Mid-Term Clinical Results of Tissue-Engineered Vascular Autografts / 日本心臓血管外科学会雑誌

Prosthetic and bioprosthetic materials currently in use lack growth potential and therefore must be repeatedly replaced in pediatric patients as they grow. Tissue engineering is a new discipline that offers the potential for creating replacement structures from autologous cells and biodegradable polymer scaffolds. In May 2000, we initiated clinical application of tissue-engineered vascular grafts seeded with cultured cells. However, cell culturing is time-consuming, and xenoserum must be used. To overcome these disadvantages, we began to use bone marrow cells, readily available on the day of surgery, as a cell source. Since September 2001, tissue-engineered grafts seeded with autologous bone marrow cells have been implanted in 44 patients. The patients or their parents were fully informed and had given consent to the procedure. A 3 to 10ml/kg specimen of bone marrow was aspirated with the patient under general anesthesia before the skin incision. The polymer tube serving as a scaffold for the cells was composed of a copolymer of lactide and ε-caprolactone (50: 50) which degrades by hydrolysis. Polyglycolic or poly-l-lactic acid woven fabric was used for reinforcement. Twenty-six tissue-engineered conduits and 19 tissue-engineered patches were used for the repair of congenital heart defects. The patients' ages ranged from 1 to 24 years (median 7.4 years). All patients underwent a catheterization study, CT scan, or both, for evaluation after the operation. There were 4 late deaths due to heart failure with or without multiple organ failure or brain bleeding in this series; these were unrelated to the tissue-engineered graft function. One patient required percutaneous balloon angioplasty for tubular graft-stenosis and 4 patients for the stenosis of the patch-shaped tissue engineered material. Two patients required re-do operation; one for recurrent pulmonary stenosis and another for a resulting R-L shunt after the lateral tunnel method. Kaplan-Meier analysis in relation to patients' survival was 95% within 3 years. There was only 1 patient (who underwent a total cavo-pulmonary connection procedure) requiring re-intervention in the tubular graft group and the material-related event-free rate was 96% within 3 years. This tissueengineering approach may provide an important alternative to the use of prosthetic materials in the field of pediatric cardiovascular surgery. As it is living tissue, these vascular structures may have the potential for growth, repair, and remodeling. However, this approach is still in its infancy, further studies to resolve the problems presented, and longer follow-up in patients are necessary to confirm the durability of this approach.

A Case of the Senning Procedure in a Patient with Transposition of the Great Arteries with Intact Ventricular Septum and Bicuspid Pulmonary Valvular Stenosis Associated with Pulmonary Hypertension / 日本心臓血管外科学会雑誌

We performed the Senning operation and pulmonary valvotomy in an 11-month-old baby with transposition of the great arteries (TGA) with an intact ventricular septum (IVS), and bicuspid pulmonary valvular stenosis associated with pulmonary hypertension (PH). Preoperative catheterization showed a pressure gradient (PG) between the left ventricle (LV) and main pulmonary artery (MPA) of 35mmHg, mean pulmonary artery pressure (MPAP) of 56mmHg, and pulmonary vascular resistance (PVR) of 11.2unit·m². The pure oxygen inhalation test showed a decrease in MPAP from 56 to 38mmHg, and a decrease in PVR from 11.2 to 5.5 unit·m². We could not perform lung biopsy to determine the surgical indications in terms of PH due to preoperative progressive congestive heart failure in this patient. Postoperative catheterization (28 days after the Senning operation) showed a decrease in PG between the LV and MPA to 8mmHg, and MPAP also decreased to 17mmHg. Two radical operations were possible in this patient. One was the arterial switch operation (ASO), and the other was the atrial switch operation, i. e. the Senning or the Mustard operation. We selected the Senning operation because there was the possibility that the new aortic valve might develop persistent stenosis and regurgitation after ASO and pulmonary valvotomy. The Senning operation may be an alternative in selected patients with TGA with IVS and pulmonary valvular stenosis.

Mid-term Clinical Results of Tissue-Engineered Vascular Autografts Seeded with Autologous Bone Marrow Cells

OBJECTIVE: Prosthetic and bioprosthetic materials currently in use lack growth potential and therefore must be repeatedly replaced in pediatric patients as they develop. Tissue engineering (TE) is a new discipline that offers the potential for creating replacement structures from autologous cells and biodegradable polymer scaffolds. In May 2000 we initiated clinical application of tissue-engineered vascular grafts seeded with cultured cells. However, cell culturing is time-consuming and xeno-serum must be used. To overcome these disadvantages, we started the usage of bone marrow cells (BMCs), readily available on the day of surgery, as a cell source. The aim of the study was to assess the safety and feasibility of this technique for creating pulmonary artery conduits. METHODS: Since August 2000, TE grafts seeded with autologous BMCs have been implanted in thirty-five patients. The patients and/or their parents were fully informed and had given consent to the procedure. Five ml/kg of bone-marrow was aspirated under general anesthesia prior to the skin incision. The polymer tube serving as a scaffold for the cells was composed of a co-polymer of l-lactide and epsiloncaprolactone (PCL-PLA, 50:50). This co-polymer is degraded by hydrolysis. The matrix is 80% porous and the diameter of each pore is 100-200micro M Polyglycolic acid (PGA) woven fabric with a thickness of 0.5 mm was used for reinforcement. Twenty-one TE conduits (TCPC grafts) and fourteen TE patches were used for the repair of congenital heart defects. The patients' ages ranged from 1 to 24 years (median, 5.5 years). All patients underwent a catheterization study and/or computed tomography (CT) scans for evaluation after operation. The patients received anticoagulation therapy for 3 to 6 months after surgery. RESULTS: Mean follow-up after surgery was 424 days (maximum, 38 months). There were no complications such as thrombosis, nor stenosis or obstruction of the tissue-engineered autografts. One late death at 3 months after TCPC was noted in HLHS patients, which was unrelated to the TE graft. There was no evidence of aneurys formation on cineangiography or CT. On examination in late period, all tube grafts were patent, and the diameter of the tube graft increased over time. (110 +/- % of the implanted size) CONCLUSIONS: Biodegradable conduits or pulmonary vessel patches seeded with autologous BMCs showed normal function (good patency up to maximum follow-up of 38 months). As living tissues these vessels may have the potential for growth, repair and remodeling. The TE approach may provide an important alternative to the use of prosthetic materials in the field of pediatric cardiovascular surgery. Longer follow-up is necessary to confirm the feasibility of this approach.

Clinical Applications and Pitfalls of Hypothermia in Patients after Fontan's Operation / 日本心臓血管外科学会雑誌

This study was designed to clarify the usefulness and pitfalls of hypothermic management after Fontan's operation. Twenty-five patients who underwent Fontan's operation and received hypothermic management in an acute postoperative phase from 1974 to 1991 were divided into two groups; the alive (S) group and the dead (D) group. The lowest rectal temperature during the procedure was 32°C on average. There were no significant differences in preoperative indices of pulmonary circulation and renal function. After rewarming, PaO₂ and daily urinary output were increased and central venous pressure decreased significantly in the S group. In all S group patients, urinary output was increased during hypothermia irrespective of peritoneal dialysis. Anuria occurred 2 days on average after induction of hypothermia in D group. Urinary output in D group decreased significantly for 4 days compared to S group. On the other hand, it was possible to save two patients who underwent take-down of Fontan's operation within 6 hours after the onset of anuria. We conclude that hypothermic management is useful in serious cases after Fontan's operation and that daily urinary output in relation to body weight during hypothermia is most important as an index of post operative circulation.