Effect of long-term electrical stimulation on vascular supply and fatigue in chronically ischemic muscles

Abstract

Fast skeletal muscles of Sprague-Dawley rats [tibialis anterior (TA) and extensor digitorum longus (EDL)] were subjected to ischemia by unilateral ligation of the common iliac artery. In some animals, ischemia was combined with indirect electrical stimulation at 10 Hz either for 3 x 2 h (strenuous activity) or for 7 x 10-min bouts/day (mild activity). After 2 wk, muscle blood flow and fatigue were measured during 5-min isometric supramaximal twitch contractions at 4 Hz. Terminal arteriole diameters were assessed in TA by intravital microscopy at rest and during contractions. Vascular perfusion pressure in the muscles was estimated from measurements in the carotid and saphenous arteries below the site of ligation. Capillary supply was expressed in TA and EDL as capillary-to-fiber ratio on the basis of histochemical staining for capillaries. Strenuous stimulation of ischemic muscles increased their atrophy, failed to restore blood flow, and actually worsened fatigue. In contrast, mild stimulation improved perfusion pressure, increased capillary-to-fiber ratio in the glycolytic part of TA, restored dilatation of terminal arterioles during muscle contractions, and improved blood flow and muscle fatigue so that they were no longer significantly different from control muscles. Thus, an attenuated intermittent protocol may be indicated in the treatment of muscle ischemia.

Arteriogenic Revascularization Does Not Induce Vascular Function Impairment

“…Further, while the resting blood supply is affected by this condition, vascular function (blood flow control) is also impaired (as previously mentioned). Furthermore, blood flow control is also important to patient health, as the earlier discussion would suggest [17]. Patients suffering from this condition commonly experience claudication (limb fatigue during activity) and pain in their feet while resting, specifically in the arch, ball or toes, and if the condition is not correctly treated, the symptoms may progress to include ulceration and tissue necrosis [18].…”

“…These factors constitute some of the pathways for vascular diameter modulation. However, in conditions of chronic ischemia blood flow control mediated by vasodilators such as adenosine and bradykinin as well as vasoconstrictors such as norepinephrine is attenuated [5,17]. The mechanism by which these vaso-active agents fail during chronic ischemia would aid in our understanding and treatment of peripheral artery disease, because even if new treatments are able to promote vascular growth it remains imperative that these new or remodeled vessels be able to function according to the needs of skeletal muscle metabolism; proper vascular function is vital for adequate tissue function.…”

“…high shear stress or hypoxia). For reasons that we aim to discover, vascular function (ability for vasodilation/vasoconstriction) is impaired following ischemic repair [5,17]. Certain arteriogenic or angiogenic physiological settings are expected to be the cause of this ischemia-induced vascular dysfunction.…”

“…To tease apart the potential reasons for vascular dysfunction it would be useful to use multiple surgical models for ischemia in which revascularization occurs under distinct physiological conditions. The previous studies, which observed impaired vasodilation to both metabolic and pharmacological stimuli were done using one rat model of hindlimb ischemia in which the iliac artery was ligated and vascular function was evaluated in the lower hindlimb [5,17]. Following ischemia-inducing surgery there are multiple factors that could influence vasculature dysfunction such as inflammation, oxygen delivery and average blood flow.…”

“…Following ischemia-inducing surgery there are multiple factors that could influence vasculature dysfunction such as inflammation, oxygen delivery and average blood flow. In the previously referred to experiments involving iliac artery ligation, vascular function in the lower limb was evaluated and observed to be impaired under conditions of significant hypoxia, ischemia and inflammation [5,17].…”