Faculty Bibliography

The objective of this study was to evaluate the feasibility of duplex scanning-derived access volume flow (DAVQ) to predict the success or failure of arteriovenous fistulae (AVF) after interventions. Eighty-eight DAVQ measurements were available for 60 AVF in 59 patients. In 25 cases, physical examination findings or inadequate dialysis suggested failing (11) or nonmaturing (14) AVF. Outflow stenoses (1-4; mean 1.2 +/- 0.8) were confirmed by contrast fistulograms in 23 cases (17 peripheral; 6 central). These 23 cases underwent successful endovascular repair (17 balloon angioplasty; 6 stents) and had pre- and postintervention DAVQ measurements within 2 weeks of the procedure. Each was measured three times in a nontortuous venous segment with laminar flow, and mean values were used for comparison. The overall mean DAVQ for 65 functioning AVF was 1,199 +/- 485 mL/min, whereas it was 652 +/- 438 mL/min (range 150-1,840 mL/min) for the remaining 23 failing or nonmaturing cases (p < .0001). Postintervention, the latter values changed to 867 +/- 517 mL/min (range 257-2,020 mL/min), with a p < .13. Of these, 11 were still nonfunctional after endovascular procedures and had a mean DAVQ of 404 +/- 111 mL/min (range 257-652 mL/min). The remaining 12 cases had a mean DAVQ of 1,280 +/- 382 mL/min (range 762-2,020 mL/min) and were functional and usable for at least 6 months of follow-up (p < .0001). It is interesting to note that none of the AVF cases with postintervention DAVQ < 700 mL/min became functional and usable, whereas all cases with a higher DAVQ underwent successful hemodialysis treatments. This early experience suggests that DAVQ can be used to predict the success or failure of an AVF following endovascular procedures. To our knowledge, this is the first such report.

PURPOSE: While diabetes and homocysteinemia have been demonstrated to be independent risk factors for progression of vascular disease, the activation of telomerase has not been linked to the potent effects of high levels of homocysteine (Hcy) and glucose on vascular smooth muscle cells (VSMC). We examined the proliferative response of VSMCs, resulting from hyperglycemia and hyperhomocysteinemia and their effects on telomerase activity. METHODS: Primary cultures of VSMC from human aorta and arteries were used in this experiment from 3rd -5th passages. Hcy or/and glucose were added to the cell culture media in doses equivalent to plasma levels of Hcy in patients with moderate, high homocysteinemia, or physiologically high concentrations of glucose as seen in diabetics. The modified telomeric repeat amplification protocol was used for telomerase activity assay. Cytotoxicity, viability, proliferation, protein phosphorylation, were determined in cultures treated and not treated with Hcy and glucose. RESULTS: The mitogenic effect of Hcy and glucose on VSMC, independently and together, was observed at 48 hours after treatment. The viable cell numbers were significantly increased at doses comparable to plasma levels of Hcy in hyperhomocysteinemia, as compared to untreated cultures (p < 0.01). Cells exposed to high levels of glucose also exhibited an increased proliferation response (p = 0.01). Telomerase activity was detected in all sets of VSMC cultures exposed to high levels of glucose or/and Hcy (p < 0.01). However, a significant difference was not observed in telomerase activity, when high Hcy or high glucose was used alone or in concert. Significant dual phosphorylation of p38 MAPK was observed in treated cultures but it did not correlate with the telomerase activity detected. CONCLUSION: These data establish a link with telomerase activation and the mitogenic effect of hyperhomocysteinemia and hyperglycemia.