The Ross procedure in children and young adults with congenital aortic valve disease.

METHODS: Thirty-three children and young adults with congenital aortic valve disease underwent pulmonary autograft replacement of the aortic valve between October 1993 and March 1997. There wer six females and 27 males; at operation, median age was 16 years (range: 3 to 41 years) and median body weight 60 kg (range: 14 to 121 kg). Fifteen patients (46%) had undergone one or more previous cardiac surgical procedures. A bicuspid aortic valve was present in 31 patients (94%); moderate to severe aortic stenosis and regurgitation was present in 10 (30%) and 26 (79%), respectively. RESULTS: All patients underwent the Ross procedure while in NYHA class I (64%) or class II (36%). A preoperative shortening fraction of 41 +/- 1.4% suggested well-preserved systolic function, but the mean left ventricular end-diastolic pressure of 16.6 +/- 1.3 mmHg was consistent with preoperative left ventricular pressure and volume overload. The aortic root was replaced using an interrupted suture technique in two patients and with three separate running sutures in 31. The right ventricular outflow tract was reconstructed in all classes with a cryopreserved pulmonary homograft valved conduit (median diameter 23 mm; range 19 to 30 mm). Intraoperative complications included transient atrioventricular dissociation (one), permanent atrioventricular dissociation (one), and left coronary artery distortion relieved by shortening the distal ascending aorta (one). Postoperatively, postpericardiotomy syndrome developed in six patients (18%), supraventricular tachycardia in three (9%), and ventricular tachycardia in one (3%). At three days after surgery, one patient developed ischemic left ventricular dysfunction requiring repositioning of the distorted left coronary artery higher on the neo-aortic root. Hospital survival rate was 100%. During a median follow-up of 17 months (range: 1 to 41 months) one patient suffered a non-cardiac death due to blunt trauma. there has been a significant postoperative improvement in NYHA class among surviving patients (class I, 94%; class II, 6%; p = 0.004 versus preoperative). Postoperative aortic regurgitation was absent or trivial in 17 (60%) and mild in the remaining 11 (40%) patients for whom follow-up echocardiographic data are available. One patient required reoperation 16.5 months after the Ross procedure to replace a rapidly degenerating pulmonary homograft, and one with moderately severe homograft stenosis and five with mild homograft stenosis are being monitored. Postoperatively, a gradual early expansion in the diameter of the neo-aortic root and reduction in echocardiographic indices of left ventricular hypertrophy and dilatation occurred. CONCLUSIONS: Pulmonary autograft replacement of the aortic valve in young patients with congenital aortic valve disease has produced excellent short-term anatomic/physiologic results and symptomatic relief with no mortality. Indices of left ventricular dilatation and hypertrophy regress after repair when the Ross operation precedes important deterioration in preoperative ventricular function. Important technical considerations include: (i) the native distal ascending aorta should be sufficiently shortened before performing the distal aortic anastomosis; and (ii) the left coronary anastomosis should be positioned relatively high on the neo-aortic root with a slight amount of tension. Both of these maneuvers reduce the likelihood of coronary artery distortion. Rapid degeneration of the pulmonary homograft and the propensity towards progressive dilatation of the neo-aorta are important postoperative considerations. Until more is known about the etiology and natural history of these two potential complications, postoperative anti-inflammatory and/or immunosuppressive therapy and strict control of hypertension should be strongly considered.

Cationic lipid-mediated transfer of the hIL-10 gene prolongs survival of allogeneic hepatocytes in Nagase analbuminemic rats.

Gene transfer techniques can be used as a drug delivery system to achieve local immunosuppression. We performed a series of experiments to identify the cationic lipid that most efficiently transfects isolated, cultured, rat hepatocytes; to optimize conditions for efficient transfection; to determine the duration of gene expression in vitro; and finally, to determine the survival of allogeneic hepatocytes transplanted into Nagase rats. Our results suggest that DOTAP is the best cationic lipid for transfection of cultured rat hepatocytes. In addition, the following conditions appear to optimize transfection efficiency: a DNA:DOTAP ratio of 1:6; a 24 exposure time of the hepatocytes to the DNA-DOTAP complex; a DNA dose of 4 microg/35 mm culture plate seeded with 2.5x10(5) rat hepatocytes. When transfected as described above, cultured hepatocytes expressed the hIL-10 gene for approximately 14 days. Accordingly, Nagase rats transplanted with 4x10(7) DOTAP-hIL-10 transfected, allogeneic hepatocytes had an abrupt rise in serum albumin levels that peaked within 7 days of the transplant, decreased abruptly after 15 days, and approached baseline by day 40. In contrast, control animals had a smaller albumin peak that returned to baseline within 10 days (P<0.01). In all animals, serum hIL-10 levels were undetectable when tested. We conclude that DOTAP is the best cationic lipid for transfection of cultured rat hepatocytes. Furthermore, hIL-10 transfected hepatocytes have a prolonged survival in an allogeneic host which is probably limited by loss of gene expression. Further studies using other vectors capable of prolonged gene expression will help determine if indefinite hIL-10 gene expression leads to indefinite graft survival.