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Ann Thorac Surg 1996;61:426-429
© 1996 The Society of Thoracic Surgeons
Division of Thoracic Surgery, Allegheny General Hospital; Allegheny-Singer Research Institute; and Allegheny Campus, The Medical College of Pennsylvania, Pittsburgh, Pennsylvania
Abstract
Background. Aortomyoplasty is a technique for achieving autogenous diastolic counterpulsation. This experiment was designed to determine if aortomyoplasty using conditioned latissimus dorsi muscle could improve regional myocardial function during coronary ischemia.
Methods. Six mongrel dogs underwent a staged operation in which the left latissimus dorsi was conditioned in situ for 4 weeks, then wrapped around the descending aorta and stimulated during diastole with each cardiac contraction. Regional ischemia was caused by occlusion of the left anterior descending coronary artery. Regional function was measured with sonomicrometry in the region of ischemia and in a control area. An intraaortic balloon pump was inserted for comparison with aortomyoplasty performance.
Results. Coronary artery occlusion caused a significant decrease in the percentage of regional shortening (14.2 ± 7.9 to -2.2 ± 4.0; p = 0.001) and thickening (11.9 ± 4.6 to -5.8 ± 3.3; p < 0.001). Aortomyoplasty improved regional motion in both percentage shortening (-2.2 ± 4.0 to 2.3 ± 3.7; p = 0.008) and thickening (-5.8 ± 3.3 to 2.8 ± 1.9; p < 0.001). The intraaortic balloon pump also improved percentage shortening (-3.7 ± 2.0 to 0.7 ± 1.9; p = 0.01) and thickening (-5.0 ± 2.8 to 2.4 ± 3.8; p < 0.001), and was not significantly different than aortomyoplasty.
Conclusions. These data show that aortomyoplasty has beneficial effects on ischemic left ventricular contractility, and may therefore be useful for treating inoperable coronary artery disease.
Congestive heart failure is a major public health problem in the United States, which affects about two million Americans. Even with the advances in medical therapy, the 1-year mortality for patients with severe congestive heart failure remains high [1]. Cardiac transplantation is an effective treatment but is limited by the small number of available donor organs. New forms of treatment for congestive heart failure are needed.
The intraaortic balloon pump (IABP) is a useful clinical tool for the support of failing myocardium and is especially useful in the setting of acute ischemia. Studies have shown that the IABP causes decreases in peak systolic pressure and myocardial oxygen consumption, as well as increases in diastolic blood pressure and coronary blood flow. Each of these factors is beneficial for the ischemic myocardium [24]. Long-term use of the IABP for support has not been possible because the device requires the use of a transcutaneous, intravascular catheter, which leads to sepsis and thromboembolism [5]. This has stimulated research into forms of totally autogenous cardiac assistance.
Early experiments in the use of skeletal muscle diastolic aortic compression date to 1959 [6]. This early research was limited by the rapid fatigue of the muscle. Advances in muscle physiology subsequently demonstrated the ability to convert skeletal muscle to fatigue-resistant forms by the use of chronic low frequency electrical stimulation [7]. This resulted in renewed interest in various methods of circulatory support using skeletal muscle power, including cardiomyoplasty, skeletal muscle ventricles, and muscle-powered ventricular assist pumps.
Research into another form of autogenous myocardial support, aortomyoplasty (AMP), has shown that compression of the thoracic aorta with skeletal muscle during diastole generates hemodynamic effects comparable with an IABP [8, 9]. Studies using untrained muscle were subsequently confirmed in experiments with conditioned skeletal muscle [10, 11]. This procedure has been successfully studied in an animal model of heart failure [12, 13]. In light of the clinical success of the IABP treatment of the acutely ischemic myocardium and previous laboratory data showing effective diastolic augmentation with AMP, we undertook this study to determine the effects of AMP on regional left ventricular function during ischemia.
Material and Methods
Six mongrel dogs were used. All animals received humane care in compliance with the ``Principles of Laboratory Animal Care'' formulated by the National Society for Medical Research and the ``Guide for the Care and Use of Laboratory Animals'' published by the National Institutes of Health (NIH publication 85-23, revised 1985). Animals were sedated with acepromazine (0.25 mg/kg), and general anesthesia was induced with thiopental sodium (20 mg/kg). Anesthesia was maintained with 1% to 2% isoflurane.
The muscle stimulator was implanted in a preliminary operation. An incision was made to expose the left latissimus dorsi (LD) muscle and the thoracodorsal neurovascular bundle, and to divide chest wall perforators to the muscle. An Itrel pulse generator (model 7420; Medtronic, Inc, Minneapolis, MN) was implanted into a subcutaneous pocket and a bipolar lead was placed adjacent to the thoracodorsal nerve. The incisions were closed, and after a 1-week recovery, the stimulator was activated for a 4-week muscle training protocol [14].
After completion of muscle training the animals were returned to the operating room for AMP as previously described by this laboratory [11, 12]. The animals were reanesthetized and the previous incision was opened. The iliac origin of the LD was divided and a 4-cm-wide strip of muscle displaying the best contraction was isolated, fed by one branch of the thoracodorsal neurovascular pedicle. A left thoracotomy was then performed through the fourth intercostal space. The distal transverse aortic arch, descending aorta, and left subclavian artery were mobilized. Esophageal and bronchial aortic perforating vessels were carefully divided. The first two or three pairs of intercostal arteries were also divided. A 4-cm segment of the second rib was resected, and the muscle flap was introduced into the chest through this defect. The muscle flap was then wrapped in a clock-wise fashion around the distal aortic arch, beginning between the left carotid and subclavian arteries and continuing distally for a distance of 10 cm.
The pericardium was opened and two epicardial sensing leads were placed on the right ventricle. These sensing leads and the previously placed stimulating lead were then connected to a Prometheus pulse generator (model 6100, Medtronic, Inc), which was programmed to stimulate the LD during diastole.
To study the hemodynamic effects of AMP during acute ischemia, we inserted the following monitoring lines. A left ventricular transducer-tipped catheter was introduced through a carotid artery cutdown and an arterial line was placed in the femoral artery. An IABP was then positioned in the descending aorta through the other femoral artery.
The left anterior descending artery (LAD) was then isolated just proximal to the first diagonal artery branch and surrounded with a pneumatic occlusion cuff. Two pairs of sonomicrometry crystals were oriented to measure both length and thickness in the ischemic region, and two additional pairs were implanted in an area with normal coronary perfusion as a control.
Data from each region were obtained under normal and ischemic conditions. The data were collected at baseline (LAD cuff deflated) with both the AMP and IABP. The cuff was then completely inflated, occluding the LAD. Data were obtained after 10 minutes of occlusion. The AMP was then activated and data were collected. The AMP was then stopped and data were obtained with the IABP functioning.
All data were recorded as the mean value ± standard deviation. A two-tailed Student's t test was used to compare data collected with IABP and AMP support with data collected at baseline and ischemia. Statistical significance was determined as a p value of 0.5 or less.
Results
Effects of Coronary Occlusion
Acute occlusion of the LAD coronary artery resulted in an increase in left ventricular end-diastolic pressure (LVEDP) (9.0 ± 2.1 to 13.1 ± 4.0 mm Hg; p < 0.05) but did not change diastolic blood pressure (62.4 ± 11 versus 58.7 ± 13 mm Hg). Coronary occlusion had a severe effect on regional function, resulting in paradoxical motion in the ischemic region during left ventricular contraction (Table 1
). A normal pressure-length loop is shown in Figure 1
and paradoxical motion is illustrated in Figure 2
, which shows lengthening during systole and shortening during diastole. No changes were observed in the control region during LAD occlusion.
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During ischemia there was lengthening and thinning of the myocardium in the ischemic region, and normal shortening and thickening in the control region. The paradoxical motion was reversed by both AMP and IABP (Table 2
), although regional function did not return to the preischemic level. These findings are illustrated in length-pressure loops (Figs 2, 3![]()
). Contractility in the control area did not change after the LAD occlusion or after initiation of diastolic counterpulsation. There were no differences between AMP and the IABP in their effects on regional function during ischemia.
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Aortomyoplasty has developed in this laboratory as a simple method to assist a failing ventricle. The advantages of this approach are (1) it uses autogenous tissue, (2) it does not require cardiopulmonary bypass or aortic cross-clamping, (3) it does not directly alter or restrict cardiac motion, and (4) it is technically simple to perform. Furthermore, AMP has the added advantage of being performed via a thoracotomy, which leaves the anterior mediastinum undisturbed for future cardiac procedures.
The disadvantages are also clear. Concerns about interruption of the spinal cord blood supply are valid but probably exaggerated. This operation can be done without dividing more than two pairs of upper thoracic intercostal vessels. This is unlikely to cause spinal cord ischemia, because spinal cord perfusion is more dependent on the lower thoracic intercostal and abdominal lumbar arteries, which are not disturbed by AMP [15, 16]. In addition, aortic cross-clamping is not necessary, which is the major threat to the spinal cord perfusion during aortic operations. Furthermore, this procedure could be done using somatosensory and motor evoked potentials to further minimize the chance of spinal cord injury [17]. Another concern is potential trauma to the aorta from repeated compression. Certainly, AMP would not be feasible in patients with a calcified or severely atherosclerotic descending aorta, but this could be determined preoperatively with a computed tomographic scan. The long-term effects of diastolic aortic compression with skeletal muscle on the histology of the aorta will need to be studied before clinical studies are considered.
Previous studies of the hemodynamic effects of this procedure have shown effects similar to those of an IABP in normal animals and in animals with congestive heart failure [11, 12]. In light of these previous studies, we sought to evaluate descending thoracic AMP in a model of acute coronary ischemia. This experiment has demonstrated that AMP can reverse paradoxical regional motion during acute ischemia. Regional motion as represented by both ventricular wall shortening and thickening was significantly improved by both AMP and IABP. Comparison of the regional motion effects of AMP and IABP demonstrated no significant differences between the two techniques.
Left ventricular end-diastolic pressure was also studied during this experiment as a measure of global ventricular function. As in the regional wall motion measurements, acute ischemia had a profound effect on LVEDP. Both AMP and IABP improved the LVEDP; however, the results only reached statistical significance in the AMP portion of the experiment. The small number of animals studied (6) probably accounts for the IABP data not reaching statistical significance.
Overall, these results confirm previous studies, which demonstrate AMP to have a hemodynamic profile similar to an IABP. The methods used in this experiment also demonstrate the utility of in situ training of the LD. The animals involved all had their LD well-trained in a fatigue-resistant form at the time of the coronary occlusion. This experiment studied the acute effects of diastolic counterpulsation with chronically conditioned skeletal muscle. Previous work has shown that the augmentation can be demonstrated for at least several months after operation.
The clinical implications of this study seem clear. For patients with a compressible descending aorta (ie, not too calcified) in whom a method of long-term ventricular assistance is required, a staged operation with in situ training of the LD followed by AMP might provide a solution. The hemodynamic effects would be similar to placement of an IABP. The descending thoracic AMP could be used in the early postoperative period for support, unlike previous protocols for cardiomyoplasty, in which a 6-week muscle training period was necessary.
We believe the potential utility of AMP as a treatment for heart failure, especially ischemic heart failure, is clear. Currently, our laboratory is studying the long-term effects of AMP on the descending aorta and ventricular remodeling after myocardial infarction. Pending the results of these trials, we anticipate a clinical feasibility trial of this procedure.
Footnotes
Presented at The Third International Conference on Circulatory Support Devices for Severe Cardiac Failure, Pittsburgh, PA, Oct 28-30, 1994.
Address reprint requests to Dr Magovern, Division of Thoracic Surgery, Allegheny General Hospital, 320 E North Ave, Pittsburgh, PA 15212.
References
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