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PREVENTION OF CLOT FORMATION ON PROSTHETIC MITRAL VALVES
P R E V E N T I O N OF CLOT F O R M A T I O N
ON
PROSTHETIC MITRAL VALVES George Schimert, M.D., and F. Craig Fisher, M.D., Buffalo, N.
Y.
LOT formation on plastic surfaces is one of the major difficulties that arises after valve replacement. This has been described by Davila, 2 Ellis, 3 Kay, 5 Kolff,6 Long,7 Starr, 11 Stuckey, 13 and Schimert.10 The clotting occurs, irrespec tive of design of the valves and the choice of material. The tendency of blood to clot when in contact with non-living surfaces constitutes an unsolved prob lem. Aside from acute thrombosis, as Ross and associates8 have emphasized, the fibrous replacement of excessive coagulum may compromise at a later date the flexibility of prosthetic leaflets or cusps. Therefore, prevention of clots is a crucial requirement in the development of artificial heart valves. Thrombosis is an early complication and has been noted to commence at the atrial suture line of the prosthesis (Pig. 1, A). The clots grow to occlude the mitral orifice and become a source of emboli. These complications, accord ing to Clark and Muller, 1 are responsible for a near 100 per cent mortality in dogs after mitral valve replacement. In humans, although clot formation seems to be delayed and less exuberant, Starr 12 insists that lifetime anticoagu lant therapy is necessary after insertion of a prosthetic mitral valve. Acute thrombosis also may proceed to organization. Scar tissue arising in the process of organization contracts and stiffens the valve leaflets. This eventually results in valvular deformities, with development of stenosis and/or insufficiency. The basic problem involves the deposition of platelets on vessel walls, in • general, and of course on plastic surfaces, specifically. Recently Sawyer and Pate 9 have suggested that bio-electrical phenomena, particularly changes in electrical potentials, are responsible for intravascular clotting. Both the formed elements of blood and the vessel wall have negative potentials. This negative charge maintains the repellent action between the platelets and the endothelium. Injury to vessel walls reverses this potential and attracts platelets, with con sequent precipitation of fibrin. Intercalation of plastic surfaces also results in a change of electrical potentials, and the recent introduction of "gold plated" valves may be interpreted as an effort to repel the agglomeration of thrombocytes. Ross and his group 8 have investigated thrombosis on plastic surfaces and
C
Prom the Department of Surgery, Buffalo General Hospital, and State University of New York at Buffalo, School of Medicine, Buffalo, N. Y. Supported in part by U. S. Public Health Grant No. H-6611, and the United Health Foundation. Received for publication April 26, 1963. 217
218
SCHIMERT AND FISHER
J. Thoracic and Cardiovas. Surg.
have concluded that the chemical nature of a surface is more important than the electrical charge or non-wettability. In construction of prosthetic valves, it is questionable whether solid, woven, or foamed plastics should be directly in contact with the blood. Probably these materials should be used as a strut or scaffold for viable tissues (Fig. 1, B). It is assumed that living cells will decrease platelet and fibrin deposition, thereby minimizing clotting tendency. In the present study a matrix is pre-invaded by the host's fibroblasts, prior to transference into the heart. The hexagonal net-like pattern of the matrix readily permits tissue ingrowth which forms an inseparable composite material. METHODS AND MATERIALS
Thrown mesh of 30 denier Dacron is used as matrix.* Similar material of heavier weight has been employed by Pirme and Adler 4 as a tissue reinforce ment in other areas of the body, particularly in hernia repair. Before implan tation, the mesh must be washed in Ivory soap to reduce surface impurities. The impurities give rise to violent foreign body reaction and can compromise the ingrowth of fibrous tissues. In a partial replacement, a 1 by 2 inch piece will suffice; for total replacement, a 2 by 2 inch piece will have to be used. The prosthetic valves are designed to duplicate some of the principal fea tures of the natural mitral valve. Thus, the prosthesis consists of two individual leaflets with chordae tendineae arising from their lower end. In total valve replacement, two equal-sized leaflets have been combined to replace the bicuspid valve. The final tailoring of the composite prosthesis is done after the heart has been opened, the original valve inspected, and the length of the natural ten dons has been measured. The experiment is performed in two stages, with the use of dogs weighing over 50 pounds. As a preliminary step, the matrix is grafted to the pre-thoracic fascia in the region of the left fifth rib. In order to prevent wrinkling, firm anchorage of the material is important. For this purpose only Dacron sutures should be used. In approximately 30 days, the matrix is covered with a thin, pliable, and semi-transparent layer of fibrous tissues. The composite material is now ready for transference into the heart. i Infection, foreign body reaction, or wrinkling may render the composite graft unsuitable for valve construction. Infection usually prevents tissue in growth, whereas granulations cause uneven distribution of the fibrous elements. In earlier experiments, the matrix was placed into the abdominal wall which resulted in a 25 per cent incidence of unsuitable graft. Since the matrix has been placed in the chest wall, failure to recover a suitable graft has dropped considerably. The second stage is timed 4 to 6 weeks after the implantation of the Dacron mesh. On the morning of surgery, the experimental animal receives 2 c.c. of penicillin with streptomycin. The anesthesia is maintained with 2.5 per cent of intravenous sodium Pentothal, given in small increments. After endotracheal • M o h a w k F a b r i c C o m p a n y , A m s t e r d a m , N e w York.
Vol. 47, No. 2 February, 1964
CLOT FORMATION ON P R O S T H E T I C VALVES
219
Fig. 1.—A, Dacron leaflet without fibrous tissue invasion. Exuberant thrombus which covers the entire atrial suture line is evident. B, Leaflet previously invaded with fibrous tissues. No evidence of thrombosis. The covering tissues are thin, pliable, and transparent.
intubation, the animal is placed on a positive pressure respirator. The com posite graft is recovered during the thoracotomy and is trimmed of excessive fibrous tissues. The prospective valve is placed in a saline penicillin solution, while the experimental animal is being connected to the pump oxygenator. Blood clotting is suppressed by 2 mg. of heparin per kilogram of body weight. The venous return is drained through a catheter in the right atrium. The arterial blood is returned through the left femoral artery. Blood pressures during and after the bypass are monitored by a mercury manometer connected to the right femoral artery through an Intracath. I n some cases, the electro cardiogram is followed on a cardioscope and the animal is wired for external defibrillation prior to the thoracotomy. Extracorporeal circulation is maintained either by the Mayo-Gibbon or the Kay-Cross pump oxygenator, Hemodilution is used routinely, with the sub-
220
SCHIMEET AND FISHER
J. Thoracic and Cardiovas. Surg.
stitution of one fourth to one third of the priming volume with 5 per cent glucose in distilled water. Bloodflows of 1.5 to 2 L. per square meter of body surface are combined with hypothermia with a range between 30° and 32° C. The tem perature is controlled by the Brown-Harrison heat exchanger. During the cardiopulmonary bypass the pulmonary artery is cross-clamped. The left atrium is opened anterior to the fold of Marshall. A sucker is placed through the mitral valve into the left ventricle and the length of the two principal chordae tendineae that hold the aortic leaflet is measured. At the same time, the distance between the tip of the individual papillary muscle and the mitral ring is ascertained as well as estimation of the circumference of the mitral ring. These parameters influence the final tailoring of the pros thetic valve. The aortic leaflet or the entire mitral valve is now excised, with a small cuff left to facilitate the placement of the sutures during the insertion of the prosthesis.
*\ •:-.**
Fig. 2.—Prosthetic leaflet with four chordae tendineae. Autopsy specimen 3 months after inser tion. The condition of the composite graft is excellent.
After the mitral valve has been removed, the papillary muscles are readily accessible for the placement of transfixing sutures to be used for the anchorage of the prosthetic chordae tendineae. These stitches are placed into the heavy aggregates of collagen tissues forming the insertion of the natural tendons. The authors are using 4-0 Dacron for this purpose, and the sutures are twice looped into the same connective tissue patch. Injury to the muscular portion should be avoided since varying degrees of A-V block can develop in conse quence of trauma to the papillary structures. The prosthesis is now ready for the final tailoring and orientation into the mitral ring. The tendons should have approximately the same length as the distance from the papillary muscle to the level of the mitral ring. Consider ing the 25 degree inclination of the mitral orifice, which is normally compen sated by the asymmetry of the leaflets, the correct length of the chordae
Vol. 47, No. 2
CLOT FORMATION ON P R O S T H E T I C VALVES
February, 1964
221 ^-
L
tendineae is of paramount importance. Bach prosthetic leaflet has four tendons which are inserted into the corresponding papillary muscle. The lateral tendons are anchored to the summit of the papillary muscles while the central tendons are fixed to more medial and inferior tendineous insertions. The landmarks are quite distinct if one has familiarized himself with the insertions of the principal chordae tendineae. The size of the leaflet itself corresponds to the measurements which have been obtained prior to the excision of the original valve. The general pattern of these leaflets has been described previously by one of the authors. 10 Fig. 2 shows a representative size of a prosthetic leaflet with its four tendons. This valve is 3 months old and the appearance of the composite graft is excellent. The prosthesis is sutured to the valve ring by closely spaced running stitches of 5-0 Dacron. The technique should be accurate as in vessel anastomosis. It is important not to traumatize the atrial endocardium, since the site of injury may serve as additional nidus for thrombus formation. Finally the tendons are anchored to the papillary muscles with the use of the previously placed sutures. The left atrium is closed by a double row of 5-0 Dacron. During the closure, a small catheter is placed into the left ventricle to prevent air embolus. This catheter is retrieved immediately after all the air has been removed. The bypass is now terminated. During the valve replacement, the heart is not routinely arrested since contractions are helpful to judge the length of the artificial chordae tendineae. Usually cooling will decrease the heart rate, as well as the force of contractions, and will permit accurate surgery. If this is not sufficient, ventricular fibrillation can be induced by the Grass stimulator. Normal rhythm is easily re-established by defibrillation, provided satisfactory oxygenation of the myocardium is main tained. The authors are using a DC defibrillator* with previously affixed ex ternal electrodes. Voluntary muscle contractions are for all practical purposes imperceptible after a shock with direct current. The use of external electrodes obviates additional handling or trauma to the heart. Satisfactory functioning of the valve is evidenced by the proper emptying of the left atrium and consequent good forward flow. Dogs have small atria and any degree of stenosis or insufficiency is followed by rapid atrial distention. In such cases cardiac output is low and the blood pressure of the animal is not maintained. Significant valvular dysfunction appears incompatible with survival. Left atrial pressures may confirm these findings in a more sophisti cated manner. After the cardiopulmonary bypass has been terminated, the heparin is neutralized with equal parts of protamine. The chest is closed after a catheter has been left in the pleural space for negative suction drainage. RESULTS
Seventy-five experiments have been performed with utilization of satis factory composite grafts for replacement of the aortic leaflet. Thirty-five dogs 'American Optical Company, Buffalo, New York.
222
SCHIMERT AND FISHER
J. Thoracic and Cardiovas. Surg.
Fig. 3.—Left heart injection of contrast medium, 14 months after valve replacement. A, Systole, the valve is closed. The mitral valve is seen by its negative shadow. There is minimal insufficiency present. B, The mitral valve in diastole.
expired either on the operating table or within hours after termination of the ex periment. The autopsy revealed gross incompetence or stenosis of the valve. Forty animals have survived the immediate consequences of the valve replacement. Of this group, twenty-one lived 24 hours, four lived 48 hours, six lived 3 days, one lived 5, 7, 8 and 11 days, respectively. Five dogs survived more than 20 days and are now studied periodically. Two dogs have now lived more than one year after the operation. None of the living animals has received anticoagulant therapy. Dogs that succumbed within 48 to 72 hours had significant mitral incompetence, usually due to a tear in the suture line. The animals that died 7 to 12 days after the procedure had peripheral emboli which arose from a thrombus on the atrial suture line. Each of these animals had signs of massive infection. The follow-up of the long-term surviving animals revealed that each had
Vol. 47, No. 2 February, 1964
CLOT F O R M A T I O N OX P R O S T H E T I C V A L V E S
TABLE
NO. DOCS
35 21 4 6 1 1 1 1 5
[
993 °
I
NO. DAYS
Less than 1 day 1-2 2-3 3-4 4-5 7-8 8-9 11-12 20-430+
|
PER CENT SURVIVAL
47.0 28.0 5.0 8.0 1.0 1.0 1.0 1.0 7.0
moderate to minimal insufficiency as evidenced by left atrial pressures and angiocardiographic studies (Fig. 3). The insufficiency is not progressive and it is believed that with more experience in the proper placement of the pros thetic valve the incidence of postoperative incompetence will decrease. One ani mal has moderate pulmonary hypertension. SUMMARY
Pre-invasion of Dacron valves with the hosts' fibroblasts has markedly decreased the incidence of thrombo-embolic phenomena. No late embolism has been noted in animals that lived beyond 3 weeks. The fibrous tissue invaded valves, and chordae tendineae readily united with the hosts' mitral ring and papillary muscle within 3 weeks. There has been no instance of shrinkage, scarring, or dislocation of the valve as evidenced by increasing incompetence. The use of composite grafts deserves further evaluation and study for possible clinical application in mitral and aortic valve surgery. The possibility of com posite valves with endocardial coverage is now under study. REFERENCES
1. Clark, R. E., and Muller, W. H . : Experimental Prosthetic Replacement of the Mitral Valve, Surgical Forum, Clinical Congress, 1962. Vol. XI11, Chicago American Col lege of Surgeons, 1962. 2. Davila, T. C.: Considerations Pertinent to the Design and Construction of Prostheses in Prosthetic Valves for Cardiac Surgery, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 3-47. 3. Ellis, T. F., Jr., and Bulbulian, A. H . : Prosthetic Replacement of the Mitral Valve, Proc. Staff Meet. Mayo Clin. 3 3 : 532, 1958. 4. Firme, C. N., and Adler, R. H . : The Use of Pliable Synthetic Mesh for the Repair of Hernia and Tissue Defects, Surg., Gynec. & Obst. 108: 199-206, 1959. 5. Kay, E. B., Suzuki, A., Postigo, T., and Nogeuira, C.: Prosthetic Replacement of the Mitral Valve in Prosthetic Valves for Cardiac Surgery, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 402-418. 6. Kolff, W. T., Seidel, W., Akatsu, T., Mirkovitch, V., and Hindberg, T.: Studies of Thrombosis on Artificial H e a r t Valves in Prosthetic Valves for Cardiac Surgery, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 199-211. 7. Long, D. M., Jr., Gott, V. L., Sterns, L. V., Finsterbusch, W., Varco, R. L., and Lillehei, C. W . : Reconstruction and Replacement of the Mitral Valve With Plastic Prosthesis in Prosthetic Valves for Cardiac Surgery, Springfield, 111., Charles C Thomas, Pub lisher, pp. 385-401. 8. Ross, T., Jr., Greenfield, L. T., Bowman, R. L., and Morrow, A. G.: The Chemical Struc ture and Surface Properties of Certain Synthetic Polymers and Their Relationship to Thrombosis, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 212-223. 9. Sawyer, P . N., and Pate, T. W . : Bio-electric Phenomena as an Etiological Factor in Intravascular Thrombosis, Am. J . Physiol. 175: 103, 1953.
224
SCHIMERT AND FISHER
J. Thoracic and Cardiovas. Surg.
10. Schimert, G., Sellers, R. D., Lee, C. B., Bilgutay, A. M., and Lillehei, C. W . : Fabrication of Mitral Leaflets and Aortic Cusps From Silastic Rubber-Coated Teflon Felt, in Prosthetic Valves for Cardiac Surgery, Springfield, 111., Charles C Thomas, Publisher, 1961, pp. 368-384. 11. Starr, A.: Discussion m Prosthetic Valves for Surgery, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 319-328. 12. Starr, A., Griswold, H. E., Bristow, V. D., Meuashe, D., and Adrauny, L. A.: Late Re sults Following Mitral Replacement With the Starr-Edwards Prosthesis, Circulation 24: 946, 1961. 13. Stuckey, T. H., Newman, M. M., Berg, E., Goodman, S., and Dennis, C.: Design and Placement of Prosthetic Valves to F i t in the Mitral Ring of the Dog After Excision of the Leaflets, in Prosthetic Valves for Cardiac Surgery, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 266-276.
ON
PROSTHETIC MITRAL VALVES George Schimert, M.D., and F. Craig Fisher, M.D., Buffalo, N.
Y.
LOT formation on plastic surfaces is one of the major difficulties that arises after valve replacement. This has been described by Davila, 2 Ellis, 3 Kay, 5 Kolff,6 Long,7 Starr, 11 Stuckey, 13 and Schimert.10 The clotting occurs, irrespec tive of design of the valves and the choice of material. The tendency of blood to clot when in contact with non-living surfaces constitutes an unsolved prob lem. Aside from acute thrombosis, as Ross and associates8 have emphasized, the fibrous replacement of excessive coagulum may compromise at a later date the flexibility of prosthetic leaflets or cusps. Therefore, prevention of clots is a crucial requirement in the development of artificial heart valves. Thrombosis is an early complication and has been noted to commence at the atrial suture line of the prosthesis (Pig. 1, A). The clots grow to occlude the mitral orifice and become a source of emboli. These complications, accord ing to Clark and Muller, 1 are responsible for a near 100 per cent mortality in dogs after mitral valve replacement. In humans, although clot formation seems to be delayed and less exuberant, Starr 12 insists that lifetime anticoagu lant therapy is necessary after insertion of a prosthetic mitral valve. Acute thrombosis also may proceed to organization. Scar tissue arising in the process of organization contracts and stiffens the valve leaflets. This eventually results in valvular deformities, with development of stenosis and/or insufficiency. The basic problem involves the deposition of platelets on vessel walls, in • general, and of course on plastic surfaces, specifically. Recently Sawyer and Pate 9 have suggested that bio-electrical phenomena, particularly changes in electrical potentials, are responsible for intravascular clotting. Both the formed elements of blood and the vessel wall have negative potentials. This negative charge maintains the repellent action between the platelets and the endothelium. Injury to vessel walls reverses this potential and attracts platelets, with con sequent precipitation of fibrin. Intercalation of plastic surfaces also results in a change of electrical potentials, and the recent introduction of "gold plated" valves may be interpreted as an effort to repel the agglomeration of thrombocytes. Ross and his group 8 have investigated thrombosis on plastic surfaces and
C
Prom the Department of Surgery, Buffalo General Hospital, and State University of New York at Buffalo, School of Medicine, Buffalo, N. Y. Supported in part by U. S. Public Health Grant No. H-6611, and the United Health Foundation. Received for publication April 26, 1963. 217
218
SCHIMERT AND FISHER
J. Thoracic and Cardiovas. Surg.
have concluded that the chemical nature of a surface is more important than the electrical charge or non-wettability. In construction of prosthetic valves, it is questionable whether solid, woven, or foamed plastics should be directly in contact with the blood. Probably these materials should be used as a strut or scaffold for viable tissues (Fig. 1, B). It is assumed that living cells will decrease platelet and fibrin deposition, thereby minimizing clotting tendency. In the present study a matrix is pre-invaded by the host's fibroblasts, prior to transference into the heart. The hexagonal net-like pattern of the matrix readily permits tissue ingrowth which forms an inseparable composite material. METHODS AND MATERIALS
Thrown mesh of 30 denier Dacron is used as matrix.* Similar material of heavier weight has been employed by Pirme and Adler 4 as a tissue reinforce ment in other areas of the body, particularly in hernia repair. Before implan tation, the mesh must be washed in Ivory soap to reduce surface impurities. The impurities give rise to violent foreign body reaction and can compromise the ingrowth of fibrous tissues. In a partial replacement, a 1 by 2 inch piece will suffice; for total replacement, a 2 by 2 inch piece will have to be used. The prosthetic valves are designed to duplicate some of the principal fea tures of the natural mitral valve. Thus, the prosthesis consists of two individual leaflets with chordae tendineae arising from their lower end. In total valve replacement, two equal-sized leaflets have been combined to replace the bicuspid valve. The final tailoring of the composite prosthesis is done after the heart has been opened, the original valve inspected, and the length of the natural ten dons has been measured. The experiment is performed in two stages, with the use of dogs weighing over 50 pounds. As a preliminary step, the matrix is grafted to the pre-thoracic fascia in the region of the left fifth rib. In order to prevent wrinkling, firm anchorage of the material is important. For this purpose only Dacron sutures should be used. In approximately 30 days, the matrix is covered with a thin, pliable, and semi-transparent layer of fibrous tissues. The composite material is now ready for transference into the heart. i Infection, foreign body reaction, or wrinkling may render the composite graft unsuitable for valve construction. Infection usually prevents tissue in growth, whereas granulations cause uneven distribution of the fibrous elements. In earlier experiments, the matrix was placed into the abdominal wall which resulted in a 25 per cent incidence of unsuitable graft. Since the matrix has been placed in the chest wall, failure to recover a suitable graft has dropped considerably. The second stage is timed 4 to 6 weeks after the implantation of the Dacron mesh. On the morning of surgery, the experimental animal receives 2 c.c. of penicillin with streptomycin. The anesthesia is maintained with 2.5 per cent of intravenous sodium Pentothal, given in small increments. After endotracheal • M o h a w k F a b r i c C o m p a n y , A m s t e r d a m , N e w York.
Vol. 47, No. 2 February, 1964
CLOT FORMATION ON P R O S T H E T I C VALVES
219
Fig. 1.—A, Dacron leaflet without fibrous tissue invasion. Exuberant thrombus which covers the entire atrial suture line is evident. B, Leaflet previously invaded with fibrous tissues. No evidence of thrombosis. The covering tissues are thin, pliable, and transparent.
intubation, the animal is placed on a positive pressure respirator. The com posite graft is recovered during the thoracotomy and is trimmed of excessive fibrous tissues. The prospective valve is placed in a saline penicillin solution, while the experimental animal is being connected to the pump oxygenator. Blood clotting is suppressed by 2 mg. of heparin per kilogram of body weight. The venous return is drained through a catheter in the right atrium. The arterial blood is returned through the left femoral artery. Blood pressures during and after the bypass are monitored by a mercury manometer connected to the right femoral artery through an Intracath. I n some cases, the electro cardiogram is followed on a cardioscope and the animal is wired for external defibrillation prior to the thoracotomy. Extracorporeal circulation is maintained either by the Mayo-Gibbon or the Kay-Cross pump oxygenator, Hemodilution is used routinely, with the sub-
220
SCHIMEET AND FISHER
J. Thoracic and Cardiovas. Surg.
stitution of one fourth to one third of the priming volume with 5 per cent glucose in distilled water. Bloodflows of 1.5 to 2 L. per square meter of body surface are combined with hypothermia with a range between 30° and 32° C. The tem perature is controlled by the Brown-Harrison heat exchanger. During the cardiopulmonary bypass the pulmonary artery is cross-clamped. The left atrium is opened anterior to the fold of Marshall. A sucker is placed through the mitral valve into the left ventricle and the length of the two principal chordae tendineae that hold the aortic leaflet is measured. At the same time, the distance between the tip of the individual papillary muscle and the mitral ring is ascertained as well as estimation of the circumference of the mitral ring. These parameters influence the final tailoring of the pros thetic valve. The aortic leaflet or the entire mitral valve is now excised, with a small cuff left to facilitate the placement of the sutures during the insertion of the prosthesis.
*\ •:-.**
Fig. 2.—Prosthetic leaflet with four chordae tendineae. Autopsy specimen 3 months after inser tion. The condition of the composite graft is excellent.
After the mitral valve has been removed, the papillary muscles are readily accessible for the placement of transfixing sutures to be used for the anchorage of the prosthetic chordae tendineae. These stitches are placed into the heavy aggregates of collagen tissues forming the insertion of the natural tendons. The authors are using 4-0 Dacron for this purpose, and the sutures are twice looped into the same connective tissue patch. Injury to the muscular portion should be avoided since varying degrees of A-V block can develop in conse quence of trauma to the papillary structures. The prosthesis is now ready for the final tailoring and orientation into the mitral ring. The tendons should have approximately the same length as the distance from the papillary muscle to the level of the mitral ring. Consider ing the 25 degree inclination of the mitral orifice, which is normally compen sated by the asymmetry of the leaflets, the correct length of the chordae
Vol. 47, No. 2
CLOT FORMATION ON P R O S T H E T I C VALVES
February, 1964
221 ^-
L
tendineae is of paramount importance. Bach prosthetic leaflet has four tendons which are inserted into the corresponding papillary muscle. The lateral tendons are anchored to the summit of the papillary muscles while the central tendons are fixed to more medial and inferior tendineous insertions. The landmarks are quite distinct if one has familiarized himself with the insertions of the principal chordae tendineae. The size of the leaflet itself corresponds to the measurements which have been obtained prior to the excision of the original valve. The general pattern of these leaflets has been described previously by one of the authors. 10 Fig. 2 shows a representative size of a prosthetic leaflet with its four tendons. This valve is 3 months old and the appearance of the composite graft is excellent. The prosthesis is sutured to the valve ring by closely spaced running stitches of 5-0 Dacron. The technique should be accurate as in vessel anastomosis. It is important not to traumatize the atrial endocardium, since the site of injury may serve as additional nidus for thrombus formation. Finally the tendons are anchored to the papillary muscles with the use of the previously placed sutures. The left atrium is closed by a double row of 5-0 Dacron. During the closure, a small catheter is placed into the left ventricle to prevent air embolus. This catheter is retrieved immediately after all the air has been removed. The bypass is now terminated. During the valve replacement, the heart is not routinely arrested since contractions are helpful to judge the length of the artificial chordae tendineae. Usually cooling will decrease the heart rate, as well as the force of contractions, and will permit accurate surgery. If this is not sufficient, ventricular fibrillation can be induced by the Grass stimulator. Normal rhythm is easily re-established by defibrillation, provided satisfactory oxygenation of the myocardium is main tained. The authors are using a DC defibrillator* with previously affixed ex ternal electrodes. Voluntary muscle contractions are for all practical purposes imperceptible after a shock with direct current. The use of external electrodes obviates additional handling or trauma to the heart. Satisfactory functioning of the valve is evidenced by the proper emptying of the left atrium and consequent good forward flow. Dogs have small atria and any degree of stenosis or insufficiency is followed by rapid atrial distention. In such cases cardiac output is low and the blood pressure of the animal is not maintained. Significant valvular dysfunction appears incompatible with survival. Left atrial pressures may confirm these findings in a more sophisti cated manner. After the cardiopulmonary bypass has been terminated, the heparin is neutralized with equal parts of protamine. The chest is closed after a catheter has been left in the pleural space for negative suction drainage. RESULTS
Seventy-five experiments have been performed with utilization of satis factory composite grafts for replacement of the aortic leaflet. Thirty-five dogs 'American Optical Company, Buffalo, New York.
222
SCHIMERT AND FISHER
J. Thoracic and Cardiovas. Surg.
Fig. 3.—Left heart injection of contrast medium, 14 months after valve replacement. A, Systole, the valve is closed. The mitral valve is seen by its negative shadow. There is minimal insufficiency present. B, The mitral valve in diastole.
expired either on the operating table or within hours after termination of the ex periment. The autopsy revealed gross incompetence or stenosis of the valve. Forty animals have survived the immediate consequences of the valve replacement. Of this group, twenty-one lived 24 hours, four lived 48 hours, six lived 3 days, one lived 5, 7, 8 and 11 days, respectively. Five dogs survived more than 20 days and are now studied periodically. Two dogs have now lived more than one year after the operation. None of the living animals has received anticoagulant therapy. Dogs that succumbed within 48 to 72 hours had significant mitral incompetence, usually due to a tear in the suture line. The animals that died 7 to 12 days after the procedure had peripheral emboli which arose from a thrombus on the atrial suture line. Each of these animals had signs of massive infection. The follow-up of the long-term surviving animals revealed that each had
Vol. 47, No. 2 February, 1964
CLOT F O R M A T I O N OX P R O S T H E T I C V A L V E S
TABLE
NO. DOCS
35 21 4 6 1 1 1 1 5
[
993 °
I
NO. DAYS
Less than 1 day 1-2 2-3 3-4 4-5 7-8 8-9 11-12 20-430+
|
PER CENT SURVIVAL
47.0 28.0 5.0 8.0 1.0 1.0 1.0 1.0 7.0
moderate to minimal insufficiency as evidenced by left atrial pressures and angiocardiographic studies (Fig. 3). The insufficiency is not progressive and it is believed that with more experience in the proper placement of the pros thetic valve the incidence of postoperative incompetence will decrease. One ani mal has moderate pulmonary hypertension. SUMMARY
Pre-invasion of Dacron valves with the hosts' fibroblasts has markedly decreased the incidence of thrombo-embolic phenomena. No late embolism has been noted in animals that lived beyond 3 weeks. The fibrous tissue invaded valves, and chordae tendineae readily united with the hosts' mitral ring and papillary muscle within 3 weeks. There has been no instance of shrinkage, scarring, or dislocation of the valve as evidenced by increasing incompetence. The use of composite grafts deserves further evaluation and study for possible clinical application in mitral and aortic valve surgery. The possibility of com posite valves with endocardial coverage is now under study. REFERENCES
1. Clark, R. E., and Muller, W. H . : Experimental Prosthetic Replacement of the Mitral Valve, Surgical Forum, Clinical Congress, 1962. Vol. XI11, Chicago American Col lege of Surgeons, 1962. 2. Davila, T. C.: Considerations Pertinent to the Design and Construction of Prostheses in Prosthetic Valves for Cardiac Surgery, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 3-47. 3. Ellis, T. F., Jr., and Bulbulian, A. H . : Prosthetic Replacement of the Mitral Valve, Proc. Staff Meet. Mayo Clin. 3 3 : 532, 1958. 4. Firme, C. N., and Adler, R. H . : The Use of Pliable Synthetic Mesh for the Repair of Hernia and Tissue Defects, Surg., Gynec. & Obst. 108: 199-206, 1959. 5. Kay, E. B., Suzuki, A., Postigo, T., and Nogeuira, C.: Prosthetic Replacement of the Mitral Valve in Prosthetic Valves for Cardiac Surgery, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 402-418. 6. Kolff, W. T., Seidel, W., Akatsu, T., Mirkovitch, V., and Hindberg, T.: Studies of Thrombosis on Artificial H e a r t Valves in Prosthetic Valves for Cardiac Surgery, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 199-211. 7. Long, D. M., Jr., Gott, V. L., Sterns, L. V., Finsterbusch, W., Varco, R. L., and Lillehei, C. W . : Reconstruction and Replacement of the Mitral Valve With Plastic Prosthesis in Prosthetic Valves for Cardiac Surgery, Springfield, 111., Charles C Thomas, Pub lisher, pp. 385-401. 8. Ross, T., Jr., Greenfield, L. T., Bowman, R. L., and Morrow, A. G.: The Chemical Struc ture and Surface Properties of Certain Synthetic Polymers and Their Relationship to Thrombosis, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 212-223. 9. Sawyer, P . N., and Pate, T. W . : Bio-electric Phenomena as an Etiological Factor in Intravascular Thrombosis, Am. J . Physiol. 175: 103, 1953.
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10. Schimert, G., Sellers, R. D., Lee, C. B., Bilgutay, A. M., and Lillehei, C. W . : Fabrication of Mitral Leaflets and Aortic Cusps From Silastic Rubber-Coated Teflon Felt, in Prosthetic Valves for Cardiac Surgery, Springfield, 111., Charles C Thomas, Publisher, 1961, pp. 368-384. 11. Starr, A.: Discussion m Prosthetic Valves for Surgery, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 319-328. 12. Starr, A., Griswold, H. E., Bristow, V. D., Meuashe, D., and Adrauny, L. A.: Late Re sults Following Mitral Replacement With the Starr-Edwards Prosthesis, Circulation 24: 946, 1961. 13. Stuckey, T. H., Newman, M. M., Berg, E., Goodman, S., and Dennis, C.: Design and Placement of Prosthetic Valves to F i t in the Mitral Ring of the Dog After Excision of the Leaflets, in Prosthetic Valves for Cardiac Surgery, Springfield, 111., 1961, Charles C Thomas, Publisher, pp. 266-276.