Coupling of transient near infrared photonic with magnetic nanoparticle for potential dissipation-free biomedical application in brain.

Combined treatment strategies based on magnetic nanoparticles (MNPs) with near infrared ray (NIR) biophotonic possess tremendous potential for non-invasive therapeutic approach. Nonetheless, investigations in this direction have been limited to peripheral body region and little is known about the potential biomedical application of this approach for brain. Here we report that transient NIR exposure is dissipation-free and has no adverse effect on the viability and plasticity of major brain cells in the presence or absence superparamagnetic nanoparticles. The 808 nm NIR laser module with thermocouple was employed for functional studies upon NIR exposure to brain cells. Magnetic nanoparticles were characterized using transmission electron microscopy (TEM), X-ray diffraction (XRD), dynamic laser scattering (DLS), and vibrating sample magnetometer (VSM). Brain cells viability and plasticity were analyzed using electric cell-substrate impedance sensing system, cytotoxicity evaluation, and confocal microscopy. When efficacious non-invasive photobiomodulation and neuro-therapeutical targeting and monitoring to brain remain a formidable task, the discovery of this dissipation-free, transient NIR photonic approach for brain cells possesses remarkable potential to add new dimension.

Cytotoxicity of Metal Ions Released from Nitinol Alloys on Endothelial Cells.

Most implantable medical devices are expected to function in the body over an extended period of time. Therefore, immersion tests under simulated conditions can be useful for assessing the amount of metal ions released in situ. In this investigation, dissolved ions from as-received binary and ternary Nitinol alloys in cell culture media were periodically measured under static and dynamic conditions. Endothelial cells were grown in aliquots of culture media obtained and the effect of dissolved ions on cell proliferation and viability of endothelial cells (HUVEC) was studied by cytotoxicity assays. The concentration of metal ions in the media was measured by inductively coupled plasma mass spectrometry.

Cytotoxicity of Ni from Surface-Treated Porous Nitinol (PNT) on Osteoblast Cells.

The leaching of nickel from the surface of porous Nitinol (PNT) is mainly dependent on its surface characteristics, which can be controlled by appropriate surface treatments. In this investigation, PNT was subjected to two surface treatments, namely, water-boiling and dry-heating passivations. Phosphate buffer saline (PBS) solutions obtained from cyclic potentiodynamic polarization tests on PNT were employed to assess the cytotoxicity of Ni contained therein on osteoblast cells by Sulforhodamine B (SRB) assay. In addition, similar concentrations of Ni were added exogenously to cell culture media to determine cytotoxic effects on osteoblast cells. The morphologies of the untreated and the surface-treated PNTs were examined using SEM and AFM. Furthermore, growth of human osteoblast cells was observed on the PNT surfaces.

Dehydration of mature and immature sickle red blood cells during fast oxygenation/deoxygenation cycles: role of KCl cotransport and extracellular calcium.

Sickle red blood cells (RBC) become dehydrated as a consequence of potassium loss. This process depends at least partly on deoxygenation and may be influenced by the presence of oxygenation/deoxygenation cycles and the frequency of cycling. In this study, sickle RBC were subjected to approximately 180 oxygenation/deoxygenation cycles during 4 hours to evaluate RBC dehydration with cycle periods more similar to in vivo cycles than those in previous studies. A continuous-flow, steady-state apparatus circulated a dilute RBC suspension through gas-permeable silicone tubing with segments that were exposed to either nitrogen or ambient oxygen. The percentage of sickling and partial pressure of oxygen were measured by means of sampling ports in the deoxygenation and oxygenation regions. The density increase (dehydration) of young (transferrin receptor-positive) and mature (transferrin receptor-negative) RBC and the requirements for calcium and chloride were evaluated. Density increase correlated with the percentage of sickled cells at the deoxygenation sampling port and was observed only in the presence of calcium, thereby implicating the calcium-dependent potassium channel (Gardos pathway). Density increase was not dependent on the presence of chloride, making it unlikely that KCl cotransport was an important pathway under these conditions. (Blood. 2000;95:2164-2168)

Myocardial kinetics of 99m technetium-Q agents: studies in isolated cardiac myocyte, isolated perfused rat heart, and canine regional myocardial ischemia models.

OBJECTIVE: Based on reports of high cellular uptake and low plasma binding of nonreducible mixed ligand Tc(III) cations (Q complexes) and high linear uptake versus blood flow of 99mTc-Q3 in canine hearts, the authors hypothesized that the two Q complexes, 99mTc-Q63 and 99mTc-Q64, would have high cell uptake and better differentiation between ischemic and nonischemic myocardium compared with other 99mTc-based compounds. METHODS: Uptake and retention kinetics of 99mTc-Q63 and 99mTc-Q64 were measured in isolated rat cardiac myocytes, isolated perfused rat hearts, and intact canines and compared with previously reported Q-based compounds, a clinically available 99mTc perfusion agent (sestamibi), and 201Tl. RESULTS: Uptake of Q63, Q64, and sestamibi by isolated cardiac myocytes was similar. Maximum extraction (Emax) of Q64 by isolated perfused rat hearts was greatest among the 99mTc agents (P < 0.02), but net extraction (Enet) of Q64 was not different from Q63 or sestamibi 3 minutes after tracer injection. By 15 minutes, 201Tl Enet was lower than Q63, Q64, and sestamibi (P < 0.05). Among 99mTc agents, the uptake versus flow of Q3, Q63, and Q64 by canine heart was superior to Q12 and sestamibi (P < 0.05). CONCLUSIONS: The activity of Q63 and Q64 in the myocardium is related to actual myocardial blood flow over a broad, clinically relevant range of flows. The ischemic-to-normal zone activity distributions of Q63 and Q64 approximate actual flow in a manner more like that of 201Tl than sestamibi or Q12. These results provide a rational foundation in support of further evaluation of Q63 and Q64 in humans.

Reliability of technetium-99m Q12 and thallium-201 myocardial activity measurements after triphenyl tetrazolium chloride myocardial staining by perfusion.

RATIONALE AND OBJECTIVES: Investigations in animal models of severe myocardial ischemia or infarction use triphenyl tetrazolium chloride (TTC) staining to document infarction size histologically and to correlate these data with uptake measurements of radiolabeled tracers. Previously published data suggest that TTC staining itself has an important impact on myocardial tracer activity measurements. The authors hypothesized that TTC staining by perfusion has no significant effect on relative regional myocardial activity measurements of technetium-99m Q12 and thallium-201 in an open-chest canine model. METHODS: Eight dogs underwent left anterior descending artery occlusion for 2 hours with 30 minutes of reperfusion, followed immediately by injection of technetium-99m Q12 (n = 4) or thallium-201. Total myocardial activity was recorded in a dose calibrator, and regional myocardial samples were obtained by Cope needle biopsies from the ischemic and normal zones, both before and after TTC staining. RESULTS: The mean percent activity retention for the whole heart after perfusion staining with TTC was significantly reduced when compared to the preperfusion value for both technetium-99m Q12 and thallium-201. Regional measurements revealed no significant difference between the mean percent retention of technetium-99m Q12 in the ischemic and normal zones. After TTC perfusion, regional mean percent retention of thallium-201 was similar in the ischemic and normal zones. CONCLUSIONS: In a canine model of myocardial ischemia and infarction with reperfusion, TTC staining can be performed by coronary artery perfusion without significantly affecting comparative regional measurements of either technetium-99m Q12 or thallium-201. Whole heart tracer retention is significantly reduced by TTC perfusion staining, but thallium-201 is more affected than technetium-99m Q12.

Uptake of seven myocardial tracers during increased myocardial blood flow by dobutamine infusion.

RATIONALE AND OBJECTIVES: Direct comparison of myocardial perfusion tracers has been made difficult by variability in experimental models, and by a virtual absence of data comparing tracer uptake to myocardial blood flow under conditions of increased myocardial oxygen consumption, similar to what occurs with dynamic exercise. METHODS: Tracer uptake versus myocardial blood flow was evaluated for thallium-201 (201TI) and six technetium-99m (99mTc) myocardial-imaging agents in 24 open-chest canines with an occluded left-anterior descending coronary artery during dobutamine infusion. Data were fitted to the exponential model y = ax(1 - exp[-PSc/x]), where y is the tissue tracer/g normalized to normal (activity at 1 mL/minute/g) and x is the blood flow measured by the radioactive microsphere method. RESULTS: With dobutamine, myocardial tracer uptake was linear across a wide range of ischemic and hyperemic flows for each tracer. Based on the permeability surface area product, 201TI and 99mTc Q3 provided the best tracer estimate of myocardial blood flow (5.30+/-0.86 mL/minute/g, r = 0.91; 5.46+/-0.58 mL/minute/g, r = 0.94, respectively). Correlation coefficient (r) values for other tracers studied were 99mTc Q4 (r =0.93), 99mTc Q12 (r = 0.93), 99mTc sestamibi (r = 0.90), 99mTc tetrofosmin (r = 0.96), and 99mTc-N-Noet (r = 0.82). CONCLUSIONS: Of the 99mTc tracers examined under conditions of dobutamine-altered myocardial contractility, the myocardial uptake properties of 99mTc Q3 were most similar to those of 201TI.

Intravascular irradiation using Re-186 liquid-filled balloon catheters: correlation between experimental and theoretical studies.

PURPOSE: Optimization of intravascular radiation to reduce stenosis following coronary angioplasty requires the ability to predict the patterns of radiation dose distribution. This investigation evaluated the agreement between Monte Carlo simulations and experimental radiation dose measurements for a radioisotope liquid-filled balloon catheter in a tissue equivalent phantom. METHODS AND MATERIALS: Direct measurements of the radiation dose from Re-186 liquid-filled balloons were made using thermoluminescent dosimeters (TLDs) and radiochromic film. Monte Carlo simulations were carried out using the Monte Carlo N-Particle code system (MCNP4B). RESULTS: The Monte Carlo generated dose values agreed with the experimentally determined results within the statistical uncertainty. A slightly higher penetration was indicated by regression analysis for the TLD data relative to the MCNP4B prediction that may be due to experimental configuration anomalies. For this balloon catheter, approximately 55 mCi of Re-186 will deliver 15 Gy at a 0.5 mm depth in tissue equivalent material in 5 min. CONCLUSIONS: Correlation between experimentally measured dose values and Monte Carlo computation supports the position that MCNP4B simulations constitute a valuable tool for investigating various clinical therapy designs. The agreement between Monte Carlo calculations and experiments provide confidence in applying MCNP4B to more sophisticated geometries of interest, and other methods of intravascular radiation dose delivery.

Technetium 99m glucarate: what will be its clinical role?

With publication of the studies by Khaw et al. and Beanlands et al. in this issue of the Journal, there is mounting evidence that 99mTc glucarate is taken up by infarcted but not by ischemic myocardium. The early myocardial distribution and rapid blood-pool clearance of 99mTc glucarate suggest important diagnostic potential in the very early detection of acute myocardial infarction and for the identification of successful acute revascularization therapy. To understand the full diagnostic implications of 99mTc glucarate accumulation in the myocardium, larger human trials are now needed. It will be critically important to document the capabilities of 99mTc glucarate to identify, early on, acute myocardial infarction in the presence of a persistently occluded infarct-related coronary artery in human beings.

Michaelis-Menten kinetics model of oxygen consumption by rat brain slices following hypoxia.

In the present study, we have measured partial pressure of oxygen (pO2) profiles through rat brain slices before and after periods of hypoxia (5 and 10 min) to determine its effect on tissue oxygen demand. Tissue pO2 profiles were measured through rat cerebral cortex slices superfused with phosphate buffer using oxygen (O2)-sensitive microelectrodes at different times in controls [40% O2 balance nitrogen (N2)], and at different times before and after 5 or 10 min of hypoxia (100% N2). A one-dimensional, steady-state model of ordinary diffusion with a Michaelis-Menten model of O2 consumption where the maximal O2 consumption (Vmax) and the rate at half-maximal O2 consumption (Km) were allowed to vary was used to determine the kinetics of O2 consumption. Actual pO2 profiles through tissue were fitted to theoretical profiles by a least-squares method. Vmax varied among penetrations in a control slice and among slices. Vmax seemed to decrease after hypoxic insult, but the change was not statistically significant. The Km value measured before hypoxia was lower than the first Km value measured after the end of hypoxia, indicating that hypoxia induced a compensatory change in the metabolic state of the tissue. Km increased immediately after both 5- and 10-min hypoxic insults and returned to normal after recovery for each case. It seems that during and immediately after short periods of hypoxia, Km increases from near zero but returns to normal values within a few minutes.

Application of a 3D volume 19F MR imaging protocol for mapping oxygen tension (pO2) in perfluorocarbons at low field.

A limited flip angle gradient-echo 3D volume acquisition imaging protocol for mapping partial pressure of oxygen (pO2) in perfluorocarbon compounds (PFCs) at low field (0.14 T) is presented. The PO2 measurement method is based on the paramagnetic effect of dissolved molecular oxygen (O2) which reduces the PFC 19F T1. Specific objectives related to imaging of PFCs through use of the protocol include improved image signal-to-noise characteristics and elimination of 19F chemical shift artifacts. A parametric Wiener deconvolution filtering algorithm is used for suppression of 19F chemical shift artifacts. Application of the protocol is illustrated in a series of calculated PO2 maps of a gas equilibrated, multi-chamber phantom containing perfluorotributylamine (FC-43). The utility of the protocol is demonstrated in vivo through images of a commercially available perfluorocarbon based blood substitute emulsion containing FC-43 sequestered in the liver and spleen of a rat.

Perfluorocarbon compound aerosols for delivery to the lung as potential 19F magnetic resonance reporters of regional pulmonary pO2.

RATIONALE AND OBJECTIVES: Perfluorocarbon (PFC) aerosols present the opportunity for simultaneous analysis of lung structure and pulmonary oxygenation patterns. The authors investigated techniques to nebulize neat liquid PFCs for inhalation as a new method of PFC administration and tested the hypothesis that PFC aerosols may be developed for efficient delivery to the lung in an experimental rat model allowing the potential for sequential monitoring of pulmonary status via quantitative fluorine-19 (19F) magnetic resonance (MR) partial pressure of oxygen (pO2) imaging. METHODS: Pneumatic aerosol generators were configured to produce a neat liquid PFC perfluorotributylamine (FC-43) aerosol. Perfluorocarbon inhalation breathing protocols for the rat model included: spontaneous direct breathing from an aerosol chamber, and use of a tracheotomy tube to bypass nasal breathing. The PFC aerosol delivery into the rat lung was documented through 19F MR imaging in correlation with high-resolution anatomic proton MR images. Theoretical model calculations for PFC mass deposition were compared with experimental results. RESULTS: The pneumatic generator produced a PFC aerosol droplet within the theoretically targeted range (geometric mean particle diameter of 1.2 microns; concentration of approximately 4 x 10(7) droplets per cm3). No measurable aerosol reached the lungs during spontaneous breathing because of the efficient filtering capabilities of the turbinated nasal passages. With tracheotomy, aerosol depositions within the lung were achieved in mass quantities consistent with theoretical expectations; however, the distribution patterns were nonuniform and unpredictable. Oxygen-enhanced 19F imaging was demonstrated. CONCLUSIONS: Perfluorocarbon aerosols of controlled size distribution can be produced at sufficient concentration with pneumatic generators for distribution to the terminal pulmonary architecture and visualization using 19F MR imaging. The potential exists for in vivo oxygen-sensitive imaging in the pulmonary system and development of sophisticated experimental animal models of systemic oxygen transport as a function of pulmonary status.

Extraction and retention of technetium-99m Q12, technetium-99m sestamibi, and thallium-201 in isolated rat heart during coronary acidemia.

Technetium-99m Q12 and 99mTc-sestamibi are cationic lipophilic myocardial perfusion imaging tracers. Because myocardium in areas of ischemia becomes acidotic, experiments were designed to differentiate the effects of myocardial perfusate pH on radiotracer extraction and retention independent of substrate availability. We hypothesized that 99mTc-Q12 and 99mTc-sestamibi single-pass uptake and retention would be unaffected by a modest reduction in coronary perfusate pH. Isolated rat hearts were perfused at constant flow with Krebs-Henseleit buffer enriched with bovine red blood cells (20%). The indicator dilution method was used to measure the maximum extraction (Emax) and net extraction (Enet) of thallium-201 and 99mTc-Q12 (n = 8) or 201Tl and 99mTc sestamibi (n = 7) during baseline perfusion (pH = 7.4), during acidemic (pH = 6.7) perfusion, and during a restitution period with normal perfusate (pH = 7.4). 201Tl Emax (0.71+/-0.03) was greater than either 99mTc-Q12 or 99mTc-sestamibi Emax (0.27+/-0.02 and 0.26+/-0.01 respectively, P<0.0001). Acidemia significantly reduced 201Tl Emax (0.65+/-0.03, P<0.02) but not 99mTc-Q12 or 99mTc-sestamibi Emax (0.25+/-0.02 and 0.24+/-0.02 respectively). During control perfusion Enet of 201Tl was greater than that of 99mTc-Q12 at 3 and 5 min and greater than that of 99mTc-sestamibi at 3 min. 99mTc-Q12 Enet was less than 99mTc-sestamibi Enet at 3, 5, and 10 min. Acidemia decreased 201Tl and 99mTc-sestamibi Enet at 3, 5, and 10 min but had no effect on 99mTc-Q12 Enet. It is concluded that Emax of 99mTc-Q12 is less than that of 201Tl but is not different from that of 99mTc-sestamibi. Enet of 99mTc-Q12 is less than that of 99mTc-sestamibi.

Flow versus uptake comparisons of thallium-201 with technetium-99m perfusion tracers in a canine model of myocardial ischemia.

UNLABELLED: We investigated the myocardial flow kinetics of six putative radioperfusion agents (99mTc-Q3, 99mTc-Q4, 99mTc-Q12, 99mTc-sestamibi, 99mTc-tetrofosmin and 99mTcN-NOET) and 201Tl in a canine model of myocardial ischemia with pharmacologic coronary artery vasodilation. METHODS: In 31 open-chest dogs with acute coronary occlusion, dipyridamole (approximately 0.56 mg/kg) was infused intravenously, followed by a perfusion tracer injection and radioactive microspheres for myocardial blood flow (MBF) measurement. The paired data were normalized using three techniques; average, normal or maximum myocardial tracer activity and MBF. RESULTS: The upper limit of MBF obtained for the group of tracers ranged from 4.2 ml/min/g to 8.2 ml/min/g. There was a statistically significant (p < 0.0001) linear correlation (r = 0.87-0.98) between the normalized myocardial activity and the normalized MBF values of each of the tracers. The slope of the curve normalized by average for 201Tl (0.83) was greater than those for the 99mTc tracers, and the intercept (0.07) was lower than those for the 99mTc tracers. Slopes and intercepts for the 99mTc agents were as follows: 99mTc-Q3, 0.81 and 0.18; 99mTc-Q4, 0.61 and 0.41; 99mTc-Q12, 0.63 and 0.39; 99mTc-sestamibi, 0.62 and 0.34; 99mTc-tetrofosmin, 0.68 and 0.32; and 99mTcN-NOET, 0.71 and 0.29, respectively. CONCLUSION: In an anesthetized open-chest canine model of regional myocardial ischemia with dipyridamole induced hyperemia, 201Tl shows a more ideal relationship between tracer uptake and MBF than do the 99mTc-based agents. Of the various 99mTc-based imaging agents studied, the myocardial flow kinetics of 99mTc-Q3 appear to be closest to ideal. This relationship is maintained regardless of the normalization technique used. This may, in theory, imply a higher sensitivity in discerning ischemic from normal myocardium and a role in diagnostic nuclear imaging for 99mTc-Q3.

Effects of ouabain on technetium-99m-Q12 and thallium-201 extraction and retention by isolated rat heart.

UNLABELLED: The mechanisms of myocardial extraction and retention of the new cationic lipophilic radionuclide imaging agent 99mTc-Q12 are currently unknown. We hypothesized that 99mTc-Q12 has satisfactory single-pass extraction independent of active transport processes and longer cellular retention than 201Tl for rapid and sustained cardiac imaging to differentiate perfusion defects. METHODS: Isolated rat hearts were perfused at constant flow with Krebs-Henseleit buffer enriched with bovine red blood cells (30%-40%). The indicator dilution method was used to measure the single-pass maximum extraction (Emax) and net extraction (Enet(t)) of 201Tl and 99mTc-Q12 over 15 min during control perfusion (n = 11) and during normal (1 microM, n = 6) and high cardiotoxic (50 microM, n = 11) dose infusions of the digitalis glycoside, ouabain. RESULTS: The Emax of 201Tl was greater than 99mTc-Q12 Emax (0.73 +/- 0.01 and 0.29 +/- 0.01, respectively). At 3 min of perfusion, 201Tl Enet was greater than 99mTc-Q12 Enet (0.40 +/- 0.01 and 0.11 +/- 0.00, respectively). Between 3 and 15 min, 201Tl Enet was decreasing by a rate of 2% per minute while 99mTc-Q1 2 Enet was decreasing by less than 0.1 % per minute. Ouabain decreased 201TI Emax but did not change 99mTc-Q12 Emax. High-dose ouabain decreased 201Tl Enet at 3 min and 99-Tc-Q12 Enet at 10 and 15 min. CONCLUSION: Ouabain reduced 201Tl Emax but not 99mTc-Q12 Emax. Therefore, the cellular extraction process for 99mTc-Q12 is different from that of 201Tl. Since the Enet(t) of 99mTc-Q12 was reduced in the presence of high doses of ouabain while Emax was unchanged, 99mTc-Q12 extraction and retention appear to be controlled by different processes. Extraction and release kinetics of 99mTc-Q12 were not changed with a low dose analogous to the human therapeutic levels of ouabain.

In vivo PO2 imaging in the porcine model with perfluorocarbon F-19 NMR at low field.

Quantitative pO2 imaging in vivo has been evaluated utilizing F-19 NMR in the porcine model at 0.14 T for the lungs, liver, and spleen following i.p. administration of the commercial perfluorotributylamine (FC-43)-based perfluorocarbon (PFC) emulsion, Oxypherol-ET. Calculated T1 maps obtained from a two spin-echo saturation recovery/inversion recovery (SR/IR) pulse protocol are converted into quantitative pO2 images through a temperature-dependent calibration curve relating longitudinal relaxation rate (1/T1) to pO2. The uncertainty in pO2 for a T1 measurement error of +/- 5% as encountered in establishing the calibration curves ranges from +/- 10 torr (+/- 40%) at 25 torr to +/- 16 torr (+/- 11%) at 150 torr for FC-43 (37 degrees C). However, additional uncertainties in T1 dependent upon the signal-to-noise ratio may be introduced through the SR/IR calculated T1 pulse protocol, which might severely degrade the pO2 accuracy. Correlation of the organ image calculated pO2 with directly measured pO2 in airway or blood pools in six pigs indicate that the PFC resident in lung is in near equilibrium with arterialized blood and not with airway pO2, suggesting a location distal to the alveolar epithelium. For the liver, the strongest correlation implying equilibrium was evident for venous blood (hepatic vein). For the spleen, arterial blood pO2 (aorta) was an unreliable predictor of pO2 for PFC resident in splenic tissue. The results have demonstrated the utility and defined the limiting aspects quantitative pO2 imaging in vivo using F-19 MRI of sequestered PFC materials.

Effect of supplemental perfluorocarbon administration on hypotensive resuscitation of severe uncontrolled hemorrhage.

Recent animal studies of acute hemorrhage in the presence of a vascular injury have demonstrated improved survival and decreased hemorrhage volume with hypotensive resuscitation, but this has occurred at the expense of tissue perfusion. It was hypothesized that addition of an oxygen-carrying perfusate would improve tissue oxygen delivery during hypotensive resuscitation. Hypotensive resuscitation of severe uncontrolled hemorrhage was compared with and without supplementation with Oxygent HT, an emulsion of perflubron (perfluorooctylbromide; PFOB; Alliance Pharmaceutical Corporation, San Diego, CA), an oxygen-carrying perfusate. Fifteen swine (15 to 22 kg) with 4-mm aortic tears were bled to a pulse pressure of 5 mm Hg and then resuscitated (estimated blood loss, 40 to 50 mL/kg). All animals were resuscitated with normal saline (6 mL/kg/min) infused as needed to maintain a mean arterial pressure of 40 mm Hg. One group (PFC) of animals also received an infusion of 6 mL/kg perfluorooctylbromide emulsion. Another group served as controls and received an equal volume of placebo (normal saline). Animals were observed for 120 minutes or until death. Data were compared using repeated measures analysis of variance (ANOVA) the Student's t test, and Fisher's exact. A P value < .05 was considered significant. Two-hour mortality rates were 12.5% and 43% for PFC-treated animals and controls, respectively (P > .05; 95% confidence interval [95% CI] for this difference in mortality is -13% to 74%). Oxygen content and delivery were significantly greater in the treatment group. In conclusion, administration of an oxygen-carrying perfusate significantly improves oxygen delivery in hypotensive crystalloid resuscitation of severe uncontrolled hemorrhage.

Myocardial uptake and kinetic properties of technetium-99m-Q3 in dogs.

UNLABELLED: We postulated that 99mTc-Q3, a cationic imaging agent, produces myocardial activity related to myocardial blood flow during myocardial ischemia and pharmacologic coronary artery vasodilation, and shows little or no myocardial redistribution over 4 hr after intravenous injection. METHODS: In six Group 1 dogs, the chest was opened, the left circumflex coronary artery was acutely ligated, and dipyridamole (0.32, 0.56 or 0.84 mg/kg) was infused into the right atrium, followed by 10 mCi of 99mTc-Q3. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized and 357 myocardial samples were assayed in a well counter for 99mTc activity. One week later, radiolabeled microsphere activity was counted and myocardial blood flow calculated. In nine Group 2 dogs, a variable occluder was placed around the left circumflex coronary artery and an ischemic level of circumflex blood flow was maintained constant over 4 hr as measured by an ultrasonic flow meter. Dipyridamole (0.56 mg/kg) was then infused into the right atrium followed by 10 mCi of 99mTc-Q3. Gamma camera images were acquired at 5, 15, 30, 60, 120 and 240 min following 99mTc-Q3 injection. Microsphere blood flow and endocardial biopsies (n = 6 dogs) were performed at 30, 60, 120 and 240 min following 99mTc-Q3 injection. RESULTS: In the Group 1 animals, 99mTc activity (y) was related to myocardial blood flow (x) from 0 to 6.1 ml/min/g by the relationship y = 0.83X + 0.18, r = 0.95, p = 0.0001. The scintigraphic ratio of myocardial perfusion defect zone counts-to-normal myocardial zone counts (0.54 +/- 0.05 at 30 min) remained constant over 4 hr, as did technetium counts from direct endocardial sampling. Scintigraphic count ratios allowed discrimination between perfusion defect and normal myocardial regions beginning at 5 min following 99mTc-Q3 injection. CONCLUSIONS: Over a range of myocardial blood flows from 0 to 6.1 ml/min/g, 99mTc-Q3 myocardial activity is related to myocardial flow at the time of tracer injection. Technetium-99m-Q3 shows no evidence of myocardial redistribution over a 4-hr period.

Kinetic properties of 99mTc-Q12 in canine myocardium.

BACKGROUND: 99mTc-Q12 is a new Tc(III) perfusion imaging agent that permits prompt myocardial visualization in humans. We postulated that 99mTc-Q12 myocardial activity is related to actual myocardial blood flow during conditions of myocardial ischemia and pharmacological coronary artery vasodilation and that 99mTc-Q12 shows little or no myocardial redistribution as long as 4 hours after intravenous injection. METHODS AND RESULTS: In seven anesthetized, open chest dogs, the left circumflex coronary artery was occluded, and dipyridamole (0.32 or 0.56 mg/kg) was infused into the right atrium, followed by 10 mCi of 99mTc-Q12. Myocardial blood flow was measured by radiolabeled microspheres. The animals were euthanized, and a total of 315 myocardial samples were assayed in a well counter for 99mTc activity. One week later, radiolabeled microsphere activity was determined, and myocardial blood flow was calculated. 99mTc activity (y) was related to myocardial blood flow (x) from 0 to 2 mL.g-1 x min-1 by the relation y = 0.64x + 0.35 (r = .88, P = .0001). In 14 additional anesthetized, open chest dogs, an occluder was placed around the left circumflex coronary artery, and an ischemic level of circumflex blood flow was maintained constant over 4 hours as measured by an ultrasonic flowmeter. Dipyridamole (0.56 mg/kg) was infused intravenously beginning 15 minutes after coronary occlusion and then followed by 10 mCi of 99mTc-Q12. Gamma camera images, hemodynamics, microsphere blood flow, and endocardial biopsies (latter in six dogs) were performed at 30, 60, 120, and 240 minutes after 99mTc-Q12 injection. Myocardial blood flow in the distribution of the left anterior descending artery decreased by 29.6% from 30 to 240 minutes (P < .05), whereas left circumflex blood flow increased by 40.4% from 30 to 120 minutes (P < .05) as the dipyridamole hemodynamic effects dissipated. Nevertheless, the ratio of myocardial perfusion defect zone counts to normal myocardial zone counts remained constant over 4 hours, as did the technetium counts from the needle biopsy endocardial samples. CONCLUSIONS: Over a limited range of myocardial blood flows from 0 to approximately 2 mL.g-1 x min-1, 99mTc-Q12 myocardial activity is related to actual myocardial flow at the time of tracer injection. 99mTc-Q12 shows no evidence of myocardial redistribution.

Perfluorocarbon distribution to liver, lung and spleen of emulsions of perfluorotributylamine (FTBA) in pigs and rats and perfluorooctyl bromide (PFOB) in rats and dogs by 19F NMR spectroscopy.

Perfluorocarbon emulsion (FCE) particles are reported to be taken up by the reticuloendothelial system (RES) and ultimately eliminated by the lung. This distribution provides an opportunity to measure oxygen partial pressure in vivo with fluorine-19 magnetic resonance imaging (19F MRI). Since the MR image signal-to-noise ratio is directly proportional to the fluorine concentration in the tissue, a greater concentration of perfluorocarbon (PFC) in the tissue will result in a greater confidence in the oxygen image and reduce measurement time. It was postulated that the biodistribution of PFC administered in emulsion form may depend on species RES or FCE composition. The distribution of an emulsion (Oxypherol-E.T.) containing perfluorotributylamine (FTBA) 5 days after administration to pigs (11 g FTBA/kg body weight i.p.) and rats (19 g FTBA/kg i.p.) and an emulsion (Oxygent) containing perfluorooctyl bromide (PFOB) 7 days after administration to dogs (11 g PFOB/kg i.v.) and 5 days after administrations to rats (19 g PFOB/kg i.p.) was analyzed by F-19 NMR spectroscopy of tissue samples. PFC concentrations in spleen are 2 to 3 times those in liver. This pattern appears to be independent of PFC emulsion or species. In contrast, lung PFC content was less than that in the liver and showed a dependence upon both species and PFC emulsion.