**6. Closed-Loop Controlled Stimulation (CLC-Stimulation)**

Since the basic experimental investigations of Salmons [7] and Pette [3], [8] it was evident, that the number of electrical pulses to a muscle fibre determines its fibre type. They showed that it is possible to transform a fast twitching fatigable IIa muscle into a fatigue resistant type I fibre muscle by increasing the number of pulses within a defined stimulation pattern. At the first glance it seemed to be ideal to substitute a damaged non-fatigable heart muscle by a slow twitching non-fatigable skeletal muscle. However, this dream was not to fulfil the expectations of muscle powered cardiac assistance clinically due to a tremendous loss of power in type I fibre muscles combined with a reduced contraction velocity. Nevertheless the DCMP showed to be effective clinically in certain limits as shown before.

Experimental investigations of Lopez-Guajardo et al. 2001 [158] demonstrated that a mean pulse reduction within certain limit results in a strong and non-fatigable muscle. But there was a limitation: the time of usage of this non-fatigable type II a muscle was restricted. Otherwise the muscle transformation would continue into type I fibres with all the negative consequences of power loss and a decreased contraction velocity. Therefore a controlled pulse management is mandatory to keep non-fatigable type IIa muscle fibres. This restriction in pulses however, goes along with a time-wise limited usage for a cardiac support. This fact has major implica‐ tions for a restricted usage in muscle powered cardiac assist with no blood contact like the DCMP and even more in muscular blood pumps [159–161].

To fulfil these demands in electrically stimulated muscular cardiac support to maintain a nonfatigable strong muscle with a preserved contraction velocity, myostimulators are mandatory to enable a closed-loop controlled stimulation.

#### **6.1. Technical basics for a closed-loop controlled muscle stimulation**

C/F ratio in muscular tissue in five boore goats of non (white block)- and pre-stimulated (black

**Figure 21.** 14 days of electrical stimulation increased the capillary to fiber ratio in goat's LDM (n=5) to 38% (black columns) in comparison to the non-stimulated contra- lateral LDM control (white columns). (\* p < 0.05; \*\* p < 0.01;

Ischemic damage in the latissimus dorsi muscle may limit the success of cardiomyoplasty. Electrical pre-stimulation of the muscle in situ is known to enhance capillarization and thoracodorsal perfusion to the distal latissimus dorsi muscle immediately after grafting. Use of a pre-stimulated graft may therefore improve the outcome of skeletal muscle cardiac

Since the basic experimental investigations of Salmons [7] and Pette [3], [8] it was evident, that the number of electrical pulses to a muscle fibre determines its fibre type. They showed that it is possible to transform a fast twitching fatigable IIa muscle into a fatigue resistant type I fibre muscle by increasing the number of pulses within a defined stimulation pattern. At the first glance it seemed to be ideal to substitute a damaged non-fatigable heart muscle by a slow twitching non-fatigable skeletal muscle. However, this dream was not to fulfil the expectations of muscle powered cardiac assistance clinically due to a tremendous loss of power in type I fibre muscles combined with a reduced contraction velocity. Nevertheless the DCMP showed

Experimental investigations of Lopez-Guajardo et al. 2001 [158] demonstrated that a mean pulse reduction within certain limit results in a strong and non-fatigable muscle. But there was

block) LDM ( p≤0.05\*; p≤0.01\*\*,n.s. = not significant;).

**6. Closed-Loop Controlled Stimulation (CLC-Stimulation)**

to be effective clinically in certain limits as shown before.

n.s. not significant)

assistance (Tang et. al,1998, [10])

812 Regenerative Medicine and Tissue Engineering

In order to protect the assisting muscle, the new Microstim myostimulator will prevent chronic overstimulation which results in an undesired muscle fiber transformation and degeneration. The fiber transformation to type I would lead to a subsequently reduced contraction velocity and muscle force accompanied by a reduced cardiac support with structural and functional muscle damage.

A closed-loop is designed to limit the amount of applied stimulation pulses below a certain maximum value of mean stimulation frequency over a given period, e.g. 0.7 Hz mean stimu‐ lation frequency within 24h. This closed-loop is used to maintain the fast and powerful twitching type IIa muscle fibres needed for a sufficient muscle powered cardiac assistance.

**Figure 22.** Closed-loop control to prevent muscular overstimulation. In feedback path 1, the patient receives a warn‐ ing message via RF from the implanted myostimulator to a wearable patient monitor. Feedback path 2 intrinsically reduces the pulse delivery in accordance to programmed parameters.

In two groups of goats, skeletal muscle ventricles (SMVs) were shaped intra-thoracically [159], [160]. In group A (n=6) goat's LDM was not pre-stimulated and SMVs contracted by bursts of a mean pulse frequency of 5 Hz. This mean frequency of approximately 5 Hz has been used clinically in more than 1000 cases up to now, resulting in severe muscle damage as shown above in chapter 2.2. Group B, LDM with pre-stimulation over 14 days as shown above and with a controlled stimulation with a mean pulse frequency not exceeding 1Hz mean pulse frequency showed a preserved muscle tissue (figure 23, right). This new stimulation regime in group B became feasible by the newly available myostimulator with an integrated feature for muscle protection (MyoSen ® Myostim GmbH, Wismar, Germany).

Musculus latissimus dorsi after 6 months of electrical stimulation

**Figure 23.** Histology of LDM 6 months after electrical stimulation with 5Hz and without pre-stimulation resulting in severe muscle damage (left) and LDM with pre-stimulation over 14 days and closed-loop controlled stimulation with a mean pulse frequency of 1Hz and preserved muscle tissue.
