Constitutive Expression of phVEGF165 After Intramuscular Gene Transfer Promotes Collateral Vessel Development in Patients With Critical Limb Ischemia
To the Editor:
Baumgartner et al1 reported a significant advance in angiogenic gene therapy. They induced collateral neovascularization in 10 critically ischemic limbs by injection of vascular endothelial growth factor (phVEGF165) into the muscles of the ischemic limbs. The effect of the therapy was demonstrated by a significant rise in ankle-brachial index, newly visible collateral blood vessels on the contrast angiogram, healing of the patients’ former ulcers, and improvement in pain-free walking time. The authors cautiously claim that such improvement has not previously been achieved spontaneously or with medical therapy in patients with critical limb ischemia.
This may very well be so, but we had a corresponding experience in May 1992 with a 72-year-old male with critical ischemia in 1 limb. He was unsuitable for any type of vascular surgery and had no other alternative than amputation, when he underwent percutaneous corticotomy (cutting of the cortex, preserving the intramedullary circulation) on both the tibial and fibular bones. The bones were slowly moved posteromedial and posterolateral by transverse distraction osteogenesis by use of an Ilizarov ring fixator device.
We found that the toe pressure rose from 10 to 40 mm Hg and ankle pressure from 95 to 128 mm Hg (ankle-brachial index from 66% to 80%) 1.5 years after the operation. Newly formed collaterals were demonstrated on the contrast angiogram. His ulcers healed, his resting pain vanished, his toenails and hair started to grow, and he regained an infinite pain-free walking time.
Today, he is still without pain in the limb that was operated on, and the distal blood pressures at toe and ankle levels are 50 and 100 mm Hg, respectively, but he is starting to experience ischemic symptoms in the other limb; therefore, we are contemplating a second corticotomy and of course hoping for similar success. What actually is the course of this success? We can only speculate that surgical distraction osteogenesis also promotes angiogenesis. Distraction osteogenesis is known to give rise to the formation of multiple new small blood vessels in the calf muscle,2 thereby creating a sustainable low-pressure vessel area in which blood flow is high enough to nourish the foot and lower limb.
In patients who undergo distraction osteogenesis for limb shortening, the total limb blood flow increases by a factor of 5 to 7 during distraction. Distraction osteogenesis probably produces many local growth factors, of which some are angiogenic, and one may be VEGF. Debatable, but possible.
- Copyright © 1999 by American Heart Association
Baumgartner I, Pieczek A, Manor O, Blair R, Kearney M, Walsh K, Isner JM. Constitutive expression of phVEGF165 after intramuscular gene transfer promotes collateral vessel development in patients with critical limb ischemia. Circulation. 1998;97:1114–1123.
Ilizarov GA. The tension-stress effect on genesis and growth of tissues, part I. Clin Orthop. 1989;238:249–281.