RESUMO
Ischemic disease represents the new epidemic worldwide. Animal models of ischemic disease are useful because they can help us to understand the underlying pathogenetic mechanisms and develop new therapies. The present review article summarizes the results of a consensus conference on the status and future development of experimentation in the field of cardiovascular medicine using murine models of peripheral and myocardial ischemia. The starting point was to recognize the limits of the approach, which mainly derive from species- and disease-related differences in cardiovascular physiology. For instance, the mouse heart beats at a rate 10 times faster than the human heart. Furthermore, healing processes are more rapid in animals, as they rely on mechanisms that may have lost relevance in man. The main objective of the authors was to propose general guidelines, diagnostic end points and relevance to clinical problems.
Assuntos
Experimentação Animal , Modelos Animais de Doenças , Extremidades/irrigação sanguínea , Oclusão de Enxerto Vascular/fisiopatologia , Isquemia/fisiopatologia , Isquemia Miocárdica/fisiopatologia , Experimentação Animal/ética , Experimentação Animal/legislação & jurisprudência , Animais , Aterosclerose/cirurgia , Comorbidade , Consenso , Diabetes Mellitus Tipo 1/fisiopatologia , Determinação de Ponto Final , Oclusão de Enxerto Vascular/terapia , Guias como Assunto , Humanos , Isquemia/terapia , Camundongos , Isquemia Miocárdica/terapia , Medicina Regenerativa , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Especificidade da Espécie , Veias/transplante , CicatrizaçãoRESUMO
The purpose of this study was to evaluate the effects of anginex on tumour angiogenesis assessed by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) on a clinical 1.5 Tesla MR system and with the clinically available contrast agent gadopentetate dimeglumine. C57BL/6 mice carrying B16F10 melanomas were treated with anginex, TNP-470 or saline. Tumour growth curves and microvessel density (MVD) were recorded to establish the effects of treatment. DCE-MRI was performed on day 16 after tumour inoculation, and the endothelial transfer coefficients of the microvessel permeability surface-area product (K(PS)) were calculated using a two-compartment model. Both anginex and TNP-470 resulted in smaller tumour volumes (P<0.0001) and lower MVD (P <0.05) compared to saline. Treatment with anginex resulted in a 64% reduction (P<0.01) of tumour K(PS) and TNP-470 resulted in a 44% reduction (P=0.17), compared to saline. DCE-MRI with a clinically available, small-molecular contrast agent can therefore be used to evaluate the angiostatic effects of anginex and TNP-470 on tumour angiogenesis.
