Calf muscle electro-stimulation:

An innovative therapeutic approach in treatment for claudicants?

Christian Ellul, BSc

Peripheral artery disease

u  Atherosclerosis resulting in a stenosis or occlusion in the artery. Diameter of the lumen is reduced resulting in chronic reduction in blood perfusion.

u  Conservative or revascularization, surgical procedures to restore blood perfusion and limit the symptoms.

u  What are the limitations in current treatment methods?

Therapeutic goals in claudicants

u  Reduce ischemic symptoms by restoring derangements caused by ischemia in the affected muscle – typically the calf muscle but also thigh muscle and buttocks can be affected.

u  Neoangiogenesis – growth of new capillaries/ development of pre-existing collaterals

u  Does physical exercise improve these derangements?

u  What’s in for Electrical Stimulation (ES)?

Electrical Stimulation

Electrical stimulation

Acute Effects Chronic Effects

Neoangiogenesis (angiogenesis, arteriogenesis) Muscle adaptation (muscle bulk, muscle fiber, muscle strength)

Arteriovenous gradient “Muscle pump hypothesis” Vasodilation through the release of a vasoactive substance

Acute effects

u  Arteriovenous gradient:

Equation for blood flow

Q = (PA-PV ) / R

Acute effects (cont’d)

u  Authors have shown that while the muscle pump may contribute to the hyperemic response, the muscle pump is neither the sole nor the major contributor of the hyperemic response (Clifford et al, 2005)

u  This is due to the fact that facilitating the muscle pump by increasing the venous pressure does not increase the hyperemic response (Tschakovsky et al, 2004; Valic et al, 2005).

u  Moreover peak blood flow is reached between 4- 7 seconds after contraction and not immediately after contraction.

u  These attribute the release of a vasoactive substance with muscle contraction that takes between 4-7 seconds to cause maximal effect (Naik et al, 1999; Clifford et al, 2005).

u  This vasoactive substance and the vasodilatory mechanism remains elusive but Naik et al (1999) shows that achetylcholine is not attributed to this effect.

Chronic effects

u  Three possible therapeutic pathways: arteriogenesis; angiogenesis; and muscle fiber adaptations.

What is the difference between arteriogenesis and angiogenesis?

u  Hershey et al (2001) describes arteriogenesis as development of pre-existing but rudimentary true- collateral vessels that are able to “save a limb”.

u  Angiongensis – growth of new capillaries from pre-existing ones. Example: proliferation of a capillary network around a muscle or tumor (Hershey et al, 2001)

CHRONIC EFFECTS

Chronic effects

u depending on the pathology of the impaired blood supply we most likely may need the therapeutic restoration either as a macrovascular repair (arteriogenesis; in case of major arterial stenosis or occlusion) or - in the case of ischemic tissue -as a microvascular repair via angiogenesis

(Heil et al, 2006)

Chronic effects

u Rehabilitation physical exercise has been attributed to improvement in claudication symptoms (attributable to angiogenesis and muscular adaptations) but exercise therapy is not evidenced to produce significant haemoydnamic blood flow improvement (Parmenter et al, 2010).

u What about Electrical stimulation?

Electrical stimulation - neovasculogenesis

u  Majority of studies on animal models

u  In claudicants, human studies have shown significant increases in walking distance, muscle strength/ bulk and tone in response to 4 weeks (Anderson et al, 2004) and 8 weeks of stimulation (Presern- Srukelj & Poredos, 2002).

u  Animal models have shown significant increases in haemodynamic blood flow attributed to collateral artery growth – arteriogenesis (Milkiewez et al, 2003)

u  Significantly increased capillary density in ischemic muscle and capillary to fiber ratio (Kanno et al, 1999; Brown et al, 2005; Hudlicka & Brown, 2009).

Electrical stimulation – muscular adaptations

u  In contrast to exercise, ES activates all muscle fibers simultaneously and therefore at low intensity levels, patients achieve high intensity therapeutic responses. “More work done” à muscle strength and tone increases (Gregory & Bickel, 2005)

u  ES favors recruitment of fatigue resistant Type 1 (Oxidative) muscle fibers in favor of fast-twitch glycolytic type IIb muscle fibers. à resistance of fatigue (Pereidos et al, 2006)

u  Increased oxidative enzyme activity is associated with increased oxygen availability in response to angiogenesis whereby capillary sprouting maximizes oxygen availability to the working muscle (Pereidos et al, 2006)

Gregory &

Bickel (2005)

GAPS in the literature

u  Small sample sizes in humans (majority between 10- 30 subjects) u  Limited duration of chronic stimulation (max. 8 weeks)

u  Studies evidencing therapeutic response mainly on animals such as rodents.

u  No current evidence attributing improvements in haemoydnamic flow in response to electrical stimulation (eg. ABPI improvement, TcPO2 etc.) in stable claudicants.

u  Only one study has reported significant increases in TcPO2 at the dorsum of the foot in response to 8 weeks of daily 2 hour stimulation on a population with previous amputations (Presern- Slrukelj & Poredos, 2002)

u  Optimal parameters of stimulation incl. dose and frequency of stimulation not defined.

conclusion

u  Research favors the use of ES in order to increase walking distance in claudicants.

u  The possibilities of ES to improve haemoydnamic blood flow are ill-defined and require further research.

Our study

u  Longest duration of stimulation (12 weeks duration)

u  Target population of patients with calf claudication and comorbid diabetes

u  Assessing three distinct parameters:

1.  Walking Capacity

2.  Haemodynamic blood flow at the ankle arteries (Spectral doppler waveforms and the ABPI)

3.  Plantar Foot temperatures utilizing thermography at rest and following a graded treadmill protocol.