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Ann Thorac Surg 1996;61:430-436
© 1996 The Society of Thoracic Surgeons
Division of Cardiothoracic Surgery, Department of Surgery, Wayne State University, Detroit, Michigan
Abstract
Background. Skeletal muscle ventricles (SMVs) are muscular pumping chambers constructed for cardiac assist. Skeletal muscle ventricles can be connected to the circulation in a variety of configurations for both left and right heart assist; when connected to the aorta and stimulated to contract during diastole, they function in a similar fashion as an intraaortic balloon pump.
Methods. Skeletal muscle ventricles were constructed in 18 dogs using the left latissimus dorsi muscle. In 10 of these dogs (group 1), the inner surface of the SMV was lined with autogenous pericardium obtained at the time of construction of the SMV. For the remaining 8, the SMVs were lined by fibrous tissue that forms in reaction to the synthetic mandrel around which the latissimus muscle is wrapped. After the muscles were electrically conditioned to a fatigue-resistant state, the mandrels were removed from the SMVs and the SMVs were connected to the descending thoracic aorta with a specially constructed base cap and two polytetrafluoroethylene conduits.
Results. Initial hemodynamic recordings revealed that the mean diastolic blood pressure increased by 24.7% in group 1 and by 29.8% in group 2. Diastolic augmentation was well maintained over time; augmentation in surviving group 1 animals was 30.0% after 18 months of pumping continuously in circulation. Long-term survival was greater in the dogs whose SMVs were constructed using an inner pericardial lining. At 90 days in circulation, 60% of the dogs in group 1 were alive with functioning SMVs, whereas only 13% of the dogs in group 2 were alive. The incidence of SMV rupture in the fibrous-lined SMVs was 63%, whereas the incidence in the pericardial-lined SMVs was 0%. No evidence of thromboembolism occurred in either group.
Conclusions. Lining the inner surface of an SMV with pericardium appears to provide structural integrity, which helps to prevent the complication of SMV rupture in this model of cardiac assist.
There are several techniques being investigated whereby skeletal muscle is applied for cardiac assist. One method, cardiomyoplasty, involves wrapping the latissimus dorsi muscle around the heart in hopes of improving systolic function [1]. Another method involves the construction of muscular pumping chambers termed skeletal muscle ventricles (SMVs) [2]. In our laboratory, SMVs connected to the descending thoracic aorta have functioned as aortic counterpulsators in the circulation for more than 27 months [3].
Prior chronic studies of SMVs in circulation revealed two major obstacles to clinical application [4, 5]. First, there was a relatively high incidence of thrombosis in the SMV cavity with resultant thromboembolism. Over time, modifications in SMV cavity design have helped to decrease the rate of embolic events to 2% to 3% [6]. The second obstacle was rupture of the SMV near the anastomotic interface with subsequent hemorrhage [5]. Recently, we reported on a series of 15 animals with pericardial-lined SMVs in circulation for up to 1
years; there was no evidence of thromboembolism or SMV rupture for the SMVs constructed with pericardial lining and conically shaped base cap [7]. The purpose of this experiment was to evaluate the efficacy of the pericardial lining in reducing the incidence of rupture and other complications.
Materials and Method
Skeletal Muscle Ventricle Construction
Skeletal muscle ventricles were constructed in 18 beagles (8 to 11 kg), which were divided into two groups. All animals were operated on in accordance with the ``Guide for the Care and Use of Laboratory Animals'' published by the National Institutes of Health (NIH publication 85-23, revised 1985). In 10 of the animals (group 1), the inner lining of the SMV was composed of autogenous pericardium excised at the time of SMV construction. In the remaining 8 animals (group 2), the SMVs were lined by the induced fibrous reaction to the polypropylene mandrel, around which the latissimus muscle is wrapped to form the SMV. The animals in group 1 were constructed as part of an ongoing study; their initial hemodynamic values have been reported previously [7]. The extended hemodynamic function to 19 months in circulation in these animals is herein reported.
For both groups, SMVs were constructed from the left latissimus dorsi muscle. All animals were anesthetized and the latissimus muscle was dissected free from the subcutaneous tissues and the chest wall, except for its humeral insertion. The muscle was divided from its attachments to the lower ribs and from its origin, taking care to maintain a 5to 10-mm-wide strip of thoracolumbar fascia along the entire dorsal edge of the muscle. The neurovascular bundle was isolated, but kept intact. A bipolar nerve cuff electrode (model 4080; Medtronic Inc, Minneapolis, MN) was placed around the thoracodorsal nerve.
For the animals in group 1, the SMVs were lined with an autogenous layer of pericardium. The pericardium was obtained through an eighth space thoracotomy. The anterior pericardium between the two phrenic nerves was excised from its diaphragmatic attachments up to the base of the heart. After the pericardium was excised, its visceral surface was applied to the outside of a conically shaped, polypropylene mandrel. The dimensions of the mandrel were a base diameter of 3 cm, a height of 6.5 cm, and a volume of 25 mL. A 5-mm ring of Dacron felt (USCI, Billerica, MA) was placed at the base of the mandrel to hold sutures. The pericardium was sewn to the sewing ring with continuous 6-0 polypropylene suture.
For both groups, the muscle was wrapped circumferentially around the mandrel, with the medial surface of the muscle applied against the mandrel or the parietal surface of the pericardium. The dorsal aspect of the muscle with the thoracolumbar fascia was sewn to the sewing ring with continuous polypropylene suture. The muscle was wrapped approximately 2.5 times around the mandrel, with each layer secured to the sewing ring with polypropylene suture. Absorbable, polyglactic suture was used to close the end of the muscle over the apex of the mandrel and to secure the layers of the muscle wrap to each other.
The SMV was positioned subcutaneously near the left shoulder and the wound was closed over the SMVs in layers using polygalactic suture. The nerve lead was connected to a neurostimulator (Itrel model 7421; Medtronic Inc). The stimulator was positioned underneath the left rectus abdominus muscle, with the stimulator initially turned off.
Electrical Conditioning
The animals were allowed to recover for a 3-week period. After this, the neurostimulator was programmed to deliver continuous stimulation to the motor nerve of the SMV at 2 Hz frequency, with a duration of 210 µs and 1 to 2 volts amplitude. This low-frequency electrical stimulation was continued for 6 weeks to induce the transformation of the muscle fibers to a uniform population of slow twitch, fatigue-resistant (type I) fibers [8].
Connection to the Circulation
After the 9-week period of vascular delay and electrical conditioning, the animals were reanesthetized and their SMVs connected to the circulation. First, the base of the SMV was exposed and the polypropylene mandrel was removed. The heart and the descending thoracic aorta were exposed through a left, fifth interspace, posterolateral thoracotomy. Two myocardial sensing electrodes were placed on the left ventricle (sutureless type 6917A-35T; Medtronic Inc). Two 12-mm ringed, Gore-Tex conduits (W. L. Gore & Associates, Inc, Flagstaff, AZ) were anastomosed to the aorta with continuous 6-0 polypropylene suture in an end-to-side fashion.
The vascular conduits were anastomosed to a conically shaped base cap made from 0.6-mm-thick Gore-Tex cardiovascular patch material, which was, in turn, anastomosed to the Dacron felt sewing ring at the base of the SMV. A schematic diagram of SMV construction and connection to the circulation is shown in Figure 1
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Hemodynamic Data Collection and Analysis
At the time of connection to the circulation, arterial pressure was measured from the femoral artery using a fluid-filled column and a pressure transducer (Spectramed Inc, Oxnard, CA). Skeletal muscle ventricle and aortic arch pressures were recorded with 5F microtransducer-tipped catheters (Millar Instruments, Inc, Houston, TX). Total cardiac output was calculated from a 16-mm ultrasonic flow probe placed around the main pulmonary artery (Transonic Systems, Inc, Ithaca, NY). After the initial pressure measurements, hemodynamic recordings were repeated initially 2 to 4 weeks after the SMVs were placed into circulation. Subsequent recordings were performed on a 2 to 3-month basis thereafter. Femoral and carotid arterial pressures were monitored by percutaneously placed catheters connected via a fluid-filled column to a pressure transducer (Spectramed Inc).
Hemodynamic data were collected with a Gould ES 1000B recording and display system (Gould Instruments, Inc, Cleveland, OH). Data were also sampled digitally at 200 Hz using a real-time data acquisition system (AT-Codas; Dataq Instruments, Inc, Akron, OH) and stored on a computer (model 386-20; Northgate Computer Systems, Plymouth, MN). Stored data were analyzed off-line using a data analysis software program (Windaq; Dataq Instruments, Inc) on a portable computer (T3200; Toshiba, Irvine, CA).
Data are expressed as mean ± standard deviation. Statistical significance was determined between groups using a repeated-measures analysis of variance calculated using a statistical software package (INSTAT; Graphical Software, San Diego, CA). Significance was accepted at the p less than or equal to 0.05 level.
Results
Hemodynamics
Hemodynamic data obtained from the time that the SMVs were placed in circulation are presented in Table 2. Skeletal muscle ventricle contraction at 33 Hz significantly increased mean diastolic arterial pressure by 15.0 ± 4.8 mm Hg (+24.7%) in group 1 and by 18.8 ± 2.0 mm Hg (+29.8%) in group 2. There was no significant difference in the degree of augmentation between the two groups. Groups 1 and 2 were statistically similar for both the control and stimulated values for peak aortic systolic pressure, mean diastolic pressure, and the control presystolic aortic pressure. The stimulated presystolic aortic pressure was decreased 8.6 ± 2.5 mm Hg in group 1 and 24.0 ± 3.5 mm Hg in group 2. Both of these values were statistically different than their respective controls. However, the presystolic pressure for the animals in group 2 was significantly lower than for group 1. The animals in group 2 also exhibited a significantly slower heart rate and a decreased cardiac output when compared to the animals in group 1. Stroke volume was not statistically different between the two groups.
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. The animals in group 1 exhibited a significantly lower mortality compared with the animals in group 2. The duration of time in circulation and the cause of death are shown in Table 3 for all animals. Three of the deaths in group 1 were iatrogenically related to pharmacologically induced heart failure obtained during the first follow-up hemodynamic measurement [9]. There were no SMV ruptures for any of the animals in group 1. One animal in group 1 had minimal thrombus formation present inside the SMV at autopsy. In this animal (dog 2), the cardiomyostimulator battery eventually failed (this stimulator had been used in a number of previous experiments). No clot had been evident during serial echocardiographic examinations up to that point. The cardiomyostimulator was replaced, but the SMV contraction was then poor, so the animal was killed. There was no evidence of embolism to distant organs at time of autopsy.
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2 analysis (p = 0.04). The other cause of death was postoperative infection.
Chronic Function
Augmentation of mean diastolic arterial blood pressure by SMV contraction was well maintained over time. Figure 3 depicts serial pressure traces during hemodynamic recordings in 1 animal whose SMV has been pumping in circulation continually for 18 months. Augmentation of diastolic pressure is noted both proximally and distally to the SMV. Figure 4 depicts the improvement in mean diastolic arterial pressure seen for all the animals in groups 1 and 2 versus the time in circulation.
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While clinical trials progress for cardiomyoplasty, we have pursued the use of skeletal muscle for diastolic counterpulsation in the form of SMVs. Skeletal muscle ventricle aortic counterpulsation has been shown to provide objective improvements in hemodynamics [7, 10, 11]. However, there remain two major roadblocks to clinical application of SMVs: thrombosis and rupture.
The presence of a pericardial lining may provide some degree of structural stability to the skeletal muscle ventricle. Skeletal muscle ventricle rupture has been problematic in prior studies of long-term function. In a report on SMVs functioning chronically in the circulation, Acker and colleagues [12] presented 6 dogs in circulation up to 11 weeks. One of these dogs' SMV was connected to the aorta as a blind-end pouch with a single conduit; this animal died after 8 days in circulation of rupture. Anderson and co-workers [4] reported on a chronic series of SMVs connected to the aorta as counterpulsators. In their study, SMVs were lined with either autogenous pleura, pericardium, or only the fibrous reaction to the mandrel. Eight of 12 SMVs in circulation for more than 24 hours ruptured; these ruptures occurred from as early as 1 day to 26 weeks in circulation. Five of these ruptures occurred at the junction of the skeletal muscle with the Teflon felt sewing ring; the remainder occurred at the apex, but this was in animals whose SMV function had not been particularly good. Of note, these SMVs were connected to the circulation in essentially the same configuration as used in this current study.
Nakajima and associates [13] most recently reported on a series of 44 SMVs connected to the aorta as counterpulsators that functioned in the circulation for varying periods of time. The incidence of rupture in their series was 34% (15 of 44). This included mostly fibrous-lined SMVs, but also pleural-lined and pericardial-lined SMVs as well. Skeletal muscle ventricle rupture occurred exclusively at the interface between the muscle and the sewing ring. Histologically, the muscle at this point was thinned and mostly fibrous in nature. In all occurrences, SMV rupture was detected within 40 days of placing the SMV in circulation.
In an effort to decrease the incidence of this complication, several slight modifications in SMV design were reported in a more recent study [7]. By lining the inner surface of the SMV with autogenous pericardium, using the posterior thoracolumbar fascia of the latissimus dorsi muscle to hold suture, and connecting the SMV to the circulation with a dome-shaped conduit to decrease stress at the anastomosis, we demonstrated the elimination of SMV rupture and thrombosis with follow-up as long as 15 months. This was in contrast to other pericardial-lined SMVs without the additional design modifications (constructed in the same fashion as Nakajima and associates' study), where there was still a 40% incidence of rupture and 20% thrombus formation [13]. Because these earlier SMVs also used an inner pericardial lining, it was unclear what effect, if any, the use of a pericardial lining had on SMV rupture.
In the present study, SMVs lined with pericardium exhibited a much lower incidence of SMV rupture than the unlined SMVs. For both groups, SMVs were constructed in a similar fashion with the exception of the presence or absence of a pericardial lining. The same size and breed of dogs were used for both groups. At the time of hemodynamic recordings, most of the hemodynamic parameters were similar. At the initial time of connection to the circulation, the animals in group 2 exhibited a lower cardiac output and a slower heart rate than did the animals in group 1. Although the reason for this is not clear, one possible explanation is that this difference reflects the depth of anesthesia at the time of placement into the circulation. In prior studies, the anesthetized heart rate has varied from around 100 to around 140 beats/min. It is unlikely that there is any inherent difference in the hemodynamics between the two groups. The difference in cardiac output is merely a reflection of the heart rate; the stroke volume for the two groups did not differ statistically.
The only other difference between the two groups was the presystolic unloading from the SMVs, as evidenced by the lower presystolic pressure in group 2. The SP1005 and model 6100 cardiomyostimulators were used for both groups because of limited availability of the model 6100. Because the model 6100 is programmed as a percentage of the R-R' interval, it can be exactly matched for heart rate to provide both diastolic augmentation and maximal presystolic unloading. The difference between the aortic presystolic values for groups 1 and 2 merely reflects the fact that more model 6100 pacemakers were available for that group. The effects of presystolic unloading can be seen in Figures 3A
through 3D, which were recorded from one of the animals in group 1.
In addition to the protective effect for rupture, the pericardial lining might provide some protection for SMV thrombosis. Anderson and co-workers [4] examined pericardial and pleural linings to address the issue of SMV thrombosis. Their findings suggested that lining the SMV with autogenous pleura decreased the presence of thrombus inside the SMV lumen, because 3 to 6 animals with pleural linings were thrombus free from 10 days until 40 days in circulation. There were only 3 animals with pericardial linings, all of which had some degree of thrombus. Since Anderson and co-workers' study, further modifications in SMV geometry have been made to improve blood flow characteristics inside the SMV and decrease the incidence of thrombosis [6]. Recent attempts to eliminate thromboembolic problems also include lining the SMV with a monolayer of endothelial cells [14, 15].
The current study also presents evidence for extended long-term function of SMVs in circulation. Previously, we reported on 4 animals with SMVs connected to the aorta as counterpulsators from 191 to 836 days [3]. In all 4 of these dogs, augmentation of diastolic blood pressure was maintained from approximately 10% to 50% during their time course in circulation. Only 1 of those dogs died of rupture. In this dog, the assist ratio was increased for a 1-month interval to 1:1, which resulted in a deterioration in function. Although the ratio was returned to 1:2 one month later, there was no improvement in function and the SMV ruptured after 191 days in circulation.
In group 1, three deaths were iatrogenic in origin. These deaths were secondary to overdosing of propranolol, which was given as part of a previous study [9]. Three deaths occurred during the SMVs' time course in circulation. One of these was early (postoperative arrhythmia within the first 24 hours after operation). One was secondary to an infection that developed near the flow probe site, which was accessed during subsequent pressure measurements. The last was the dog that was electively euthanized for poor SMV function after the pacemaker battery had failed. The remaining 4 dogs continue to exhibit good SMV function, as demonstrated by augmentation of diastolic pressure. If the three deaths that occurred iatrogenically are eliminated from the actuarial survival analysis, survival is 71% at 1 year and 57% after 19 months in circulation.
In conclusion, this study suggests that the inclusion of a pericardial lining is protective against the complication of SMV rupture. Pericardial-lined SMVs connected to the descending aorta as diastolic counterpulsators provide effective chronic cardiac assistance, in this study up to 617 days in circulation, as of November 8, 1994. Although these data need to be reproduced in a larger experiment and additional questions regarding the optimal configuration of SMVs in the circulation still remain unanswered, these results provide encouragement that SMVs for circulatory assist will reach clinical trials in the near future.
Acknowledgments
This work was supported by NIH grant HL 34778. Doctor Thomas was supported by National Institute of Health National Research Service Award HL08384.
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 Stephenson, Division of Cardiothoracic Surgery, Wayne State University School of Medicine, Harper Professional Bldg, Suite 228, 3990 John R St, Detroit, MI 48201.
References
This article has been cited by other articles:
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  I. R. Ramnarine, M. Capoccia, Z. Ashley, H. Sutherland, M. Russold, N. Summerfield, S. Salmons, and J. C. Jarvis Counterpulsation From the Skeletal Muscle Ventricle and the Intraaortic Balloon Pump in the Normal and Failing Circulations Circulation, July 4, 2006; 114(1_suppl): I-10 - I-15. [Abstract] [Full Text] [PDF]
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