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Biomedical subjects

K Kandarpa

Publications and source records attributed to K Kandarpa.

43 records · Page 3Linked to original sources

Technical determinants of success in catheter-directed thrombolysis for peripheral arterial occlusions.

Local intraarterial thrombolytic therapy restores blood flow to the ischemic limb by dissolving the occlusive thrombus and identifies culprit lesions for treatment by means of surgical and/or percutaneous procedures. The techniques used for administration of the thrombolytic agent, the drug used, and the criteria for termination of the therapy are all factors that can influence both technical success and speed of lysis. This article discusses these factors and their influence on thrombolytic success.

Arterial Occlusive Diseases↗

Assessment of peripheral intraarterial thrombolysis versus surgical revascularization in acute lower-limb ischemia: a review of limb-salvage and mortality statistics.

PURPOSE: To review the risks and benefits of using peripheral intraarterial thrombolysis (PIAT) versus surgical revascularization (SR) as the initial treatment of acute lower-limb ischemia (ALLI). MATERIALS AND METHODS: Two prospective, randomized trials that compared PIAT with SR in the treatment of ALLI were analyzed along with recent large, retrospective studies. Overall, 1,051 SR cases and 895 PIAT cases were included; when possible, the ischemic events were further categorized as acute, chronic, embolic, or thrombotic. Limb salvage and mortality at 30-day and 6-12-month follow-up were assessed. Combined percentages were derived by proportionally weighing each study. RESULTS: When all studies were combined, limb salvage rates were 93% for PIAT and 85.5% for SR at 30 days and 89% versus 73%, respectively, at 6-12-month follow-up. Mortalities were 4% versus 15%, respectively, at 30 days and 8% versus 29%, respectively, at 6-12-month follow-up. CONCLUSION: PIAT is associated with a substantially better limb-salvage rate and mortality than SR in the treatment of ALLI.

Acute Disease↗

Mural delivery of iloprost with use of hydrogel-coated balloon catheters suppresses local platelet aggregation.

PURPOSE: To develop reproducible and quantifiable methods for mural delivery of iloprost, a potent agent against platelet aggregation, with use of hydrogel-coated angioplasty balloons, and to determine the in vivo effect of direct iloprost delivery on platelet aggregation at the angioplasty site. MATERIALS AND METHODS: Drug loading of tritiated iloprost from an immersion solution onto hydrogel-coated balloons was evaluated as a function of balloon size (3 mm x 2 cm, 6 mm x 2 cm, 8 mm x 3 cm; n = 4 each), drug concentration (0.0715 mg/mL, 0.1072 mg/mL, 0.1430 mg/mL; n = 3 each), and duration of immersion (40 seconds, 60 seconds, 120 seconds; n = 3 each). In another set of experiments, optimal drying methods were tested to minimize drug loss within a protective delivery sheath (n = 3 each). Ex vivo angioplasty was performed on excised swine arteries to estimate how much of the drug present on the balloon could be delivered to the wall (n = 3 iliac segments). Finally, in vivo angioplasty was performed in three Yorkshire pigs (n = 6 iloprost-treated and 6 control arteries) and indium-111-labeled platelet aggregation was measured at these sites, which were harvested 1 hour after the procedure. RESULTS: In the initial set of experiments, the authors found that the volume of drug loaded is determined by the wet-volume of the hydrogel coating, that the majority of volume loading occurs within the first 2 minutes, and that the volume uptake is independent of the drug concentration. The optimal drying method resulting in the least loss of iloprost within the sheath (only 4%) was prolonged drying (5 hours) under ambient conditions. Ex vivo angioplasty experiments showed that approximately 33% of the drug present on the balloon can be delivered to the wall. Finally, in vivo experiments showed that platelet aggregation is significantly suppressed at treated sites (by approximately 33% compared to control sites; P = .03) by minuscule mural doses of iloprost (roughly estimated at under 1 microg). CONCLUSION: Quantifiable and reproducible methods for loading iloprost onto hydrogel-coated angioplasty balloons were developed. The best of these methods was able to deliver enough iloprost into the wall to significantly reduce local platelet aggregation.

Angioplasty, Balloon↗

Site-specific delivery of iloprost during experimental angioplasty suppresses smooth muscle cell proliferation.

PURPOSE: The authors have previously reported that intramural delivery of iloprost during angioplasty suppresses local platelet aggregation at 1 hour in undiseased porcine arteries. In this study, the authors sought to quantify the effect of such treatment on medial vascular smooth muscle cell proliferation, an event implicated in the development of intimal hyperplasia. MATERIALS AND METHODS: Three Yorkshire pigs underwent percutaneous transluminal angioplasty with hydrogel-coated balloons for a total of 10 iloprost-treated (experimental) and 10 saline-treated (control) arterial sites. The balloons were prepared with previously reported techniques and loaded with 2.25 microg of iloprost for the experimental sites. On the eighth day after angioplasty, these sites were harvested and prepared for immunohistochemical staining. Thin (4 microm) sections of the specimens were stained with use of monoclonal antibody to proliferating cell nuclear antigen (PCNA). Appropriate positive and negative controls were used. Approximately 350-500 vascular smooth muscle cells were randomly counted under high power (100x) by an experienced physician who was blinded to the origin of the specimen. A PCNA index (%) was calculated as follows: [(#PCNA [+] cells)/(#PCNA [+] cells + #PCNA [-] cells)]x 100. A paired t test was used for statistical comparison. RESULTS: The PCNA indices for eight (n = 8) paired large vessels (iliac, carotid, subclavian) were 7.98 (+/- 1.8)%, for the iloprost-treated experimental sites, and 14.58 (+/- 3.8)% for the saline-treated control sites. This difference was statistically significant (P = .003). One large vessel pair was not available for analysis. When the pair of renal arteries of animal 3 were included (n = 9), the PCNA indices were 8.32 (+/- 2.3)% for the experimental sites, and 13.79 (+/- 4.2)% for the control sites. The differences were again significant (P = .01). CONCLUSION: Intraarterial site-specific delivery of iloprost during angioplasty with drug-loaded, hydrogel-coated balloons significantly suppresses medial smooth muscle cells in swine at the expected peak period of proliferation of 7 days after angioplasty.

Angioplasty, Balloon↗