Ann Thorac Surg 2001;71:852-861
© 2001 The Society of Thoracic Surgeons
Original article: cardiovascular
Combination of preconditioning and delayed flap elevation: evidence for improved perfusion and oxygenation of the latissimus dorsi muscle for cardiomyoplasty
David J. Barron, FRCSa,
Phillip J. Etherington, BScb,
C. Peter Winlove, DPhilb,
Jonathon C. Jarvis, PhDc,
Stanley Salmons, PhDc,
John R. Pepper, FRCSa
a Department of Cardiac Surgery, National Heart and Lung Institute, London, United Kingdom
b Physiological Flow Studies Group, Imperial College, London, United Kingdom
c Department of Human Anatomy and Cell Biology, University of Liverpool, Liverpool, United Kingdom
Accepted for publication September 14, 2000.
Address reprint requests to Dr Barron, Department of Cardiac Surgery, Birmingham Children’s Hospital, Steelhouse Lane, Birmingham B4 6NH, United Kingdom
e-mail: dbarron{at}bhamchildrens.wmids.nhs.uk
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Abstract
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Background. Atrophy and fibrosis of the distal part of the latissimus dorsi muscle (LDM) wrap is a recognized complication of cardiomyoplasty that has been attributed to ischemia. Failure of the muscle wrap contributes to the late attrition seen in clinical cardiomyoplasty. In this study we examined the role of two-staged mobilization and of preconditioning by electrical stimulation on the regional perfusion and oxygenation of the LDM.
Methods. In a rabbit model (n = 36) the LDM was preconditioned as follows: group A muscles received preconditioning in situ; group B muscles were partially mobilized by dividing the intercostal perforators and then preconditioned; and group C muscles were completely mobilized and wrapped around a silicone-rubber mandrel before conditioning. Controls received no conditioning. The preconditioning regimen consisted of 2 weeks of continuous stimulation at 2.5 Hz. At completion of preconditioning the muscles were fully mobilized and mounted on a muscle-testing apparatus. Purpose-built microelectrodes measured regional Po2 and perfusion using a diffusible gas tracer technique. Muscles were weighed and processed for fiber typing and capillary counting.
Results. All preconditioned muscles demonstrated fiber transformation, with increased fatigue resistance. Perfusion of preconditioned muscles both at rest and during contraction was higher than control in the proximal part of the muscle. Distal regions of group B muscles had higher perfusion and capillary density than any other group (p < 0.05). Distal regions of group C had the lowest perfusion and capillary density, and showed muscle atrophy and histologic evidence of necrosis. During fatigue testing there was a decrease in the Po2 in the distal regions of the control and group C muscles (p < 0.05), whereas it was maintained at resting levels in both group A and B muscles.
Conclusions. Conditioning in situ improves perfusion of the distal LDM and prevents a fall in tissue Po2 during contraction. Two-stage mobilization further improves distal perfusion and capillary density. In contrast, short-term elevation followed by conditioning produces impaired distal perfusion, decrease in Po2, and fiber necrosis in the distal muscle. The present study suggests that partial mobilization of the LDM performed at the same time as placement of electrodes for preconditioning may prepare the LDM better for the demands of cardiomyoplasty.
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Introduction
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Skeletal muscle has a unique ability to adapt its structure and function according to the demands placed on it. The discovery that a muscle can be transformed from one phenotype to another by the appropriate neural stimulation has generated extensive research into muscle transformation and conditioning [1]. The physiologic changes that accompany transformation are still being unraveled, particularly with respect to metabolism, vascularity, and perfusion. Only recently it was discovered that a range of muscle phenotypes could be engineered through alteration of the muscle-training protocol and that intermediate muscle types, typified by a predominance of type IIA fibers, could be achieved and maintained without progression to a slow muscle [2].
Cardiomyoplasty (CMP) is the most ambitious and successful application of transformed skeletal muscle in clinical practice, and the procedure represents a considerable achievement, not only in overcoming the technical and surgical problems, but also in the successful application of muscle transformation protocols in a clinical situation. More than 800 cases of CMP have been performed world-wide, and despite improvements in early survival the disappointing feature of this procedure has been the failure to demonstrate reliable, long-term hemodynamic benefit [3]. The integrity of the LDM is of central importance to the success of CMP. There has been increasing evidence that poor outcome is related to fibrosis and atrophy of the muscle wrap and that the cause of these changes is ischemia [4–8]. An improvement in LDM viability is likely to be reflected in improved clinical outcome of CMP.
Surgical mobilization can impair the blood flow to the distal regions of the LDM owing to interruption of the perforating branches of the intercostal arteries, and we have demonstrated how this is reflected in decreased perfusion at the level of the microcirculation [9]. It is well documented in the field of plastic surgery that gradual mobilization of pedicled muscle flaps in stages can improve their viability by abolishing any collateral supply and thereby promoting expansion of the vascular territory of the pedicle vessels.
Furthermore, the long-term stimulation required to induce fatigue-resistant properties could be damaging to a muscle whose blood supply has been disturbed [6]. Long-term stimulation regimens currently in use (typically 8 weeks of pulsed stimulation) may involve a degree of muscle atrophy as part of the adaptive process [10], and may even damage the muscle because of an overdemanding stimulation regimen [11]. The role of preconditioning has been the subject of increasing interest as a means of improving LDM perfusion before CMP. Stimulation-induced transformation increases the capillary network within the muscle and improves nutrition at the level of the microcirculation [12]. It has also been shown to recruit more of the capillary bed by opening up choke-point arteries in the precapillary circulation [13].
This study was designed to determine whether the benefits of these strategies are additive by examining their effects on fatigue resistance and changes in regional intramuscular perfusion and oxygenation. The effects of preconditioning are examined when used independently and when used in combination with two-stage LDM mobilization.
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Material and methods
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Male New Zealand White rabbits weighing 2.5 kg were used. All animals received humane care in accordance with the guidelines published by the National Society for Medical Research (Principles of Laboratory Animal Care) and by the National Institutes of Health (Guide for Care and Use of Laboratory Animals). The project was licensed and performed in accordance with the Animals (Scientific Procedures) Act 1986, which governs animal experimentation in the United Kingdom.
Operative procedures
All animals were anesthetized by intramuscular injection of fentanyl-fluanisone (fentanyl citrate 0.315 mg/mL, fluanisone 10 mg/mL; Hypnorm, [Janssen Pharmaceuticals, Ridgeland, MS] 0.2 mL/kg) and intravenous midazolam 1 mg/mL. Anesthesia was maintained by continuous infusion of midazolam and further boluses of fentanyl-fluanisone 0.1 mg/kg at 1-hour intervals.
Muscle stimulators were made to a published design specifically for use in the rabbit [14]. They form part of a family of implantable stimulators that can be preprogrammed to deliver single impulses at specific frequencies (Fig 1). The electrodes consisted of a pair of polyvinyl chloride–insulated multistranded stainless steel wires ending in a bared loop that could be fixed in position with an integral polyethylene terephthalate fiber velour pad. The stimulators were gas sterilized in ethylene oxide, and all recovery procedures were performed under aseptic conditions. A 2.5-cm incision was made parallel to the anterior border of the LDM, close to the axilla, and the muscle border was dissected free to expose the thoracodorsal vessels as they enter the costal surface. Electrodes were sutured in place on either side of the nerve, and the device was implanted underneath the skin by creating a pouch inferior to the incision. The stimulator was switched on for a few seconds at this stage to verify operation. The stimulators delivered pulses of 0.2-ms duration and 3.2-V amplitude at a frequency of 2.5 Hz and could be switched on or off by a light-sensitive switch triggered by a flash gun placed against the skin. Wounds were closed in layers, and the animals were left to recover for 48 hours, after which the stimulators were switched on. Effective stimulation was confirmed daily by palpation over the LDM.
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Fig 1. Photograph of the implantable stimulator and electrodes used in this study, with centimeter scale. The device can be switched on or off while implanted by means of flashes of light through the overlying tissues. (Such devices and similar, more versatile programmable devices are available for experimental work from the University of Liverpool.)
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Experimental groups
Animals (n = 36) were divided equally into a control group that received no muscle conditioning and three experimental groups (Fig 2). Group A received 2 weeks of in situ conditioning without any other intervention. In group B the muscle was partially mobilized by dividing the intercostal perforators and placing a sterile Gore-Tex (W.L. Gore & Assoc, Flagstaff, AZ) sheet underneath the costal surface of the muscle to prevent revascularization; these muscles then received 2 weeks of conditioning as above. In group C the muscle was completely mobilized as a pedicled flap, and the distal end was wrapped circumferentially around a silicone-rubber mandrel (Porgès SA, Brussels, Belgium) to simulate the mobilization performed in clinical CMP. The ends of the mandrel were then fixed to the thoracic wall to maintain normal muscle length, after which these muscles were also stimulated for 2 weeks at 2.5 Hz.
Final experiments
After completion of the allotted stimulation period the animals were anesthetized by the same technique as above, a tracheostomy was performed, and the animals were ventilated using a standard Harvard rodent ventilator. The implanted stimulator was switched off before induction of anesthesia. Blood pressure was monitored by means of a carotid artery catheter, which also allowed access for blood gas sampling. Ventilation was controlled to maintain a pH of 7.36 to 7.44 and arterial carbon dioxide partial pressure at 3.5 to 5.0 kPa. Body temperature was maintained at 36.5° to 38°C with a heating blanket, and saline was given at 5 mL · kg-1 · h-1 intravenously to replace insensible loss.
Measurements of tissue oxygenation and perfusion were performed with microelectrodes, using a gas-tracer technique to measure perfusion. A longitudinal incision was made immediately below the point of the scapula to expose the LDM, and two microelectrode needles were placed intramuscularly, one distally, one proximally. The microelectrodes were purpose-built to our own design [9] and consisted of a 125-µm-diameter insulated silver wire embedded in epoxy resin within a 23G butterfly needle. The epimysium was removed with a scalpel blade, and the microelectrode was introduced along the plane of the muscle fibers so that it lay within the muscle 1 to 2 mm below the surface. The exposed muscle was coated with a warm saline-soaked swab.
A calomel electrode (Russell, Inc, Chicago, IL) acting as counter and reference was placed subcutaneously in the groin and connected to a potentiostat (Energy Microsystems, Oxford, UK) interfaced by an A/D Converter (Strawberry Tree Graphics, Cleveland, OH) to a personal computer.
The microelectrodes measured tissue oxygen tension (Po2) voltametrically at a single voltage between -0.6 V and -0.7 V, set by constructing a current-voltage curve before each experiment. Perfusion was measured by an adaptation of the hydrogen washout technique with nitrous oxide as the gaseous tracer [15]. Each electrode could measure the Po2 current and the partial pressure for N2O current simultaneously by means of a voltage-switching technique that we have described elsewhere [9, 15]. Perfusion measurements were made by ventilating the animal with 20% N2O in air for a wash-in phase until a plateau level was reached, and then returning to air ventilation to allow washout. This process could then be repeated to generate a series of wash-in and clearance curves from which tissue perfusion could be derived. Perfusion measurements were made before and after mobilization in groups A and B.
The LDM was completely mobilized as a pedicled flap and wrapped around a latex tube 12 mm in diameter in a circumferential wrap. This formed part of the muscle-testing apparatus shown in Figure 3. In group C the muscle had already been mobilized with a complete wrap and so this procedure simply involved removing the silicone-rubber mandrel and mounting the muscle directly onto the muscle-testing apparatus.
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Fig 3. Muscle loading apparatus for electrical stimulation and fatigue testing of the latissimus dorsi muscle.
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The muscles were stimulated using a programmable pulse generator (Master-8-cp, A.M.P.I., Jerusalem, Israel) by means of two epimysial electrodes placed on either side of the thoracodorsal nerve. The muscles were stimulated at 50 Hz for 200 ms, each pulse being of 14-µs duration. This produced a sustained tetanic contraction that was repeated once every second, in accordance with the protocol of Burke and coworkers [16]. This has become a standard protocol for fatigue testing and so facilitates comparison with earlier data on the fatigue behavior of stimulated muscle.
Tissue samples and histochemistry
After completing the procedure animals were given an intravenous injection of Evan’s Blue–labeled albumin (100 mg/kg), which was allowed to circulate for 10 minutes before muscles were dissected out, trimmed of superficial fat, and weighed. The contralateral muscle was dissected out in the same way, and muscle weight was expressed as a ratio of the experimental muscle to the contralateral control. Biopsy specimens were taken from each muscle for histologic examination. The specimens were 3 to 4 mm wide and 10 mm long, cut parallel to the fiber orientation. Two specimens were taken from the proximal region and two from the distal region.
Each biopsy sample was wrapped in aluminum foil and frozen in isopentane suspended over a bath of liquid nitrogen. The samples were then stored at -40°C until required for sectioning. Frozen sections 20 µm thick were stained as follows.
General morphologic assessment
Sections were stained with hematoxylin and eosin for histologic examination.
Succinate dehydrogenase
Succinate dehydrogenase was demonstrated histochemically with the nitroblue tetrazolium technique. The air-dried sections were incubated in a medium of 0.2 mol/L sodium succinate and 25 mmol/L nitroblue tetrazolium in phosphate buffer (disodium hydrogen phosphate and potassium dihydrogen phosphate) at pH 7.0 for 1 hour at 37°C. Sections were then fixed in 10% phosphate-buffered formalin, washed, dehydrated, cleared, and mounted.
Fast and slow myosin heavy chains
Sections were air-dried and first incubated with normal serum at room temperature. After washing with saline they were then incubated with the primary antibody (Novocastra, Newcastle, UK) either for fast (MHC.f) or slow (MHC.s) myosin heavy chain at a 1:50 dilution for 1 hour at room temperature, followed by biotinylated rabbit anti-mouse IgG for a further 1 hour. Slides were then washed in saline and incubated with the avidin-biotin complex for 1 hour. Peroxidase activity was developed with diaminobenzidine solution containing 8.8 mmol/L H2O2. Sections were counterstained with Carazzi’s hematoxylin for 4 minutes, dehydrated, cleared, and mounted.
Sections from each biopsy were examined under light microscopy at x250 magnification, and the proportions of fiber types were measured in five representative areas containing 100 to 150 fibers. Fibers were classified as one of three types: types I and II were distinguished by their specific staining with antibodies to MHC.f or MHC.s, respectively. Subtypes IIA and IIB were distinguished by the intensity of staining for succinate dehydrogenase: heavy for IIA, light for IIB. Four sections were prepared from each animal, and the mean fiber counts from all four specimens were used to derive the mean fiber type composition for that animal.
Evan’s Blue fluorescence was used to demonstrate perfused capillaries [17]. Unstained 20-µm sections were viewed at x100 magnification with a fluorescence microscope (Leitz Aristoplan, Lubeck, Germany) equipped for epi-illumination and a facility for storing images by means of a low-light camera (Photonic Science, Robertsbrige, East Sussex, UK) and video digitizer (Truevision, Calgary, Canada). The number of capillaries and muscle fibers per square millimeter were counted. Four sections were made from each tissue block (a total of 16 from each muscle), and representative areas from each section were counted to give a mean value for capillary density and for the ratio of capillaries to muscle fibers.
Statistical methods
Differences among the three groups in fiber type composition, capillary density, perfusion, oxygenation, and pressure were examined by analysis of variance with equal variance. The Student-Newman-Keuls post hoc test was used to examine for differences between pairs of groups where indicated. Results were taken to have statistical significance at p less than 0.05. All results were expressed as mean ± standard error of the mean.
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Results
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The fiber type composition of the muscles is shown in Figure 4. The control (unconditioned) muscles had a composition typical of a fast muscle with a predominance of type IIB fibers. The conditioned muscles (groups A, B, and C) all showed a predominance of oxidative, type IIA fibers (49.3% ± 5.7%, 45.7% ± 5.7%, and 57.5% ± 6.4%, respectively). The proportions of both type I and type IIA fibers in conditioned muscles were significantly greater than control, and there was a corresponding decrease in the proportion of type IIB fibers (p < 0.01). There were no significant differences for the proportions of type I and type IIA fibers in the three conditioned groups.
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Fig 4. Fiber-type composition of the control and conditioned latissimus dorsi muscles. Group A received in situ preconditioning, group B underwent combined preconditioning and delayed elevation, and group C underwent complete elevation followed by conditioning. Results are the mean values from each group (n = 8). Error bars represent standard error of the mean.
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In fatigue tests the control muscles rapidly fatigued, the force declining to less than 50% of initial values after a mean time of 54 seconds, whereas the conditioned muscles all demonstrated an increased resistance to fatigue (the force remaining greater than 50% throughout the test; Fig 5). The muscles of groups A, B, and C did not differ in fatigue resistance.
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Fig 5. Mean pressure curves. Values show the mean pressure developed by control and conditioned muscles during a fatigue test of repeated tetanic contractions for a period of 10 minutes. Pressures were expressed as a percentage of the initial pressure generated.
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The three groups of conditioned muscles differed in histologic appearance. There was no evidence of fiber degeneration in either group A or group B, but the distal regions of the group C muscles showed evidence of fiber atrophy and dense inflammatory infiltrates (Fig 6).
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Fig 6. Photomicrographs of muscle biopsies taken from the distal region of the latissimus dorsi muscle. Hematoxylin-eosin stain, x250 magnification. (A) Group B muscle showing maintenance of normal muscle architecture. (B) Group C muscle, which had undergone complete elevation 2 weeks earlier and subsequent conditioning. There is a dense inflammatory cell infiltrate, extensive muscle fiber necrosis, and vacuolation with loss of the muscle architecture.
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Muscle weights are shown in Table 1. Stimulation alone (group A) did not cause a change in muscle weight, nor did partial mobilization followed by stimulation (group B). However, there was a significant decrease in weight of the muscles that had been fully mobilized before training (group C). These fell to 85% of control weight, with associated histologic findings of fiber degeneration, predominantly in the distal muscle.
Data on capillary to fiber ratio are given in Table 2, and representative computer-enhanced photomicrographs are shown in Figure 7. Conditioned muscles of groups A and B had a higher capillary to fiber ratio than controls, the greatest difference being in the distal regions. In contrast, muscles of group C showed no increase over controls. The capillary to fiber ratio in the distal region of group B muscles was greater than that of any other group, including group A (p < 0.05).
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Table 2. Comparison of Capillary to Fiber Ratios Within the Proximal and Distal Regions of Latissimus Dorsi Muscle
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Fig 7. Computer-enhanced images of capillary fluorescence in 20-µm muscle sections from control (A), group A (B), group B (C), and group C (D) muscles. Capillaries are visualized by fluorescence of Evan’s Blue–labeled albumin viewed under a mercury light. (magnification x150.)
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The results for muscle perfusion and oxygenation are shown in Figures 8 and 9. The effect of muscle transformation alone can be examined by comparing group A with control. Resting perfusion was greater than control before and after mobilization in both proximal (p < 0.05) and distal (p < 0.05) regions. The same benefit of preconditioning was seen in the muscles of group B compared with control (p < 0.01). Furthermore, distal perfusion after mobilization in group B was significantly greater than that of group A (29.2 ± 2.9 versus 23.5 ± 2.2 mL · min-1 · 100 g-1, p < 0.05). The procedure of complete LDM mobilization caused a decrease in perfusion of distal regions of all muscles, but group B muscle perfusion remained significantly higher than all other groups (p < 0.05).
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Fig 8. Muscle perfusion recorded in the proximal (A and C) and distal (B and D) regions of the latissimus dorsi muscle. (A and B) Effect of complete flap elevation on muscle perfusion. (C and D) Effect of repeated tetanic contraction on muscle perfusion. Differences from the control value are marked (*p < 0.05).
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Fig 9. Tissue oxygenation of the proximal (A and B) and distal (C and D) regions of the latissimus dorsi muscle. (A and C) Effect of complete flap elevation on the mean tissue Po2. (B and D) Effect of repeated tetanic contraction on the mean tissue Po2. Significant differences from the control value are marked (*p < 0.05).
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Complete mobilization followed by preconditioning (group C) resulted in distal perfusion that was no different from controls and significantly less than in groups A and B (p < 0.01). These differences were accentuated during tetanic contraction, when perfusion of group C muscles was no better than that of control muscles. In contrast, the conditioned muscles of groups A and B maintained better perfusion than control during contraction. These differences were most pronounced in distal regions, where group B had higher perfusion than any other experimental group (p < 0.05).
Tissue oxygenation at rest did not differ among the groups, but after mobilization the Po2 of the distal region of control muscles was less than that of all the experimental groups (p < 0.05). During muscular contraction Po2 within the distal regions of the control muscles and group C muscles decreased from baseline, whereas it was maintained in groups A and B (Fig 9). In the proximal regions of the preconditioned muscles the Po2 did not change from baseline during contraction.
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Comment
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Cardiomyoplasty makes two different metabolic demands on the LDM: first, mobilization of the muscle with interruption of collateral arteries followed by, second, repeated tetanic contractions. The effect that each of these has on the perfusion and oxygenation of the muscle is not fully understood, particularly in combination. A more detailed picture of the individual changes may help us to plan strategies for improving the viability of the muscle wrap.
This study has confirmed that a fast, fatigue-resistant form of the LDM can be generated through the application of appropriate continuous low-frequency stimulation for just 2 weeks. This is very different from the incremental protocol currently favored in CMP, which requires up to 12 weeks and can produce muscle damage [5, 6]. A muscle that is composed predominantly of type IIA fibers has distinct advantages in terms of cardiac assistance, not only because it can be generated more quickly, but also because it possesses fatigue resistance without excessive sacrifice of speed of contraction and relaxation. A loss of contraction and relaxation speed has been cited as a possible reason for CMP failure in muscles consisting of type I fibers, particularly through impairment of diastolic filling [9, 18]. It has already been shown in previous work that this type IIA muscle phenotype can be maintained indefinitely as long as the intensity of the stimulation protocol does not increase [2].
The microelectrode technique has the advantage of being able to measure both perfusion and Po2 simultaneously and continuously throughout the experiments. This has several advantages over particulate tracer techniques such as microspheres, which can only be used to give a limited series of snapshots and do not give good spatial resolution. In addition, microspheres can only measure flow down to the size of precapillary arterioles and can overestimate flow that bypasses the capillary bed through arteriovenous shunts. They are particularly poor at determining flow in poorly perfused and heterogenous vascular beds and cannot detect flow in small capillary beds, nor give indication of lymphatic flow, both of which become increasingly important for nutrient supply under conditions such as ischemia [19].
The microelectrode data provided evidence of ischemia in the distal regions of the LDM that were fully mobilized before conditioning (the technique currently used in clinical CMP). There was a decrease in perfusion of the distal region of the LDM, which was further accentuated when the muscle was stimulated to contract. A decrease in perfusion alone does not necessarily indicate ischemia unless there is evidence that tissue demands are not being met. This study indicates that both impaired tissue perfusion and oxygenation can occur in the distal region of LDM, together with histologic evidence of tissue necrosis, supporting an ischemic basis for muscle damage.
Preconditioning the LDM before mobilization (groups A and B) improved distal perfusion, increased capillary to fiber ratio, and maintained tissue Po2 levels during mobilization and muscular contraction. When preconditioning was combined with partial mobilization, distal perfusion was further improved. In some previous studies the LDM was preconditioned before performing CMP, with overall improvement in the functional performance of the muscle and the clinical condition of patients [20, 21]. The present study suggests a scientific basis for these clinical findings. Although the detrimental effects of mobilization were not prevented, perfusion remained higher than in control, and Po2 was better maintained during repeated tetanic contraction.
Delayed transfer of skin and musculocutaneous flaps has been recognized as a method of improving flap survival since the 16th century, although understanding of the mechanisms involved is still incomplete. Dilation of precapillary shunts, possibly triggered by division of the sympathetic nerve supply, has been shown to occur in mobilized flaps, with subsequent reduced perfusion of the capillary bed (the ‘second vasoconstrictive effect’) [22]. During a period of 2 weeks this deleterious effect subsides, and arteriovenous shunts regain normal tone. Capillary beds in muscles subject to prior partial mobilization appear to be protected from the shunting phenomenon as they appear to be insensitive to this vasoconstrictive stimulus [23]. There is evidence that preconditioning may have a similar effect, opening up these arteriovenous anastomotic channels between the proximal and distal vascular territories in the LDM [18]. The raising of a flap generates a hyperadrenergic state, but after partial mobilization the tissues are better able to tolerate this and to recover from it [24]. Other benefits of delay are a regression of inflammation and edema owing to the operation, opening of lymphaticovenous communications that improve the egress of lymph, and most important, changes in the vascular architecture. This involves new vessel formation as well as an opening up of dormant vessels analogous to the enlargement of the collateral circulation seen after occlusion of a major limb vessel [25]. The technique used for capillary mapping in this study identifies only open capillary beds, and it is possible that some of the increase in capillary to fiber ratio that occurred with two-stage elevation resulted from the opening up of dormant channels.
There has also been a suggestion that a metabolic adaptation occurs within delayed flaps. Short-term elevation of a muscle flap results in an increase in the glycolytic enzyme content in the distal region accompanied by very low glucose levels. These observations suggest that short-term elevation is likely to stimulate metabolism of the distal flap in the direction exactly contrary to that intended by muscle transformation protocols. In contrast, a bipedicled delay process results in a gradual normalization of these enzyme levels within 10 to 14 days that persists after the flap elevation is completed [26]. This is supported by experimental models of CMP in which the poor function of acutely raised LDM flaps was improved if they were allowed to rest for 2 weeks [27]. Although preconditioning appears to be the most important factor in improving perfusion and oxygenation, delayed flap elevation appears to have an additive effect. This would support a strategy of combining preconditioning and two-stage elevation, borne out by the fact that group B demonstrated better perfusion characteristics than any of the other groups.
In conclusion, this study has demonstrated that preconditioning improves the distal perfusion of the LDM and maintains tissue Po2 even during repeated contraction. Perfusion of the LDM is further improved by staged elevation, which could be achieved by ligating intercostal perforators at the same time as inserting the electrodes for preconditioning.
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Acknowledgments
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David Barron was supported by a British Heart Foundation fellowship.
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Abstract
Introduction
