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Ann Thorac Surg 1998;66:977-979
© 1998 The Society of Thoracic Surgeons
a Division of Cardiothoracic Surgery, Department of Surgery, Wayne State University School of Medicine, Detroit, Michigan, USA
Address reprint requests to Dr Stephenson, Cardiothoracic Surgery, Suite 2102 Harper Professional Bldg, 3990 John R, Detroit, MI 48201
The skeletal muscle cardiac assist research that has been conducted in our research laboratory, first at the University of Pennsylvania and now at Wayne State University, has gone through several phases, starting in 1979 with my research associate John Macoviak. We resected full-thickness portions of canine left and right ventricles, but mainly right ventricles, and replaced them with pedicled grafts of diaphragm. When we stimulated the pedicled muscle graft, it contracted and generated active tension [1, 2]. We stimulated some of these muscle grafts with r-wave–synchronous pacemakers for many weeks [3, 4]. The muscle graft used to replace part of the right ventricular heart wall continued to contract and generate active tension and formed collateral circulation with the myocardium. During this time, we became aware of other investigators who had used skeletal muscle for various types of cardiac assist. We found that in most cases, they had given up on this research because of the problems related to muscle fatigue. We also learned of research by Stanley Salmons and Dirk Pette in which they stimulated the motor nerve to skeletal muscles and could change the muscle fiber type from fast twitch to slow twitch muscle, which is more fatigue resistant [5, 6]. At this point, we thought it might be possible to condition skeletal muscle, make it more fatigue resistant, and use it for some form of cardiac assistance.
In the second phase of our research, we tested four muscles: diaphragm, serratus anterior, rectus abdominis, and latissimus dorsi [7–12]. We showed in all cases that when the muscle was stimulated electrically over several weeks, it became more fatigue-resistant. Initially, we used the gold standard, which was 10 Hz stimulation (or 600 times a minute), as Salmons and Pette had done. But we realized that it would be important to be able to condition a muscle close to the animal’s own heart rate at 2 Hz (120 times a minute). During this phase of our research, we published articles on different stimulation techniques to condition muscle, including the use of burst stimulation, which would eventually be necessary to cause the muscle to contract forcefully enough to do cardiac-type work.
In the third phase of our research, models were developed in which this relatively fatigue-resistant skeletal muscle could be tested for some form of cardiac assistance. One model we tested was cardiomyoplasty, where the muscle is wrapped around the heart and then stimulated during cardiac systole to contract in synchrony with the heart [13, 14]. The main thrust of our research, however, was to develop separate pumping chambers, which we term "skeletal muscle ventricles" (SMVs) and then test them with mock circulation devices and eventually in the circulation [15–19]. Bridges and associates [20], from our laboratory, showed that the entire right heart could be bypassed and the flow routed into an SMV and then back into the pulmonary artery. Bridges and associates’ experiments, however, were all acute and we concluded that we probably needed higher filling pressures for this model to work well chronically. Ruggiero and colleagues [21], from our laboratory, created a heart failure model by tricuspid valvulectomy, which caused higher right atrial filling pressures. A valved conduit was connected from the right atrium to the SMV and another valved conduit from the SMV to the pulmonary artery. This was an acute experiment followed up over 3 hours. The results showed that the SMVs were able to pump blood. The animals all had significant tachycardia caused by the right-sided heart failure. The tachycardia was not conducive to this type of right ventricular assist model, which resulted in its limited success.
These previous experiments led to the study presented in "Skeletal Muscle Ventricle in the Pulmonary Circulation: Up to 16 Weeks’ Experience" [22]. Doctor Niinami and associates from our laboratory took advantage of the idea that higher filling pressures for the SMV might be better and connected the SMVs from the right ventricle to an SMV and then from the SMV to the pulmonary artery. The proximal pulmonary artery was ligated. The model was first tested in a series of acute experiments [23]. Eight animals with this model in circulation were followed up for several weeks [22]. This was the first time we were able to obtain results beyond the acute period with a right-sided SMV assist model. Unfortunately, after 3 or 4 weeks in circulation there was some deterioration in SMV function. With further work, this model might eventually be useful for patients suffering from right heart failure and pulmonary hypertension, whether from an idiopathic cause or related to some form of congenital heart disease.
Experiments were also being conducted with SMVs assisting the left-sided circulation. We used these SMVs in three ways: as an aortic diastolic counterpulsator [24], to route the blood from the left atrium to an SMV and from the SMV to the aorta [25], and to route the blood from the left ventricular apex through a valved conduit to the SMV and then from the SMV to the aorta [26]. Our chronic experiments with the aortic diastolic counterpulsation model and with the LV apex to aorta model have seemed more promising than the left atrium–SMV–aorta model, perhaps in part because of the higher filling pressures associated with the former two models.
This has led to the current phase of our laboratory research, in which, based on our previous research, we are focusing only on clinically applicable models. With the aortic counterpulsation model, the SMV is connected to the descending thoracic aorta with two limbs of a conduit. The aorta is ligated between the limbs of the conduit to obligate blood flow through the SMV. We currently line these SMVs with autogenous pericardium. We have had several animals in which this reproducible SMV model has pumped blood and effectively augmented diastolic aortic pressure for more than a year [27]. One animal was electively sacrificed after the SMV had been effectively pumping blood in the circulation for more than 4 years. In many of these animals, there has been no clot at the time of sacrifice in the SMV and no evidence of thromboembolism. These SMVs function well during profound low cardiac output induced by propranolol. With minor refinement, this model could be used in humans suffering from chronic left ventricular failure.
The other model that we are now focusing on for clinical application is the left ventricular apex to aorta model, in which a valved conduit is connected between the animal’s left ventricular apex and the SMV and a second valved conduit from the SMV to the aorta. This is the most hemodynamically effective skeletal muscle cardiac assist model that we have tested in our laboratory. Recently, we have been successful with this model in chronic experiments [28]. Our longest survival has been 8 months, and that animal died of causes not related to the SMV. Currently there is another animal with such an SMV functioning well beyond 6 months. With this model, we have shown that SMV stroke work and power output over time are similar to those of the animal’s own left ventricle. With further refinement, this too will likely become a clinically applicable model for patients suffering from left ventricular failure.
Footnotes
As originally published in 1992:
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References
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