Mechanism of antiarrhythmic action of beta-blocking agents

We investigated the antiarrhythmic effect of beta-blocking agents. Using 35 anesthetized dogs, the chest was opened and the left anterior descending coronary artery (LAD) was ligated for 30 min and the ventricular multiple response threshold (VMRT) was observed in the time course. The dogs were divided into five groups premedicated intravenously ten min before LAD ligation with either isotonic saline (the control group), D,L-propranolol (0.5 mg/kg), D-propranolol (0.5 mg/kg), D,L-pindolol (0.1 mg/kg), or D,L-acebutolol (2.5 mg/kg). Thirty min after ligation, myocardial mitochondria were prepared from the ischemic and the non-ischemic areas, and then the content of mitochondrial long-chain acyl-CoA and Ca++-binding activity were measured. The value of VMRT 1.59 +/- 0.21 mA before ligation decreased to 0.99 +/- 0.13 mA 30 min after ligation. Content of acyl-CoA in mitochondria from the ischemic area increased significantly compared to those from the non-ischemic area. Mitochondrial Ca++-binding activity in the ischemic area decreased significantly compared to that in the non-ischemic area. Each administration of three beta-blocking agents prevented the decreases in VMRT and Ca++-binding activity and excessive accumulation of acyl-CoA; D-propranolol had no effect. These results suggest that the antiarrhythmic action of beta-blocking agents is based, at least in part, on the protection from decrease in Ca++-binding activity due to mitochondrial dysfunction induced by the excessive accumulation of long-chain acyl-CoA in mitochondria.     

The effect of Coenzyme Q10 on reperfusion injury in canine myocardium

The mechanism of mitochondrial damage during reperfusion injury of ischemic myocardium was studied using mongrel dogs in vivo and isolated mitochondria in vitro. Seventy-seven adult dogs were divided into three groups: the control group (n = 38), the Coenzyme Q10 (CoQ10)-5 mg group (n = 24), and the CoQ10-15 mg group (n = 15). In the control group, the left anterior descending coronary artery (LAD) of the dog was occluded for 15 min followed by 5 min of reperfusion after 40 min of premedication with physiological saline. In both CoQ10 groups, 5 mg/kg or 15 mg/kg of CoQ10 was infused intravenously for 20 min and then physiological saline was administered for 20 min before 15 min occlusion of the LAD. Subsequently, reperfusion was allowed for 5 min. Each group was further divided into two subgroups depending on the presence (arrhythmia group) or the absence (non-arrhythmia group) of ventricular arrhythmias. Immediately after 15 min occlusion, myocardial samples were taken from the normal and reperfused areas to measure CoQ10 content of myocardium. Heart mitochondria were prepared after 5 min of reperfusion from both areas. Arrhythmias appeared in 12 of 38 dogs in the control group (32%), two of 24 dogs in the CoQ10-5 mg group (8%) and none of 15 dogs in the CoQ10-15 mg group (0%). Premedication with CoQ10 increased tissue CoQ10 content in a dose-dependent manner. In the CoQ10-5 mg group, the increase in CoQ10 content of dogs with reperfusion arrhythmias was relatively less than that of dogs without reperfusion arrhythmias. In each group, mitochondrial function was decreased in the arrhythmia group compared to that of the non-arrhythmia group. The increase in free fatty acid (FFA) content and the decrease in phospholipid content were also observed in mitochondria from the reperfused area of each arrhythmia group. The increase in FFA and mitochondrial dysfunction were induced by the incubation of mitochondria in vitro with phospholipase (PLase) A2 or PLase C, and protected by the addition of CoQ10. These results suggest that PLase plays an important role in the development of mitochondrial damage associated with reperfusion.     

Adrenal pheochromocytoma with multiple neurofibromatosis on the trunk

We report a case of adrenal pheochromocytoma in a patient with neurofibromatosis type 1 (NF1). A 65-year-old female patient was admitted to our hospital for examination of a right adrenal mass. The adrenal tumor was incidentally discovered by abdominal computed tomography during examination for hypertension in another hospital. She had large multiple neurofibromatous lesions and café-au-lait spots on the trunk. We thought that it was difficult to make a skin incision on normal skin. Serum and urinary catecholamines were markedly increased. Magnetic resonance imaging revealed a solid round tumor 3 cm in diameter, located in the right adrenal gland. Laparoscopic right adrenalectomy was performed. Serum and urinary catecholamines returned to the normal range on post-operative day 10. Laparoscopic surgery may be a good option for NF1 patients with pheochromocytoma, especially those who had multiple neurofibromatosis on the trunk.     

Ruptured aneurysm of a posterior inferior cerebellar artery communicating artery. Case report and histological findings

A hypertensive 60-year-old man presented with a rare aneurysm arising from the posterior inferior cerebellar artery (PICA) communicating artery, manifesting as subarachnoid hemorrhage with intraventricular hemorrhage. Angiography showed a small aneurysm arising from a fine and tortuous artery interconnecting the bilateral vermian branches of distal PICAs. The right PICA was absent and its vermian territory was supplied by the left PICA through this communicating artery. The right anterior inferior cerebellar artery was also connected to the vermian branch of the right PICA. At surgery, a reddish and apparent fusiform aneurysm was noted at the top of the arterial loop under the cerebellar vermis. Microsurgical trapping and removal of the aneurysm was performed without complication. Histological examination demonstrated typical findings of a true aneurysm. Only four previous cases of aneurysm of the communicating artery between the bilateral distal PICAs have been reported. In all five reported cases including ours, the PICA communicating artery contributed to the collateral blood supply of the contralateral vermian territory based on vascular anomalies. Hemodynamic stress and congenital vulnerability may have caused this aneurysm. Trapping is suitable to treat this precarious aneurysm if other collateral vessels supply the contralateral vermian territory.     

Magnetic resonance cholangiopancreatography for postoperative follow-up of intraductal papillary-mucinous tumors of the pancreas

BACKGROUND: After resection of an intraductal papillary-mucinous tumor (IPMT), benign tumors or portions of the resected tumor are sometimes left in place to avoid total pancreatectomy. We evaluated the role of magnetic resonance cholangiopancreatography (MRCP) in postoperative follow-up. METHODS: Twenty-two patients underwent MRCP 0.5 to 6.5 years after pancreatic resection for IPMT. RESULTS: Two patients with surgical margin involvement of the main pancreatic duct showed mildly enhanced ductal dilatation due to anastomotic stenosis. In 4 patients with residual IPMT of the branch ducts, postoperative MRCP demonstrated no changes. MRCP revealed new IPMT 1 year after surgery in 1 patient. No patients showed intraductal or intracystic mural nodules postoperatively. In 3 patients with postoperative pancreatitis or recurrent abdominal discomfort, MRCP demonstrated ductal dilatation and poor secretin-stimulated pancreatic secretion into the gastrointestinal tract, which suggested pancreatoenterostomic stenosis. CONCLUSIONS: MRCP is useful for postoperative follow-up of IPMT, in terms of investigating residual or recurrent IPMT and evaluating postpancreatectomy long-term complications.     

Complement C4d deposition in transplanted kidneys: preliminary report on long-term graft survival

Abstract:  The effects of antibody-mediated rejection on long-term graft survival have not been fully investigated. The aim of this study is to clarify the influence on long-term survival of deposition of the complement split product C4d in allografts using polyclonal anti-C4d antibody. Inclusion criteria were recipients who underwent graft biopsy during acute deterioration of graft function within the first 2 yr after transplantation. Patients whose graft did not survive more than 1 yr and who received graft from an human leucocyte antigen (HLA)-identical sibling or an ABO-incompatible donor were excluded. Among the 92 recipients investigated, 22 (23.9%) had peritubular capillary C4d deposition, 15 (16.3%) had glomerular capillary C4d deposition and seven (7.6%) had both peritubular and glomerular capillary C4d deposition. Twenty of these 22 patients revealed acute cellular rejection, including borderline changes. There was no significant relationship between pathological severity of acute rejection and presence or absence of peritubular capillary C4d deposition. Graft survival was inferior in patients with peritubular capillary C4d deposition to that in patients without C4d deposition (p = 0.0419). Graft survival in patients with glomerular C4d deposition did not differ from that in patients without C4d deposition. In conclusion, C4d deposition in peritubular capillaries has a substantial impact on long-term graft survival.     

Falciform ligament in pancreatoduodenectomy for protection of skeletonized and divided vessels

Background/purpose  Pancreatic fistula, which is one of the main causes of late postpancreatectomy hemorrhage (PPH), is a common complication of pancreatoduodenectomy (PD). It may erode the anastomosis site and vascular wall in its vicinity, resulting in pseudoaneurysm formation and/or the rupture of major vessels. To protect the vessels near the area for pancreaticojejunostomy from potential pancreatic fistula, we have adopted a surgical option by which such vessels are separated from the pancreaticojejunostomy using a pedicled falciform ligament. We reviewed 36 patients who underwent PD that included this option. Methods  After the PD was completed (before reconstructions), the pedicled falciform ligament was spread widely on the major vessels exposed during resection, and was fixed to the surrounding retroperitoneal connective tissue. These procedures enabled the complete separation of these vessels from the pancreaticojejunostomy. Results  The mobilization and placement of the falciform ligament in the space between the pancreaticojejunostomy and the major vessels were successfully carried out without any complications. Although ten (28%) patients developed pancreatic fistula and three (8%) developed intraabdominal infection, none of the patients developed late PPH. Conclusions  The present surgical option is technically simple and easy, and may be an effective prophylactic measure against late PPH following PD.     

Impaired expression of hepatic multidrug resistance protein 2 is associated with posthepatectomy hyperbilirubinemia in patients with biliary cancer

Background and aims Hyperbilirubinemia is a critical complication following hepatectomy for biliary cancer. Hepatic multidrug resistance protein 2 (MRP2), a bilirubin transporter, is shown to be down-regulated by acute biliary obstruction in rats. However, little is known about the effect of chronic obstruction by malignancy on the MRP2 expression in patients or the association of MRP2 expression with posthepatectomy hyperbilirubinemia.Materials and Methods The MRP2 expression before hepatectomy was determined by immunostaining and Western blotting in patients with biliary cancer. To directly determine the effect of chronic bile duct obstruction on the MRP2 expression, the expression levels were compared between the cholestatic and noncholestatic lobes in each of seven patients. In another 39 patients, the correlation of the MRP2 expression of the anticipated remnant liver with the posthepatectomy severe hyperbilirubinemia, defined as a serum total bilirubin concentration200 mol/l, was evaluated.Results The MRP2 staining in the cholestatic lobes was weak and not restricted to the canalicular membrane, unlike the noncholestatic lobes. The expression levels in the cholestatic lobes were 45% of those in the noncholestatic lobes. Postoperative maximum bilirubin levels were significantly correlated with MRP2 expression of the anticipated remnant liver. The MRP2 expression had been already impaired before hepatectomy in all patients who eventually developed severe hyperbilirubinemia.Conclusions Decreased MRP2 expression, caused by biliary obstruction due to cancer, is a possible risk factor for posthepatectomy severe hyperbilirubinemia.     

Solitary retroperitoneal neurofibroma: a case report

A solitary neurofibroma arising in the retroperitoneal space without any other stagma of von Recklinghausen's disease is reported. Confusion with another nerve sheath tumor, a schwannoma is a diagnostic pitfall. Histochemical and immunohistochemical stainings of the tumor are useful for the diagnosis of solitary neurofibroma.     

Prevention of naphthalene-1,2-dihydrodiol-induced lens protein modifications by structurally diverse aldose reductase inhibitors.

The effects of aldose reductase inhibitors on lens protein modifications induced by naphthalene-1,2-dihydrodiol were investigated in vitro to confirm the role of aldose reductase on naphthalene cataract formation. HPLC analysis of naphthalene-1, 2-dihydrodiol incubated with aldose reductase and NAD+indicated the formation of a metabolite peak corresponding to 1,2-naphthoquinone. Soluble proteins from rat lenses prepared by gel filtration of crude lens extracts through Sephadex PD-10, incubated with naphthalene-1, 2-dihydrodiol in the presence of NAD+displayed an absorbance ca 450 nm and their spectra were essentially identical to those of 1, 2-naphthoquinone-protein adducts. Similar spectra were also obtained from proteins isolated from the intact rat lens after in vitro incubation in medium containing naphthalene-1,2-dihydrodiol. The spectra obtained from lens proteins incubated with 1, 2-dihydroxynaphthalene were distinct from those of either naphthalene-1,2-dihydrodiol or 1,2-naphthoquinone. Aldose reductase inhibitors possessing either hydantoin or carboxylic acid groups prevented protein modification induced by naphthalene-1, 2-dihydrodiol but not protein modification induced by 1, 2-dihydroxynaphthalene or 1,2-naphthoquinone. Therefore, the metabolite formed from naphthalene-1,2-dihydrodiol by aldose reductase is 1,2-naphthoquinone. Lens proteins modified by naphthalene-1,2-dihydrodiol appear essentially identical to protein adducts formed with 1,2-naphthoquinone and their formation can be prevented by both hydantoin and carboxylic acid containing aldose reductase inhibitors.