Safe performance of magnetic resonance of the heart in patients with magnetic resonance conditional pacemaker systems: the safety issue of the ESTIMATE study.

BACKGROUND: No published data exist about the safety of diagnostic magnetic resonance (MR) of the heart performed in a larger series of patients implanted with MR conditional pacemakers (PM). The purpose of our study is to analyse safety and potential alterations of electrical lead parameters in patients implanted with the EnRhythm/Advisa MRI SureScan PM with 5086MRI leads (Medtronic Inc.) during and after MR of the heart at 1.5 Tesla. METHODS: Patients enrolled in this single center pilot study who underwent non-clinically indicated diagnostic MR of the heart were included in this analysis. Heart MR was performed for analyses of potential changes in right and left ventricular functional parameters under right ventricular pacing at 80 and 110 bpm. Atrial/ventricular sensing, atrial/ventricular pacing capture threshold [PCT], and pacing impedances were assessed immediately before, during, and immediately after MR, as well at 3 and 15 months post MR. RESULTS: Thirty-six patients (mean age 69 ± 13 years; high degree AV block 18 [50%]) underwent MR of the heart. No MR related adverse events occurred during MR or thereafter. Ventricular sensing differed significantly between the FU immediately after MR (10.3 ± 5.3 mV) and the baseline FU (9.8 ± 5.3 mV; p < 0.05). Despite PCT [V/0.4ms] was not significantly different between the FUs (baseline: 0.84 ± 0.27; in-between MR scans: 0.82 ± 0.27; immediately after MR: 0.84 ± 0.24; 3-month: 0.85 ± 0.23; 15-month: 0.90 ± 0.67; p = ns), 7 patients (19%) showed PCT increases by 100% (max. PCT measured: 1.0 V) at the 3-month FU compared to baseline. RV pacing impedance [Ω/5V] differed significantly at the FU in-between MR scans (516 ± 47), and at the 15-month FU (482 ± 58) compared to baseline (508 ± 75). CONCLUSION: The results of our study suggest MR of the heart to be safe in patients with the MR conditional EnRhythm/Advisa system, albeit although noticeable but clinically irrelevant ventricular PCT changes were observed.

High-resolution cartilage imaging of the knee at 3T: basic evaluation of modern isotropic 3D MR-sequences.

PURPOSE: To evaluate qualitative and quantitative image quality parameters of isotropic three-dimensional (3D) cartilage-imaging magnetic resonance (MR)-sequences at 3T. MATERIALS AND METHODS: The knees of 10 healthy volunteers (mean age, 24.4±5.6 years) were scanned at a 3T MR scanner with water-excited 3D Fast-Low Angle Shot (FLASH), True Fast Imaging with Steady-state Precession (TrueFISP), Sampling Perfection with Application-optimized Contrast using different flip-angle Evolutions (SPACE) as well as conventional and two individually weighted Double-Echo Steady-State (DESS) sequences. The MR images were evaluated qualitatively and quantitatively (signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), SNR efficiency, CNR efficiency). Quantitative parameters were compared by means of a Tukey-test and sequences were ranked according to SNR/CNR, SNR/CNR efficiency and qualitative image grading. RESULTS: The highest SNR was measured for SPACE (34.0±5.6), the highest CNR/CNR efficiency (cartilage/fluid) for the individually weighted DESS (46.9±18.0/2.18±0.84). SPACE, individually weighted and conventional DESS were ranked best with respect to SNR/CNR and SNR/CNR efficiency. The DESS sequences also performed best in the qualitative evaluation. TrueFISP performed worse, FLASH worst. The individually weighted DESS sequences were generally better than the conventional DESS with the significant increase of cartilage-fluid contrast (46.9±18.0/31.9±11.4 versus 22.0±7.3) as main advantage. CONCLUSION: Individually weighted DESS is the most promising candidate; all tested sequences performed better than FLASH.

Discovery of 2-hydroxy-N,N-dimethyl-3-{2-[[(R)-1-(5- methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobut-1-enylamino}benzamide (SCH 527123): a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist.

Structure-activity studies on lead cyclobutenedione 3 led to the discovery of 4 (SCH 527123), a potent, orally bioavailable CXCR2/CXCR1 receptor antagonist with excellent cell-based activity. Compound 4 displayed good oral bioavailability in rat and may be a potential therapeutic agent for the treatment of various inflammatory diseases.

Synthesis and structure-activity relationships of 3,4-diaminocyclobut-3-ene-1,2-dione CXCR2 antagonists.

A novel series of 3,4-diaminocyclobut-3-ene-1,2-diones was prepared and found to show potent inhibitory activity of CXCR2 binding and IL-8-mediated chemotaxis of a CXCR2-expressing cell line. Microsome stability and Caco2 studies were subsequently used to show that compounds of this chemotype are predicted to have good oral bioavailability and are thus suitable for pharmaceutical development.