blood into their right stifle joint and saline into their left stifle joint. These dogs were studied with 99mTcO4 joint scintigraphy at monthly intervals. The dogs were periodically taken out of the study and explored surgically. Pathologic examination of synovial tissue was performed. Serial radiographs were also obtained and correlated with the scan and surgical findings. There was a striking abnormal increase in blood-pool activity of [99mTc]PYP in the treated stifle joints, commencing at the first examination after 1 mo of blood injections and continuing for the length of the study. All radiographs showed only minimal joint space widening and some soft-tissue swelling. On pathologic examination, both grossly and microscopically, there was profuse pannus formation, with intense inflammatory infiltrate replacing much of the subsynovial fat. The scintigraphic findings correlated well with these pathologic findings. This study not only validates this method for simulating hemophilic hemarthrosis but also suggests that [99mTc]PYP joint scintigraphy is a simple, and noninvasive method for monitoring the early changes in hemophilic arthropathy and is superior to pertechnetate imaging for this disease process. Instead of the previously recommended delayed bone images, we recommend, in addition, flow studies to assess joint hypervascularity and immediate static images to visualize the synovium and joint capsule.

Topics: Animals; Blood; Diphosphates; Disease Models, Animal; Dogs; Hemarthrosis; Hindlimb; Injections, Intra-Articular; Joints; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Technetium; Technetium Tc 99m Pyrophosphate

Topics: Animals; Diphosphates; Disease Models, Animal; Dogs; Female; Leg Injuries; Male; Osteomyelitis; Pentetic Acid; Radionuclide Imaging; Technetium; Technetium Tc 99m Pentetate; Technetium Tc 99m Pyrophosphate

An animal model of arthritis in the rabbit was employed to assess the radioactivity contribution of joint tissues to externally monitored scintigram positivity. Bone contained the greatest total amount of radioactivity whether the imaging agent was technetium pertechnetate or pyrophosphate, although the greatest percent increase in the arthritis joints over control joints was seen in synovium. Mid-shaft bone in the same region as the arthritic joint also showed increased radioactivity compared with control.

Topics: Animals; Arthritis; Diphosphates; Disease Models, Animal; Evaluation Studies as Topic; Femur; Injections, Intra-Articular; Knee Joint; Rabbits; Radionuclide Imaging; Sodium Pertechnetate Tc 99m; Synovial Fluid; Synovial Membrane; Technetium; Technetium Tc 99m Pyrophosphate; Tissue Distribution