Vascular endothelium-specific overexpression of human catalase in cloned pigs.

The objective of this study was to develop transgenic Yucatan minipigs that overexpress human catalase (hCat) in an endothelial-specific manner. Catalase metabolizes hydrogen peroxide (H(2)O(2)), an important regulator of vascular tone that contributes to diseases such as atherosclerosis and preeclampsia. A large animal model to study reduced endothelium-derived H(2)O(2) would therefore generate valuable translational data on vascular regulation in health and disease. Yucatan minipig fetal fibroblasts stably co-transfected with human catalase (Tie2-hCat) and eGFP expression constructs were isolated into single-cell populations. The presence of the Tie2-hCat transgene in individual colonies of fibroblasts was determined by PCR. Transgenic fibroblasts were used for nuclear transfer into enucleated oocytes by electrofusion. A minimum of 140 cloned embryos were transferred per surrogate sow (n = 4). All four surrogates maintained pregnancies and piglets were delivered by cesarean section. Nine male piglets from three of the four litters carried the Tie2-hCat transgene. Expression of human catalase mRNA and overall elevated catalase protein in isolated umbilical endothelial cells from transgenic piglets were verified by RT-PCR and western blot, respectively, and endothelial localization was confirmed by immunohistochemistry. Increased enzymatic activity of catalase in transgenic versus wild-type endothelial cells was inferred based on significantly reduced levels of H(2)O(2) in culture. The similarities in swine and human cardiovascular anatomy and physiology will make this pig model a valuable source of information on the putative role of endothelium-derived H(2)O(2) in vasodilation and in the mechanisms underlying vascular health and disease.

Abnormal digital neurovascular response to local heating in systemic sclerosis.

OBJECTIVES: To investigate neurovascular dysfunction using the axon reflex-dependent hyperaemia (initial peak of skin local heating response) in fingers of patients with SSc or primary RP. METHODS: Ten healthy subjects were initially enrolled to compare axon reflex-dependent thermal hyperaemia between the finger and forearm cutaneous circulations. Then, 10 patients with primary RP and 16 patients with SSc participated in a similar protocol focusing on the finger circulation only. Lidocaine/prilocaine cream was applied for 1 h to produce local blockade of cutaneous sensory nerves. After lidocaine/prilocaine pre-treatment, laser Doppler probes were heated from skin temperature to 42 degrees C for 30 min, and 44 degrees C for 5 min to achieve maximal skin blood flow. Data were expressed as a percentage of maximal cutaneous vascular conductance. RESULTS: In healthy volunteers, we observed a significantly higher initial peak on the finger compared with the forearm, with both responses blunted following topical anaesthesia. In primary RP patients, we observed a decreased initial peak following lidocaine/prilocaine pre-treatment in the finger circulation [96.7% (33.4) vs 75.9% (29.5) with anaesthesia, P = 0.02]. In contrast, pre-treatment did not alter the initial peak in patients with SSc. A minute-by-minute analysis showed no delay of the initial peak. CONCLUSIONS: We show an abnormal digital neurovascular response to local heating in SSc. Thermal hyperaemia could be monitored as a clinical test for neurovascular function in SSc. Further studies are required to test whether the abnormal digital neurovascular response correlates to the degree of peripheral vascular involvement.

Impaired Coronary Endothelial Vasorelaxation in a Preclinical Model of Peripheral Arterial Insufficiency.

The present study was designed to determine whether adult swine with peripheral artery insufficiency (PAI) would exhibit vascular dysfunction in vessels distinct from the affected distal limbs, the coronary conduit arteries. Moreover, we sought to evaluate the effect of exercise training on coronary vasomotor function in PAI. Eighteen female healthy young Yucatan miniature swine were randomly assigned to either occluded exercise trained (Occl-Ex, n=7), or occluded-sedentary (Occl-Sed, n=5), or non-occluded, non-exercised control (Non-Occl-Con, n=6) groups. Occl-Ex pigs were progressively trained by running on a treadmill (5days/week, 12 weeks). The left descending artery (LAD) and left circumflex (LCX) coronary arteries were harvested. Vasorelaxation to adenosine diphosphate (ADP), bradykinin (BK), and sodium nitro-prusside (SNP) were assessed in LAD's; while constrictor responses to phenylephrine (PE), angiotensin II (Ang II), and endothelin-1 (ET-1) were assessed in LCX's. Vasorelaxation to ADP was reduced in LADs from Occl-Sed and Occl-Ex pigs (P<0.001) as compared to Non-Occl-Con pigs; however, Occl-Ex pigs exhibited partial recovery (P<0.001) intermediate to the other two groups. BK induced relaxation was reduced in LADs from Occl-Ex and Occl-Sed pigs (P<0.001), compared to Non-Occl-Con, and exercise modestly increased responses to BK (P<0.05). In addition, SNP, PE, Ang II, and ET-1 responses were not significantly different among the groups. Our results indicate that 'simple' occlusion of the femoral arteries induces vascular dysfunction in conduit vessels distinct from the affected hindlimbs, as evident in blunted coronary vasorelaxation responses to ADP and BK. These findings imply that PAI, even in the absence of frank atherogenic vascular disease, contributes to vascular dysfunction in the coronary arteries that could exacerbate disease outcome in patients with peripheral artery disease. Further, regular daily physical activity partially recovered the deficit observed in the coronary arteries.

A non-linear programming method for optimizing parallel-hole collimator design.

A new method for optimizing the design of multi-aperture parallel-hole collimators for the gamma scintillation camera is presented. The method takes into account the frequency spectrum of a plane source object distribution as well as the energy of the radiation. A frequency dependent statistical figure of merit is calculated and combined with a weighted object distribution frequency spectrum to obtain an objective function which, when maximized, yields the optimum collimator design according to the chosen criteria. The optimization is performed by means of a sequential pattern search technique. The results show a positive correlation between te objective function and an experimental performance index evaluated for existing collimators. The optimal designs obtained by maximizing the objective function, under the assumption of no scatter within the source, exhibit somewhat higher sensitivity and lower resolution than the commercial low energy collimators tested. It is concluded that much of the resolution capability of very high resolution collimators is unused because of the limitation imposed by the intrinsic resolution of the detector assembly.

Acute toxicity of latex microspheres.

The distribution and acute lethality of i.v. administered 3 micrometers latex spheres were determined in rats. The results extend previous studies demonstrating the similarity between dog and rat in the dynamics of microspheres in these species and the inverse relationship between sphere diameter and hemodynamic toxicity. The results suggest that 3 micrometers spheres may be safe imaging agents or drug delivery systems for spleen and liver when administered slowly. Acute hemodynamic toxicity appears to be a function of the total volume of the spheres injected.

Acute hemodynamic effects and blood pool kinetics of polystyrene microspheres following intravenous administration.

The acute hemodynamic effect of intravenous administration of polystyrene microspheres was investigated and correlated with their distribution pattern and kinetics. Microspheres of three diameters (3.4, 7.4, and 11.6 micrometer) were administered. The 7.4- and 11.6-micrometer diameter microspheres were filtered by the pulmonary capillary network following intravenous administration, the majority during the first pass. There was no significant hemodynamic effect following administrations of the 7.4- and 11.6-micrometer diameter microspheres in doses as high as 3.0 X 10(9) and 6.1 X 10(8) respectively (total cross-sectional area of 1.3 X 10(11) and 6.4 X 10(10) micrometer2, respectively). Intravenous administration of 3.4-micrometer diameter microspheres produced significant dose-dependent systemic hypotension and depression of myocardial performance at dosages as slow as 1.0 X 10(10) (cross-sectional area of 9.1 X 10(10) micrometer2). These differences in acute hemodynamic effect from the 7.4- and 11.6-micrometer diameter microspheres may be due to the differences in distribution kinetics and fate of the 3.4-micrometer diameter microspheres, which readily pass through the lungs to the spleen. Although elimination of the smaller spheres from the blood during the first 6-8 min was rapid, i.e., t 1/2 = 1.62 and 1.72 min from the venous and arterial blood circulation, respectively, levels of 10(3) spheres/g of blood were present in the circulation for greater than 1 hr. These findings must be considered in the planning of intravenous administration of microspheres as a drug delivery system to target organs.

ACR survey results: diagnostic imaging scientists and engineers.

The American College of Radiology's Committee on Physics Resources of the Commission on Human Resources conducted a survey of diagnostic imaging scientists and engineers to assess who is providing radiologic physics and related services in diagnostic imaging departments. The survey forms were distributed through the members of the American Healthcare Radiology Administrators. Survey results showed a predominance of M.S. and Ph.D. degrees in physics and medical/radiological physics. Nearly all respondents had their time split between numerous categories of work, such as clinical and research, and between different modalities such as diagnostic x-ray, nuclear medicine and radiation oncology. To enhance physics services in important areas such as CT, which currently receive little time, support is needed for work prioritization, for training, and for positions for physics and physics-support personnel.

No effect of systemic isocapnic hypoxia on α-adrenergic vasoconstrictor responsiveness in human skin.

UNLABELLED: Hypoxia impairs body temperature regulation and abolishes the decline in skin temperature associated with cold exposure, suggesting that cutaneous vasoconstriction is impaired. AIM: The purpose of this study was to test the hypothesis that cutaneous vasoconstriction to intradermal tyramine, an index of post-junctional vasoconstrictor responsiveness, is reduced during hypoxia. METHODS: Twelve subjects (six males, six females) had three microdialysis fibres placed in the ventral forearm. Fibres received either lactated ringers, 5 mm yohimbine (α-adrenergic blockade), or 10.5 µm BIBP-3226 (to antagonize neuropeptide Y Y(1) receptors). Skin blood flow was assessed at each site (laser-Doppler flowmetry) and cutaneous vascular conductance (CVC) was calculated (red blood cell flux/mean arterial pressure) and scaled to baseline. Vasoconstrictor responses to tyramine (173 µm) were tested during normoxia and steady-state isocapnic hypoxia (SaO(2) = 80%) in random order. RESULTS: During normoxia, tyramine reduced CVC by 56.0±5.6 and 50.3±8.0% in control and BIBP-3226 sites (both P<0.05 vs. pre-tyramine; P=0.445 between sites) whereas CVC in the yohimbine site did not change (P=0.398 vs. pre-tyramine). During isocapnic hypoxia, tyramine reduced CVC by 55.9±5.1 and 54.2±5.4% in control and BIBP-3226 sites (both P<0.05 vs. pre-tyramine; P=0.814 between sites) whereas CVC was unchanged in the yohimbine site (P=0.732 vs. pre-tyramine). Isocapnic hypoxia did not affect vasoconstrictor responses at any site (all P>0.05 vs. normoxia). CONCLUSION: We conclude that post-junctional α-adrenergic vasoconstrictor responsiveness is not affected by hypoxia in non-acral skin.

111In-chloride thorax scintigraphic study for demonstration of pulmonary edema: canine model.

Pulmonary edema induced by injections of oleic acid was demonstrated using 111In-chloride lung/heart image in five anesthetized dogs. The anesthetized dogs were positioned under a gamma camera interfaced to a computer. After 111In-chloride IV injections, dynamic data were recorded at 1 frame/min before and after induced pulmonary edema. The computer generated the curve of the lung-to-heart activity ratio; the ratio rose from 0.5-0.6 at baseline to 0.85-1.5 at the end of the study in the dogs. At the end of each study, the removed lungs demonstrated edematous fluid, and a few red blood cells were seen in the alveoli. The results indicating pulmonary edema exhibited in the 111In-chloride lung-to-heart ratio obtained from a computerized gamma camera were compatible with the pathological result. Since 111In-chloride instantly binds to plasma transferrin, an excellent intravascular imaging agent, leakage of this tracer into alveoli indicates loss of membranous wall competence. Pulmonary edema, as in the adult respiratory distress syndrome, is sometimes difficult to diagnose; and this 111In-chloride lung-to-heart imaging technique may be potentially useful.