Protective effect of radical scavenger edaravone against puromycin nephrosis.

AIM: Recent studies have indicated that reactive oxygen species (ROS) play a role in the pathogenesis of glomerular injury leading to proteinuria in nephrotic syndrome. In the present investigation, we examined the effects of the radical scavenger edaravone administered at various time points to rats with puromycin nephrosis. MATERIALS AND METHODS: 35 Wistar rats were divided into five groups: treatment with puromycin aminonucleoside (PAN) alone, treatment with PAN followed by edaravone in the early period, treatment with PAN followed by edaravone administration in the late period, treatment with PAN and administration of edaravone for the whole experimental period, and untreated controls. On Days 3, 6 and 9, urinary protein excretion was measured. The levels of glomerular thiobarbituric acid-reactive substance (TBArs) were determined in all animals on Day 10. RESULTS: On Day 9, rats that had been administered edaravone showed reduced urinary protein excretion and reduced glomerular TBArs. In particular, edaravone administration in the late period, during which proteinuria was most acute, had the effect of reducing the severity of proteinuria. Glomerular TBArs were suppressed to the control level. Our results indicate that edaravone exerts a protective effect in the acute phase of PAN nephrosis when administered as antioxidant therapy at the onset of proteinuria. CONCLUSIONS: Edaravone can ameliorate urinary protein excretion after the onset of proteinuria in nephrotic syndrome.

Pharmacodynamic monitoring of mycophenolic acid in rabbit heterotopic heart transplant model.

Pharmacodynamic (PD) monitoring of immunosuppressive drugs provides a novel approach to optimization of drug therapy in transplant recipients. We chose to investigate this using mycophenolic acid (MPA), an immunosuppressive drug that mediates its effect by the inhibition of inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the de novo biosynthesis of purines. A comparison of the relationship between PD versus drug level monitoring was performed using a heterotopic cardiac transplant in New Zealand white rabbits. The animals were divided into four different treatment groups. Control animals were administered the drug vehicle, the treatment groups were administered mycophenolate mofetil (MMF) at doses of 40, 80, and 160 mg/kg/day. Statistically significant (p < 0.05) prolongation of graft survival was obtained at the 160 mg/kg/day dose group. The mean MPA concentration at this dose was approximately 2.5 mg/l, suggesting that this concentration may provide adequate immunosuppression. An increase in IMPDH activity appeared a few days prior to rejection, suggesting that measurement of enzyme activity may have potential for use as a marker of graft rejection. A significant (p < 0.05) relationship exists between MPA concentration and graft survival and the former with dose of MMF. There was a negative correlation (p = 0.17) between MPA concentration and IMPDH activity, while a trend (p = 0.37) to inverse relationship between graft survival and IMPDH activity was found. The data suggests that the measurement of the biological response may provide a useful adjunct to traditional therapeutic drug monitoring (TDM) for optimization of dosing of immunosuppressive drugs.

[A case report of pseudocoarctation associated with aneurysm of the distal aortic arch].

A 42-year-old female was admitted to our hospital for abnormal shadow in the left superior mediastinum on chest X-ray. Her blood pressure was 120/70 mmHg in the left arm and 134/72 in the right. Aortography revealed pseudocoarctation of the aortic arch distal to the left carotid artery with two aneurysm, and showed elongation between the left carotid artery and the left subclavian artery. Aneurysmectomy and graft replacement using a woven Dacron graft were successfully performed under cardio-pulmonary bypass. In 1969, Gay et al reported a case of pseudocoarctation which led to a fatal rupture of the thoracic aorta, so we recommend surgical therapy in cases of pseudocoarctation associated with aneurysm formation.

[Adjunctive methods during surgery for thoracoabdominal aneurysms--effect of selective visceral arteries perfusion incorporated with partial femoro-femoral bypass].

In this study, we report the effect of selective perfusion to the visceral arteries during aortic cross-clamping at surgery for thoracoabdominal aortic aneurysms with an adjunct of femoro-femoral (F-F) extracorporeal bypass. The total series comprising 28 patients were divided into 3 groups according to the perfusion mode to the celiac and the renal arteries, i.e., group I; the arteries were continuously perfused by the extracorporeal bypass, group II; aortic cross-clamp excluded the branches from the bypass flow but selective perfusion was employed, and group III; the liver or the kidneys were subjected to ischemia. As a result, group III developed hepatic failure at the incidence of 50% which was characterized by hepatocellular damage followed by cholestatic dysfunction. As for postoperative renal function, this group revealed persistently high level of serum creatinine, and 60% of this series resulted in renal failure. On the contrary, group II showed a comparable effect to group I on the preservation of hepato-renal function, and there were no differences in the incidence of hepatic or renal failure between the two groups. Multiple organ failure was a predominant cause of hospital death, and it developed only in the cases with aortic cross-clamp time more than 90 minutes. However, avoiding ischemia achieved in group I or II significantly reduced the incidence of MOF and its related deaths. It is concluded that selective perfusion system incorporated with an aid of F-F partial bypass was a useful measure to protect vulnerable organs from ischemia and to reduce postoperative mortality and morbidities.

[Closure of median sternotomy incision with EPTFE sutures].

EPTFE (CV-0) suture was utilized for closure of median sternotomy incision in 100 patients under 6 years of age who underwent open heart surgery. During 3 years follow up, except for one dislocation of sternum, all patients have healed without complication. EPTFE suture is swanged to a needle that has the same diameter as the thread, which reduces bleeding from the needle hole. It is radiologically lucent, and therefore does not disrupt chest X-ray, angiography or MRI investigations, in contrast to sternal wires. In addition, in the case of life threatening postoperative complication, EPTFE suture allows rapid and simple access to the heart, without the need to cut wires. We concluded that EPTFE suture can be utilized for closure of median sternotomy in patients under the age of six, without an increased risk of postoperative or long-term complications.

[Surgical treatment of pulmonary atresia with intact ventricular septum in infancy--analysis of right ventricular growth potential after pulmonary valvotomy].

Our surgical experience involving pulmonary atresia with intact ventricular septum (PPA) between the years 1981 and 1989 is reviewed. Twelve infants aged 3 days to 11 months were studied for right ventricular growth potential with angiocardiography and hemodynamics after transventricular pulmonary valvotomy (TVPV). Ten infants were divided into two groups, 5 infants (Group I) were treated with TVPV only, and the other 5 infants (Group II) required additional surgery after the initial operation (TVPV in 2 cases and TVPV with shunt in 3 cases). Post-operative RV growth potential was evaluated with right ventricular index (RVI) based on the tricuspid valve annulus, right ventricular inlet, and right ventricular outlet dimensions, and with tricuspid annular index (TVI) based on the tricuspid valve annulus normalized by aortic diameter. Follow-up (3-69 months after initial operation) studies demonstrated that the RV cavity increased in Group I (RVI of 15.75 +/- 2.92 preoperatively versus 17.00 +/- 1.57 postoperatively, TVI of 3.04 +/- 0.63 versus 3.85 +/- 0.40). In contrast, the RV cavity in Group II demonstrated a lack of growth (RVI of 9.24 +/- 2.60 versus 9.85 +/- 2.76, TVI of 1.46 +/- 0.46 versus 1.70 +/- 0.80). PPA infants with RVI greater than 11 have been treated successfully with TVPV alone, which may maximize the potential for RV growth, but infants with RVI less than 11 have not experienced RV growth + postoperatively and, therefore, have required second intracardiac operations.

[A case of cardiomyoplasty with synchronous stimulated latissimus dorsi muscle].

In December, 1988, a 57-year-old man sustained an acute myocardial infarction. He suffered from progressive cardiac failure, despite bed rest and intensive medical treatment. Finally, he developed hepatic and renal failure. Subsequent angiographic studies revealed the total occluded LAD (Seg. 6) and a large LV aneurysm. In January 1989, a left ventricular aneurysmectomy and cardiomyoplasty using the latissimus dorsi muscle were performed successfully. Two years after the operation, he is alive and well.

[A case report of isolated congenital tricuspid regurgitation].

Reports of isolated congenital tricuspid regurgitation are very rare. A 20-year-old female with severe tricuspid regurgitation was reported. The patient was admitted to our hospital with complaints of easy fatigability and palpitation. Right ventriculogram showed severe tricuspid regurgitation. She was treated with tricuspid valve replacement with a 33 mm bioprosthetic valve. Seven surgical treated cases of isolated congenital tricuspid regurgitation including our case were collected from literature and reviewed.

[A case of giant bullae of the lung with thrombosis in the inferior vena cava and the pulmonary artery].

A case of giant bullae of the lung is rarely accompanied with thrombosis in the inferior vena cava and the pulmonary artery, and because of the risk of pulmonary infarction, this case needed a surgical treatment. At this time, we removed the thrombus from the IVC as the first step of the operation, and two months later a bullectomy and the exploratory incision of the right main pulmonary artery were attempted as the second step of the operation. However, the thrombus in the pulmonary artery had spontaneously disappeared. The postoperative course was uneventful and there has been no evidence of recurrence with anticoagulant therapy.

[Modified Fontan operation of single ventricle with D-TGA].

An 8-year-old boy who had previously received two systemic pulmonary shunts, underwent successfully direct anastomosis between SVC and right pulmonary artery (bidirectional Glenn shunt), and proximal side of SVC and main pulmonary artery. Post operative course was uneventful with pleural effusion during a shot period. Post operative right atrial pressure was 9/5 mmHg without evidence of live swelling.

[Effectiveness of the bidirectional Glenn shunt for the univentricular heart].

Two cases underwent a modified Fontan operation with simultaneous superior vena cava-right pulmonary artery end-to-side anastomosis, which we called "bidirectional Glenn shunt". This anastomosis seems to be so effective for reduction of right arterial volume loading, and could proved life-saving in the case with the acute obstruction at the site of the right atriopulmonary artery anastomosis immediately after surgery.