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Complications associated with the use of heterologous bovine pericardium for pericardial closure
J
THORAC CARDIOVASC SURG
92:446-454, 1986
Brief communications Complications associated with the use of heterologous bovine pericardium for pericardial closure Stephen A. Mills, M.D., C.M., Winston-Salem, N. C. From the Section on Cardiothoracic Surgery, Department of Surgery, Wake ForestUniversity Medical Center, Bowman Gray School of Medicine, Winston-Salem, N. C. Two complicatiolti necessitating removal of bovine pericardium used as a pericardial patch graft in 60 patients are reported. These complicatiom, plus a few others reported in the literature, suggest that caution in the clinical use of bovine pericardium remains appropriate.
Complete closure of the pericardium after cardiac operations is generally accepted as being advantageous should repeat sternotomy prove to be necessary. However, pericardial closure is not always possible, because of a previous cardiac operation, use of an external conduit, use of pericardium to correct the cardiac defect, increased heart size after a cardiac procedure, or placement of aorta-coronary bypass grafts. For those situations, use of various pericardial substitutes, including fascia lata,' silicone rubber," rubber-coated Dacron' or polyester,' polytetrafluoroethylene (PTFE),2 as well as heterologous porcine," 7 equine," and bovines. 6 pericardium have been tried. The synthetic materials have produced severe scarring; the heterologous grafts appear to be satisfactory, especially experimentally, but a recent report of late clinical results suggests that they too cause a fibrous reaction that may complicate later reopera-
tion."
We have recently used bovine pericardium (PeriGuard, Genetic Laboratories, Inc., St. Paul, Minn.) in 60 patients. In two patients we encountered complications that we believe were related to the use of this material. In each, reoperation was required for the removal of the graft. Address for reprints: Stephen A. Mills, M.D., Section on Cardiothoracic Surgery, Bowman Gray School of Medicine, 300 S. Hawthorne Rd., Winston-Salem, N. C. 27103. .
446
Case reports. I. A 46-year-old woman underwent three-vessel coronary artery bypass grafting, with glutaraldehyde-prepared bovine pericardium being placed over the anterior aspect of the heart. The pericardial patch was rinsed and handled in accordance with the manufacturer's directions. The patient's postoperative course was uneventful. Cultures of pre-wash and post-wash fluid as well as the ethyl alcohol preservative were negative. Ten weeks after operation the patient returned with a 4 day history of midsternal soft tissue swelling. She was afebrile. She had a tender, 6 cm diameter area of subcutaneous swelling overlying the third to fifth costal cartilages to the left of the sternum. Chest roentgenograms and laboratory studies showed no abnormalities. Computed tomography (CT) of the chest (Fig. I) showed a 12 em long, cystic, tubular structure to the left of the sternum extending from the aortic arch to the diaphragm. Superiorly it lay anterior to the chest wall; it passed posteriorly through the chest wall just inferior to the aortic arch. It did not appear to involve the great vessels. With the patient under general anesthesia, the previous midline sternotomy scar overlying the mass was opened to show drainage of purulent material through a small opening in the intercostal muscles to the left of the sternum. Resection of a 3 em portion of costal cartilage unroofed a cavity corresponding to the lesion seen on CT scan. The previously placed bovine pericardium was rolled up within the cavity. The pericardium was removed and the cavity was irrigated and packed. Gram stain showed white blood cells but no organisms. Cultures (aerobic, anaerobic, acid-fast bacillus, and fungus) were negative. After 8 weeks of drainage, the cavity was closed without complication. CASE 2. A 54-year-old man underwent three-vessel coronary bypass, with ethanol-preserved bovine pericardium being placed over the anterior aspect of the heart before closure of the sternum. The pericardial patch was rinsed and handled in accordance with the manufacturer's recommendations. Cultures of the pre-wash and post-wash fluid as well as the ethanol preservative were negative. The patient's postoperative hemodynamic status was excellent, but on the second postoperative day his temperature rose to 102° F (38.9° C). Over the subsequent 5 days it spiked to 101° to 102.5° F (38.3° to 39.2° C) (Fig. 2); there was no other evidence suggesting systemic toxicity, and cultures of sputum, blood, and urine were negative. The incisions appeared satisfactory and the sternum remained stable. On the seventh postoperative day a CT scan of the chest demonstrated a fluid and gas collection in the anterior mediastinum, which was believed to be compatible with a diagnosis of mediastinitis. The mediastinum was reexplored through a subxiphoid incision, and 35 mI of old blood was removed. No gross CASE
Volume 92 Number 3, Part 1 September, 1986
Brief communications
447
Fig. 1. Computed tomographic view of chest showing a cystic, tubular structure to the left of the sternum (arrow). The structure was 12 em long and was located anterior to the chest wall passing posteriorly through the chest wall just inferior to the aortic arch.
Re-exploration
!
Aortocoronary bypass
102
~
101
OJ
100
C;;
!
E 98.699 1=:::s,:::'--:r--------.L.:....,~~--i_~......~.J-_+4--~p.+l/_~......, ...._Q)
I-
98
97 96 95 .L.-----.--.--------r--.--------r----.------,----r------.---r-----.--~-_ Hospital Days Post-op Day
2 OR
3
4
1
2
5 3
6
7
8
4
5
6
7
10
11
12
13
8/PO
9/1
10/2
11/3
Fig. 2. Temperature chart showing fever commencing on the second postoperative day and resolving with reexploration and removal of bovine pericardium on the eighth postoperative day.
evidence of infection was noted. The previously placed bovine' pericardium was easily removed and appeared clean. Gram staining of chest fluid showed no organisms. Cultures of fluid and pericardium were negative. After removal of the bovine pericardium the patient's temperature returned to normal (Fig. 2), and he was discharged home on the tenth postoperative day. Histologic examination of the bovine pericardium showed no evidence of rejection or infection. At 6 months' follow-up he remains asymptomatic.
Discussion, Pericardial patch materials have been studied experimentally for many years. In 1963, Youmans, White, and Derrick' evaluated a silicone rubber pericardial substitute in dogs after pericardial and epicardial dry sponge abrasion. Firm adhesions formed under remaining pericardium but not under the silicone rubber patch, although in one dog moderate thickening
and chronic inflammation developed under the patch. They then used a siliconerubber pericardial substitute in one patient with congenital absence of the left pericardium. In 1973 Bonnabeau, Armanious, and Tarnay' studied placement of a silicone rubber-coated Dacron patch in dogs, finding it reduced adhesions but tended to cause infections. In 1983 Meus and co-workers' evaluated six synthetic and two different bovine pericardium preparations in a dog model. Each material was histologically examined in dogs killed 3, 6, 9, and 12 months after implantation. They found both bovine preparations (glutaraldehydefixed, formaldehyde- and ethanol-preserved) to be excellent, lacking epicardial reaction and not obscuring underlying structures; minimal adhesions were easily
The Journal of Thoracic and Cardiovascular Surgery
4 4 8 Briefcommunications
dissected. In contrast, silicone-treated Dacron film and high-porosity PTFE film reduced adhesions but caused a severe epicardial reaction. It was suggested that bovine pericardium was the material of choice for use as a pericardial patch. Gallo and colleagues,' in 1978, evaluated glutaraldehyde-preserved porcine pericardium in 20 dogs reoperated on between 15 and 300 days. The majority of dogs had no adhesions between the graft and epicardium, but several animals had loose-to-dense adhesions in that area. Their experimental work led to the use of porcine pericardium in eight patients; none had undergone reoperation at the time of their report. In 1984 Frasca and colleagues" reported implanting glutaraldehyde-fixed grafts of bovine pericardium in the orthotopic position in 3- to 4-month-old sheep. Samples were harvested 1 to 3 weeks later for study by scanning electron microscopy and energy dispersive x-ray microanalysis. A pseudoneointima, or porous layer, consisting of a dense mesh of fibers interspersed with blood cells, could be seen on the blood-contacting surface of the graft. Calcium phosphate deposits were noted in discrete regions in the pseudoneointima and appeared to be associated with thrombi; mineralization in the pericardium was diffusely distributed within the collagen matrix. It is not known how frequently bovine pericardium is used clinically throughout the world, although Dietzman and associates? compiled a report in 1984 of its having been placed in 2,200 patients after cardiac procedures. They also reported the use of glutaraldehyde-fixed propylene oxide-ethanol-preserved bovine pericardium in 112 patients, one of whom underwent reoperation at 3 months and one of whom underwent reoperation at 4 months. In the former patient (and in one patient dying 3 months after operation and examined at autopsy) the epicardial architecture was preserved; in the latter patient there was epicardial fibrosis. Skinner and colleagues" found a dense epicardial reaction to processed bovine pericardium when reoperating 3 months later in a patient requiring repeat coronary revascularization. A thick coagulum on the epicardial surface made identification of surface structures difficult. Gallo, Artifiano, and Duran" reported on five of 87 patients with heterologous glutaraldehyde-preserved pericardial grafts (porcine, bovine, equine) who underwent reoperation with removal of the graft 1.5, 3, 4.5, 6, and 59 months after the initial operation. A space free of adhesions was noted between the graft and epicardium, whereas the remainder of the pericardial cavity present-
ed a typical fibrous reaction. No species differences were noted. Microscopically, it could be seen that the original structure of the graft was maintained and that there was no cellular infiltration; the removed epicardial layer facing the two grafts that had been in place for less than 3 months showed organized fibrinoid material with numerous fibroblastic cells; heavy collagen bundles with neovascularization were noted in the grafts that had been in place for 4.5, 6, and 59 months. The epicardial reaction greatly impeded the recognition of the anterior coronary vessels. They suggested that placing a pericardial incision to the right of the midline might keep the left anterior descending coronary artery covered by autogenous pericardium, and that fibrosis of the underlying right ventricular epicardial surface would be clinically unimportant in most cases. Discussing those findings, Spencer" warned that the value and safety of heterologous pericardium has not been well documented experimentally or clinically. Our complications, one a sterile abscess cavity and one a persistent high fever, both required removal of the graft for resolution. In view of these adverse reactions, coupled with the reports of Gallo.v? Dietzman," and Skinner" of a dense epicardial inflammatory reaction, caution regarding the clinical use of bovine pericardium remains appropriate. REFERENCES
2
3
4
5
6
7
8
Kohanna FH, Adams PX, Cunningham IN Jr, Spencer FC: Use of autologous fascia lata as a pericardial substitute following open-heart surgery. J THORAC CARDIOVASC SURG 74:14-19, 1977 Bonnabeau RC Jr, Armanious AW, Tarnay TJ: Partial replacement of pericardium with dura substitute. J THORAC CARDIOVASC SURG 66:196-201, 1973 Laks H, Hammond G, Geha AS: Use of silicone rubber as a pericardial substitute to facilitate reoperation in cardiac surgery. J THORAC CARDIOVASC SURG 82:88-92, 1981 Youmans CR Jr, White J, Derrick JR: The prevention of pleural and pericardial adhesions with Silastic. J THORAC CARDIOVASC SURG 55:383-388, 1968 Meus PJ, Wernly JA, Campbell CD, Takanashi Y, Pick RL, Qui Z-K, Replogle RL: Long-term evaluation of pericardial substitutes. J THORAC CARDIOVASC SURG 85:54-58, 1983 Gallo I, Artifiano E, Duran CG: Late clinical results with the use of heterologous pericardium for closure of the pericardial cavity. J THORAC CARDIOVASC SURG 89:709712, 1985 Gallo JI, Pomar JL, Artifiano E, Val F, Duran CMG: Heterologous pericardium for the closure of pericardial defects. Ann Thorac Surg 26: 149-154, 1978 Frasca P, Buchanan JW, Soriano RZ, Dunn JM, Marmon
Volume 92 Number 3, Part 1 September, 1986
L, Melbin J, Buchanan SJ, Chang SH, Golub EE, Shapiro 1M: Mineralization of short term pericardial cardiac patch grafts. Scan Electron Microsc 2:973-977, 1984 9 Dietzman RH, Holter AR, Lynch MF, Mindich BP, Ochsner JL: Protection of the heart during reoperation using a bovine pericardial shield. Clinical experience. Contemp Surg 24:35-39, 1984 10 Skinner JR, Kim H, Toon RS, Kongtahworn C, Phillips SJ, Zeff RH: Inflammatory epicardial reaction to processed bovine pericardium. Case report. J THORAC CARD10VASC SURG 88:789-791, 1984 11 Spencer FC: Discussion of Gallo et al"
Steroid-responsive bronchiolitis after human heart-lung transplantation M. D. Allen, M.D., C. M. Burke, M.B., M.R.C.P., C. G. A. McGregor, M.B., F.R.C.S., J. C. Baldwin, M.D., S. W. Jamieson, M.B., F.R.C.S., and 1. Theodore, M.D., Stanford. Calif. From Departments of Medicine and Cardiovascular Surgery, Stanford University Medical Center, Stanford, Calif. 94305. This report describes the clinical course of a patient who developedobliterative bronchiolitis after viral infection on three separate occasioes. Long-term follow-up is given. It is suggested that the syndrome of late pulmonary deterioration after traffiplantation may be steroid responsbe if treatment is initiated early in the natural history of the syndrome. In addition, it is suggested that increased emphasis should be placed on the documentation of viral infection in tramplant recipients to define a possible interaction between infection and rejection.
Late deterioration in pulmonary function, associated with physiologic evidence of air flow obstruction and pathologic evidence of bronchiolitis, is the most important complication in long-term survivors of heart-lung transplantation. To date, the precise pathophysiology and optimal treatment of this syndrome have not been fully determined. Case report. A 21-year-old man with advanced primary pulmonary hypertension underwent heart-lung transplantation on July 12, 1984. His postoperative hospital course was uncomplicated and he was discharged well on Aug. 10, 1984, on an immunosuppressive regimen of cyclosporine (to mainSupported by Grant H 13108 from the National.Heart, Lung, and Blood Institute. Address for reprints: Dr. C. M. Burke, Division of Respiratory Medicine, Stanford University Medical Center, Stanford, Calif. 94305.
Brief communications
449
tain serum blood levels of 100 to 150 ng/rnl) and prednisone (15 mg/day). Pulmonary function and gas exchange are documented in Table I and were essentially normal on postoperative day 52. Two months later he developed a cough productive of mucopurulent sputum without fever or dyspnea. On examination he was found to have coarse bibasilar rales without wheezes. Chest radiograph was within normal limits. Cyclosporine levels were subtherapeutic (50 ng/ml). Pathologic evidence of rejection with myocyte necrosis was seen on endomyocardial biopsy. At bronchoscopy, widespread suppurative bronchitis with mucosal sloughing was found, but only below the tracheal anastomosis. Pathologic examination of transbronchial biopsy specimens revealed acute exudative bronchiolitis. Bartlett catheter cultures grew heavy Staphylococcus aureus and parainfluenza III virus. Fungal, tuberculosis, and Legione//a cultures were negative as was Gomorimethenamine silver stain for Pneumocystis carinii. Pulmonary function tests at this time (postoperative day 118) revealed significant impairment of oxygenation, air flow obstruction, and increased airway resistance when compared to previous post-transplant studies. Cardiac rejection was managed with augmented prednisone, 100 mg/day for 3 days, followed by a 2 week course tapering to his maintenance level of 15 rug/day. Azathioprine was added to the immunosuppressive regimen and gradually built up to 2 mg/kg/day. A 7 day course of intravenous cefamandol was given, as well as an intensive airway toilet program, which included inhaled bronchodilators, physiotherapy, and breathing exercises. Clinical improvement was rapid with diminished sputum production and improved pulmonary functional indices (postoperative day 130). Bibasilar rales persisted but diminished in intensity and extent. Three weeks after maintenance doses of steroids had been resumed, the symptoms recurred. The patient complained of cough productive of what appeared to be airway casts, again without fever or dyspnea. Coincident with this, a second deterioration in pulmonary function occurred, with hypoxemia and air flow obstruction again evident on postoperative day 155. Cardiac biopsy at this time was normal. At bronchoscopy, a generalized suppurative bronchitis was again found, this time without demarcation at the tracheal anastomosis. Pathologic examination of bronchial biopsy tissue again showed bronchitis and bronchiolitis. Bartlett catheter cultures did not grow significant bacterial pathogens. Viral cultures on bronchoscopy specimens isolated respiratory syncytial virus (RSV). This time the patient was treated only with augmented steroids without antibiotics. Prednisone was begun at 60 mg/day for 1 week, with a more gradual taper over a 2 month period to maintenance levels. Pulmonary function returned to normal within 9 days (postoperative day 164) and continued to surpass immediate postoperative values on slow tapering of prednisone to the maintenance dose of 15 mg/day, Before discharge, tracheal swabs and throat washings were negative on viral cultures. After discharge he remained well with normal cardiopulmonary function and returned to work for 5 months. A flulike illness then developed, with nonproductive cough, sore throat, and fever. His parents and cousin who were living with him complained of similar symptoms that had resolved spontane-
THORAC CARDIOVASC SURG
92:446-454, 1986
Brief communications Complications associated with the use of heterologous bovine pericardium for pericardial closure Stephen A. Mills, M.D., C.M., Winston-Salem, N. C. From the Section on Cardiothoracic Surgery, Department of Surgery, Wake ForestUniversity Medical Center, Bowman Gray School of Medicine, Winston-Salem, N. C. Two complicatiolti necessitating removal of bovine pericardium used as a pericardial patch graft in 60 patients are reported. These complicatiom, plus a few others reported in the literature, suggest that caution in the clinical use of bovine pericardium remains appropriate.
Complete closure of the pericardium after cardiac operations is generally accepted as being advantageous should repeat sternotomy prove to be necessary. However, pericardial closure is not always possible, because of a previous cardiac operation, use of an external conduit, use of pericardium to correct the cardiac defect, increased heart size after a cardiac procedure, or placement of aorta-coronary bypass grafts. For those situations, use of various pericardial substitutes, including fascia lata,' silicone rubber," rubber-coated Dacron' or polyester,' polytetrafluoroethylene (PTFE),2 as well as heterologous porcine," 7 equine," and bovines. 6 pericardium have been tried. The synthetic materials have produced severe scarring; the heterologous grafts appear to be satisfactory, especially experimentally, but a recent report of late clinical results suggests that they too cause a fibrous reaction that may complicate later reopera-
tion."
We have recently used bovine pericardium (PeriGuard, Genetic Laboratories, Inc., St. Paul, Minn.) in 60 patients. In two patients we encountered complications that we believe were related to the use of this material. In each, reoperation was required for the removal of the graft. Address for reprints: Stephen A. Mills, M.D., Section on Cardiothoracic Surgery, Bowman Gray School of Medicine, 300 S. Hawthorne Rd., Winston-Salem, N. C. 27103. .
446
Case reports. I. A 46-year-old woman underwent three-vessel coronary artery bypass grafting, with glutaraldehyde-prepared bovine pericardium being placed over the anterior aspect of the heart. The pericardial patch was rinsed and handled in accordance with the manufacturer's directions. The patient's postoperative course was uneventful. Cultures of pre-wash and post-wash fluid as well as the ethyl alcohol preservative were negative. Ten weeks after operation the patient returned with a 4 day history of midsternal soft tissue swelling. She was afebrile. She had a tender, 6 cm diameter area of subcutaneous swelling overlying the third to fifth costal cartilages to the left of the sternum. Chest roentgenograms and laboratory studies showed no abnormalities. Computed tomography (CT) of the chest (Fig. I) showed a 12 em long, cystic, tubular structure to the left of the sternum extending from the aortic arch to the diaphragm. Superiorly it lay anterior to the chest wall; it passed posteriorly through the chest wall just inferior to the aortic arch. It did not appear to involve the great vessels. With the patient under general anesthesia, the previous midline sternotomy scar overlying the mass was opened to show drainage of purulent material through a small opening in the intercostal muscles to the left of the sternum. Resection of a 3 em portion of costal cartilage unroofed a cavity corresponding to the lesion seen on CT scan. The previously placed bovine pericardium was rolled up within the cavity. The pericardium was removed and the cavity was irrigated and packed. Gram stain showed white blood cells but no organisms. Cultures (aerobic, anaerobic, acid-fast bacillus, and fungus) were negative. After 8 weeks of drainage, the cavity was closed without complication. CASE 2. A 54-year-old man underwent three-vessel coronary bypass, with ethanol-preserved bovine pericardium being placed over the anterior aspect of the heart before closure of the sternum. The pericardial patch was rinsed and handled in accordance with the manufacturer's recommendations. Cultures of the pre-wash and post-wash fluid as well as the ethanol preservative were negative. The patient's postoperative hemodynamic status was excellent, but on the second postoperative day his temperature rose to 102° F (38.9° C). Over the subsequent 5 days it spiked to 101° to 102.5° F (38.3° to 39.2° C) (Fig. 2); there was no other evidence suggesting systemic toxicity, and cultures of sputum, blood, and urine were negative. The incisions appeared satisfactory and the sternum remained stable. On the seventh postoperative day a CT scan of the chest demonstrated a fluid and gas collection in the anterior mediastinum, which was believed to be compatible with a diagnosis of mediastinitis. The mediastinum was reexplored through a subxiphoid incision, and 35 mI of old blood was removed. No gross CASE
Volume 92 Number 3, Part 1 September, 1986
Brief communications
447
Fig. 1. Computed tomographic view of chest showing a cystic, tubular structure to the left of the sternum (arrow). The structure was 12 em long and was located anterior to the chest wall passing posteriorly through the chest wall just inferior to the aortic arch.
Re-exploration
!
Aortocoronary bypass
102
~
101
OJ
100
C;;
!
E 98.699 1=:::s,:::'--:r--------.L.:....,~~--i_~......~.J-_+4--~p.+l/_~......, ...._Q)
I-
98
97 96 95 .L.-----.--.--------r--.--------r----.------,----r------.---r-----.--~-_ Hospital Days Post-op Day
2 OR
3
4
1
2
5 3
6
7
8
4
5
6
7
10
11
12
13
8/PO
9/1
10/2
11/3
Fig. 2. Temperature chart showing fever commencing on the second postoperative day and resolving with reexploration and removal of bovine pericardium on the eighth postoperative day.
evidence of infection was noted. The previously placed bovine' pericardium was easily removed and appeared clean. Gram staining of chest fluid showed no organisms. Cultures of fluid and pericardium were negative. After removal of the bovine pericardium the patient's temperature returned to normal (Fig. 2), and he was discharged home on the tenth postoperative day. Histologic examination of the bovine pericardium showed no evidence of rejection or infection. At 6 months' follow-up he remains asymptomatic.
Discussion, Pericardial patch materials have been studied experimentally for many years. In 1963, Youmans, White, and Derrick' evaluated a silicone rubber pericardial substitute in dogs after pericardial and epicardial dry sponge abrasion. Firm adhesions formed under remaining pericardium but not under the silicone rubber patch, although in one dog moderate thickening
and chronic inflammation developed under the patch. They then used a siliconerubber pericardial substitute in one patient with congenital absence of the left pericardium. In 1973 Bonnabeau, Armanious, and Tarnay' studied placement of a silicone rubber-coated Dacron patch in dogs, finding it reduced adhesions but tended to cause infections. In 1983 Meus and co-workers' evaluated six synthetic and two different bovine pericardium preparations in a dog model. Each material was histologically examined in dogs killed 3, 6, 9, and 12 months after implantation. They found both bovine preparations (glutaraldehydefixed, formaldehyde- and ethanol-preserved) to be excellent, lacking epicardial reaction and not obscuring underlying structures; minimal adhesions were easily
The Journal of Thoracic and Cardiovascular Surgery
4 4 8 Briefcommunications
dissected. In contrast, silicone-treated Dacron film and high-porosity PTFE film reduced adhesions but caused a severe epicardial reaction. It was suggested that bovine pericardium was the material of choice for use as a pericardial patch. Gallo and colleagues,' in 1978, evaluated glutaraldehyde-preserved porcine pericardium in 20 dogs reoperated on between 15 and 300 days. The majority of dogs had no adhesions between the graft and epicardium, but several animals had loose-to-dense adhesions in that area. Their experimental work led to the use of porcine pericardium in eight patients; none had undergone reoperation at the time of their report. In 1984 Frasca and colleagues" reported implanting glutaraldehyde-fixed grafts of bovine pericardium in the orthotopic position in 3- to 4-month-old sheep. Samples were harvested 1 to 3 weeks later for study by scanning electron microscopy and energy dispersive x-ray microanalysis. A pseudoneointima, or porous layer, consisting of a dense mesh of fibers interspersed with blood cells, could be seen on the blood-contacting surface of the graft. Calcium phosphate deposits were noted in discrete regions in the pseudoneointima and appeared to be associated with thrombi; mineralization in the pericardium was diffusely distributed within the collagen matrix. It is not known how frequently bovine pericardium is used clinically throughout the world, although Dietzman and associates? compiled a report in 1984 of its having been placed in 2,200 patients after cardiac procedures. They also reported the use of glutaraldehyde-fixed propylene oxide-ethanol-preserved bovine pericardium in 112 patients, one of whom underwent reoperation at 3 months and one of whom underwent reoperation at 4 months. In the former patient (and in one patient dying 3 months after operation and examined at autopsy) the epicardial architecture was preserved; in the latter patient there was epicardial fibrosis. Skinner and colleagues" found a dense epicardial reaction to processed bovine pericardium when reoperating 3 months later in a patient requiring repeat coronary revascularization. A thick coagulum on the epicardial surface made identification of surface structures difficult. Gallo, Artifiano, and Duran" reported on five of 87 patients with heterologous glutaraldehyde-preserved pericardial grafts (porcine, bovine, equine) who underwent reoperation with removal of the graft 1.5, 3, 4.5, 6, and 59 months after the initial operation. A space free of adhesions was noted between the graft and epicardium, whereas the remainder of the pericardial cavity present-
ed a typical fibrous reaction. No species differences were noted. Microscopically, it could be seen that the original structure of the graft was maintained and that there was no cellular infiltration; the removed epicardial layer facing the two grafts that had been in place for less than 3 months showed organized fibrinoid material with numerous fibroblastic cells; heavy collagen bundles with neovascularization were noted in the grafts that had been in place for 4.5, 6, and 59 months. The epicardial reaction greatly impeded the recognition of the anterior coronary vessels. They suggested that placing a pericardial incision to the right of the midline might keep the left anterior descending coronary artery covered by autogenous pericardium, and that fibrosis of the underlying right ventricular epicardial surface would be clinically unimportant in most cases. Discussing those findings, Spencer" warned that the value and safety of heterologous pericardium has not been well documented experimentally or clinically. Our complications, one a sterile abscess cavity and one a persistent high fever, both required removal of the graft for resolution. In view of these adverse reactions, coupled with the reports of Gallo.v? Dietzman," and Skinner" of a dense epicardial inflammatory reaction, caution regarding the clinical use of bovine pericardium remains appropriate. REFERENCES
2
3
4
5
6
7
8
Kohanna FH, Adams PX, Cunningham IN Jr, Spencer FC: Use of autologous fascia lata as a pericardial substitute following open-heart surgery. J THORAC CARDIOVASC SURG 74:14-19, 1977 Bonnabeau RC Jr, Armanious AW, Tarnay TJ: Partial replacement of pericardium with dura substitute. J THORAC CARDIOVASC SURG 66:196-201, 1973 Laks H, Hammond G, Geha AS: Use of silicone rubber as a pericardial substitute to facilitate reoperation in cardiac surgery. J THORAC CARDIOVASC SURG 82:88-92, 1981 Youmans CR Jr, White J, Derrick JR: The prevention of pleural and pericardial adhesions with Silastic. J THORAC CARDIOVASC SURG 55:383-388, 1968 Meus PJ, Wernly JA, Campbell CD, Takanashi Y, Pick RL, Qui Z-K, Replogle RL: Long-term evaluation of pericardial substitutes. J THORAC CARDIOVASC SURG 85:54-58, 1983 Gallo I, Artifiano E, Duran CG: Late clinical results with the use of heterologous pericardium for closure of the pericardial cavity. J THORAC CARDIOVASC SURG 89:709712, 1985 Gallo JI, Pomar JL, Artifiano E, Val F, Duran CMG: Heterologous pericardium for the closure of pericardial defects. Ann Thorac Surg 26: 149-154, 1978 Frasca P, Buchanan JW, Soriano RZ, Dunn JM, Marmon
Volume 92 Number 3, Part 1 September, 1986
L, Melbin J, Buchanan SJ, Chang SH, Golub EE, Shapiro 1M: Mineralization of short term pericardial cardiac patch grafts. Scan Electron Microsc 2:973-977, 1984 9 Dietzman RH, Holter AR, Lynch MF, Mindich BP, Ochsner JL: Protection of the heart during reoperation using a bovine pericardial shield. Clinical experience. Contemp Surg 24:35-39, 1984 10 Skinner JR, Kim H, Toon RS, Kongtahworn C, Phillips SJ, Zeff RH: Inflammatory epicardial reaction to processed bovine pericardium. Case report. J THORAC CARD10VASC SURG 88:789-791, 1984 11 Spencer FC: Discussion of Gallo et al"
Steroid-responsive bronchiolitis after human heart-lung transplantation M. D. Allen, M.D., C. M. Burke, M.B., M.R.C.P., C. G. A. McGregor, M.B., F.R.C.S., J. C. Baldwin, M.D., S. W. Jamieson, M.B., F.R.C.S., and 1. Theodore, M.D., Stanford. Calif. From Departments of Medicine and Cardiovascular Surgery, Stanford University Medical Center, Stanford, Calif. 94305. This report describes the clinical course of a patient who developedobliterative bronchiolitis after viral infection on three separate occasioes. Long-term follow-up is given. It is suggested that the syndrome of late pulmonary deterioration after traffiplantation may be steroid responsbe if treatment is initiated early in the natural history of the syndrome. In addition, it is suggested that increased emphasis should be placed on the documentation of viral infection in tramplant recipients to define a possible interaction between infection and rejection.
Late deterioration in pulmonary function, associated with physiologic evidence of air flow obstruction and pathologic evidence of bronchiolitis, is the most important complication in long-term survivors of heart-lung transplantation. To date, the precise pathophysiology and optimal treatment of this syndrome have not been fully determined. Case report. A 21-year-old man with advanced primary pulmonary hypertension underwent heart-lung transplantation on July 12, 1984. His postoperative hospital course was uncomplicated and he was discharged well on Aug. 10, 1984, on an immunosuppressive regimen of cyclosporine (to mainSupported by Grant H 13108 from the National.Heart, Lung, and Blood Institute. Address for reprints: Dr. C. M. Burke, Division of Respiratory Medicine, Stanford University Medical Center, Stanford, Calif. 94305.
Brief communications
449
tain serum blood levels of 100 to 150 ng/rnl) and prednisone (15 mg/day). Pulmonary function and gas exchange are documented in Table I and were essentially normal on postoperative day 52. Two months later he developed a cough productive of mucopurulent sputum without fever or dyspnea. On examination he was found to have coarse bibasilar rales without wheezes. Chest radiograph was within normal limits. Cyclosporine levels were subtherapeutic (50 ng/ml). Pathologic evidence of rejection with myocyte necrosis was seen on endomyocardial biopsy. At bronchoscopy, widespread suppurative bronchitis with mucosal sloughing was found, but only below the tracheal anastomosis. Pathologic examination of transbronchial biopsy specimens revealed acute exudative bronchiolitis. Bartlett catheter cultures grew heavy Staphylococcus aureus and parainfluenza III virus. Fungal, tuberculosis, and Legione//a cultures were negative as was Gomorimethenamine silver stain for Pneumocystis carinii. Pulmonary function tests at this time (postoperative day 118) revealed significant impairment of oxygenation, air flow obstruction, and increased airway resistance when compared to previous post-transplant studies. Cardiac rejection was managed with augmented prednisone, 100 mg/day for 3 days, followed by a 2 week course tapering to his maintenance level of 15 rug/day. Azathioprine was added to the immunosuppressive regimen and gradually built up to 2 mg/kg/day. A 7 day course of intravenous cefamandol was given, as well as an intensive airway toilet program, which included inhaled bronchodilators, physiotherapy, and breathing exercises. Clinical improvement was rapid with diminished sputum production and improved pulmonary functional indices (postoperative day 130). Bibasilar rales persisted but diminished in intensity and extent. Three weeks after maintenance doses of steroids had been resumed, the symptoms recurred. The patient complained of cough productive of what appeared to be airway casts, again without fever or dyspnea. Coincident with this, a second deterioration in pulmonary function occurred, with hypoxemia and air flow obstruction again evident on postoperative day 155. Cardiac biopsy at this time was normal. At bronchoscopy, a generalized suppurative bronchitis was again found, this time without demarcation at the tracheal anastomosis. Pathologic examination of bronchial biopsy tissue again showed bronchitis and bronchiolitis. Bartlett catheter cultures did not grow significant bacterial pathogens. Viral cultures on bronchoscopy specimens isolated respiratory syncytial virus (RSV). This time the patient was treated only with augmented steroids without antibiotics. Prednisone was begun at 60 mg/day for 1 week, with a more gradual taper over a 2 month period to maintenance levels. Pulmonary function returned to normal within 9 days (postoperative day 164) and continued to surpass immediate postoperative values on slow tapering of prednisone to the maintenance dose of 15 mg/day, Before discharge, tracheal swabs and throat washings were negative on viral cultures. After discharge he remained well with normal cardiopulmonary function and returned to work for 5 months. A flulike illness then developed, with nonproductive cough, sore throat, and fever. His parents and cousin who were living with him complained of similar symptoms that had resolved spontane-