Coronary-artery thrombi play an important part in the pathogenesis of unstable angina and acute myocardial infarction. However, the appearance of the thrombi is different in the two conditions, possibly reflecting differences in the composition of age of the thrombi or the presence or absence of blood flow in the artery. This difference may account for the contrasting results of thrombolytic therapy.
The capacity of lymph nodes to eradicate cancer is a controversial issue. The purpose of this study was to determine the interplay between tumor growth and host resistance at early stages of lymph node metastasis. A metastasis model was made in the rat mesenteric lymph node, and migration of cancer cells was visualized in vivo. The lymph node was removed for histologic analysis and cytokine measurement. Migrant cancer cells were initially arrested in the marginal sinus. After an initial increase, the number of cancer cells in the marginal sinus declined until 48 hours after inoculation. Germinal centers and lymphoid cells in the medulla proliferated before 48 hours. ED3؉ macrophages incorporated apoptotic cancer cells, but significant cancer proliferation occurred after 4 days. Lymph nodes depleted of macrophages were massively invaded by cancer cells. Tumor necrosis factor ␣ and interleukin (IL)-1 in the nodes transiently increased after 1 hour and 3 hours, respectively, and were expressed in ED3 ؉ and ED2 ؉ macrophages, respectively. These changes were followed by a transient increase in IL-2. Interferon-␥ and IL-12 did not increase during the early stages of metastasis, but they decreased after 48 hours. In conclusion, the marginal sinus constitutes a mechanical barrier against cancer cell passage. Early pathological manifestations in the regional lymph node are consistent with those in cancer patients with improved survival. Parasinus macrophages play a role in the transient antimetastatic capability of the node, and cytokines secreted by these cells increased at the early stages of metastasis. Deterioration of cytokine induction may be responsible for subsequent cancer proliferation.
Background-Radiofrequency ablation has limitations, largely related to creation of lesions by heating. Here, we report the first nonthermal ablation by applying photodynamic therapy (PDT) to cardiac tissues using a custom-made deflectable laser catheter. The present study investigated the feasibility of PDT for cavotricuspid isthmus ablation in a canine model. Methods and Results-We evaluated the pharmacokinetic profiles of 17 canines after administration of a photosensitizer (talaporfin sodium) by various protocols. We succeeded in maintaining the photosensitizer concentration at a level in excess of the clinically effective dose for humans. Using a 4-polar 7-French deflectable laser catheter, we performed PDT-mediated cavotricuspid isthmus ablation in 8 canines. PDT caused oxidative injury only to the irradiated area and successfully produced a persistent electric conduction block. No acute, gross changes such as edematous degeneration, thrombus formation, steam pops, or traumatic injury were observed after irradiation. Hematoxylin and eosin staining of tissues samples also showed well-preserved endothelial layers. Testing of the blood samples taken before and after the procedure revealed no remarkable changes. Lesion size at 2 weeks after the procedure and the temperature data collected during irradiation were compared between the PDT and irrigated radiofrequency ablation procedures. A ventricular crosssection revealed a solid PDT lesion, which was as deep as a radiofrequency lesion. In addition, endocardial, surficial, and intramural temperature monitoring during the PDT irradiation clearly demonstrated the nonthermal nature of the ablation technique. Conclusions-Nonthermal PDT-mediated catheter ablation is a potentially novel treatment for cardiac arrhythmias.(Circ Arrhythm Electrophysiol. 2013;6:1025-1031.)
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