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Ann Thorac Surg 1997;64:404-408
© 1997 The Society of Thoracic Surgeons
King Fahad Hospital, Riyadh, Saudi Arabia
Accepted for publication January 13, 1997.
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Abstract |
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 TopFootnotes Abstract IntroductionMaterial and MethodsResultsCommentReferences |
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Methods. The collateral circulation to the latissimus dorsi was ligated in all animals before cardiomyoplasty to reduce the risk of ischemic injury to the muscle during mobilization. Two weeks after collateral ligation, the atrophy group had the tendinous attachment of the latissimus dorsi severed and then 2 weeks later underwent cardiomyoplasty. The control group had a 2-week delay after collateral ligation followed by cardiomyoplasty. Biopsies were performed before collateral ligation and before cardiomyoplasty. After heart failure was induced, hemodynamic function was assessed during synchronized contraction of the latissimus dorsi by measuring the maximum systolic elastance, stroke volume, preload recruitable stroke work index, and diastolic compliance.
Results. Comparison of muscle morphology between the two groups demonstrated the presence of muscle atrophy in those animals that had been randomized to the atrophy protocol. During synchronized contraction of the latissimus dorsi, there was no significant increase in maximum systolic elastance in either group. However, both stroke volume and pulmonary recruitable stroke work index were significantly higher in the control animals during assisted beats. The left ventricle was less compliant in the atrophy group, suggesting that muscle atrophy had adversely affected diastolic function.
Conclusions. Delayed electrical stimulation of the latissimus dorsi may result in atrophy and loss of function.
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Introduction |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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Cardiomyoplasty has become a well-recognized treatment for end-stage heart failure [1, 2]. The operation is performed as a single-stage procedure. The latissimus dorsi muscle is mobilized and then passed into the thorax and wrapped around the heart. The muscle is then left unstimulated for 2 weeks to allow it to recover from the loss of the collateral blood supply. The delay period is followed by 6 to 8 weeks of graduated electrical conditioning.
Skeletal muscle atrophy occurs when a limb is immobilized after a fracture [3, 4]. It is therefore conceivable that the latissimus dorsi may undergo atrophy during the initial 2-week recovery period after cardiomyoplasty when the muscle has traditionally been left unstimulated. To test this hypothesis, we have examined the effects of delayed stimulation on muscle morphology and function after dynamic cardiomyoplasty.
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Material and Methods |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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To preserve the integrity of the latissimus dorsi and to prevent ischemic injury from loss of the collateral circulation, we performed cardiomyoplasty in a two-stage procedure. During the first operation the animals were anesthetized with sodium phenobarbital (25 mg/kg) and ventilated with a volume-regulated ventilator. General anesthesia was maintained with 3% enflurane. After preparing and draping the left chest, we made an incision parallel to the anterior boarder of the latissimus dorsi muscle. The muscle was gently elevated and all collateral blood vessels were ligated. Biopsy specimens were then taken from the proximal, middle, and distal portions of the muscle. A sterile silicone sheath was placed between the undersurface of the muscle and the chest wall to reduce adhesions and to prevent the formation of new collateral blood vessels. The incision was then closed and the animals were allowed to recover for 2 weeks to allow the latissimus dorsi to adapt to the loss of the collateral circulation.
Randomization
The animals were randomized into two groups using a random number table. Animals in the atrophy group were returned to the operating theater 2 weeks after collateral ligation. The humeral attachment of the latissimus dorsi was severed, care being taken not to injure the neurovascular bundle. Two weeks later the animals underwent cardiomyoplasty. The 2-week delay after severing the tendon of the latissimus dorsi was used to simulate the delay in initiating fiber type conversion after clinical cardiomyoplasty. The control animals underwent cardiomyoplasty 2 weeks after ligation of the collateral circulation.
Cardiomyoplasty
The animals were returned to the operating room and placed under general anesthesia. The dogs were placed in the lateral decubitus position and the left latissimus dorsi was mobilized. Muscle biopsy specimens were obtained from the proximal, middle, and distal regions of the latissimus dorsi muscle in both groups. Two Medtronic intramuscular leads, model SP 5528 (Medtronic Corp, Minneapolis, MN) were woven into the proximal position of the muscle near the neurovascular bundle. A portion of the fourth rib was removed and the muscle was passed into the thoracic cavity. The tendon of the latissimus dorsi was fixed to the third rib to avoid traction on the neurovascular pedicle. The incision was then closed and the animals were repositioned for a median sternotomy.
Instrumentation and Cardiomyoplasty
Heparin was administered in a dose of 4 mg/kg after sternotomy. A 5F Millar microtransducer-tipped catheter (Millar Instruments Inc, Houston, TX) and a specially designed 7F conductance catheter were inserted through the apex of the left ventricle through separate pursestrings. A 16F USCI arterial cannula (Bard Inc, Billerica, MA) was positioned in the left femoral artery for volume loading. Cardiomyoplasty was performed by wrapping the muscle clockwise around the heart. The latissimus dorsi was fixed to the pericardium in the region of the right and left atrioventricular grooves to prevent migration of the wrap. A Medtronic epicardial sensing electrode (model 5071) was placed in the region of the pulmonary outflow tract. The sensing electrode and the two Medtronic muscle-stimulating electrodes (model SP5528) were connected to a Medtronic cardiomyostimulator pulse train generator (model SP 1005).
Hemodynamic Measurements
Systolic elastance (EMAX), preload recruitable stroke work (PRSW), stroke volume (SV), and end-diastolic compliance (EDC) of the left ventricle were determined from simultaneous measurements of left ventricular volume and pressure. Pressure was measured using a 5F Millar microtransducer-tipped catheter (frequency response, 0 to 24 kHz). Volume was measured using a specially constructed 7F conductance catheter containing eight electrodes. The proximal and distal electrodes were excited by a 24-V, 20-kHz source, which delivered a constant current of 100 µA. The other six electrodes were used as sensing electrodes to monitor the voltages created when the 100-µA current flowed through the blood in proximity to each pair of adjacent electrodes. The simultaneous volume and pressure measurements were processed with a PC 486 computer. Pressure–volume loops could be stored and processed every 2 seconds during volume loading. Specially designed software computed the Emax, PRSW, SV, and EDC. The PRSW was indexed to heart weight. The PRSW, EMAX, and EDC were derived from the following formulas:
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where SV represents the stroke volume. The constant (1.33 x 10-4) converts the data into indices of work.
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where V is the left ventricular volume and Vc is the volume constant. The constant represents the baseline electrical charge that is present when the ventricle is empty. The constant was measured after the experiment once the heart has been emptied of blood.
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where V is the end-diastolic volume and Vc represents the constant.
Measurements were obtained in both groups after heart failure was induced with incremental doses of intravenous propranolol. Heart failure was defined as a 30% drop in systolic pressure and a two-fold increase in the end-diastolic pressure. After establishing a stable hemodynamic state, the animals were volume loaded through the femoral artery catheter. The femoral artery catheter was not only used to infuse volume but to withdraw volume to repeat experimental observations at the same preload. At least three pressure–volume loops were obtained under each loading condition. The EMAX, PRS, and EDC have been reported at an end-diastolic pressure of 10 mm Hg. The measurements were made during synchronized contraction of latissimus dorsi.
The cardiomyostimulator was programmed at a pulse amplitude of 5 V, a pulse width of 210 ms, and a pulse train duration of 185 ms. The contraction was synchronized with the cardiac cycle in a ratio of 1:1 and at a heart rate of 100 beats/min. The cardiomyostimulator was allowed to stimulate the latissimus dorsi continuously for no more than 30 seconds so that the nonconditioned muscle would not fatigue. The muscle was allowed to rest for 5 minutes between measurements. The measurements were then repeated until the data were reproducible under identical loading conditions.
Histologic Examination
Muscle biopsy specimens were taken from the proximal, middle, or distal muscle bundles. The specimens were then preserved in 10% formalin then transferred to 70% ethanol. Specimens were processed through graded ethanols, cleared in xylene, embedded in paraffin, and sectioned into 4-µm slices. The 4-µm sections were then mounted on glass slides and stained with hematoxylin and eosin stains for morphometric analysis. Specimens were viewed under x630 magnification using a computer-assisted Interactive Image Analyzing System (Zeiss Corp, Munich, Germany). Circumferentially oriented fibers were imaged and analyzed. A hand-held, computer-assisted pointer was used to outline each muscle fiber. The cross-sectional area of each fiber was calculated by the computer and the area extrapolated to a circle of equivalent cross-sectional area. The diameter of the fiber was calculated using the equation for a circle. Muscle fiber diameter was determined from 24 ± 1.4 fibers from each slide. A total of 15 slides were examined from each biopsy specimen.
Statistical Analysis
Results have been reported as the arithmetic mean ± the standard error of the mean. Analysis of variance was used for statistical comparisons.
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Results |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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Histology
Histologic examination of the muscle bundles, before collateral ligation, demonstrated that the diameter of the muscle fibers was similar in both groups. However, the muscle fibers were significantly different when sampled just before cardiomyoplasty. Muscle fiber diameter in the atrophy group measured 12 ± 0.5 µm in comparison with 23 ± 0.5 µm in the control group (p < 0.01).
Left Ventricular Function
Hemodynamic function was assessed after the latissimus dorsi was wrapped around the heart and after the induction of heart failure. The EMAX tended to be lower in both groups after cardiomyoplasty but the results did not reach significance. However, comparison of EMAX before and after the induction of heart failure in each group indicated that EMAX had decreased by 0.59 ± 0.2 mm Hg/mL (p < 0.04) in the control group and by 0.4 ± 0.2 mm Hg/mL (p < 0.01) in the atrophy group. The EMAX did not increase significantly in either group with synchronized pacing of the latissimus dorsi (Table 1
).
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). The effect of synchronized contraction of the latissimus dorsi on PRSW index in an animal from each group is illustrated in Figure 1.
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).
Diastolic compliance was not affected by cardiomyoplasty. However, the compliance of left ventricle was lower in the atrophy group during synchronized pacing, which suggests that the atrophied latissimus dorsi adversely affected diastolic function (see Table 1).
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Comment |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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Cardiomyoplasty is performed as a single-stage operation, but for this experiment the operation was performed in two stages. The collateral circulation was ligated during the first operation to reduce the likelihood of ischemic injury to the muscle flap. Tobin and colleagues [5] have previously quantitated the vascular supply of the latissimus dorsi in dogs and in humans. Interestingly, the percentage of the muscle supplied by the collateral circulation is similar, the collateral circulation providing 67% ± 6% of the circulation in humans and 68% ± 9% of the circulation in dogs. After collateral ligation in dogs, the flow is reduced to less than 10% of normal in the distal portions of the flap, the region that is most susceptible to ischemic injury. Flow remains low for at least 5 days, a situation that has been associated with fibrosis and fatty infiltration of the latissimus dorsi. Isoda and associates [6] have demonstrated that ischemia may be avoidable if the muscle is mobilized in two stages. Blood flow was measured in the resting state in a control group immediately after collateral ligation and flap elevation. In the treatment group, the collateral blood vessels were ligated and then the flap was elevated 4 weeks later. Resting blood flow was significantly higher in the distal portion of the flap in those animals that had undergone vascular delay. Furthermore, blood flow during exercise increased in the proximal, middle, and distal regions of the flap in the delayed group but decreased in the distal region of the flap in those animals that had undergone collateral ligation and flap elevation as a single procedure. Data from our laboratory support a two-stage procedure, as we have demonstrated that two-stage mobilization preserves the morphology of the latissimus dorsi [7]. Finally, this concern over the collateral circulation is not merely a theoretical consideration, as Moreira and associates [8] have reported high serum creatine kinase level and marked fibrosis and fatty infiltration of the distal flap in patients dying of low cardiac output early after cardiomyoplasty; the presence of fibrosis and fatty infiltration implies that the muscle may have suffered ischemic injury during mobilization.
Our observations have shown that cardiomyoplasty may adversely affect systolic function despite the fact that we were able to place two fingers between the wrap and the anterior surface of the left ventricle. These observations have been reported previously by our laboratory [7] and are not entirely unexpected considering that cardiomyoplasty has a remodeling effect on the left ventricle. Barbier and colleagues [9] have demonstrated that ventricular geometry is altered by cardiomyoplasty, the right ventricle becoming more elongated and the left ventricle becoming more spherical. Although most of the patients in that study were not compromised by the muscle wrap, hypotension and an increase in pulmonary artery wedge pressure were observed in some patients.
After the induction of heart failure, systolic function deteriorated significantly in both groups in our study. Interestingly, synchronized stimulation of the latissimus dorsi only effectively increased PRSW index and SV in the control group. This observation is not surprising considering that the muscle fibers were much smaller in the animals that had been randomized to the atrophy protocol. Diastolic function also appeared to have been adversely affected in the atrophy group in that the left ventricle was less compliant during synchronized pacing of the latissimus dorsi. Although we did not observe fibrosis under the light microscope, the muscle may have been stiffer as a result of the overall reduction and contraction of the muscle mass.
Causes of muscle atrophy include myopathy, neuropathy, denervation, metabolic disease, and disuse atrophy. Congestive heart failure has also been associated with muscle wasting [10, 11]. Immobilization rapidly results in atrophy and may lead not only to loss of muscle mass but to fibrosis and fatty infiltration. This process may be accelerated, as evidenced by an increased rate of protein breakdown, if the muscle is immobilized in the nonstretched position [12, 13]. El Oakley and associates [14] compared the influence of electrical stimulation, loss of normal resting tension, and reduction in vascular supply on muscle atrophy. The single most important factor leading to muscle atrophy was the loss of normal resting tension. When all three factors were present at one time, 60% of the muscle was replaced with connective tissue and fat.
The data from recent studies demonstrating that the latissimus dorsi may suffer ischemic injury during mobilization and that unstimulated muscle may atrophy, particularly when the normal resting tension is decreased, suggest that it may be more appropriate to recommend a two-stage procedure for patients undergoing cardiomyoplasty. The collateral circulation could be ligated during the primary procedure. At the same time, electrodes could be implanted for in situ muscle training. Chachques and colleagues [15] have shown that a latissimus dorsi muscle expander, containing stimulating electrodes, may be used not only to increase the length of the latissimus dorsi but to condition the muscle during the period of vascular delay. Vascular delay, therefore, would not only reduce the risk of ischemic injury to the muscle flap during cardiomyoplasty but could provide an opportunity to train the muscle before cardiomyoplasty. The use of trained muscle at the second procedure would be a distinct advantage as the muscle would be able to provide cardiac assist almost immediately for the failing heart. The down side of this technique would be related to the fact that a second operation would be necessary. However, considering that collateral ligation and implantation of stimulating electrodes is a relatively minor procedure, the benefits of a two-stage procedure may outweigh the disadvantages of two operations.
Limitations
The experimental model used in this study did not exactly replicate the human situation. Latissimus dorsi mobilized for clinical cardiomyoplasty is detached from the humerus and reattached to a rib to avoid traction on the neurovascular bundle, the rib attachment and the wrap around the heart providing some degree of resting tension. In the experimental scenario, the tendon was severed, which may have magnified the loss of the normal resting tension, although there was still some degree of tension because only the undersurface of the muscle had been mobilized. The other limitation of the study is related to the fact that the muscle was not conditioned and therefore repetitive simulation could have influenced the results. However, we were careful not to simulate the muscle for periods that exceeded more than 30 seconds, and stimulation was always followed by a rest period to avoid fatigue. Furthermore, Chekanov and associates [16] have recently demonstrated that untrained latissimus dorsi is able to performed sustained work for short periods even as soon as 1 hour after complete mobilization.
Summary
Our data indicate that delayed stimulation in partially unstretched latissimus dorsi muscle may result in atrophy and loss of function. A planned two-stage procedure with vascular delay may be preferable, therefore, to preserve the integrity of the latissimus dorsi and to initiate in situ muscle conversion before the cardiomyoplasty operation is performed.
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Footnotes |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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References |
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TopFootnotesAbstractIntroductionMaterial and MethodsResultsCommentReferences |
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  G. Rigatelli, U. Carraro, M. Barbiero, R. Riccardi, F. Cobelli, M. Gemelli, and G. Rigatelli A Review of the Concept of Circulatory Bioassist Focused on the "New" Demand Dynamic Cardiomyoplasty: The Renewal of Dynamic Cardiomyoplasty? Angiology, May 1, 2003; 54(3): 301 - 306. [Abstract] [PDF]
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