RESUMO
Mechanical circulatory support for children under 6 years of age remains a challenge. This article describes the preclinical status and the results of recent animal testing with the Penn State Infant Left Ventricular Assist Device (VAD). The objectives have been to 1) demonstrate acceptably low thromboembolic risk to support Food and Drug Administration approval, 2) challenge the device by using minimal to no anticoagulation in order to identify any design or manufacturing weaknesses, and 3) improve our understanding of device thrombogenicity in the ovine animal model, using multicomponent measurements of the coagulation system and renal ischemia quantification, in order to better correlate animal results with human results.The Infant VAD was implanted as a left VAD (LVAD) in 18-29 kg lambs. Twelve LVAD and five surgical sham animals were electively terminated after approximately 30 or 60 days. Anticoagulation was by unfractionated heparin targeting thromboelastography R times of 2x normal (n = 6) or 1x normal (n = 6) resulting in negligible heparin activity as measured by anti-Xa assay (<0.1 IU/ml). Platelet inhibitors were not used.There were no clinically evident strokes or evidence of end organ dysfunction in any of the 12 electively terminated LVAD studies. The degree of renal ischemic lesions in device animals was not significantly different than that found in five surgical sham studies, demonstrating minimal device thromboembolism.In summary, these results in a challenging animal test protocol support the conclusion that the Penn State Infant VAD has a low thromboembolic risk and may allow lower levels of anticoagulation.
Assuntos
Insuficiência Cardíaca/cirurgia , Coração Auxiliar/efeitos adversos , Tromboembolia/prevenção & controle , Animais , Anticoagulantes/uso terapêutico , Coagulação Sanguínea , Desenho de Equipamento , Feminino , Insuficiência Cardíaca/complicações , Heparina , Humanos , Lactente , Masculino , Modelos Animais , Ovinos , Carneiro DomésticoRESUMO
Ventricular septal defects are one of the most common congenital cardiac malformations in animals, and most often affect the membranous portion of the septum. These defects may rarely close spontaneously. An adult male black-tailed prairie dog ( Cynomys ludovicianus) had a smooth shiny botryoid red mass arising from the area of the septal cusp of the right atrioventricular (tricuspid) valve and membranous interventricular septum, and bulging into the right ventricular lumen. Histology and special staining demonstrated a membranous ventricular septal defect closed by the adherence of the septal cusp of the tricuspid valve to the muscular septum (so-called membranous ventricular septal aneurysm or aneurysm of the [peri]membranous ventricular septum). This is a rare finding in animals, and the histologic appearance has not been documented previously, to our knowledge.
Assuntos
Aneurisma/veterinária , Comunicação Interventricular/veterinária , Doenças dos Roedores/diagnóstico , Sciuridae , Aneurisma/diagnóstico , Aneurisma/patologia , Animais , Comunicação Interventricular/diagnóstico , Comunicação Interventricular/patologia , Masculino , Doenças dos Roedores/patologiaRESUMO
We report here a detailed time course study of the individual and combined chemopreventive effects of Tamoxifen (Tam) and a high fish oil (FO) diet on multiple histologic parameters of mammary carcinogenesis. Groups of female Sprague-Dawley rats were injected ip with 1-methyl-1-nitrosourea at 50 days of age and assigned to either a control diet (20% corn oil [CO]) or a FO-rich diet (10% FO + 10% CO) in the presence and absence of Tam in the diet (0.6 ppm). Rats were sacrificed at weeks 4 (before palpable tumors), 8 and 12 (when â¼90% of control rats had palpable tumors). Our results demonstrate a major effect of Tam in inhibiting the development of early preneoplastic lesions. FO, while having a marginal protective effect of it own, enhanced the antitumor action of Tam on all histologic parameters of carcinogenesis, although the effects of the combination were not statistically different from those of Tam alone. The combination of FO and Tam was the only intervention that induced regression of established preneoplastic lesions. We also found that in contrast to plasma, only target tissue n-3 fatty acids (FAs) levels correlated with select tissue biomarkers of carcinogenesis whose expression was altered in a manner predictive of a protective effect. Our results demonstrating the potentially superior chemopreventive efficacy of Tam and n-3FA have important translational implications. Our data also emphasize the importance of local factors in affecting target tissue levels and biologic effects of n-3FA.