Percutaneous cryoablation of the kidney in a porcine model.

Several reports have documented that renal cryoablation when used either via open or laparoscopic surgical techniques can be well tolerated in animal models. We sought to examine the feasibility of performing renal cryoablation percutaneously, under ultrasound guidance, in a porcine model. A total of 13 juvenile swine was treated. In each animal the lower pole of the left kidney was used as the target. Each animal had serum drawn for Hct, Wbc, CK, BUN, creatinine, and myoglobin pre- and postcryoablation and again at the time of sacrifice. Animals were sacrificed at 0-42 days postoperatively, and the treated renal units were harvested and submitted for histologic examination. The procedures were divided into three groups based on the extent of the freeze time. Group 1 (n = 4) was treated for 3-4 min, single freeze; Group 2 (n = 3), 6-7 min, single freeze; and Group 3 (n = 6), a double freeze-thaw cycle, each for 10 min. None of the animals in this experiment died or experienced significant clinical deteriorations at any time post-treatment. No significant differences in any of the measured serum markers were noted between pre- and post-treatment values. For animals in Groups 1 and 2 discrete cryolesions were created with sharp 1-mm borders and no perirenal reaction/damage to surrounding structures. For animals in Group 3 large areas of renal infarction/cryolesions were produced, with significant perirenal reaction in 5/6 animals and gross hydronephrosis/total renal loss in 2/6. Percutaneous renal cryoablation appears to be well tolerated in the porcine model which we used. Associated morbidity appears to be related to the extent of freezing, with a safety tolerance in the present study limited to target areas of approximately 3-5 cm3. These findings suggest that a pilot study of percutaneous renal cryoablation for patients with 3-4-cm exophytic lesions may be warranted.

Estrogen inhibits the response-to-injury in a mouse carotid artery model.

The atheroprotective effects of estrogen are well documented, but the mechanisms responsible for these effects are not well understood. To study the role of physiologic (nanomolar) estrogen levels on the arterial response-to-injury, we applied a mouse carotid artery injury model to ovariectomized C57BL/6J mice. Mice were treated with vehicle (-E2, n = 10) or 17 beta-estradiol (+E2, n = 10) for 7 d, subjected to unilateral carotid injury, and 14 d later contralateral (normal = NL) and injured carotids from -E2 and +E2 animals were pressure fixed, harvested, and analyzed by quantitative morphometry. E2 levels in +E2 mice were consistently in the nanomolar range (2.1-2.5 nM) at days 0, 7, and 14. At 14 d, measures of both intimal and medial area were markedly increased in the -E2 group: (-E2 vs NL, P < 0.05 for both), but were unchanged from normal levels in the +E2 group (+E2 vs NL, P = NS and +E2 vs -E2, P < 0.05 for both). Cellular proliferation, as assessed by bromodeoxyuridine (BrdU) labeling, was significantly increased over NL in the -E2 mice, but this increase was markedly attenuated in the estrogen replacement group (total BrdU positive cells/section: NL = 6.4 +/- 4.5; -E2 = 113 +/- 26, +E2 = 40 +/- 3.7; -E2 vs NL, P < 0.05; +E2 vs NL, P = NS; -E2 vs +E2, P < 0.05). These data (a) demonstrate significant suppression of the mouse carotid response-to-injury by physiologic levels of estrogen replacement; (b) support the utility of this model in the study of the biologic effects of estrogen on the vascular-injury response; and (c) suggest a direct effect of estrogen on vascular smooth muscle cell proliferation in injured vessels.

A new platinum balloon-expandable stent (Angiostent) mounted on a high pressure balloon: acute and late results in an atherogenic swine model.

BACKGROUND: Randomized studies have proven the efficacy and safety of stent placement to treat de novo coronary stenosis. However, the poor radio-opacity and the use of an additional high-pressure balloon to fully expand the stent are the major limitations of the currently clinically-approved stents. OBJECTIVE: We evaluated the safety, efficacy, angiographic and histologic effect of a new platinum balloon expandable stent mounted on a high-pressure balloon in Yucatan miniature swine fed high cholesterol diet. METHODS: Fifteen Angiostents (NuMED, Inc., Hopkinton, NY and Angiodynamics, Glens Falls, NY) (coronary stent was 3, 3.5, or 4 mm in diameter and 12 mm long; renal and carotid stents were 5 mm in diameter and 13 mm long) mounted on a high-pressure balloon were placed percutaneously in blood vessels of 10 pigs [5 in circumflex (CX), 2 in left anterior descending (LAD), 5 in renal and 3 in carotid arteries]. The stent was 10-20% larger than the native vessel diameter. All animals received 5000 I.U. of heparin during the procedure and were maintained on 325 mg aspirin daily. Follow-up angiography and histology in the animals was performed at 2, 4, 12, 20, 26 and 52 weeks. RESULTS: The stents were easily visualized with fluoroscopy and placed in all animals without episodes of balloon rupture or embolization. There was no episode of acute thrombosis. Follow-up angiography in the animals revealed patency of all renal and carotid stents, however, 2/7 coronary stents in the animals revealed angiographic lumen narrowing (> 20%) at 20 and 52 weeks. Histologic examination revealed neointimal formation at the stent site with an average neointimal thickness ranging from 325-650 microns. CONCLUSION: This stent was safe in this animal model, easily deployed, had excellent radio-opacity and with good short-term patency without anticoagulation. Clinical trials and experience is underway.