Johnson, Lynne L. M.D., F.A.C.C.; Seldin, David W. M.D.; Muschel, Michael M.D.; Smith, Kevin B.S.; Blood, David K. M.D., F.A.C.C.; Cannon, Paul J. M.D., F.A.C.C. Author Information
We investigated treatment with a receptor for advanced glycation endproduct (RAGE) blocking antibody on angiogenic response to hind limb ischemia in diabetic mice. Streptozotocin treated C57BL/6 mice received either murine monoclonal anti-RAGE F(ab′) 2 intraperitoneally ( n=10) or saline ( n=9) for 9 weeks. Diabetic plus 10 non-diabetic C57BL/6 mice underwent left femoral artery ligation and 5 days later angiogenesis imaging with 99m Tc-Arg–Gly–Asp (RGD) nanoSPECT/CT. Twenty-four days later, hind limb blood flow was measured with ultrasound, the mice were euthanized, and tissue was taken for immunohistochemistry. The angiogenic imaging signal in ischemic limbs was higher in RAGE-ab treated versus saline treated mice at day 5 (3.1±1.4 vs 1.68±0.35, p=0.02) and blood flow was higher at day 24 (1.49±0.5 vs 0.61±0.39, p=0.04). Immunohistochemistry of ischemic muscles showed greater capillary density in the RAGE-ab treated group versus the vehicle-treated group ( p<0.001) (NS from non-diabetic mice). In conclusion, treatment with anti-RAGE F(ab′) 2 in diabetic mice improves neovascularization in the ischemic leg.
Myocardial blood flow/unit mass (MBF) and the determinants of myocardial oxygen consumption were measured in seven control subjects (group I) and 15 patients (pts) with cardiomyopathy (CM), group II (group IIa-congestive CM: 10 pts; group IIb-hypertrophic CM: 5 pts). In group I left ventricular (LV) MBF was 64 +/- 8 (SD) ml/100g-min; it was significantly lower in IIa (45 +/- 15 ml/100g-min, P less than 0.01) and IIb (39 +/- 7 ml/100g-min, P less than 0.01). However, calculated total LV flow (LV mass X MBF) was increased in the two CM groups. In nine CM pts, LV MBF increased in response to atrial pacing from 41 +/- 7 to 63 +/- 13 ml/100g-min. In group IIa, calculated peak wall stress was normal (4.39 +/hortening (MVcf) was significantly reduced (0.53 +/- 0;18 vs 1.26 +/- 0.12 circum/sec, P less than 0.01). In IIb, MVcf was normal but peak stress was significantly reduced (2.80 +/- 0.75 vs 4.51 +/- 1.10 dynes/cm2 X 10(5), P less than 0.05). Multiple regression analysis based on all pts yielded, MBF - 16.9 MVcf + 9.30 Stress + 0.26 Heart Rate - 26.4 (r=0.79). The data indicate that MBF is reduced in CM patients and the regression analysis suggests that MBF in these 22 pts with normal coronary arteriograms was determined largely by heart rate, peak stress, and ventricular performance.
Purpose: For brain CT perfusion it is well established that 80 kVp is optimal. Although neuro‐CT angiography is somewhat similar, emphasis is on the detection of aneurysms and related vascular pathologies throughout the brain. Thus it is necessary to visualize small and large blood vessels with contrast material, as well as form multi‐planar views and 3D images, so image quality and noise in addition to contrast are important for thin slices. A study was initiated to determine the optimal kVp for neuro‐CTA. Methods: A customized version of a commercial head phantom (CIRS 007TE‐27 medium adult head CT dose phantom) was purchased to facilitate quantitative measurements with iodinated contrast material, contrast for white and gray matter, and to maintain the ability to perform dosimetry. The customization consisted of adding four 25 mm holes, 35 mm from the center arranged at 45 degree angles from the center, with solid rods equivalent with brain, white, and gray matter, as well as four fillable vials were included for study of contrast agents. Dosimetry measurements were carried out with standard pencil chamber and with 0.6 cc ionization chamber. For study of the optimal kVp for a head CTA, the vials were filled with four different concentrations of contrast, approximating low to medium concentrations that would be expected in such a study. The standard CTA protocol was followed, 64 × 0.625, pitch 0.53, rotation speed 0.5 second, and CTDIvol was kept constant for each kVp. Results: The best contrast was observed at 80 kVp; however, in order to achieve noise in CTA low enough to be clinically useful there may be issues with tube current capability for a clinical technique. Clinical investigation is underway. Conclusions: The best balance of contrast and noise currently possible will be achieved at 100 kVp in a clinical scan.
The cardioprotective effects of mesenchymal stem cells (MSCs) include reducing myocyte apoptosis, and this effect can be enhanced by preconditioning and encapsulation in a fibrin scaffold. This study aimed to test the hypothesis that apoptosis imaging can detect the cardioprotective effects of a conditioned MSC patch grafted in a rat model of acute myocardial infarction. Methods: Cell culture experiments simulating engraftment of fibrin patches onto beating rat ventricular myocytes exposed to hypoxia showed an effect of conditioned cells to reduce apoptosis. Twenty-three nude rats underwent successful left anterior descending coronary artery occlusion and were divided into 3 groups: transforming growth factor β1–conditioned human MSC-laden patches (CP), infarct alone without patch (no patch [NP]), and patch alone (patch only [PO]). Twenty-four hours after myocardial infarction, all rats were injected with 99mTc-hydrazinonicotinamide (99mTc-HYNIC) annexin V and 201Tl and underwent dual-isotope SPECT/CT imaging. Six rats were sacrificed for histology and counting. The remaining rats (n = 17; 1 rat was eliminated) were injected and imaged on day 7; of those, 3 rats were sacrificed for histology and counting, and the remaining 13 rats survived to day 21, when they were sacrificed for histology. Numbers of rats imaged on day 7 in the 3 groups were 7 in the CP group, 5 in the NP, and 5 in the PO. Perfused myocardium, infarct size, and 99mTc-HYNIC annexin V uptake were quantified from the scans from days 1 and 7. 99mTc-HYNIC annexin V uptake was correlated with quantitative caspase staining, and infarct size as percentage fibrosis was quantified at day 21. Results:99mTc-HYNIC annexin V uptake as percentage injected dose (×10−4) decreased between days 1 and 7 by 1.04 ± 0.28 in the CP group, 0.44 ± 0.17 in the NP group, and 0.34 ± 0.27 in the PO group (P = 0.003 for NP vs. CP, P = 0.005 for PO vs. CP, and P = 0.5 for NP vs. CP). The changes in defect size as percentage myocardium between days 1 and 7 were −8.83 ± 4.40 in the CP group, +1.00 ± 2.24 in the NP group, and −0.50 ± 4.20 in the PO group (P = 0.003 for NP vs. CP, P = 0.005 for PO vs. CP, and P = 0.50 for NP vs. PO). 99mTc-HYNIC annexin V uptake as percentage left ventricle by scanning correlated with caspase staining (r = 0.931, P = 0.002). Conclusion: Transforming growth factor β1–conditioned human MSC-laden patches reduce myocyte apoptosis in the setting of acute infarction, and this effect can be detected by in vivo imaging with 99mTc-HYNIC annexin V.
Male rats exposed to a novel environment exhibited a marked rise of plasma corticosterone in response to the initial exposure. These animals showed a significant but not complete habituation of their adrenal response after 18 exposures. Following their first exposure to a novel environment, animals with bilateral lesions in the dentate gyrus of the hippocampus had plasma corticosterone concentrations which were significantly lower than those observed for the control animals. Whereas the control groups demonstrated a significant decrease in their adrenal response following 18 exposures (habituation), there was no decrease of the adrenocortical response to novelty stress within the dentate-lesioned group between trials 1 and 18. The effect of the dentate lesions appeared to be specific to the behavioral stress: dentate lesions failed to alter resting levels, or the animal's adrenal responses to laparotomy stress and ether inhalation.
