Kenneth N. Giedd

Radioactive beta-emitting solution-filled balloon treatment prevents porcine coronary restenosis.

PURPOSE Intracoronary gamma or beta radiation from centrally located sources at the time of overstretch balloon injury inhibits neointimal proliferation. In an effort to deliver homogeneous, centered radiation fields in a technically straightforward fashion, we studied the effects of a beta-emitting solution used as a balloon inflation fluid to deliver radiation at the time of coronary injury. METHODS Twenty-one coronary arteries in 13 juvenile swine underwent irradiation (control and 11 or 25 Gy media dose). Radiation was delivered using a perfusion balloon inflated with an Re-188 solution. Subsequently, overdilatation percutaneous transluminal coronary angioplasty was performed at the pretreated segment. Histopathologic and histomorphometric analysis was performed at 30 days after injury on the entire irradiated artery. RESULTS Balloon overdilation was associated with significant vascular injury and marked neointimal proliferation in control and low-dose (11 Gy)-treated arteries. High-dose radiation (25 Gy) significantly inhibited neointima formation compared with controls (neointimal area: 0.49 +/- 0.29 mm2 vs. 1.51 +/- 0.22 mm2, respectively; p = 0.02) and low-dose radiation (neointimal area 1.75 +/- 0.54 mm2, p > 0.1 compared with controls). CONCLUSIONS Liquid Re-188 is an effective beta-emitting vehicle to deliver intracoronary radiation and prevent restenosis in this model. Intracoronary radiation treatment using aqueous radioisotope sources is technically straightforward and provides the optimally achievable radiation dose distribution.

T-Cell Lymphokines, Interleukin-4 and Gamma Interferon, Modulate the Induction of Vascular Smooth Muscle Cell Tissue Plasminogen Activator and Migration by Serum and Platelet-Derived Growth Factor

Platelet-derived growth factor (PDGF)-induced smooth muscle cell (SMC) fibrinolysis is necessary for SMC migration. In order to determine whether the T-cell lymphokines interleukin-4 (IL-4) and gamma interferon (gamma-IFN) affect SMC fibrinolysis and migration, we examined the effects of human recombinant IL-4 and gamma-IFN on human aortic SMC tissue-type plasminogen activator (TPA), urokinase-type plasminogen activator (UPA), and plasminogen activator inhibitor type-1 (PAI-1) antigen production, as determined by enzyme-linked immunosorbent assays. Although IL-4 had no direct effect on SMC TPA antigen, IL-4 potentiated SMC TPA antigen levels and activity in conditioned media and cellular lysates in media containing 2% fetal bovine serum but did not change UPA or PAI-1 production. gamma-IFN attenuated IL-4 augmentation of SMC TPA antigen production in conditioned media, although gamma-IFN itself had no direct effects on SMC TPA and PAI-1 antigen production. IL-4 augmented PDGF induction of SMC TPA antigen. gamma-IFN inhibited PDGF induction of SMC TPA antigen and IL-4 potentiation of this process. gamma-IFN diminished the promigratory effects of both IL-4 and PDGF on in vitro SMC migration. Tranexamic acid, a plasmin inhibitor, abrogated the stimulation of SMC migration by IL-4. Therefore, IL-4 and gamma-IFN modulate the induction of SMC TPA and SMC migration by 2% fetal bovine serum and PDGF.

Silent ischemia: unsafe at any time*

Percutaneous coronary intervention (PCI) using balloon angioplasty with stenting has become a mainstay in the treatment of patients with coronary artery disease (CAD). Over one million PCI procedures were performed in the U.S. alone in 2000, nearly one-half of which involved placement of a coronary