Ann Thorac Surg 1998;65:1288-1290
© 1998 The Society of Thoracic Surgeons
Growth Potential and Left Ventricular Diastolic Function in Cardiomyoplasty
Yoshio Misawa, MD, PhDa,
Katsuo Fuse, MD, PhDa,
Tsuguo Hasegawa, MD, PhDa,
Hiroaki Konishi, MDa
a Department of Cardiovascular Surgery, Jichi Medical School, Tochigi, Japan
Accepted for publication December 13, 1997.
Address reprint requests to Dr Misawa, Department of Cardiovascular Surgery, Jichi Medical School, Yakushiji 3311-1, Minami-Kawachi, Tochigi, 329-04, Japan
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Abstract
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Background. Dynamic cardiomyoplasty is an experimental operation for advanced heart failure. Current clinical results bring the possibility of its application to children. This study was designed to obtain information about the relationship between cardiomyoplasty and growth of the heart.
Methods. Six beagles, 9 to 10 weeks old, underwent cardiomyoplasty without electric stimulation (cardiomyoplasty group), and another 5 beagles underwent median sternotomy and pericardiotomy (control group). Six months later, weights of hearts, wrapped latissimus dorsi muscles, and unwrapped right latissimus dorsi muscles and pressurevolume relationships were obtained.
Results. Wrapped latissimus dorsi muscles weighed 33 ± 3 g (mean ± standard deviation), and unwrapped muscles weighed 68 ± 5 g. The heart weight was 82 ± 3 g in the cardiomyoplasty group and 89 ± 7 g in the control group. Left ventricular maximum elastance was 3.8 ± 0.8 mm Hg/mL in the cardiomyoplasty group and 3.9 ± 0.9 mm Hg/mL in the control group. End-diastolic pressure versus end-diastolic volume ratios were 0.52 ± 0.03 and 0.54 ± 0.05, respectively. Pathologic examination showed fat infiltration and muscle fiber atrophy in the cardiomyoplasty group.
Conclusions. The wrapped latissimus dorsi muscle flaps were growing and the diastolic function was not impaired. This indicates a potentially safe clinical application of dynamic cardiomyoplasty for children.
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Introduction
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Shortness in the availability of donor organs precipitates the need for new medical or surgical treatments for patients with advanced heart failure. Dynamic cardiomyoplasty is an experimental operation for such patients, especially patients with dilated cardiomyopathy, showing hopeful clinical results. To date, the operation has been applied only to adult patients. We now consider the possibility of its application to children.
A skeletal muscle sarcomere can be changed by reducing or adding fibers in a given physiologic milieu. Wrapping a heart with a pedicled latissimus dorsi muscle produces a new milieu for muscle tension. It has been thought that the latissimus dorsi muscle might impair the diastolic function of the left ventricle and subsequently impair the growth of the heart or the individual with this condition. We hypothesized that the latissimus dorsi muscle flaps wrapped around the heart in children grow and do not impair left ventricular diastolic function. For clinical application of dynamic cardiomyoplasty in children, studies confirming the growth potential of the heart and the prevention of abnormal left ventricular relaxation are necessary.
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Material and methods
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Six beagles, 9 to 10 weeks old, underwent cardiomyoplasty without electric stimulation (cardiomyoplasty group). The latissimus dorsi muscle was wrapped around the heart in a left posterior cardiosubcutaneous fashion [1]. The left latissimus dorsi muscle was harvested through a posterolateral skin incision, and wrapping around the heart was performed through median sternotomy. Five beagles, 9 to 10 weeks old, underwent median sternotomy and pericardiotomy as a control group. Another 2 beagles of the same age were sacrificed to obtain basic data about heart weight and latissimus dorsi muscle weight. Six months after the operation, each dog was killed after collection of hemodynamic data with a Swan-Ganz catheter through the right jugular vein, a Leycom conductance catheter through the left carotid artery, and a Millar-tip catheter transducer through the left ventricular free wall. A cross-clamp was positioned at the inferior vena cava for varying cardiac preload by occluding venous return. Pressure studies and pressurevolume relationships were obtained. The hearts, wrapped latissimus dorsi muscles, and unwrapped right latissimus dorsi muscles were obtained for weighing, and latissimus dorsi muscle flaps were examined pathologically. Proximal, central, and distal sites of the latissimus dorsi muscle flaps were selected for histologic examination. Fat infiltration was classified into three grades: grade 1, sparse fat infiltration with a couple of fat layers; grade 2, moderate fat infiltration between grades 1 and 3; and grade 3, extended fat infiltration occupying most of the muscle flap. Atrophy of the residual muscle fibers was also classified into three grades: grade 1, no muscle fiber atrophy and no fiber caliber difference; grade 2, moderate fiber atrophy; and grade 3, severe fiber atrophy. In addition, the differences in histologic changes between muscle specimens from different harvesting sites were graded: grade 1, no histologic difference; grade 2, moderate difference; and grade 3, severe difference.
General anesthesia with an endotracheal tube was used for operative procedures. Anesthesia was induced with intravenous pentobarbital (20 mg/kg) and maintained with intravenous pancuronium and additional pentobarbital. The experiment was performed with the approval of the management committee at the Jichi Medical School of Experimental Medicine, based on the schools 1993 Guide for Laboratory Animals.
All data were analyzed by t test. Each reported value indicates the group mean ± standard deviation. Values were compared between the two groups.
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Results
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The changes in body weight, heart weight, and right and left latissimus dorsi muscle weights were as follows: for the cardiomyoplasty group: 9.3 ± 0.8 kg, 76 ± 3 g, 35 ± 2 g, and 67 ± 3 g, respectively, and for the control group: 9.1 ± 0.3 kg, 88.7 g, 68 ± 5 g, and 67 ± 4 g, respectively. Baseline weights taken from the two normal dogs were as follows: body weight, 2.7 kg and 3.2 kg; heart weight, 26 g and 28 g; and latissimus dorsi muscle weight, 12 g and 12 g. Body weights of the cardiomyoplasty group and the control group were similar, 3.2 ± 0.2 kg at initial operation. Six months after operation body weights were 9.3 ± 0.8 kg and 9.1 ± 0.3 kg, respectively.
In the cardiomyoplasty group, wrapped latissimus dorsi muscles weighed 33 ± 3 g, and unwrapped right latissimus dorsi muscles weighed 68 ± 5 g. In the control group, latissimus dorsi muscles weighed 67 ± 4 g. Wrapped latissimus dorsi muscle flap weight increased, but it was lower than that of unwrapped in situ latissimus dorsi muscle in the control group. The heart weight of the cardiomyoplasty group was 82 ± 3 g, and that of the control group was 89 ± 7 g.
The stroke volume was 12 ± 2 mL in the cardiomyoplasty group and 16 ± 4 mL in the control group. There were no significant differences in left ventricular end-diastolic pressure (12 ± 2 versus 10 ± 8), pulmonary artery wedge pressure (5 ± 2 versus 7 ± 2), central venous pressure (4 ± 1 versus 5 ± 1), and mean pulmonary artery pressure (19 ± 7 versus 17 ± 7) in the cardiomyoplasty group versus the control group.
A typical left ventricular pressurevolume loop of the cardiomyoplasty group is shown in Figure 1. The left ventricular maximum elastance in the cardiomyoplasty group was 3.8 ± 0.8 mm Hg/mL, and that in the control group was 3.9 ± 0.9 mm Hg/mL. The end-diastolic pressure versus end-diastolic volume ratio was 0.52 ± 0.03 mm Hg/mL in the cardiomyoplasty group, and 0.54 ± 0.05 mm Hg/mL in the control group.

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Fig 1. Pressurevolume loops of the cardiomyoplasty group. These loops were obtained while a cross-clamp was positioned at the inferior vena cava. The maximum elastance in the left ventricle was 4.5 mm Hg/mL.
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Table 1 shows histologic changes in the muscle flaps of the cardiomyoplasty group. Sparse fat infiltration was seen in only one dog, moderate fat infiltration in three, and extended fat infiltration in three. In four dogs, fat infiltration at the distal sites was more advanced than at the proximal sites. Atrophy of the residual muscle fibers was seen in 2 dogs (moderate in 1 and severe in the other). No relationship between fat infiltration and muscle fiber atrophy was recognized.
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Comment
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Dilated cardiomyopathy can occur in children, but at present donors for children are limited. Thus, dynamic cardiomyoplasty might become a surgical option for such patients. However, to date, little information about the relationship between dynamic cardiomyoplasty and growth of the heart has been available. Brady and colleagues [2] reported that latissimus dorsi muscle flaps wrapped around piglet hearts grew in a manner compensating for subsequent size mismatch and there were no statistically significant differences in the growth of paced latissimus dorsi muscle flaps and that of nonpaced flaps. However, they did not mention cardiac function after wrapping. We chose nonpaced muscle flaps in this study to show the effects on cardiac function after wrapping.
According to body weight changes in the two groups, cardiomyoplasty did not impair overall weight gain and growth of the individual dogs, and the wrapped skeletal muscle flaps grew reasonably. We chose tissue wet weights in this study, as we believed that muscle flap mass, including fat tissue, can contribute to improve hemodynamic condition in dynamic cardiomyoplasty, reducing left ventricular wall stress [3, 4]. The rate of growth was approximately half that of normal in situ latissimus dorsi muscles. The weight difference between wrapped and unwrapped latissimus dorsi muscle flaps implies the skeletal muscles can change their phenotype, adapting to their new physiologic milieu [5]. There was no significant weight difference between hearts with wrapping and those without wrapping.
Pressurevolume loops have been used to show left ventricular diastolic function [6, 7]. Cardiomyoplasty has the possibility of preventing the heart from relaxing during the diastolic phase. However, a clinical study by Magovern and associates [8] revealed no impairment in diastolic function 6 weeks after dynamic cardiomyoplasty. Other clinical studies showed excellent effects on clinical and hemodynamic status after dynamic cardiomyoplasty [9, 10]. The end-diastolic pressure to volume ratio can be a reliable index of the passive elastic properties of the ventricular chamber, as it is not influenced by changes in cycle length, preload, or afterload in the physiologic range [11]. Our study showed that latissimus dorsi muscle flaps wrapped around normal hearts in young dogs did not impair cardiac diastolic function even when body weight was tripled.
Fat infiltration in the wrapped muscle was clinically recognized. Muscle fiber atrophy is a common finding after denervation, but we could not see the nerve damage in our two dogs showing muscle fiber atrophy. Histologic changes in wrapped skeletal muscle flaps were not consistent among the animals. Although blood flow difference could be a cause, a definite conclusion requires additional study. The atrophic nature of the wrapped muscle flaps did not affect the left ventricular diastolic function. In addition, the muscle flap weights increased in all dogs. This might implicate that the wrapped muscle flaps adapt to their new physiologic milieu [5].
In conclusion, the unstimulated wrapped latissimus dorsi muscle flaps grew acceptably around normal hearts without impairing the growth of individual dogs, and left ventricular diastolic function was not affected. This study provides an indication for safe clinical use of dynamic cardiomyoplasty for children. To obtain more clinically relevant information, we have to study stimulated muscle flaps.
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Acknowledgments
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We appreciate the great contributions to the experiment from Mr Takao Suzuki and Mr Hideki Niwayama, Department of Medical Engineering, Jichi Medical School Hospital. This study was funded by a grant-in-aid for scientific research C (no. 08671541) from the Ministry of Education, Science, Sports and Culture in Japan.
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References
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- Furnary A.P., Christlieb I.Y., Magovern J.A., Magovern G.J. A standard nomenclature for latissimus dorsi cardiomyoplasty. J Cardiol Surg 1991;6:74-79.
- Brady P., Dionisopoulos T., Desrosiers C., Chiu R.C.-J. Growth potential of latissimus dorsi muscle flaps used in the cardiomyoplasty procedure. Ann Thorac Surg 1989;48:636-638.[Abstract]
- Misawa Y., Chiu R.C.-J., Kamisawa O., Hasegawa T., Fuse K. Dynamic cardiomyoplasty in 1995. Jpn J Artif Organs 1996;25:749-752.
- Misawa Y., Mott B.D., Lough J.O., Chiu R.C.-J. Pathological findings of latissimus dorsi muscle graft in dynamic cardiomyoplasty: clinical implication. J Heart Lung Transplant 1997;16:585-595.[Medline]
- Chiu R.C.-J. Dynamic cardiomyoplasty. Efficacy and mechanisms. Cardiac Chronicle 1992;6:1-6.
- Kass D.A., Baughman K.L., Pak P.H., et al. Reverse remodeling from cardiomyoplasty in human heart failure: external constraint versus active assist. Circulation 1995;91:2314-2318.[Abstract/Free Full Text]
- Capouya E.C., Gerber R.S., Drinkwater D.C., et al. Girdling effect of nonstimulated cardiomyopathy on left ventricular function. Ann Thorac Surg 1993;56:867-871.[Abstract]
- Magovern J.A., Park S.E., Cmolik B.L., Trumble D.R., Christlieb I.Y., Magovern G.J. Early effects of right latissimus dorsi cardiomyoplasty on left ventricular function. Circulation 1993;88:298-303.
- Grandjean P.A., Austin L., Chan S., Terpstra B., Bourgeois I.M. Dynamic cardiomyoplasty: clinical follow-up results. J Card Surg 1991;6:80-88.[Medline]
- Moreira L.F.P., Stolf N.A.G., Bocchi E.A., et al. Clinical and left ventricular function outcomes up to five years after dynamic cardiomyoplasty. J Thorac Cardiovasc Surg 1995;109:353-363.[Abstract/Free Full Text]
- Sagawa K., Maughan L., Suga H., Sunagawa K. Physiologic determinants of the ventricular pressure-volume relationship. In: Sagawa K., Maughan L., Suga H., Sunagawa K., eds. Cardiac contraction and the pressure-volume relationship. New York: Oxford University Press, 1988:110-170.
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