C-type natriuretic peptide for reduction of restenosis: gene transfer is superior over single peptide administration.

BACKGROUND: Restenosis is still a significant clinical problem limiting the long-term therapeutic success following balloon dilation or stent implantation. New approaches are necessary inhibiting neointima formation and simultaneously promoting re-endothelialization. Therefore, long-term therapeutic effects of adventitial liposome-mediated C-type natriuretic protein (CNP) gene and CNP peptide applications in a porcine model for restenosis post-angioplasty were investigated. METHODS: For in vitro applications, primary cultures of porcine vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) were used. Gene transfer was performed with cationic lipid DOCSPER [1,3-dioleoyloxy-2-(N5-carbamoylspermine)propane]. In vivo treatment of pig femoral arteries was adventitial using a needle injection catheter following balloon angioplasty. Arteries were investigated by angiography, Evan's blue staining, histomorphometry, immunohistochemistry, PCR and RT-PCR. RESULTS: Using CNP gene transfer in vitro, 29.4+/-7.2% reduction of cell proliferation in VSMCs was observed. In ECs, the CNP gene did not compromise cellular growth. For the CNP peptide the optimal concentration was 1 mM with 50.7+/-11.3% reduction of VSMC proliferation and 12.1+/-5.3% enhancement of growth of ECs. Three weeks following application in vivo complete re-endothelialization was observed in all treated groups. At 3 months significant reduction of neointima formation was observed using CNP gene vs. CNP peptide (85.9+/-7.8% vs. 63.3+/-27.6% reduction, P<0.05) compared to control treatment. CONCLUSION: Periadventitial liposome-mediated CNP gene transfer in vivo resulted in a significant long-term reduction of neointima formation without compromising endothelial repair and was superior over single CNP peptide administration. Advantages of CNP are its physiological origin and simultaneous inhibition of VSMC proliferation and promotion of EC growth.

Interleukin-6 and procalcitonin in serum of children undergoing cardiac surgery with cardiopulmonary bypass.

OBJECTIVE: The aim of our study was to investigate the systemic inflammatory response in children with congenital heart disease undergoing surgical correction with cardiopulmonary bypass. We wanted to discuss interleukin 6 and procalcitonin as components of the systemic inflammatory response syndrome to cardiopulmonary bypass and evaluate postoperative kinetics of these parameters in case of an uncomplicated course. METHODS: Procalcitonin and interleukin 6 were determined before and after cardiopulmonary bypass surgery in 37 children on the day of surgery, the first and fourth postoperative day. The increased procalcitonin and interleukin 6 levels were evaluated in relationship to intraoperative variables such as duration of aortic cross clamping, incisional trauma and cardiac bypass temperature. RESULTS: Peak levels of procalcitonin were detected on the first postoperative day, while interleukin 6 reached its highest values on the day of surgery. In contrast to interleukin 6 the median values of procalcitonin differed significantly between short versus long aortic clamping time and atriotomy versus ventriculotomy. Interleukin 6 reached normal levels on the fourth postoperative day, while procalcitonin was still clearly above normal. CONCLUSIONS: Serum concentrations of procalcitonin and interleukin 6 were influenced by systemic inflammatory response syndrome following cardiac surgery with cardiopulmonary bypass. Even in case of an uncomplicated course both parameters were elevated for at least four days. While procalcitonin serum concentrations were dependent on aortic clamping time or incisional trauma, interleukin 6 showed no significant relation with these intraoperative variables.