|
|
||||||||
J Thorac Cardiovasc Surg 1998;115:1264-1268
© 1998 Mosby, Inc.
SURGERY FOR CONGENITAL HEART DISEASE |
Medtronic, Inc., Minneapolis, Minn., is gratefully acknowledged for financial support of this study.
Received for publication June 13, 1997. Revisions requested August 29, 1997; revisions received Oct. 14, 1997. Accepted for publication Jan. 30, 1998. Address for reprints: P. H. Schoof, MD, Department of Cardiothoracic Surgery, D6-50, University Hospital Leiden, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
| Abstract |
|---|
|
|
|---|
0.003). The rate of increase did not differ significantly from that of the control group with a native pulmonary valve. However, there was a rapid adaptation of the autograft valves resulting in a significantly higher mean cuspal weight, height, and width. In the valveless autograft group, wall circumference, thickness, and height increased significantly (p
0.001). The circumference increased significantly more than that of the native pulmonary wall. Compared with the native aortic wall, the pulmonary autograft media showed retained pulmonary architecture on microscopic study.| Introduction |
|---|
|
|
|---|
| Methods |
|---|
|
|
|---|
|
In group 2 piglets, normothermic cardiopulmonary bypass was initiated after similar aortic and atrial cannulation. After aortic clamping and cold cardioplegic arrest, the aorta was transected and a segment of aortic wall was excised and fixed in 3.6% formaldehyde to serve as a reference sample. Subsequently, the main pulmonary artery was excised from the top commissural level up to the bifurcation. A sample was taken from the valveless autograft and fixed in 3.6% formaldehyde to serve as a reference sample. Aortic continuity was reestablished with the remaining autograft after the height of the segment was measured with a ruler. Anastomoses were made with 6-0 Prolene suture in a continuous fashion. The right ventricular outflow tract was reconstructed by mobilization of the pulmonary artery branches and direct anastomosis with 6-0 Prolene suture.
At normothermia the extracorporeal circulation was discontinued, the heart decannulated, and the chest closed, with drains being left in the pericardium and beneath the sternum.
Postoperative course
All animals were extubated primarily or within a few hours after the operation and transported to a temperature- and oxygen-regulated intensive care unit, where appropriate guidelines for postoperative care were followed. All animals stayed in the laboratory for 2 to 3 weeks before they were returned to the farm, where they were fed unrestrictedly.
Throughout the study period, all animals received humane care in compliance with the "Dutch Animal Welfare Act." The experimental protocol was reviewed and approved by the University of Leiden Committee on the Care and Use of Laboratory Animals.
Euthanasia
Animals not dying of a natural cause were put to death when they became seriously ill, symptoms of heart failure developed, or when they had reached considerable weight (more than 100 kg) in group 1.
In group 2 all animals were put to death at 10 months of age with the use of metomidate hydrochloride, azaperone, pancuronium, and potassium chloride.
Autopsy
In all animals that died of a natural cause, an extensive autopsy was performed to establish a cause of death. In all other animals a limited thoracotomy was made to excise the heart and proximal great vessels. After transection and inspection of the ventricles, the autograft was dissected free together with the homograft or bioprosthesis in group 1 animals. The coronary remnants were sutured and autograft valve sufficiency was checked by filling the root with Ringer's solution. Other means of assessment of valvular function were considered, such as echocardiography and auscultation, but could not be carried out in the often huge and uncooperative animals. Macroscopic photographs were made after longitudinal transection between the left and right coronary cusps after fixation in 3.6% formaldehyde (Fig. 2). In group 2, transverse sample rings were taken from the pulmonary autograft, native aorta, and native main pulmonary artery.
|
In group 2, inner circumference was determined by measuring the length of the opened tissue sample rings. Height of the pulmonary autograft was measured with a vernier calliper on the outside of the specimen after the anastomoses had been cleared. Sample thickness was measured microscopically with a microscopic grid at 10x magnification; the wall thickness was measured from external elastic lamina to internal luminal surface, precluding measuring faults from adventitial irregularities.
Controls
A separate control group was introduced to create a normal growth curve of the pulmonary valve. The pulmonary root was procured from 20 healthy Dutch Landrace pigs. Ten pigs operated on for another experiment weighed 25.5 ± 2.8 kg (mean ± SD; range 20.0 to 30.7 kg), and 10 pigs weighing 86.0 kg (mean) were slaughtered for consumption. All roots were fixed in 3.6% formaldehyde and transected. Cuspal width, height, and weight were measured as in group 1 specimens.
Because there is a linear relationship between age and body weight between 20 and 200 kg in Dutch Landrace piglets,
14,15 the assumption was made that valve growth is also linearly related to body weight and thus to age in this particular weight range. This linear relationship is also found in human beings above a certain body surface area equaling approximately 10 kg body weight.
17,18 Thus the created normal growth curves can be extrapolated and compared with the curves of the study group.
In the valveless autograft group 2, the values of the autopsy specimens were compared with the similarly measured samples taken at operation.
Microscopy
Longitudinal sections of the transition zone between the native aorta and the pulmonary autograft were stained with hematoxylin-eosin and elastin van Gieson stains and were studied with a light microscope. More extensive microscopy was considered beyond the scope of this project and will be the subject of further study.
Statistics
Comparison of means was done with unpaired Student's t tests and correlations were calculated by means of Pearson's product moment correlation coefficients. The relations between body weight and cuspal width, height, and weight of group 1 animals were estimated with linear regression. The slopes of the regression lines between the cuspal weight, height, and width and the body weight of the group 1 animals and the control group animals were compared by means of covariance analysis, in which we evaluated the interaction tests between body weight and group membership.
| Results |
|---|
|
|
|---|
30 days) occurred in six pigs in the Ross group. Cause of death was myocardial ischemia caused by coronary artery kinking in one, an ill-defined anesthetic problem in one, early tamponade in one, severe bioprosthetic and autograft endocarditis in one, and an unknown cause unrelated to the autograft in two pigs. Two pigs were put to death after 2 and 12 weeks for the purpose of a pilot study; their autograft was not studied according to the protocol. One autograft was damaged at dissection and could not be reliably measured.
Finally, 11 pigs were the subject of study and their autograft valves were measured. They lived for more than 3 months (6.6 ± 2.3, mean ± SD, range 3 to 11), acquiring a mean weight of 109.3 ± 48.4 kg (mean ± SD, range 63.0 to 191 kg). Six pigs died during follow-up: Four died of right ventricular failure caused by outflow tract obstruction or insufficiency (three of them had a stentless bioprosthesis in the right ventricular outflow tract); one died of pneumonia; and one pig died of an unknown cause. Five pigs were put to death at a weight of 143.3 ± 37.4 kg (mean ± SD, range 85.5 to 191 kg), four being in good health and one showing signs of right ventricular failure.
No operative or early deaths occurred in the valveless autograft group. All animals were in good health when put to death at 10 months of age and at a weight of 179.2 ± 10.4 kg (mean ± SD, range 161 to 186 kg).
At autopsy the pulmonary autograft was found to have enlarged in proportion with or slightly more than adjacent native structures. In large animals, a remarkable size discrepancy between right-sided homograft and autograft was observed (Fig. 2
). In the transected autograft, all valve cusps showed the transparent, smooth, and shiny appearance of a healthy valve with good pliability and coaptation. Small tracks left by the Prolene stitches could be seen at anastomotic lines where sutures were still visible (Fig. 3). No insufficiency of any autograft was found when the valve was tested with Ringer's solution after coronary closure.
|
|
|
The sum of the pulmonary autograft valve cuspal widths was 83 ± 9 mm (mean ± SD, range 69 to 100 mm), which correlated significantly with body weight in both the autograft (r = 0.81, p = 0.003) and the control group (p < 0.0001). The rates of cuspal width increase did not differ significantly (p = 0.18), but the mean cuspal width was significantly greater in the autograft group (p
0.001) (Fig. 4
).
A remarkable size increase could be observed by comparing the operative and autopsy samples in the valveless autograft group (Fig. 5). The inner circumference increased from 38.8 ± 4.9 to 88.6 ± 6.3 mm in the pulmonary autograft, 38.8 ± 4.9 to 66.0 ± 4.0 mm in the native pulmonary artery, and 34.4 ± 1.6 to 77.0 ± 7.2 mm in the aorta (all mean ± SD and p
0.001). The circumference had increased significantly more in the pulmonary autograft than in the native pulmonary artery (p = 0.002) (Fig. 6).
|
Both height and volume of the transplanted segment increased significantly (5 ± 0.9 to 16.2 ± 3.1 mm [mean ± SD], p = 0.001, and 174.6 ± 40.2 to 3014.8 ± 687.2 mm3 [mean ± SD], p = 0.001, respectively) (Fig. 6
). Microscopic sections of pulmonary autograft to the native aortic wall transition zone, stained with hematoxylin-eosin and elastin van Gieson stains, showed a restorative response that had caused fibrosis with numerous vasa vasorum on the outside and intact endothelium on the inside. On the outside, irregular thickening of the adventitia was seen as a possible result of operative trauma. The architectural differences between the aortic media and the pulmonary media of the autograft were retained, with the thick, densely packed, and well-organized elastic lamellae of the aortic media and the thinner less-organized elastic lamellae of the pulmonary media (Fig. 7).
|
| Discussion |
|---|
|
|
|---|
In group 1, cuspal weight, height, and width increased significantly with body weight and at a rate that is comparable with growth of the native pulmonary valve. However, there was a rapid adaptation in the autograft valves resulting in a significantly higher mean cuspal weight, height, and width. Weight increase of the cusps may be a sign of remodeling, for example, caused by increased collagen content as a response to increased pressure load. The higher mean cuspal height and width, however, indicate that the dimensional increase of the valve is determined not only by growth alone but also by dilatation. It is additionally reflected in the significant difference in circumference between autograft and native pulmonary wall after growth (Fig. 6
). We think this dilatation occurs early, causing the step-up of the autograft curve that can be observed in the cuspal width curve (Fig. 4
). Considering the in vitro experiments of Sievers and associates,
20 demonstrating a steep diameter increase at the commissural level of the loaded porcine pulmonary artery up to a static pressure of 50 mm Hg and our own clinical impression that the autograft exhibits unvariably a certain dilatation after aortic unclamping, we think that the most important dilatation of the pulmonary root occurs intraoperatively at unclamping. It probably is not equally distributed throughout the autograft but rather is more pronounced in those parts of the root that are not fixed in circumferential anastomoses. This may also cause some parts to dilate later than others and might explain the different clinical echocardiographic findings of several authors.
8,20,21 Our experimental findings are in agreement with the clinical findings of Elkins and coworkers,
8 who demonstrated that growth of the pulmonary autograft root replacement is associated with dilatation.
Another sign of growth was the finding of small tracks left by the Prolene sutures and visible at the anastomotic sites of the luminal surface of the macroscopic specimen (Fig. 3
). The continuous suture may represent a spiral whose coil becomes smaller with increasing diameter of the growing vessel. It is pulled in the direction of the anastomosis, leaving small scars in the growing vessel wall, perpendicular to the suture line.
Now that growth and dilatation have been found to be responsible for the dimensional increase of the pulmonary autograft in the aortic position, the question of adaptation should be addressed. Like the semilunar valve cusps, with their intricate, stress-minimizing shearing properties, the vessel wall is also an active integrated organ that is composed of endothelial, smooth muscle, and fibroblast cells coupled to each other in a complex autocrine-paracrine set of interactions.
22 A sudden and persisting increase in wall stress and shearing force exerted on the autograft and the sudden passage of oxygen-rich blood constitute strong stimuli that should lead to a remodeling response in both wall and valvular tissue. Elucidating the expression of this remodeling might enable the physician to predict the fate of the pulmonary autograft. As for some early vascular changes in systemic hypertension, future degeneration can be predicted.
22 The pulmonary autograft wall showed retained pulmonary characteristics at both microscopic and macroscopic inspection. These findings demonstrate that remodeling is a subtle process that does not lead to conversion of the pulmonary wall to an aortic wall but probably remains restricted to the differentiation of a few cell types with the potential to respond to altered mechanical load.
In conclusion, the dimensional increase of the pulmonary autograft in the aortic position in the growing pig is caused by growth and dilatation. The autograft valve acquires more weight than does the native growing pulmonary valve. During growth, the histologic differences between pulmonary autograft and native aortic media are retained.
| Acknowledgments |
|---|
| References |
|---|
|
|
|---|
This article has been cited by other articles:
![]() |
B. Chiappini, B. Absil, J. Rubay, P. Noirhomme, J.-C. Funken, R. Verhelst, A. Poncelet, and G. El Khoury The Ross Procedure: Clinical and Echocardiographic Follow-Up in 219 Consecutive Patients Ann. Thorac. Surg., April 1, 2007; 83(4): 1285 - 1289. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. G. Hazekamp, H. B. Grotenhuis, P. H. Schoof, M. E.B. Rijlaarsdam, J. Ottenkamp, and R. A.E. Dion Results of the Ross operation in a pediatric population Eur. J. Cardiothorac. Surg., June 1, 2005; 27(6): 975 - 979. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. G Raja and M. Pozzi Growth of Pulmonary Autograft After Ross Operation in Pediatric Patients Asian Cardiovasc Thorac Ann, December 1, 2004; 12(4): 285 - 290. [Abstract] [Full Text] [PDF] |
||||
![]() |
V. Hraska, M. Krajci, Ch. Haun, K. Ntalakoura, V. Razek, F. Lacour-Gayet, J. Weil, and H. Reichenspurner Ross and Ross-Konno procedure in children and adolescents: mid-term results Eur. J. Cardiothorac. Surg., May 1, 2004; 25(5): 742 - 747. [Abstract] [Full Text] [PDF] |
||||
![]() |
J.J.M. Takkenberg, K.M.E. Dossche, M.G. Hazekamp, A. Nijveld, E.W.L. Jansen, T.W. Waterbolk, and A.J.J.C. Bogers Report of the Dutch experience with the Ross procedure in 343 patients Eur. J. Cardiothorac. Surg., July 1, 2002; 22(1): 70 - 77. [Abstract] [Full Text] [PDF] |
||||
![]() |
E. A. Bacha, G. M. Satou, A. M. Moran, D. Zurakowski, G. R. Marx, J. F. Keane, and R. A. Jonas Valve-sparing operation for balloon-induced aortic regurgitation in congenital aortic stenosis J. Thorac. Cardiovasc. Surg., July 1, 2001; 122(1): 162 - 168. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. Simon, C. Aschauer, R. Moidl, M. Marx, F.P. Keznickl, E. Eigenbauer, E. Wolner, and G. Wollenek Growth of the pulmonary autograft after the Ross operation in childhood Eur. J. Cardiothorac. Surg., February 1, 2001; 19(2): 118 - 121. [Abstract] [Full Text] [PDF] |
||||
![]() |
P. H. Schoof, A. C. Gittenberger-de Groot, E. de Heer, J. A. Bruijn, M. G. Hazekamp, and H. A. Huysmans Remodeling of the porcine pulmonary autograft wall in the aortic position J. Thorac. Cardiovasc. Surg., July 1, 2000; 120(1): 55 - 65. [Abstract] [Full Text] [PDF] |
||||
![]() |
L. Solymar, G. Sudow, and D. Holmgren INCREASE IN SIZE OF THE PULMONARY AUTOGRAFT AFTER THE ROSS OPERATION IN CHILDREN: GROWTH OR DILATION? J. Thorac. Cardiovasc. Surg., January 1, 2000; 119(1): 4 - 9. [Abstract] [Full Text] [PDF] |
||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |