Abstract 16455: Limb Threatening Ischemia: Promoting Arteriogenesis
Collateral growth is promoted by increased shear stress, which leads to activated endothelial cells capturing circulating monocytes/ progenitor cells. These migrate into the sub-endothelium to initiate arteriogenesis. This process is impaired in patients with chronic limb-threatening ischemia (CLI) because: 1) the shear stress stimulus is nearly absent caudal to multi-level arterial occlusive disease, and 2) the needed circulating progenitor cell population is typically diminished in number and function in these patients. We hypothesize that 1) cyclic programmed external compression of the ischemic calf and foot can provide the lacking shear stress stimulus, and 2) boosting the number of circulating progenitor cells with Granulocyte Colony Stimulation Factor (G-CSF) will boost efficacy. Neither strategy alone has been consistently effective in promoting limb salvage in CLI patients. Our hypothesis is that both are needed together. Starting in 2008, we tested this hypothesis in unreconstructable Fontaine IV patients (N=3) following 2-3 previous revascularization failures each. Co-morbidities included CAD/CABG, Stage III renal disease, IDDM, antiphospholipid syndrome, HIV, carotid disease, hypertension, and CHF. G-CSF 10 mcg/kg (Filgrastim, Amgen Inc) was injected SQ every 3rd day for 1 month. Cytometry confirmed cell mobilization. Each patient wore the ArtAssist device (ACI Inc.) for 1 hour at a time TID in the seated position until wounds healed. Ischemic rest pain resolved over 2 weeks. Ulcers over exposed tendons healed (5-17 months). ABI’s increased from <0.2 to 0.6 in two patients, and from 0.4 to 1.0 in the third. Foot TcPO2 rose from 1 to 35, 3 to 24, and 0 to 22 mmHg over 6 months. One patient with non-pulsatile forefoot PPG waveforms on enrollment in 2008 was re-evaluated in 2009 when she traumatized her 5th toe. The strategy was repeated when the toe became cyanotic and ulcerated. Five months later pulsatility was detected in all 5 toes. The 5th toe healed. The 3 patients remain ambulatory at 4 years. Angiograms confirm rich collateral growth. This approach eliminates marrow harvest and ex vivo processing used in other cell therapy neovascularization strategies and warrants further study.
- © 2012 by American Heart Association, Inc.