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THE GRADUAL CLOSURE OF AORTOPULMONARY SEPTAL DEFECTS
THE G R A D U A L CLOSURE OF A O R T O P U L M O N A R Y SEPTAL DEFECTS Robert L. Rets, M.D., William A. Gay, Jr., M.D., Nina S. Braunwald, M.D., and Andrew G. Morrow, M.D., Betbesda,
Aid.
I N patients with congenital aortopulmonary septal defects, the communication * between the aorta and pulmonary artery is always large and usually results in a substantial left-to-right shunt, a significant elevation of pulmonary arterial pressure, but little elevation of total pulmonary vascular resistance. In such pa tients, the pulmonary artery pressure promptly returns to normal or near nor mal levels when the defect is closed and a gratifying clinical and hemodynamic result can be expected. 1 In other patients, however, there is high pulmonary vascular resistance and the circulatory shunt is balanced and bidirectional. Under these circumstances, sudden and complete closure of the defect is poorly tolerated, since the pressure in the right ventricle remains extremely high, and death may result from acute right heart failure in the early postoperative period. Similar hemodynamic circumstances exist postoperatively in certain patients with atrial septal defect and pulmonary hypertension, and, in them, gradual closure of the defect by means of a perforated prosthesis has been shown to be beneficial.2 The time and manner of closure of perforated prostheses in the atrial septum has been established in both man and experimental animals, 2 ' 3 but there have been no data concerning the fate of such a prosthesis placed in an opening between the aorta and pulmonary artery, where flow and pressure are high rather than low. I n the present study, Teflon fabric patches with perforations of varying size and number were utilized to close aortopulmonary septal defects created experimentally in calves. METHODS
Holstein calves, weighing 35 to 69 kilograms, were employed. Anesthesia was induced with ether and maintained with oxygen and halothane. A com plete median sternotomy was made and the ductus arteriosus, which is frequently patent in young calves, was ligated (Fig. 1). The aorta, brachiocephalic artery, and main pulmonary artery were dissected free. Heparin (2.5 mg. per kilogram) was given intravenously and the venae cavae, femoral artery, and internal mamFrom the Clinic of Surgery, National Heart Institute, Bethesda, Md. Received for publication Jan. 8, 1965. §55
956
REIS ET AL.
J. Thoracic and Cardiovas. Surg.
Fig". 1.—Experimental method utilized for the creation and closure of aortopulmonary septal defects in calves. After median stemotomy, the ductus is divided and the venae cavae, femoral artery, and internal mammary artery are cannulated.
mary artery were cannulated. Cardiopulmonary bypass was then instituted with a disposable bubble oxygenator primed with 5 per cent glucose and low molecular weight dextran. Venous blood was drained from the venae cavae and arterialized blood was returned to both the femoral and internal mammary arteries. General hypothermia (30° C.) was induced with a Brown-Harrison heat exchanger in the extracorporeal circuit. A curved vascular clamp was then placed on the side of the ascending aorta, excluding a portion of the aortic wall at its junc tion with the brachiocephalic artery (Fig. 2). The aorta was not totally oc cluded, however, which permitted uninterrupted coronary perfusion. The brachiocephalic artery was occluded distally and perfusion of the upper por tion of the body was maintained through the internal mammary artery cannula. The main pulmonary artery was occluded at its bifurcation, and a longitudinal arteriotomy was made in its anterior wall. Using a cork borer, circular defects, measuring 1.3 cm. in diameter, were then created in the posteromedial wall of the main pulmonary artery, just above the pulmonic annulus, and in the aorta at its junction with the brachiocephalic artery. The margins of the two defects
AORTOPULMONARY SEPTAL DEFECTS
957
Fig. 2.—After institution of cardiopulmonary bypass, the great vessels are occluded as shown and the main pulmonary artery is opened vertically. With a cork borer, circular defects, 1.3 cm. in diameter, are created in the posterior wall of the pulmonary artery and the anterior wall of the aorta.
were apposed with 12 interrupted, horizontal, mattress sutures which terminated within the pulmonary artery (Fig. 3). The sutures were then passed through the edges of a knitted Teflon fabric patch, 2 cm. in diameter, in which single or multiple central perforations had been made with a punch (Pig. 4). The in cision in the pulmonary artery was closed and bypass discontinued. Postoperatively, the presence of a left-to-right shunt through the prosthesis was confirmed by the presence of a continuous thrill, and by indicator-dilution curves recorded immediately after operation and at intervals in the postopera tive period. Digoxin, 0.03 mg. per kilogram, was administered in divided doses on the day of operation and the animals were given penicillin, streptomycin, and digoxin for 10 days postoperatively. The calves were sacrificed when a nor mal indicator-dilution curve was apparent, and gross and microscopic examina tions of the prosthesis in the aortopulmonary septal defect were carried out. RESULTS
Twenty-five calves survived operation and chronic observations were made in 16 of them. Nine calves died at various intervals in the early postoperative period. At 24 hours, the Teflon fabric was covered with a thin layer of fibrin,
Fig. 3.—The margins of the two defects are apposed by mattress sutures which terminate within the pulmonary artery.
Fig. 4.—After the sutures have been placed, they are passed through the margins of a knitted Teflon patch (above); approximation of the vessels and closure of the defect Is accom plished by tying the sutures within the pulmonary artery (below).
Vol. 49, No. C June, 1965
AORTOPULMONARY SEPTAL DEFECTS
959
.„_ F l £ - 5.—Microscopic appearance of an experimental aortopulmonary septal defect closed with a prosthesis containing a single 3 mm. perforation. Both sides of the Teflon fabric (T) are covered with fibrous tissue which extends around the perimeter of the perforation. Final closure resulted from the formation of a central thrombus plug, indicated by the arrow. PA and AO indicate the walls of the pulmonary artery and aorta, respectively. (X8.6.)
• ^ F ) f J-—Higher magnification of the area outlined in Fig. 5. The edge of the perforation in the Teflon fabric is seen to the left; on the right are the layers of flbrous tissue around the perimeter of perforation. (X87.)
960
EEIS ET
AL.
J. Thoracic and Cardiovas. Surg.
but the perforations were entirely open. Subsequently, the fibrin became or ganized, invaded by fibroblasts, and fixed in position. Additional fibrin was then deposited around the perimeter of the opening, this was progressively replaced by fibrous tissue, and the size of the orifice gradually decreased. Final closure, when the perforation was not too large, was usually effected by the formation of a central thrombus plug. The microscopic appearance of a closed perforation is shown in Pigs. 5 and 6. Six prostheses contained single 2 mm. perforations, and all closed com pletely in 23 to 41 days. Three prostheses contained multiple perforations, 1.5 mm. or 2 mm. in diameter; all of the 2 mm. perforations closed in 21 to 36 days, and the 1.5 mm. ones in 14 days. In six calves, patches with single 3 mm. per forations were used; three were completely closed at 30, 51, and 63 days, re spectively; in the remaining three, residual openings of 1.0 to 1.5 mm. in di ameter were found at sacrifice 29, 43, and 80 days postoperatively, although nor mal indicator-dilution curves had been recorded. One calf was sacrificed 6 months after the insertion of a prosthesis with a single 4 mm. perforation; the orifice was found to have decreased in size to 1.6 mm. DISCUSSION
Because of the significant anatomic and physiologic differences between atrial and aortopulmonary septal defects, it is not surprising that perforated prostheses between the aorta and pulmonary artery close at a different rate, and in a different manner, than those in the atrial septum. The pressure gradient between the atria and the velocity of flow through an interatrial communication are both low, and the shunt often takes place during only a portion of the cardiac cycle. A perforated prosthesis in this position closes by being bridged by strands of fibrin which are gradually replaced with fibrous tissue. Openings up to 8.1 mm. in the dog, and 6 mm. in man, close within 30 days. 2 ' 3 Flow be tween the aorta and pulmonary artery, however, is of high velocity and con tinues through diastole as well as systole. Here, closure of a perforation occurs more slowly and is effected by a repetitive sequence of fibrin deposition around the perimeter of the orifice, followed by fibroblastic ingrowth firmly attaching the rim of fibrin to the margins of the hole. Thus, in one calf, complete closure of a 4 mm. perforation had not occurred after 6 months, and 3 mm. ones were still patent for as long as 80 days. The residual shunt which might remain subsequent to incomplete closure of perforations of these larger sizes would probably be of little clinical significance, but complete closure can be assured by utilizing smaller ones. Since a prosthesis with multiple perforations closes in approximately the same time as a prosthesis containing a single opening of similar size, a shunt adequate to effect decompression of the pulmonary circula tion can be constructed without altering eventual time of closure. This technique of gradual closure of aortopulmonary septal defects has application in patients in whom the malformation is associated with marked elevation of the pulmonary vascular resistance and in whom the circulatory shunt is bidirectional. Preoperatively, the right-to-left shunt through the defect
Vol. 49, No. 6
AOKTOPULMONARY S E P T A L D E F E C T S
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serves to decompress the pulmonary artery and protects the right ventricle from acute elevations in pressure. Sudden and complete surgical closure of the defect deprives the heart of this protective mechanism in the early postoperative period, before regression of the pulmonary vascular changes has occurred, and when atelectasis, arrhythmia, and impaired myocardial function may further em barrass the right ventricle. The use of a perforated prosthesis allows the pro tective shunt to be maintained during this critical period. The principle of gradual closure may also be applicable in patients with patent ductus arteriosus. Since the anatomic and hemodynamic environment of the ductus does not differ significantly from that of an aortopulmonary septal defect, the experimental data obtained in the present study would seem to be applicable in this situation as well. Recent evidence indicates that substantial decreases in pulmonary vascular resistance are more likely to occur in patients following closure of extracardiac left-to-right shunts (patent ductus arteriosus and aortopulmonary septal defects) than those with intracardiac left-to-right shunts (atrial and ventricular septal defects). 4 This technique of gradual closure, therefore, may have its most beneficial application in patients with aortopul monary septal defect or patent ductus arteriosus. The methods described were recently applied in a 7-year-old girl with aorto pulmonary septal defect, equal systemic and pulmonary arterial pressures, and balanced right-to-left and left-to-right shunts. A Teflon patch, containing two 3 mm. perforations, was sutured into the defect through an incision in the ascending aorta. In the early postoperative period, a substantial right-to-left shunt through the perforations was evident by indicator-dilution curves and an arterial oxygen saturation of 68 per cent. Subsequently, the child has evidenced progressive symptomatic improvement, striking reduction in heart size, and the arterial oxygen saturation is 87 per cent, increasing to 97 per cent during oxy gen inhalation. Both left-to-right and right-to-left shunts are still evident, how ever, on indicator-dilution curves recorded 1 year postoperatively. Since the coagulation time in the calf is shorter than in man, closure times of perforated prostheses are probably longer in patients than those observed experimentally. On the basis of the present laboratory study, and the course of the patient de scribed, it would appear that, when a perforated prosthesis is to be used be tween the aorta and pulmonary artery in man, multiple perforations 1.5 or 2.0 mm. in diameter would be most suitable. SUMMARY
Perforated Teflon patches were used to repair aortopulmonary septal defects experimentally created in 25 calves. Single or multiple perforations 1.5 or 2 mm. in diameter completely closed in 14 to 41 days, while 3 or 4 mm. perforations were only partially closed at 2 to 6 months. Multiple perforations closed in approximately the same time as single ones of the same size. On the basis of these experimental data, and a consideration of the different coagulation mech anisms in calf and man, it is considered that a prosthesis with multiple per forations, 1.5 to 2.0 mm. in diameter, would be most suitable for the gradual
E E I S E T AL.
962
J. Thoracic and Cardiovas. Surg.
closure of an aortopulmonary septal defect or patent ductus arteriosus in a patient. The physiologic basis for the use of this technique, and an example of its clinical application, are presented. REFERENCES
1. Morrow, A. G., Greenfield, L. J., and Braunwald, E . : Congenital Aortopulmonary Septal Defect, Circulation 25: 463, 1962. 2. Braunwald, N . S., and Morrow, A. G.: The Delayed Closure of Atrial Septal Defects With Perforated Prosthesis, Surg., Gynec. & Obst. 116: 579, 1963. 3. Benjamin, E. B., Flom, R. S., McLean, L. D., and Lewis, F . J . : The Gradual Closure of Atrial Septal Defects, J . THORACIC & CARDIOVAS. SURG. 34: 679, 1957.
4. Braunwald, N . S., Braunwald, E., and Morrow, A. G.: The Effects of Surgical Abolition of Left-to-Eight Shunts on the Pulmonary Vascular Dynamics of Patients With Pulmonary Hypertension, Circulation 26: 1270, 1962.
Aid.
I N patients with congenital aortopulmonary septal defects, the communication * between the aorta and pulmonary artery is always large and usually results in a substantial left-to-right shunt, a significant elevation of pulmonary arterial pressure, but little elevation of total pulmonary vascular resistance. In such pa tients, the pulmonary artery pressure promptly returns to normal or near nor mal levels when the defect is closed and a gratifying clinical and hemodynamic result can be expected. 1 In other patients, however, there is high pulmonary vascular resistance and the circulatory shunt is balanced and bidirectional. Under these circumstances, sudden and complete closure of the defect is poorly tolerated, since the pressure in the right ventricle remains extremely high, and death may result from acute right heart failure in the early postoperative period. Similar hemodynamic circumstances exist postoperatively in certain patients with atrial septal defect and pulmonary hypertension, and, in them, gradual closure of the defect by means of a perforated prosthesis has been shown to be beneficial.2 The time and manner of closure of perforated prostheses in the atrial septum has been established in both man and experimental animals, 2 ' 3 but there have been no data concerning the fate of such a prosthesis placed in an opening between the aorta and pulmonary artery, where flow and pressure are high rather than low. I n the present study, Teflon fabric patches with perforations of varying size and number were utilized to close aortopulmonary septal defects created experimentally in calves. METHODS
Holstein calves, weighing 35 to 69 kilograms, were employed. Anesthesia was induced with ether and maintained with oxygen and halothane. A com plete median sternotomy was made and the ductus arteriosus, which is frequently patent in young calves, was ligated (Fig. 1). The aorta, brachiocephalic artery, and main pulmonary artery were dissected free. Heparin (2.5 mg. per kilogram) was given intravenously and the venae cavae, femoral artery, and internal mamFrom the Clinic of Surgery, National Heart Institute, Bethesda, Md. Received for publication Jan. 8, 1965. §55
956
REIS ET AL.
J. Thoracic and Cardiovas. Surg.
Fig". 1.—Experimental method utilized for the creation and closure of aortopulmonary septal defects in calves. After median stemotomy, the ductus is divided and the venae cavae, femoral artery, and internal mammary artery are cannulated.
mary artery were cannulated. Cardiopulmonary bypass was then instituted with a disposable bubble oxygenator primed with 5 per cent glucose and low molecular weight dextran. Venous blood was drained from the venae cavae and arterialized blood was returned to both the femoral and internal mammary arteries. General hypothermia (30° C.) was induced with a Brown-Harrison heat exchanger in the extracorporeal circuit. A curved vascular clamp was then placed on the side of the ascending aorta, excluding a portion of the aortic wall at its junc tion with the brachiocephalic artery (Fig. 2). The aorta was not totally oc cluded, however, which permitted uninterrupted coronary perfusion. The brachiocephalic artery was occluded distally and perfusion of the upper por tion of the body was maintained through the internal mammary artery cannula. The main pulmonary artery was occluded at its bifurcation, and a longitudinal arteriotomy was made in its anterior wall. Using a cork borer, circular defects, measuring 1.3 cm. in diameter, were then created in the posteromedial wall of the main pulmonary artery, just above the pulmonic annulus, and in the aorta at its junction with the brachiocephalic artery. The margins of the two defects
AORTOPULMONARY SEPTAL DEFECTS
957
Fig. 2.—After institution of cardiopulmonary bypass, the great vessels are occluded as shown and the main pulmonary artery is opened vertically. With a cork borer, circular defects, 1.3 cm. in diameter, are created in the posterior wall of the pulmonary artery and the anterior wall of the aorta.
were apposed with 12 interrupted, horizontal, mattress sutures which terminated within the pulmonary artery (Fig. 3). The sutures were then passed through the edges of a knitted Teflon fabric patch, 2 cm. in diameter, in which single or multiple central perforations had been made with a punch (Pig. 4). The in cision in the pulmonary artery was closed and bypass discontinued. Postoperatively, the presence of a left-to-right shunt through the prosthesis was confirmed by the presence of a continuous thrill, and by indicator-dilution curves recorded immediately after operation and at intervals in the postopera tive period. Digoxin, 0.03 mg. per kilogram, was administered in divided doses on the day of operation and the animals were given penicillin, streptomycin, and digoxin for 10 days postoperatively. The calves were sacrificed when a nor mal indicator-dilution curve was apparent, and gross and microscopic examina tions of the prosthesis in the aortopulmonary septal defect were carried out. RESULTS
Twenty-five calves survived operation and chronic observations were made in 16 of them. Nine calves died at various intervals in the early postoperative period. At 24 hours, the Teflon fabric was covered with a thin layer of fibrin,
Fig. 3.—The margins of the two defects are apposed by mattress sutures which terminate within the pulmonary artery.
Fig. 4.—After the sutures have been placed, they are passed through the margins of a knitted Teflon patch (above); approximation of the vessels and closure of the defect Is accom plished by tying the sutures within the pulmonary artery (below).
Vol. 49, No. C June, 1965
AORTOPULMONARY SEPTAL DEFECTS
959
.„_ F l £ - 5.—Microscopic appearance of an experimental aortopulmonary septal defect closed with a prosthesis containing a single 3 mm. perforation. Both sides of the Teflon fabric (T) are covered with fibrous tissue which extends around the perimeter of the perforation. Final closure resulted from the formation of a central thrombus plug, indicated by the arrow. PA and AO indicate the walls of the pulmonary artery and aorta, respectively. (X8.6.)
• ^ F ) f J-—Higher magnification of the area outlined in Fig. 5. The edge of the perforation in the Teflon fabric is seen to the left; on the right are the layers of flbrous tissue around the perimeter of perforation. (X87.)
960
EEIS ET
AL.
J. Thoracic and Cardiovas. Surg.
but the perforations were entirely open. Subsequently, the fibrin became or ganized, invaded by fibroblasts, and fixed in position. Additional fibrin was then deposited around the perimeter of the opening, this was progressively replaced by fibrous tissue, and the size of the orifice gradually decreased. Final closure, when the perforation was not too large, was usually effected by the formation of a central thrombus plug. The microscopic appearance of a closed perforation is shown in Pigs. 5 and 6. Six prostheses contained single 2 mm. perforations, and all closed com pletely in 23 to 41 days. Three prostheses contained multiple perforations, 1.5 mm. or 2 mm. in diameter; all of the 2 mm. perforations closed in 21 to 36 days, and the 1.5 mm. ones in 14 days. In six calves, patches with single 3 mm. per forations were used; three were completely closed at 30, 51, and 63 days, re spectively; in the remaining three, residual openings of 1.0 to 1.5 mm. in di ameter were found at sacrifice 29, 43, and 80 days postoperatively, although nor mal indicator-dilution curves had been recorded. One calf was sacrificed 6 months after the insertion of a prosthesis with a single 4 mm. perforation; the orifice was found to have decreased in size to 1.6 mm. DISCUSSION
Because of the significant anatomic and physiologic differences between atrial and aortopulmonary septal defects, it is not surprising that perforated prostheses between the aorta and pulmonary artery close at a different rate, and in a different manner, than those in the atrial septum. The pressure gradient between the atria and the velocity of flow through an interatrial communication are both low, and the shunt often takes place during only a portion of the cardiac cycle. A perforated prosthesis in this position closes by being bridged by strands of fibrin which are gradually replaced with fibrous tissue. Openings up to 8.1 mm. in the dog, and 6 mm. in man, close within 30 days. 2 ' 3 Flow be tween the aorta and pulmonary artery, however, is of high velocity and con tinues through diastole as well as systole. Here, closure of a perforation occurs more slowly and is effected by a repetitive sequence of fibrin deposition around the perimeter of the orifice, followed by fibroblastic ingrowth firmly attaching the rim of fibrin to the margins of the hole. Thus, in one calf, complete closure of a 4 mm. perforation had not occurred after 6 months, and 3 mm. ones were still patent for as long as 80 days. The residual shunt which might remain subsequent to incomplete closure of perforations of these larger sizes would probably be of little clinical significance, but complete closure can be assured by utilizing smaller ones. Since a prosthesis with multiple perforations closes in approximately the same time as a prosthesis containing a single opening of similar size, a shunt adequate to effect decompression of the pulmonary circula tion can be constructed without altering eventual time of closure. This technique of gradual closure of aortopulmonary septal defects has application in patients in whom the malformation is associated with marked elevation of the pulmonary vascular resistance and in whom the circulatory shunt is bidirectional. Preoperatively, the right-to-left shunt through the defect
Vol. 49, No. 6
AOKTOPULMONARY S E P T A L D E F E C T S
Ofil
serves to decompress the pulmonary artery and protects the right ventricle from acute elevations in pressure. Sudden and complete surgical closure of the defect deprives the heart of this protective mechanism in the early postoperative period, before regression of the pulmonary vascular changes has occurred, and when atelectasis, arrhythmia, and impaired myocardial function may further em barrass the right ventricle. The use of a perforated prosthesis allows the pro tective shunt to be maintained during this critical period. The principle of gradual closure may also be applicable in patients with patent ductus arteriosus. Since the anatomic and hemodynamic environment of the ductus does not differ significantly from that of an aortopulmonary septal defect, the experimental data obtained in the present study would seem to be applicable in this situation as well. Recent evidence indicates that substantial decreases in pulmonary vascular resistance are more likely to occur in patients following closure of extracardiac left-to-right shunts (patent ductus arteriosus and aortopulmonary septal defects) than those with intracardiac left-to-right shunts (atrial and ventricular septal defects). 4 This technique of gradual closure, therefore, may have its most beneficial application in patients with aortopul monary septal defect or patent ductus arteriosus. The methods described were recently applied in a 7-year-old girl with aorto pulmonary septal defect, equal systemic and pulmonary arterial pressures, and balanced right-to-left and left-to-right shunts. A Teflon patch, containing two 3 mm. perforations, was sutured into the defect through an incision in the ascending aorta. In the early postoperative period, a substantial right-to-left shunt through the perforations was evident by indicator-dilution curves and an arterial oxygen saturation of 68 per cent. Subsequently, the child has evidenced progressive symptomatic improvement, striking reduction in heart size, and the arterial oxygen saturation is 87 per cent, increasing to 97 per cent during oxy gen inhalation. Both left-to-right and right-to-left shunts are still evident, how ever, on indicator-dilution curves recorded 1 year postoperatively. Since the coagulation time in the calf is shorter than in man, closure times of perforated prostheses are probably longer in patients than those observed experimentally. On the basis of the present laboratory study, and the course of the patient de scribed, it would appear that, when a perforated prosthesis is to be used be tween the aorta and pulmonary artery in man, multiple perforations 1.5 or 2.0 mm. in diameter would be most suitable. SUMMARY
Perforated Teflon patches were used to repair aortopulmonary septal defects experimentally created in 25 calves. Single or multiple perforations 1.5 or 2 mm. in diameter completely closed in 14 to 41 days, while 3 or 4 mm. perforations were only partially closed at 2 to 6 months. Multiple perforations closed in approximately the same time as single ones of the same size. On the basis of these experimental data, and a consideration of the different coagulation mech anisms in calf and man, it is considered that a prosthesis with multiple per forations, 1.5 to 2.0 mm. in diameter, would be most suitable for the gradual
E E I S E T AL.
962
J. Thoracic and Cardiovas. Surg.
closure of an aortopulmonary septal defect or patent ductus arteriosus in a patient. The physiologic basis for the use of this technique, and an example of its clinical application, are presented. REFERENCES
1. Morrow, A. G., Greenfield, L. J., and Braunwald, E . : Congenital Aortopulmonary Septal Defect, Circulation 25: 463, 1962. 2. Braunwald, N . S., and Morrow, A. G.: The Delayed Closure of Atrial Septal Defects With Perforated Prosthesis, Surg., Gynec. & Obst. 116: 579, 1963. 3. Benjamin, E. B., Flom, R. S., McLean, L. D., and Lewis, F . J . : The Gradual Closure of Atrial Septal Defects, J . THORACIC & CARDIOVAS. SURG. 34: 679, 1957.
4. Braunwald, N . S., Braunwald, E., and Morrow, A. G.: The Effects of Surgical Abolition of Left-to-Eight Shunts on the Pulmonary Vascular Dynamics of Patients With Pulmonary Hypertension, Circulation 26: 1270, 1962.