RESUMO
BACKGROUND: An increasing number of conditions appear to benefit from control and modulation of temperature, but available techniques to control temperature often have limitations, particularly in smaller patients with high surface to mass ratios. We aimed to evaluate a new method of temperature modulation with an esophageal heat transfer device in a pediatric swine model, hypothesizing that clinically significant modulation in temperature (both increases and decreases of more than 1°C) would be possible. METHODS: Three female Yorkshire swine averaging 23 kg were anesthetized with inhalational isoflurane prior to placement of the esophageal device, which was powered by a commercially available heat exchanger. Swine temperature was measured rectally and cooling and warming were performed by selecting the appropriate external heat exchanger mode. Temperature was recorded over time in order to calculate rates of temperature change. Histopathology of esophageal tissue was performed after study completion. RESULTS: Average swine baseline temperature was 38.3°C. Swine #1 exhibited a cooling rate of 3.5°C/hr; however, passive cooling may have contributed to this rate. External warming blankets maintained thermal equilibrium in swine #2 and #3, demonstrating maximum temperature decrease of 1.7°C/hr. Warming rates averaged 0.29°C/hr. Histopathologic analysis of esophageal tissue showed no adverse effects. CONCLUSIONS: An esophageal heat transfer device successfully modulated the temperature in a pediatric swine model. This approach to temperature modulation may offer a useful new modality to control temperature in conditions warranting temperature management (such as maintenance of normothermia, induction of hypothermia, fever control, or malignant hyperthermia).
Assuntos
Temperatura Corporal , Esôfago , Reaquecimento/instrumentação , Reaquecimento/métodos , Animais , Feminino , Modelos Animais , SuínosRESUMO
Human HSP70iQ435A carries a single amino-acid modification within the dendritic cell activating region and tolerizes dendritic cells in vitro. The underlying DNA was used to prevent and treat disease in vitiligo mouse models through reduced dendritic cell activation and diminished skin T-cell infiltration, suggesting the same may be useful for patients. Physiologic differences between mouse and human skin then called for studies in large animals with human-like skin. We established the efficiency of DNA jet injection into swine skin before subcloning HSP70iQ435A into clinically suitable vector pUMVC3. Vitiligo lesions in Sinclair swine were treated with plasmid DNA to measure changes in depigmentation, T-cell infiltration, expression of HSP70i in skin, serum HSP70i, and anti-HSP70i serum titers. Remarkable repigmentation following HSP70iQ435A-encoding DNA treatment persisted throughout the 6-month follow-up period. Repigmentation was accompanied by an initial influx of T cells accompanied by increased CD4/CD8 ratios, waning by week 15. Melanocytes spanned the border of repigmenting skin, suggesting that melanocyte repopulation precedes skin melanization. Serum titer fluctuations were not treatment-associated. Importantly, treatment did not interfere with melanoma immunosurveillance. These data encourage clinical testing of HSP70iQ435A.
Assuntos
Células Dendríticas/imunologia , Proteínas de Choque Térmico HSP70/metabolismo , Imunoterapia/métodos , Melanoma/imunologia , Pigmentação da Pele/genética , Pele/patologia , Linfócitos T/imunologia , Vitiligo/imunologia , Animais , Diferenciação Celular , Movimento Celular , Células Cultivadas , DNA/genética , Modelos Animais de Doenças , Terapia Genética , Proteínas de Choque Térmico HSP70/genética , Humanos , Tolerância Imunológica , Vigilância Imunológica , Injeções a Jato , Ativação Linfocitária , Melanoma/genética , Melanoma/terapia , Mutação/genética , Neoplasias Experimentais , Pele/metabolismo , Suínos , Vitiligo/genética , Vitiligo/terapiaRESUMO
The chemistry and hemostatic parameters of class B vendor cats (Felis catus) can show wide levels of variation, possibly because of initial health status. We compared prothrombin time, partial thromboplastin time, common pathway assay and thrombin time between Class B vendor cats (n = 30) and a control group of healthy cats (n = 16). The antiprotease activities of antiXa, antiIIa, heparin cofactor II, and antithrombin were measured also. Plasma samples from citrated blood were analyzed by using standard clotting assays and commercially available chromogenic substrate assays. Tests for homogeneity of variances and 1-way ANOVA were used to test for significant differences between groups. Results of ANOVA were highly significant between groups for heparin cofactor II and Heptest activity levels. Variances were significantly different between groups for prothrombin time; therefore, an ANOVA was not done. These studies suggest that the class B cats exhibited sufficiently wide variations in their coagulation parameters that they may not be optimal subjects for vascular or cardiovascular research.