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Background-Therapeutic angiogenesis is thought to be beneficial for serious ischemic diseases. This investigation was designed to establish a simple and practical procedure applicable to therapeutic angiogenesis. Methods and Results-When cultured skeletal muscle cells were electrically stimulated at a voltage that did not cause their contraction, vascular endothelial growth factor (VEGF) mRNA was augmented at an optimal-frequency stimulation. This increase of VEGF mRNA was derived primarily from transcriptional activation. Electrical stimulation increased the secretion of VEGF protein into the medium. This conditioned medium then augmented the growth of endothelial cells. The effect of electrical stimulation was further confirmed in a rat model of hindlimb ischemia. The tibialis anterior muscle in the ischemic limb was electrically stimulated. The frequency of stimulation was 50 Hz and strength was 0.1 V, which was far below the threshold for muscle contraction. After a 5-day stimulation, there was a significant increase in blood flow within the muscle. Immunohistochemical analysis revealed that VEGF protein was synthesized and capillary density was significantly increased in the stimulated muscle. Rats tolerated this procedure very well, and there was no muscle contraction, muscle injury, or restriction in movement. Conclusions-We propose this procedure as a simple and practical method of therapeutic angiogenesis. (Circulation.1999;99:2682-2687.)

A multichannel functional electrical stimulation (FES) system for the restoration of quadriplegic upper extremity function is described. The system is composed of a personal computer NEC PC-8801mkII, peripheral electronic circuits, CRT display and respiratory sensors for volitional control by the patient, and percutaneous electrodes. A C4 quadriplegic patient could drink canned tea by herself by using this FES system. Distinct features of the system are as follows: 1) Versatile volitional control was realized by controlling the memory allocation of the stored stimulation data by voluntary respiratory signals. 2) Sophisticated fine control of the fingers, wrists, and elbow was realized by creating the multichannel stimulation data from recorded myoelectric activities of normal subjects during movements of the upper limb.

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