RESUMEN
BACKGROUND: The effectiveness of local endovascular photodynamic therapy (PDT) in preventing tissue hyperplasia was evaluated in a vascular injury model. METHODS: Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries (n = 180). Animals (n = 72) were randomly allocated to unidirectional injury only (Group 1), injury followed by drug delivery of photosensitizer with a porous balloon (Group 2), or by local exposure to monochromatic light (Group 3). In Group 4, injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (PDT). Up to 21 days after treatment, all experimental vessels were excised, fixed and processed for histology, immunohistochemistry and transmission electron microscopy. RESULTS: After vascular injury an inflammatory and myoproliferative response was observed in Groups 1, 2 and 3 (mean tissue hyperplasia/media ratio 1.0 +/- 0.5 at 21 days; area tissue hyperplasia: 1.57 +/- 0.9 mm2). Proliferation in injured vascular segments (Group 1-3) reached a maximum at 7 days, with 6%. Only in Group 4, after injury followed by photodynamic therapy, was there no significant vascular response (mean tissue hyperplasia/media ratio 0.3 +/- 0.2: area tissue hyperplasia: 0.1 +/- 0.05 mm2 p < 0.001, proliferating cells 0.3%). CONCLUSION: Vascular response after unidirectional injury was suppressed only by endovascular photodynamic therapy.
Asunto(s)
Arterias Carótidas , Arteria Femoral , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/uso terapéutico , Enfermedades Vasculares/tratamiento farmacológico , Animales , Arterias Carótidas/efectos de los fármacos , Arterias Carótidas/ultraestructura , Traumatismos de las Arterias Carótidas , Cateterismo Periférico , División Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Arteria Femoral/efectos de los fármacos , Arteria Femoral/lesiones , Arteria Femoral/ultraestructura , Hiperplasia/patología , Hiperplasia/prevención & control , Inmunohistoquímica , Microscopía Electrónica , Microscopía Fluorescente , Fotoquimioterapia/instrumentación , Fármacos Fotosensibilizantes/administración & dosificación , Porcinos , Enfermedades Vasculares/patologíaRESUMEN
Local photodynamic therapy may have potential in preventing myointimal hyperplasia after angioplasty. In this study, the effect of photodynamic therapy was evaluated in an experimental model of restenosis. Standardized unidirectional arterial injury with a directional atherectomy catheter was performed in porcine arteries. Animals were randomly allocated to four groups: group 1, unidirectional injury only; group 2, injury followed by local delivery of photosensitizer; group 3, injury followed by local exposure to monochromatic light; and group 4, where injury was followed by local drug delivery of photosensitizer and subsequent exposure to light (photodynamic therapy). Seven, 14 or 21 days after treatment, all experimental vessels were excised, fixed and processed for histology. An inflammatory and myoproliferative response was observed after injury in vessels from groups 1, 2 and 3. In group 4, after injury followed by photodynamic therapy, the myoproliferative response was significantly reduced. Thus, in this study, tissue hyperplasia after unidirectional injury was effectively suppressed by photodynamic therapy.
Asunto(s)
Arteriopatías Oclusivas/tratamiento farmacológico , Arteriopatías Oclusivas/patología , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes/farmacología , Túnica Íntima/efectos de los fármacos , Túnica Íntima/patología , Animales , Modelos Animales de Enfermedad , Hiperplasia , PorcinosRESUMEN
OBJECTIVE: To measure changes in haemodynamics and myocardial blood flow after acute intravenous (i.v.) and intracoronary (i.c.) injection of bisoprolol in patients with coronary heart disease. PATIENTS AND METHODS: A prospective, randomized controlled study of 14 patients (12 men, 2 women; mean age 65 [50-73] years) with angio-graphically proven coronary artery stenosis (reduced in lumen of at least 70%) in one or more major vessels. Seven patients received, before balloon angioplasty, either 0.01 mg/kg body weight directly into the coronaries (group 1, infusion through the guiding catheter) or 2.5 mg (group 2, via the sheath). Heart rate and blood pressure were measured before and after bisoprolol injection. Coronary blood flow was measured by the thermodilution method via two indwelling catheters in the coronary sinus. RESULTS: After bisoprolol there was a reduction in heart rate (group 1: from 83/min to 75/min; group 2: from 77/min to 72/min) and blood pressure (group 1: from 137/80 mm Hg to 125/70 mm Hg; group 2: from 135/86 mm Hg to 126/80 mm Hg). Coronary blood flow was lower after i.c. bisoprolol injection than before (group 1: 383 ml/min vs 352 ml/min, but higher after i.v. injection (group 2: 353 ml/min vs 384 ml/min). These differences were statistically not significant. CONCLUSION: While after-load was clearly reduced and myocardial blood flow remained unchanged, bisoprolol improved myocardial oxygen balance. No different effects could be detected after intracoronary vs intravenous application of bisoprolol.