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T h e re are three m ajor goals in the de velopm ent o f new transform ation protocols for modifying skeletal muscle : To improve muscle power output, to reduce fatiguability and to avoid or reduce m uscle damage. Theoretically each of the follow ing situations might improve one or more of these factors.

2.4.1. Im proving wrap geometry

If transposed muscles were made to work at the peak o f their force-velocity, force-length c u rv e s there m ight be less reduction in pow er as a result of poor c o n fig u ratio n or geometry. Direct circulatory assistance by cai'diomyoplasty or aortom yoplasty cuiTently presents the simplest clinical option since the circulation itself remains intact with minimal risk of thrombo-embolism. The major disadvantage of these procedures is that the muscle m ust be configured to the heart or aorta, which m eans that the loading conditions under which the muscle operates may force it to work far from the peak of its pow er cui-ve. One w ay to optimise the muscle loading conditions is to configure it into a skeletal muscle ventricle designed to allow the muscle to be loaded so that it operates nearer to its peak of efficiency (Bridges et al 1989, 1991; Oda et al, 1993). Alternatively the geom etry of the c ardiom yoplasty wrap could be optimised, perhaps by using different m uscles (left, right and even bilateral latissimus dorsi flaps have been used for cardiom yoplasty -Kao et al, 1990; M agovern et al, 1991; 1992;), redesigning the wrap arrangement, or by creating a

latissim us dorsi free flap with reim plantation of the nerve and blood supply (G uelinckx 1991). No objective data on the relative efficiency of these aiTangements is available.

There is an ai'gument for using latissimus dorsi in situ (where it presum ably operates under peak loading conditions) to drive a m echanical pum ping device via a m echanical or hydraulic linkage, or a generator which would pow er a pum ping device (Chiu et al, 1987; Li et al, 1990). Significant problem s associated with the developm ent o f these devices remain, including the risks associated with inuoducing foreign material into the ciiculation, the problem of forming a reliable bond between a muscle and any m echanised linkage, and the high cost of the devices. Calculation by Salmons and others indicate that flow rates of only 1 to 2 lities a minute (Salmons and Jaiwis 1992) would be achieved if skeletal muscle w as to be used in such an application because of the losses of pow er o ccu n in g in energy tiansfer processes and drive lines. An advantage w ould be that m ore pow erful m uscles, such as those in the thigh, could be employed, since the device would not necessaiily have to be positioned near the chest. A remote device may not need to be diiven in synchrony with the heait, thereby allowing the muscle to function under m ore favourable conditions which m ight take account of the changing contraction and relaxation kinetics w hich are a natuial result o f the dynamic nature of tiansfoiTnation.

2.4.2. M u scle bulk addition

Increasing the cross sectional area o f the m uscle does result in an increase in m uscle stiength which m ight be atuibutable to an increase in the num ber of saicom eres in pai'allel, thereby increasing the num ber of individual saicom eres contributing to the resultant force generated (G oldspiiik, G, 1971). Only about 50% of the gain in m uscle strength is atti'ibutable to the increase in cross sectional aiea of the muscle, and many other factors may be involved in an increase in m uscle strength rather than the n um ber o f m yofibrils contributing to the contraction. These include neural m echanism s which m ay be modified with training to allow a more maximal activation of the m uscle, possibly by increased recruitm ent of the lai'ger motor units (Komi, 1986). A lterations in the com position o f the muscle which might theoretically improve stiength include changes in fibre architectuie and packing, and increases in the connective tissue elements.

Changes in the fibre type com position to a greater proportion of large type 2 fibres would increase both strength and muscle cross sectional aiea, but the evidence for this occurring during strength training regim es is contioversial (for a review see Edstrom and G rim by, 1986). High force tiaining might result in m icro tears in the sarcom ere stincture which provides a stim ulus for repair. This m ay occur only after m any w eeks of tiain in g and include an increase in m yofibril num bers (Friden et al 1983). A t p resen t the m uscle tiansform ation regim es tend to produce a gross reduction in m uscle bulk, by as m uch as 50% or more. This may be partly due to the reduction in fibre cross sectional aiea rather than num ber, since type 1 fibres aie smaller in section than type 2. Even the m aintenance of the existing m uscle volume would be a significant im provem ent on the current regim es while an increase in muscle bulk remains a more distant goal.

At present, pre-operative training regimes aie being used by some surgeons (Lorusso et al, 1993; d ia d iq u e s et al, 1995) in order to try to increase the bulk of the latissim us dorsi m uscle prior to translocation. The benefits of this practice rem ain undeterm ined. M any patients with chronic heart failure are only able to exercise to a m inim al degree. O ur understanding o f the effects of chronic heart failure on the physiology of exercise also rem ain limited (Sullivan et al, 1990; M ancini, 1992;). Im proved know ledge in this area may lead to more effective pre-operative uaining programmes.

T here has been a revival of interest in the use and effect of steroidal di'ugs on skeletal m uscle (Hohenhaus et al, 1992). Work by Salmons (1992) indicated the selective effect of the steroid nandiolone decanoate on rabbit skeletal muscle, and noted the highly significant increase in cross-sectional area and m axim um isom etric tension in the m uscles under review. The study indicated that a tm e increase in the am ount of contractile protein present in the muscle had occurred, but also dem onstiated that a decrease in the oxidative capacity and an increase in glycolytic pathways had occurred, with a deduced reduction in fatigue resistance. There was no evidence, how ever of a change in population from type I to type II fibres. Unfortunately long term steroid therapy is usually unacceptable to patients due to the many adverse side effects and this is paiticularly true in those with heait failuie.

There has been renew ed interest in the use of di'ugs such as clem buterol (a beta agonist) w hich m ight be given in com bination with electrical stim ulation and m ight achieve an optim um steady state fibre type population with increased stiength and fatigue resistance, but this work is at an early stage of development (Petrou et al, 1995).

2 .4 .3 . S a r c o m e r e addition

The addition of saicom eres to the m uscle filaments (i.e. increasing the num ber in series) will increase the velocity of shortening with a proportionate increase in power. A ttem pts to increase sarcom ere num bers under com bined regim es o f electrical stim u latio n and stretching have been published for many yeais by certain gioups (W illiams et al; 1986). It is w ell recognised that subjecting a muscle to continuous electrical stim ulation alone will resu lt in a loss o f bulk o f the m uscle, some o f which may be attributed to a loss of sai'comere num bers in series. A regim e of electrical stim ulation and shortening o f the m uscle or holding the muscle to a shortened length alone leads to a m aiked reduction in sai'comere num bers in series (W illiams and Goldspink, 1978, G oldspink and W interbaun, 1991), whereas passive stietch alone or passive stretch plus electrical stim ulation leads to a m aiked increase in the wet weight of the muscle and to the numbers of sarcom eres in series (Cox et al, 1993). It is strongly felt by these workers that the application o f passive stretch to a m uscle will preseiwe its mass, com pliance and pow er output (G oldspink et al, 1985), and that a m ore rapid transform ation occurs when the conditioning pattern of electrical stim ulation is com bined with passive stietch. They also im ply a reduction in m uscle d am ag e based on a reduction in the collagen co ncentration in the m uscle d u rin g conditioning when com paied to immobilised muscle. The im plications of these findings for cai'diomyoplasty aie interesting. Translocation of the latissimus dorsi m uscle into the chest inevitably involves a loss of passive stretch on the muscle due to sectioning of the hum eral

tendon, and the difficulty in estim ating the original length of the m uscle once it is translocated. In addition, applying the muscle too tightly around a dilated irritable heart in an attempt to maintain skeletal muscle length inevitably leads to filling constraints at the very least, and may initiate fatal ventricular dysrrhythmias.

The problem of further atrophy is com pounded by the period of inactivity that follows surgery due to the vascular delay imposed by the theoretical need for the muscle to recover its peripheral blood supply and form stable adhesions within the pericardial cavity before electrical conditioning can com m ence (Mannion et al, 1985). W hilst the "vascular delay" tim e cannot be avoided at present (although it's absolute necessity and c urre nt length should be questioned), maintenance of passive stretch on the translocated m uscle during this time might at least maintain the num ber of sarcom eres in series, thus he lping to maintain power output of the muscle. This may lead to a shortened conditioning period and allow earlier haem odynam ic benefit to the patient. Unfortunately, this is not currently a practical possibility.

2.4.4. M odifying stim ulation regimes

T he electrical stim ulation regime used clinically to date (C arpentier et al, 1985) has successfully solved the problem of fatigue resistance (by transforming the muscle to a type 1 population of fibres) this having been a major stum bling block to progress for many years. H ow ever consideration of the factors described above and in the previous chapter indicates that, at least theoretically, the potential exists to m anipulate the training regime initiating and maintaining muscle transformation to produce a more appropriate fibre-type population. A more effective muscle wrap could be achieved not only by optim ising m uscle wrap geometry but by affecting an improved biochemical profile resulting from alterations in our approach to both the training and m aintenance stim ulation regimes. Preliminary work (Jarvis, 1992; 1996) suggests that a more rapidly contracting yet fatigue- resistant muscle flap may not be an unrealistic goal. Further im provem ent in efficiency could result from a stimulation regime that results in less reduction in the muscle bulk than obseiwed with current regimes.