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Ann Thorac Surg 1996;62:1706-1707
© 1996 The Society of Thoracic Surgeons
DR JAMES A. MAGOVERN (Pittsburgh, PA): Doctor Thomas and his colleagues from Dr Stephenson's laboratory at Wayne State should be commended for this important work. Chronic experimental studies are difficult, very time consuming, and expensive, but are essential for the development of new procedures in cardiac surgery.
A scientific study should be judged on how well it answers the questions that have been posed. This study has asked the question whether a skeletal muscle ventricle connected to the descending aorta can provide long-term counterpulsation. The answer to this question is a clear yes. Doctor Thomas and co-workers have shown both augmentation of diastolic blood pressure and reduction in presystolic blood pressure in serial studies in dogs for periods of months and years.
The larger question, which they have not addressed, is how chronic counterpulsation will affect the heart, especially in the context of congestive heart failure. It is logical to assume that counterpulsation with a skeletal muscle ventricle will be very similar to that with an intraaortic balloon pump, but these data will need to be generated before starting clinical applications.
Another question is whether this type of work will eventually lead to clinical application. There have been three major problems with skeletal muscle ventricle research:
The first is the structural integrity of the ventricles. There are high stresses applied to the ventricle, and over time rupture of the ventricle can occur. This problem appears to be solved with technical modifications in the operative technique.
The second problem is thromboembolism. As you can imagine, when blood is pumped there is a large potential for thromboembolism. This problem also appears to be largely resolved with technical modifications of the skeletal muscle ventricle, especially with the pericardial lining. However, this is still an area of concern. There are only about 6 animals in this experiment followed up long term, and I think it is premature to conclude that thrombus will not be a problem.
The third problem is the stiffness of the skeletal muscle ventricle. Over time these muscles become quite noncompliant and require very high filling pressures. The most logical way to use a skeletal muscle ventricle would be to pump left atrium to aorta, but this is not feasible because in the long term the muscle requires a high filling pressure. This leaves us with a left ventricular apex-to-aorta or an aorta-to-aorta configuration. Both of these are satisfactory but amount to diastolic counterpulsation as opposed to doing systolic work.
I have several questions for Dr Thomas. This laboratory has published multiple configurations for the skeletal muscle ventricle. What technique will they use in the preclinical studies leading to ultimate clinical application in patients?
What is the current incidence of detecting thrombus in the skeletal muscle ventricle at any time during the procedure, including the early postoperative period? Is any type of anticoagulation used, including aspirin, warfarin, or heparin?
Most of the rest of the questions have to do with the skeletal muscle ventricle itself. What is the histologic appearance of the ventricle after 1 or 2 years in circulation? Many other studies in skeletal muscle cardiac assistance have shown some degree of muscle fibrosis. Have you seen fibrosis and to what extent is the ventricle viable?
Another question has to do with the histologic appearance of the pericardial lining itself. This is basically a lining of an assist device. Is it still pericardium or has it been replaced with a pseudointima?
And finally, have you looked at flow dynamics in the muscle ventricle itself? For example, is there washout? Is there continuous flow through the device? And in addition, when the ventricle contracts, is the augmentation equal in the ascending and the descending aorta?
Similar hemodynamic effects can be achieved with direct compression of the ascending aorta or the descending aorta aortomyoplasty. Would you consider comparing the effects of these two approaches? The aortomyoplasty has the advantage of being simpler but may not have equal hemodynamic effects.
DR THOMAS: I thank Dr Magovern for his comments and interesting questions. As far as the technique that we think we may use preclinically, obviously the best long-term results have come with this simple aortic diastolic counterpulsator model.
However, another configuration that we have been pursuing recently has been that of a left ventricular apex-to-skeletal muscle ventricle-to-aorta configuration using two valved conduits. This configuration has had advantages in that it has been able to pump more than 50% of the left ventricular blood flow. In addition, although diastolic augmentation in our aortic counterpulsator model averages 35%, it has been roughly 50% or greater with this left ventricular apex-to-aorta configuration. If possible we would like to take the benefits of a pericardial lining in preventing skeletal muscle ventricle thrombosis and rupture and apply them to this model as a potential preclinical or clinical application.
In regard to anticoagulation, what we have used in this series, as in all our previous series, is aspirin. We have attempted to avoid systemic anticoagulation with warfarin.
Your questions about the histologic appearance are quite appropriate. We have seen in the histologic appearance of these muscles, after they have been in circulation, increased fibrosis and some fatty tissue deposition that tends to occur early. In a large series, where we looked at skeletal muscle ventricles in circulation long term over a varying time period, there was no correlation with the time frame in circulation and the degree of fibrosis, so it did not appear to be continually occurring but occurred early within the time frame.
We did look, in a few dogs in this series, at myosin transformation in the muscle. With sodium dodecyl sulfate gel electrophoresis, we were able to see that there was only the slow myosin heavy chains that were in the skeletal muscle after they had been in circulation for this 2-year period. We did not address the flow dynamics specifically in this study. One of our collaborators, Dr Stanley Salmons in England, has been looking at that with a computer-generated model, and we hope to apply some of his findings to our construction of the shape of the skeletal muscle ventricles in the future.
Considering aortomyoplasty, that definitely is a viable option for chronic counterpulsation, and I think time will tell whether a muscular blood pump, such as the skeletal muscle ventricle, or compression of the aorta will be a more efficacious method to apply this mechanism of skeletal muscle cardiac assist.
DR ALAIN F. CARPENTIER (Paris, France): I congratulate Dr Stephenson and his group for their continuous effort to develop skeletal muscle ventricles. I will take this opportunity to give you some up-to-date information on our clinical experience with dynamic cardiomyoplasty and then ask a few questions.
As far as dynamic cardiomyoplasty is concerned, we have now an experience of 84 patients. The mortality in the past 5 years, hospital mortality, has been reduced to 12%, which is actually not very different from that of cardiac transplantation if one includes patients dying while awaiting a donor.
Now, the problem remains the late mortality, and the cause for late mortality is admittedly arrhythmia and sudden deaths. I would think these problems, which accounted for 28% in our series up to 10 years, can be minimized by incorporating the stimulator/defibrillator. Some improvement has been achieved recently by our group by extensive dissection of the pedicle, which permits better wrapping of the heart.
Now, I would like to ask Dr Thomas a few questions. It has been, of course, striking to hear that they have not experienced any evidence of thromboembolic episodes. Is the pericardium glutaraldehyde treated? You mention the histologic picture of these pericardiums after 2 years. This is a unique occasion to tell us whether you have seen some calcification of these pericardiums and the type of lining you had, whether neoendothelium or not. And finally, which mode of stimulation (1:1 or 1:2) did you use? We have demonstrated the 1:1 mode may lead to early fibrosis.
DR THOMAS: Thank you very much for your comments, Dr Carpentier. With regard to your first question, the pericardium was not treated; it was applied directly to the mandrel and then excised at the time of skeletal muscle ventricle construction. As far as our morphologic and histologic examination of the skeletal muscle ventricles, we did not note any calcifications in the muscle but just some degree of fibrosis, along with fatty deposition and decrease in the number of muscle branches. With regard to the mode, we used a 1:2 mode at 33-Hz burst stimulation frequency for all chronic stimulation, and then at the time of measurements we recorded stimulations at other various parameters and returned it to the 33-Hz 1:2 mode for continued chronic function.
DR RAINALD SEITELBERGER (Vienna, Austria): I also congratulate Dr Thomas and his colleagues for this excellent experimental protocol and for his really wonderful presentation. In the recent year we have worked on a somewhat different experimental approach to develop a biological model for eventual long-term aortic counterpulsation.
Using an acute sheep model, we excised the ascending and descending aorta of the donor sheep, including the root of the aortic valve. Distal to the aortic valve, a pouch was created by enlargement of the aorta with two strips of pericardium. The prepared aortic pouch conduit was then anastomosed to the proximal and distal descending aorta of a different sheep using the aortic valve as an inflow valve to the conduit.
The aortic pericardial pouch containing a volume of 60 to 80 mL of blood was then wrapped with the musculus latissimus dorsi, and the muscle was stimulated in the diastolic counterpulsation fashion.
Stimulation of the muscle at every second heartbeat facilitated significant and reproducible aortic pressure increases during diastole. The long-term reliability of this model, however, has yet to be determined in a chronic preparation.
I have one question for Dr Thomas. Do you think that the inclusion of an inflow biological valve conduit would actually make it not necessary to ligate the descending aorta and, therefore, make the model more efficient also in terms of hemodynamic use of the inflow blood?
DR THOMAS: Thank you also for your comments. I found your preparation quite interesting and would be interested in seeing your chronic results with conditioned muscle. We can always get excellent augmentation in acute studies by using unconditioned muscle, but I would be interested in seeing what augmentation you achieve in a chronic model.
With regard to your question, we have previously looked at inclusion of a valved efferent conduit in this model with the idea that when the skeletal muscle ventricle relaxes the majority of the blood that is going to fill it during relaxation will be coming from the ascending aorta and the arch and, therefore, provide a little bit further presystolic unloading for the heart. Indeed, in acute studies we found this to be true. However, during chronic studies we found that the valve function was not maintained over time. Whether this was secondary to the valves we were using or our technique I really cannot comment on, other than it would be advisable to repeat those studies again in a chronic setting to see whether an efferent homograft or an efferent valve conduit would provide greater presystolic unloading in this preparation.
Related Article
Ann. Thorac. Surg. 1996 62: 1698-1706.
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