Improved, Shorter-Latency Carcinogen-Induced Hepatocellular Carcinoma Model in Pigs.

Large animal models are important tools for hepatocellular carcinoma (HCC) research, especially in studies of hepatic vasculature, interventional techniques, and radiofrequency or microwave hyperthermia. Currently, diethylnitrosamine (DENA)-induced HCC in pigs is the only large animal model for in situ HCC with a tumor latency of 10-26 months. While phenobarbital (PB) is often used to accelerate DENA-induced HCC in rodents, it has not been previously studied in the porcine model. Therefore, we hypothesize that the addition of PB in the DENA-induced HCC porcine model will accelerate tumor latency compared to DENA alone. HCC and benign lesions were seen on serial MRI and confirmed on histopathology. Liver and tumors were further characterized by CT angiography, vascular corrosion casting, and permittivity measurements.

Stent treatment of inferior vena cava compression in an ovine with a total artificial heart.

Although current continuous-flow total artificial hearts (CFTAHs) are much smaller than previous models, venous kinking may still occur after device implantation, especially in smaller animals. By inserting a self-expanding stent at the site of venous narrowing in a sheep model implanted with a CFTAH, we were able to restore the normal venous geometry and dramatically increase the CFTAH output. Because this percutaneous approach avoids the challenges associated with reoperation in these cases, it may be useful to other CFTAH investigators.

Acute in vivo performance evaluation of the fluorescence affinity sensor in the intravascular and interstitial space in Swine.

OBJECTIVE: We assessed and compared the performance levels of a fiber-coupled fluorescence affinity sensor (FAS) for glucose detection in the intradermal tissue and intravascular bed during glucose clamping and insulin administration in a large animal model. RESEARCH DESIGN AND METHODS: The FAS (BioTex Inc., Houston, TX) was implanted in interstitial tissue and in the intravenous space in nondiabetic, anesthetized pigs over 6-7 h. For intradermal assessment, a needle-type FAS was implanted in the upper back using a hypodermic needle. For intravenous assessment, the FAS was inserted through a catheter into the femoral artery and vein. Blood glucose changes were induced by infusion of dextrose and insulin through a catheterized ear or jugular vein. RESULTS: Based on retrospective analysis, the mean absolute relative error (MARE) of the sensor in blood and interstitial tissue was 11.9% [standard deviation (SD) = ± 9.6%] and 23.8% (SD = ± 19.4%), respectively. When excluding data sets from sensors that were affected by exogenous insulin, the MARE for those sensors tested in interstitial tissue was reduced to 16.3% (SD = ± 12.5%). CONCLUSIONS: The study demonstrated that the performance level of the FAS device implanted in interstitial tissue and blood can be very high. However, under certain circumstances, exogenous insulin caused the glucose concentration in interstitial tissue to be lower than in blood, which resulted in an overall lower level of accuracy of the FAS device. How significant this physiological effect is in insulin-treated persons with diabetes remains to be seen. In contrast, the level of accuracy of the FAS device in blood was very high because of high mass transfer conditions in blood. While the use of the FAS in both body sites will need further validation, its application in critically ill patients looks particularly promising.

Imaging long-term fate of intramyocardially implanted mesenchymal stem cells in a porcine myocardial infarction model.

The long-term fate of stem cells after intramyocardial delivery is unknown. We used noninvasive, repetitive PET/CT imaging with [(18)F]FEAU to monitor the long-term (up to 5 months) spatial-temporal dynamics of MSCs retrovirally transduced with the sr39HSV1-tk gene (sr39HSV1-tk-MSC) and implanted intramyocardially in pigs with induced acute myocardial infarction. Repetitive [(18)F]FEAU PET/CT revealed a biphasic pattern of sr39HSV1-tk-MSC dynamics; cell proliferation peaked at 33-35 days after injection, in periinfarct regions and the major cardiac lymphatic vessels and lymph nodes. The sr39HSV1-tk-MSC-associated [(18)F]FEAU signals gradually decreased thereafter. Cardiac lymphography studies using PG-Gd-NIRF813 contrast for MRI and near-infrared fluorescence imaging showed rapid clearance of the contrast from the site of intramyocardial injection through the subepicardial lymphatic network into the lymphatic vessels and periaortic lymph nodes. Immunohistochemical analysis of cardiac tissue obtained at 35 and 150 days demonstrated several types of sr39HSV1-tk expressing cells, including fibro-myoblasts, lymphovascular cells, and microvascular and arterial endothelium. In summary, this study demonstrated the feasibility and sensitivity of [(18)F]FEAU PET/CT imaging for long-term, in-vivo monitoring (up to 5 months) of the fate of intramyocardially injected sr39HSV1-tk-MSC cells. Intramyocardially transplanted MSCs appear to integrate into the lymphatic endothelium and may help improve myocardial lymphatic system function after MI.