W hen skeletal m uscle is used for cardiac assistance chronic electrical stim ulation is required to stimulate muscle contraction at the desired phase of the caidiac cycle and is also central to the transform ation process. To date, the electi'ical stim ulation regim es used (Caipentier 1985) appeal* to achieve full ti ansformation of the muscle fibre population from a predom inant population of glycolytic, fast, fatiguable type 2b fibres to a virtually com plete population o f type 1 fibres, w hich are slow to co n tract and relax, with a corresponding reduction in power, but which aie highly resistant to fatigue. Under the p r e s e n t t r a n s f o r m a t io n p r o t o c o ls th e c le a r c o st o f a c q u i r i n g f a t ig u e resistance is a loss o f power: W hile fatigue resistance is fundam ental to the use of skeletal m uscle in this application the resultant loss of speed o f both co n ü ac ü o n and relaxation due to the expression of slow m yosin isoform s and alteration in other specific biochem ical system s is highly undesirable and these fundam ental problem s aie o f great importance when skeletal muscle is used for circulatory assistance.
2.3.1. R ed uction in contraction velocity and d iastolic function
In dynam ic cardiom yoplasty one would expect the skeletal m uscle wrap to function by conüacüng during systole, thus augmenting or reinforcing the action of the ventricular wall; This is only possible if the transform ed muscle graft follows closely the v enu icular wall m ovem ent, which may not be possible if transform ation results in a fibre type population which con üacts more slowly. In addition if relaxation of the m uscle occurs m ore slowly than the ventricle during diastole, then diastolic filling will be lim ited, w ith a consequent reduction in the subsequent stroke volume. These effects are even m ore evident at higher heart rates (during exercise) which is precisely the time when greater haem odynamic benefit is required. T he reduction in latissim us dorsi m uscle graft contraction and relaxation velocities may therefore lead to consü aints on the volume changes that can occur within the space of a cardiac cycle.
2.3.2. R ed uction in power and work capacity
The reduction in contractile speed also leads to a co n esp o n d in g drop in pow er output, perhaps by as m uch as 90%, (Salmons and Jai'vis 1992), which has a profound effect on
skeletal muscle work capacity. A ce nain work capacity is essential if the skeletal muscle is to provide circulatoi"y assistance, which requires a particular level of power output. Power (m easured in W atts) is defined as the rate of perform ing work, and it is equal to the product o f force and the distance through which that force acts over time. Force is a difficult word to define because most forces (e.g. gravitational or magnetic) cannot be seen. W e can however, measure the effect of a force by measuring the distance and times over which a force acts to move a known mass at a specified acceleration.
The subtle difference between power generation and work generation can be illustrated by the example shown in Fig. 2.2.
10kg
A
Lift 2 m e tr e s in 1 s e c o n d 10kg Lift 2 m etr es in 2 s e c o n d sFigure 2.2: T he subtle difference between p o w e r g e n era tio n and w o r k
generation Tw o men stoop to pick up a lOKg w eight and lift it through 2 metres. If A takes one second and B two seconds, they will both have done the same am ount o f work - i.e. 100 Newtons (10 Kg against gravity) over 2 metres equals 200 Joules; but the faster of the two will have produced a power output of 200W , while the slower man, having taken 2 seconds has a power output of lOOW.
This illustrates clearly how the power output of a muscle is a function o f the time taken to perform work, and leads logically to an understanding of why a reduction in the contractile speed of any muscle leads to a reduction in the eventual work output over time o f that muscle.
The importance of this decline in power output can be illustrated as follow s : A realistic estimate of the total circulatory requirement of a 70kg subject might be a cardiac output of 6 1/min at a mean blood pressure of lOOmmHg. This c orresponds to a left ventricular working power output of 1.3W, based on the equation power = flow x mean pressure. In the cardiomyoplasty application we might use a latissimus dorsi m uscle initially weighing 450g, which is harvested and uansform ed to assist the circulation (Fig. 2.3.). Calculations based on rabbit tibialis an te rio r m uscle (S a lm o n s and Jarvis 1992) s u g g e st that
transformation to a predominant population of type I fibres will result in a loss of m ass by 50%, and a reduction in contractile speed at optimum velocity (Vopt) o f contraction to 25%. The net result is a loss of power by up to 90%. Added to this are theoretical mass losses associated with the sectioning of the humeral tendon (Guelinckx 1988) by up to 25% and any losses associated with ischaemic damage. The efficiency of energy transfer from the muscle to the circulation (coupling) also needs to be calculated, and an optimistic estimate for this procedure would be 15% (Geddes and Badylak, 1990).
A h u m an la tissim u s dorsi m uscle, after tra n slo c a tio n and tra n s fo r m a tio n m ight optimistically be expected to produce about 4.5W. If all of this power was c o n v e n e d into useful work this would produce a flow of 10.4 1/minute, a ssu m in g a m ean systolic pressure of lOOmmHg at 60 beats/minute. In the cardiomyoplasty application, where only one third to one half of the muscle is performing work which can usefully augm ent the circulation, and where energy coupling would be of the order of 10-15%, sustained flows of only 500m ls/minute (at best) might be expected. If the m uscle were used to pow er a hydraulic device or was configured to form a skeletal m uscle ventricle, energy coupling might approach 50% efficiency and flows of 4.5 1/minute might then be expected. A flow of 2.0 1/minute is all that can be expected if the muscle powers an electrohydraulic device where energy coupling is only around 25%.
The power produced by the skeletal muscle may be adequate to provide some circulatory support in the cardiom yoplasty or aortom yoplasty application, and even theoretically improved if the skeletal muscle was configured to operate at the peak of its pow er cui-ve - which might be achieved for example, in a skeletal muscle ventricle, but there w ould be little reserve for increasing power output during exercise. At the present time the pow er available in a suitable, fully transformed muscle such as adult latissimus dorsi is inadequate to power an implantable mechanical heart or auxiliary pum ping device independently of external power sources.
Figure 2.3: Theoretical power outputs and correspon d in g circu latory flows from Human latissim us dorsi following tra n sfo rm a tio n , tran slocation and application to the circulation in a number of different ways. A com parison with transformed rabbit muscle is drawn.