Youichi Kawahira

Gene transfection of hepatocyte growth factor attenuates reperfusion injury in the heart.

BACKGROUND Hepatocyte growth factor (HGF), a ligand for the c-Met receptor tyrosine kinase, plays a role as organotrophic factor for regeneration of various organs. HGF has an angiogenic activity and exhibits a potent antiapoptotic activity in several types of cells. Although HGF and the c-Met/HGF receptor are expressed in the heart, the role of HGF in the heart has remained unknown. METHODS After we analyzed changes in expression of endogenous HGF and c-Met mRNA levels in the rat left ventricle after myocardial infarction, the human HGF gene in hemagglutinating virus of Japan (HVJ)-liposome was transfected into the normal whole rat heart. Three days after transfection, the heart was subjected to global warm ischemia and subsequent reperfusion, followed by assessment of its cardiac functions. RESULTS Both HGF and c-Met/HGF receptor mRNAs were expressed in adult rat heart, and c-Met/HGF receptor mRNA was upregulated in response to myocardial infarction. HGF-transfected heart showed significant increase of human HGF protein level in the heart. Cardiac functions in terms of the left ventricular developed pressure, maximum dp/dt, and pressure rate product in hearts with HGF gene transfection were significantly superior to those in control hearts. In addition, leakage of creatine phosphokinase in the coronary artery effluent in hearts with HGF gene transfection was significantly lower than that in control hearts. CONCLUSIONS These data indicated that both HGF and c-Met/HGF receptor mRNAs were upregulated in response to myocardial ischemic injury, and that HGF is likely to have a cytoprotective effect on cardiac tissue, presumably through the c-Met/HGF receptor.

Result of surgical treatments in patients with coronary-arterial obstructive disease after Kawasaki disease.

OBJECTIVE To determine the efficacy of coronary artery bypass grafting (CABG) in young patients with coronary-arterial obstructive disease subsequent to Kawasaki disease. METHODS CABG was employed in 100 patients. Age at operation ranged from 1 to 23 years at a mean of 10+/-5 years. The number of bypass grafts placed was 1-5/patient (a mean of 1.7+/-0.8). The left internal-thoracic artery (ITA) was used as a graft in 99 patients; the right internal thoracic artery in 39, the gastroepiploic artery in nine and the saphenous vein in 21. RESULTS All patients survived the procedures. In the follow-up of 6.7+/-4.5 years, two patients died, one because of a traffic accident and the other due to sudden death. Considerable myocardial ischemia recurred postoperatively in 15, because of either obstruction of the bypass grafts or progression of other coronary-arterial obstructions. Of these, symptoms spontaneously regressed without interventional procedures in four, reoperation was indicated in four and catheter intervention was efficiently carried out in the remaining seven. Another two patients had episodes of critical ventricular arrhythmia; one of them with severe left ventricular dysfunction subsequently underwent cardiac transplantation. The patency rates of the arterial grafts were 94, 82 and 78% at 1, 5 and 10 years, respectively, and this was higher than that of the venous grafts (82, 63 and 36%, respectively). Strenuous exercise is currently prohibited in 15 patients, while the remaining 83 patients are doing well with no obvious restriction in their daily lives. CONCLUSION Collaborating with catheter interventions, CABG using the arterial grafts can provide attractive results in patients with obstructive coronary arteries associated with Kawasaki disease.

Redirection of Hepatic Venous Drainage After Total Cavopulmonary Shunt in Left Isomerism

BACKGROUND Conversion from total cavopulmonary shunt (TCPS) to the Fontan circulation can improve cyanosis in patients with potential risks of development of pulmonary arteriovenous fistula (PAVF). METHODS Inclusion of the hepatic veins in the pulmonary circulation was employed using an intra-atrial tube graft in 5 patients with left isomerism previously undergoing TCPS. Prior to the conversion, abnormal communication was identified between the azygos vein and either the hepatic or the portal vein in all. PAVF was seen in 3. RESULTS All patients survived the procedure. Postoperative catheterization showed 13 +/- 2 mm Hg of superior caval venous pressure, and 2.3 +/- 0.4 L/min/m2 of cardiac index. Pulmonary arteriovenous fistula progressed markedly in the right lung even after the conversion in 2 patients, in whom the hepatic veins had been exclusively diverted to the left lung. Arterial oxygen saturation became below 65%, with exercise capacity reduced, in these 2 patients. The other patients remain asymptomatic. CONCLUSIONS Total cavopulmonary shunt can be efficiently converted to the Fontan circulation by appropriately redirecting hepatic venous drainage to perfuse both lungs in a balanced fashion.

Renewal of the Fontan circulation with concomitant surgical intervention for atrial arrhythmia

BACKGROUND Atrial arrhythmia remains one of the major complications in the longer term after the Fontan procedure. METHODS Conversion to total cavopulmonary connection was carried out concomitantly with surgical intervention for atrial arrhythmia in 4 patients undergoing the Fontan procedure by atriopulmonary connection and having continual atrial fibrillation or flutter in the longer term after the initial procedure. RESULTS The surgical intervention restored sinus rhythm. Transient atrial fibrillation occasionally occurred after the reoperation in 1 patient in whom duration of preoperative arrhythmic period had been 6 years, and defibrillation was needed twice. In the other 3 patients, no episodes of paroxysmal arrhythmia have been noted. Subsequent to renewal of the Fontan circulation, cardiac index increased, with systemic venous pressure decreasing. All 4 patients are currently doing well with their functional status of New York Heart Association functional class I. CONCLUSIONS Combination of conversion to total cavopulmonary connection and concomitant surgical intervention for atrial arrhythmia is effective, when used appropriately and in a timely manner in patients with atrial arrhythmia in the longer term after the initial Fontan procedure by atriopulmonary connection.

Total cavopulmonary connection in children with body weight less than 10 kg

OBJECTIVE To evaluate the results after total cavopulmonary connection (TCPC) in small children, our clinical experience was retrospectively reviewed. METHODS Of 164 patients undergoing TCPC, the body weight at operation was less than 10 kg (8.8+/-1.1 kg) in 54, including 21 with visceral heterotaxy. The superior caval vein (SVC) was anastomosed to the pulmonary arteries in a bidirectional fashion. To construct a channel draining the inferior caval vein (IVC), an extended polytetrafluoroethylene (ePTFE) tube was placed intraatrially (in 15 patients) or outside the heart (in 13), its diameter being 14 mm in two patients, 16 mm in 12, and 18 mm or greater in 14. A heterologous pericardial baffle was used for intraatrial rerouting in 12 patients. A pedicled autologous pericardial roll was tailored as an extracardiac conduit in 11 patients, and the pulmonary trunk was directly anastomosed to IVC orifice in three. RESULTS Seven patients, including five with right isomerism, died in the intermediate term because of infection of the ePTFE tube in two, respiratory problems in three, atrioventricular valvar regurgitation in one, and pulmonary venous obstruction in one. Postoperative catheterization showed; SVC pressure, 11+/-2 mmHg without a pressure gradient between SVC and IVC; systemic ventricular end diastolic pressure, 5+/-2 mmHg; end diastolic volume, 122+/-54% of the anticipated normal value; ejection fraction, 0. 56+/-0.11; and cardiac index, 2.9+/-0.7 l/min per m(2). With the follow-up of 1-116 (35+/-31) months, the IVC channel has not become obstructive in all, except for one, in whom a pedicled pericardial roll was severely obstructed because of its tortuous extracardiac course crossing in front of the vertebrae. Postoperative growth was generally stable, although body weights and heights were smaller in the majority of patients when compared with the anticipated standards for Japanese children. CONCLUSION TCPC can be justifiably established in small children. The use of autologous tissues seemed preferable for constructing the IVC channel unless anatomic orientation was unsuitable.

Staged unifocalization and anatomic repair in a patient with right isomerism

Anatomic biventricular repair was successfully achieved subsequent to bilateral unifocalizations of the pulmonary blood supply using heterologous pericardial rolls in a patient with isomeric right appendages and major aortopulmonary collateral arteries.

Ventricular outflow tracts after Kawashima intraventricular rerouting for double outlet right ventricle with subpulmonary ventricular septal defect

OBJECTIVE To determine whether or not the ventricular outflow tracts can be efficiently constructed in patients with double outlet right ventricle with subpulmonary ventricular septal defect by the Kawashima intraventricular rerouting in which the morphologically right ventricular outlet is divided into two, one for the systemic and the other for the pulmonary circulations. METHODS The intraventricular rerouting procedure was carried out in nine patients with this particular malformation. Age at repair ranged from 35 days to 3 years old. The distance between the attachments of the tricuspid and the pulmonary valves was 10 mm or greater in all except one patient in whom the measured value was 3 mm. Resecting subaortic musculature appropriately, a tailored patch, either oval-shaped (in seven) or heart-shaped (in two), was placed to construct an unobstructed channel for the left ventricular outflow tract with its diameter greater than that of the anticipated normal aortic orifice at the time of repair. For an unobstructed channel to the pulmonary arteries, enlargement of the right ventricular outflow tract was carried out using a patch in six. RESULTS All patients survived the operative procedure. On postoperative catheterization, mean pulmonary arterial pressure was 15 +/- 8 mmHg, and cardiac index was calculated as 3.3 +/- 0.6 l/min per m2. It proved that the constructed left ventricular outflow tract can become larger in the longer term. Pressure gradient across the left ventricular outflow tract was greater than 20 mmHg in two patients in the intermediate term. One of these two underwent reoperation for the obstruction 10 years after the initial repair. It was suspected that use of a heart-shaped internal conduit, which seems to result from inadequate conal resection, was one of the possible causes of such obstruction in the longer term. Pressure gradient of 47 mmHg was seen across the right ventricular outflow tract in one patient, although this patient has undergone no reoperation. Enlargement of the right ventricular outflow tract could minimize postoperative obstruction for the pulmonary pathway. CONCLUSIONS The intraventricular rerouting remains one of the attractive surgical options for repair in this particular setting, in terms of successful construction of the ventricular outflow tracts.

Use of expanded polytetrafluoroethylene sutures as artificial tendinous cords in children with congenital mitral regurgitation

OBJECTIVE To determine the efficacy in the intermediate term of artificial cords inserted in children with congenital mitral regurgitation. METHODS We reconstructed the tendinous cords using expanded polytetrafluoroethylene (ePTFE) sutures in 11 children with severe mitral regurgitation. In these patients, the aortic (anterior) leaflet of the mitral valve had been markedly prolapsed, the tendinous cords being partially lacking in seven, and elongated in the remaining four. In addition, one of the papillary muscles was hypoplastic in five and absent in three. The number of artificial cords constructed varied from two to six. Conventional annuloplasty was performed in all to plicate the dilated annular attachment of the valve. Ventricular septal defect was present in four patients, and other associated malformations in another two. Age at operation ranged from 9 months to 9 years old, with a mean of 4.5 years. RESULTS All patients survived the operation. No reoperation has been needed thus far. No complications were encountered related to the use of the prosthetic materials or anticoagulation. As judged by echocardiography, regurgitation became trivial or slight immediately after the repair. In two patients, however, regurgitation recurred within 1 year of the operation. Coaptation between the leaflets was maintained by a compensatory growth at the site of attachment of the artificial cords. Catheterization demonstrated significant improvements in the end-diastolic volume of the left ventricle. CONCLUSION Expanded polytetrafluoroethylene sutures can be used as artificial cords when attempting to repair the malformed mitral valve in children, providing excellent results in the short- and the intermediate-term after the surgical procedure.

Mortality and risk factors for late deaths in tetralogy of Fallot: the Japanese Nationwide Multicentric Survey

OBJECTIVES We have compared mortality and risk factors for late deaths in patients with tetralogy of Fallot undergoing surgical repair in 1972 and 1982 in a Japanese multicentric study, examining in particular the impact of time of repair. BACKGROUND There is limited information on the effect that time of repair, and our constantly changing approach to it, has on late outcome in repaired tetralogy of Fallot. METHODS We analysed the Japanese registry of deaths occurring after surgical repair of tetralogy of Fallot. We studied two postoperative 1-year cohorts of survivors of surgery performed in 12 centers. Of the patients, 122, aged 29+/-12 years, had undergone repair in 1972, their age at repair being 9.6 years. An additional 186 patients, aged 23+/-8.7 years, had been repaired in 1982 at the age of 7.7 years. RESULTS Annual mortality, as judged per 100,000 population of patients with tetralogy of Fallot, declined from 0.387 in 1972 to 0.196 in 1982. Significant differences were deaths following surgery (27% vs. 13%, p < 0.001), patching of the subpulmonary outflow tract (48% vs. 89%, p < 0.001), and transjunctional patching (13% vs. 63%, p < 0.001). Late death was observed in 6 vs. 3 patients (9/308, 2.9%). The actuarial rate of survival calculated over 14 years was 97% vs. 98%. Reoperation was performed in 5 vs. 9 patients (14/308, 4.5%). Risk factors for late death were age at repair (p = 0.01), and history of reoperation (p < 0.001). Transjunctional patching (p = 0.01) proved to be associated with late mortality only in patients repaired in 1972. CONCLUSIONS Late survival was excellent, with a low incidence of reoperations in both groups of patients. The era of repair has a big influence on total and operative mortality, but has only a small impact on late mortality. Ongoing analysis of follow-up will possibly reveal subsequent changes with time.

Anatomic biventricular repair by intraatrial and intraventricular re-routing in patients with left isomerism.

OBJECTIVE To determine the efficacy of anatomic biventricular repair by a combination of intraatrial and intraventricular re-routing in patients with isomerism of the left atrial appendages. METHODS Anatomic biventricular repair by means of combined intraratrial and intraventricular re-routing was achieved in 5 of the 63 patients with left isomerism in whom we attempted a definitive surgical procedure. The inferior caval vein was interrupted in 3. The Mustard procedure was chosen for intraatrial redirection of blood in 4, and the Senning procedure in the other. Intraventricular re-routing was carried out via a right ventriculotomy in all patients, using an external conduit to reconstruct the morphologically right ventricular outflow tract. RESULTS One patient died one month after the procedure because of low cardiac output and bronchial bleeding. Obstruction across the superior caval venous channel occurred after the Senning procedure in this particular patient, related to the interrupted inferior caval vein draining via the azygous vein. The other 4 patients are currently doing well. Postoperative catheterization showed excellent cardiac performance, with no obstruction across the venous channels or the ventricular outflow tracts in these 4. No episode of significant arrhythmia has been noted, all patients having a regular atrial rhythm, although the P wave vector was unusual in each patient. Reoperation has been needed thus far in one patient, 128 months after the initial repair, because of obstruction of the external conduit. CONCLUSION With precise recognition of the morphologic features, a combination of intraatrial and intraventricular re-routing can successfully be established in patients with isomeric left atrial appendages, with functional results in the intermediate term being reasonable.