Several reports have established the concept of nitric oxide synthase (NOS) gene transfer for inhibiting smooth muscle cell (SMC) proliferation after vascular injury. To minimize potential risks associated with viral gene transfer, we developed a liposome-based gene transfer approach employing inducible NOS (iNOS) overexpression for inhibition of stent-induced neointimal lesion formation. Therapeutic lipoplexes were transferred to femoral or coronary arteries of Goettingen minipigs, using the Infiltrator local drug delivery device. Efficiency of local iNOS lipoplex transfer was analyzed by iNOS-specific immunohistochemistry. NO-mediated inhibition of stent-induced neointimal lesion formation was analyzed by intravascular ultrasound (IVUS) and computerized morphometry. Gene transfer efficiency increased dose dependently to a maximum of 44.3 +/- 4.2% iNOS-positive vessel area (dose, 2 microg of iNOS lipoplex). Proliferating cell nuclear antigen (PCNA) expression of medial SMCs (immunohistochemistry) was inhibited significantly by transfer of 2 microg of iNOS lipoplexes (111 +/- 27 cells [iNOS] versus 481 +/- 67 cells [control; PCNA-positive medial cells]). IVUS analysis demonstrated that local transfer of iNOS lipoplexes resulted in a significant reduction of femoral in-stent plaque area (control, 40.85 +/- 6.37 mm(2); iNOS, 24.69 +/- 1.8 mm(2); p = 0.03). Coronary in-stent lesion formation was reduced by about 45% as determined by histologic morphometry (control, 4.0 +/- 0.29; iNOS, 2.2 +/- 0.30; p < 0.01). In conclusion, this study demonstrates that local intramural delivery of iNOS lipoplexes can exert therapeutic effects in inhibiting stent-induced neointimal lesion formation. Together with the nonviral character of this gene therapy approach, these findings may have important impact on the transition of NOS-based gene therapy to clinical practice.

The risk of late coronary artery lesions must be considered when catheter ablation at the RA wall is planned in children with free-wall accessory AV pathways.

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Affection of the RCA as a late sequel after RF current application at the lateral right atrial wall occurred in 3 out of 8 long-term surviving pigs. Three to six months seem to be the time frame for the development of intimal lesions after RF delivery. In this experimental setting, angiography failed to detect these intimal changes. The potential risk of coronary affection may be important for catheter ablation procedures at the right atrial myocardium in infants and small children.

It has been known that the first generation quantitative coronary analysis systems overestimate small vessel sizes. In the 2nd generation the contour detection algorithms, e.g., of the new Cardiovascular Measurement System (CMS), were modified to correct for the limited resolution of the X-ray imaging chain. This study validated and compared the CMS with the well-known Coronary Angiography Analysis System (CAAS) and the vessel tracking program ARTREK in a phantom study and a clinical study. In addition, the influence of different acquisition media (cinefilm vs. digitally acquired angiograms) on the accuracy of quantitative analysis was examined. The phantom study comprised 19 stenotic or non-stenotic glass tubes with a diameter range from 0.54 mm to 4.9 mm. In the clinical study the mean diameters of 322 coronary segments were analysed and the results of the systems were compared among each other. The results of the phantom study were presented in terms of the mean difference (accuracy) between true and measured values. In the phantom study the overall accuracy of the CMS was -6 pm (ARTREK: 85 pm; CAAS: 35 pm) with an overestimation of small vessels of only -11 pm (ARTREK: 97 pm: CAAS: 51 pm). The clinical study showed that the CMS corrected the usually occurring overestimation of small coronary arteries and that the influence on the accuracy of different acquisition media is minor. Due to the modified algorithms the new CMS is able to measure coronary diameters down to 0.5 mm accurately. Therefore, the CMS seems to provide more precise measurements in quantitative analysis of small coronary diameters than CAAS and ARTREK.

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The estimation of respiratory rates from contineous respiratory signals is commonly done using either fourier transformation or the zero-crossing method. This paper introduces another method which is based on the autocorrelation function of the respiratory signal. The respiratory signals can be measured either directly using a flow sensor or chest strap or indirectly on the basis of the electrocardiogram (ECG). We compare our method against other established methods on the basis of real-world ECG signals and use a respiration-based breathing frequency as a reference. Our method achieved the best agreement between respiration rates derived from directly and indirectly measured respiratory signals.

No abstract