Involvement of stem cell factor and its receptor tyrosine kinase c-kit in pain regulation.

The c-kit receptor tyrosine kinase is expressed in a subpopulation of small- and medium-sized neurons of the dorsal root ganglia (DRG) and in the superficial layer of the spinal cord. Stem cell factor (SCF), a ligand of the c-kit receptor, induces neurite outgrowth from DRG and supports the survival of c-kit-expressing neurons. To clarify the possible function of the SCF/c-kit receptor system in the adult animal, we investigated the expression of c-kit receptor in the spinal cord and DRG in relation to pain by using H2C7, a newly developed anti-c-kit monoclonal antibody. S.c. and intrathecal injection of SCF markedly reduced the paw withdrawal threshold to mechanical stimuli and intrathecal SCF at 10 pg maximally induced mechanical allodynia in conscious mice. Intrathecal SCF also reduced the paw withdrawal latency to heat stimuli significantly but transiently. The c-kit receptor was co-expressed in 58.4% of calcitonin gene-related peptide (CGRP) -positive, but only 5.1% of isolectin B4-positive, DRG neurons. In the spinal cord, the c-kit receptor was detected in the superficial layer of the dorsal horn and co-localized there with CGRP in central terminals of DRG neurons. Selective elimination of unmyelinated C-fibers by neonatal capsaicin treatment resulted in marked reduction of the c-kit receptor and CGRP expression in the superficial layer of the spinal cord. Cell-size profiles showed that c-kit receptor expression was significantly up-regulated and down-regulated in medium-sized DRG neurons after neonatal capsaicin treatment and nerve injury, respectively. These results suggest that the c-kit receptor is mainly expressed in peptidergic small-sized DRG neurons and may be involved in pain regulation both peripherally and centrally.

[Total aortic arch replacement with a right femur neck fracture on chronic renal dialysis; report of a successful case].

Although recent operative outcome for aortic arch aneurysm has been improved by various newly-devised assistant measures, satisfactory results have not been obtained in cases with serious preoperative complications, such as chronic renal failure. We present here an operative case of a 67-year-old woman on chronic hemodialysis with a calcified aortic arch aneurysm and a right femur neck fracture. First, we performed femur head replacement under careful hemodynamic control. After her mobilization was achieved, total aortic arch replacement was performed in "arch-first technique" using deep hypothermia plus retrograde cerebral perfusion in consideration of her calcified vessels. Her postoperative course was uneventful. We believe that early mobilization was a key for her recovery, because it was useful to prevent postoperative complications such as pulmonary infection and atelectasis. Our experience suggested that meticulous management throughout the whole perioperative course is very important for total aortic arch replacement in such complicated cases.

[Dor operation combined with redo coronary artery bypass grafting; report of two successful cases].

Case 1. A 69-year-old male, who had undergone coronary artery bypass grafting with saphenous vein graft for acute myocardial infarction 16 years previously, was admitted into our hospital for heart failure and recurrent angina. Coronary angiography showed occlusion of the graft and 75% stenosis in the proximal circumflex artery. Left ventriculography showed end-diastolic volume of 216 ml and ejection fraction of 24%. Dor operation combined with redo coronary artery bypass grafting was performed. Postoperatively, the ejection fraction improved to 53% and the cardiac index improved from 1.8 to 2.2 l/min/m2. Case 2. A 67-year-old male, who had undergone double coronary artery bypass grafting using saphenous vein grafts for acute myocardial infarction 8 years previously, was admitted into our hospital for heart failure and recurrent angina. Coronary angiography showed occlusion of the 2 grafts and 99% stenosis of the proximal left anterior descending artery. Although the left ventricle was slightly dilated, echocardiography demonstrated a thrombus in the left ventricle. Dor operation was performed concomitantly with removing of the thrombus and redo coronary artery bypass grafting. Postoperatively, the ejection fraction improved to 68% and the cardiac index improved from 1.6 to 2.3 l/min/m2. When the patients underwent coronary artery bypass surgery with saphenous vein grafts for acute myocardial infarction, they could be susceptible to left ventricular asynergy and graft failure on the long run. Therefore, the patients who need redo coronary revascularization may be potential candidates for Dor operation, and they require close examination regarding the myocardial viability, volume and shape of the left ventricle.

Pedunculated hemangioma in the right ventricle.

We report a rare case of right ventricular hemangioma. In an asymptomatic 56-year-old man, echocardiography as a part of medical checkup demonstrated a pedunculated tumor, 1.0 x 1.3 x 1.5 cm, arising from the free wall of the right ventricle. No findings were seen of a feeding artery to the tumor or vascular blush in preoperative coronary angiography. Successful resection was done through right atriotomy under total cardiopulmonary bypass. The histological examination revealed capillary hemangioma. The postoperative clinical course was uneventful, but requires careful follow-up for possible coronary cardiac fistula. This is the fifth case of right ventricular hemangioma, to our knowledge, ever reported in Japan.

The nutritional status of elderly bed-ridden patients receiving tube feeding.

Long-term enteral feeding by tube has become a frequently used procedure in elderly patients. However, only a few studies dealing with the nutritional assessment of such patients are currently available. This study was designed to clarify this issue. Anthropometric and biochemical variables, energy expenditure and dietary intake were investigated in 44 hospitalized bed-ridden patients with and without tube feeding over 65 years of age and 41 age-matched free-eating elders in a nursing home. All patients with tube feeding received enteral nutrition by nasogastric tube. The body weight, body mass index, mid-upper-arm circumference, arm muscle circumference and serum level of albumin were significantly lower in the patients with and without tube feeding, compared with free-eating elders of both genders (p<0.05). Energy intakes of the patients with tube feeding were 1,171+/-286 kcal/d (about 26 kcal/kg/d), which is comparable to the predicted total energy expenditure (1.2 x basal energy expenditure). Protein intake was 44.9+/-13.1 g/d (about 1.0 g/kg/d) and the percentage of protein per total energy was 15%. These intakes are generally considered to be optimal for bed-ridden patients receiving tube feeding. However, the incidence of protein-malnutrition, as evidenced by decreased arm muscle circumference (<80% of normal) and hypoalbuminemia (<35 g/L), in the patients with tube feeding was significantly higher than that in the healthy elders. In addition, the orally fed bed-ridden patients were also malnourished, suggesting that the bed-ridden patients easily became malnourished even if they were fed energy and protein which approximated calculated predicted values. These findings raise a problem concerning nutritional management of bed-ridden patients.

Ultrasound vasography evaluation of radial arterial grafts used for coronary arterial bypass surgery.

OBJECTIVES: For coronary bypass surgery, radial arteries are often used as bypass grafts. Some of these arteries however, have arteriosclerotic lesions. We attempted to evaluate the relationship between arteriosclerosis and vasodilation. METHODS: Prior to bypass surgery, 20 patients underwent ultrasound vasography to determine the condition of their radial and brachial arteries. Flow-mediated dilation, which is the same as endothelium-dependent vasodilation, was measured in the brachial artery of the nondominant arm by reactive hyperemia after 5-minute forearm ischemia. Vasodilation after application of a sublingual glyceryl trinitrate spray was also measured. RESULTS: During surgery, 4 of 20 radial arteries demonstrated calcification, and 3 of the 4 could be used by removing the calcified part. However, the other artery, which had extensive calcification that could not be detected by ultrasound vasography, was discarded. The amount of vasodilation seen after the administration of sublingual glyceryl trinitrate had no correlation with calcified grafts. Calcified radial arteries demonstrated significantly poor brachial artery vasodilation by an endothelial-dependent vasodilation test. CONCLUSIONS: Calcification in radial arteries can thus only be evaluated by flow-mediated dilation.

Exercise improved accumulation of visceral fat and simultaneously impaired endothelium-dependent relaxation in old rats.

Exercise decreases plasma total cholesterol and triglycerides, and simultaneously, increases high density lipoprotein (HDL) cholesterol. Furthermore, it has been reported that exercise improves insulin resistance. As a result, exercise is believed to aid in preventing atherosclerosis. However, we do not know whether exercise protects against the development of atherosclerosis in the elderly. The aim of this study was to ascertain whether exercise prevented atherosclerosis in aorta of old rats. Exercise for three months did not affect plasma lipid levels but decreased accumulation of visceral fat and body weight without the reduction of food intake in two year old rats. Exercise also decreased triglycerides in liver and gastrocnemius white muscle. Exercise resulted in an elevation of plasma lipid peroxide (LPO) levels without affecting superoxide dismutase (SOD). Exercise impaired the endothelium-dependent relaxation of the thoracic aorta caused by acetylcholine in old rats. In summary, the results of our study indicate that exercise induces the reduction of visceral fat, body weight and triglyceride contents in tissues in old rats. These results seems to show that exercise improves insulin resistance. However, exercise simultaneously may cause impaired endothelium-dependent relaxation by elevation of LPO in old rats.

Angiographic assessment of surgical reconstructions for left ventricular asynergy with indices of abnormally contracting segments.

BACKGROUND: In surgical reconstruction for left ventricular asynergy after myocardial infarction, the conventional linear closure technique second to simple resection and endoventricular circular patch plasty, which is the so-called Dor technique, are commonly utilized. We assessed these techniques using an abnormally contracting segment (ACS) in the left ventriculogram. METHODS: We reviewed 10 and 15 patients who underwent the linear technique (group L) and the Dor technique (group D), respectively. %ACS was determined as the percent ratio of both akinetic and dyskinetic chords among the total chords in the centerline method of regional wall motion analysis. A difference between preoperative and postoperative ejection fraction (EF) was generated by preoperative EF and this percentage ratio was determined as %EF. RESULTS: Postoperative EF improved from 31% to 41% in group L and from 33% to 49% in group D (p<0.05). Postoperative EF in group D was higher than in group L (p<0.05). %ACS decreased from 41% to 34% in group L and from 41% to 19% in group D (p<0.05). Postoperative %ACS was lower in group D than in group L (p<0.05). The significant correlation between preoperative %ACS and %EF was negative in group L and positive in group D (p<0.05). CONCLUSIONS: The Dor technique is more effective for the postoperative systolic function than the linear technique because more extensive reduction in %ACS is possible with the Dor technique than with the linear technique. Dor technique becomes more crucial to the postoperative systolic function as the preoperative %ACS becomes larger.

[Clinical evaluation of cardiac valve surgery combined with coronary artery bypass grafting].

Between 1991 and 1999, 23 cases underwent cardiac valve surgery concomitant with myocardial revascularization at our institution. Twelve cases (group I) had a primary valvular disease combined with coronary atherosclerosis, and other 11 cases (group II) were due to ischemic mitral insufficiency. There were 2 hospital deaths in group I (17%) and 4 in group II (36%). Three deaths in group II underwent left ventricular volume reduction surgery. On the basis of this observation, we concluded severe mitral regurgitation with ischemic cardiomyopathy was a particularly difficult management problem with disappointing clinical results. On the other hands, we considered concomitant revascularization should be done in the case of primary valvular disease when angiographically significant coronary artery stenosis was present.

Effect of the lipoprotein lipase activator NO-1886 on adriamycin-induced nephrotic syndrome in rats.

Hyperlipidemia associated with nephrotic syndrome may play a role in the deterioration of renal function. Tsutsumi et al have previously reported that the novel compound NO-1886 increases lipoprotein lipase (LPL) activity, resulting in a reduction of plasma triglycerides and an elevation of high-density lipoprotein (HDL) cholesterol in normal rats. The aim of this study was to ascertain whether NO-1886 suppresses the renal injury by treatment of the hyperlipidemia in an Adriamycin (Kyowa Hakko Kogyo, Tokyo, Japan) induced nephrosis rat model fed a high-protein diet that induced renal dysfunction and tubulointerstitial injury. Administration of Adriamycin caused hyperlipidemia, proteinuria, and edema with ascites in rats in 4 weeks. Furthermore, a combination of Adriamycin and a high-protein diet increased plasma creatinine and blood urea nitrogen (BUN) and decreased plasma albumin. Histologically, in Adriamycin-treated rats, marked interstitial cellular infiltration, tubular lumen dilation, and tubular cast formation in the kidney were observed. NO-1886 decreased plasma triglyceride and increased HDL cholesterol in Adriamycin-induced nephrotic rats. NO-1886 treatment reduced plasma creatinine and BUN levels and increased plasma albumin in Adriamycin-treated rats; it also ameliorated the ascites and proteinuria. Histologically, NO-1886-treated rats showed a quantitatively significant preservation of tubulointerstitial lesions. These data suggest that NO-1886 may have a protective effect against Adriamycin-induced nephrosis with tubulointerstitial nephritis in rats by a modification of the plasma lipid disorder.

Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes.

BACKGROUND: Taurine, a potent antioxidant, has been reported to improve streptozotocin-induced diabetes mellitus, in which the development of diabetes results from an attack by oxygen free radicals on pancreatic beta cells. However, taurine also increases the excretion of cholesterol via conversion to bile acid and would be expected to improve insulin resistance. OBJECTIVE: The effects of taurine on insulin sensitivity were examined in a model rat of insulin resistance and type 2 diabetes-the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. DESIGN: Male OLETF rats were divided into 2 groups at the age of 16 wk: a taurine-supplemented group and an unsupplemented group. As a nondiabetic control, Long-Evans-Tokushima-Otsuka rats were used. An oral-glucose-tolerance test and hyperinsulinemic euglycemic clamp were performed at the ages of 23 and 25 wk. RESULTS: The OLETF rats had hyperglycemia and insulin resistance and they had a greater accumulation of abdominal fat than did control rats. Abdominal fat accumulation, hyperglycemia, and insulin resistance were significantly lower in the taurine-supplemented group than in the unsupplemented group. Serum and liver concentrations of triacylglycerol and cholesterol were significantly higher in the OLETF rats than in the control rats and were significantly lower in the taurine-supplemented group than in the unsupplemented group, presumably because of the increased secretion of cholesterol into bile acid. Taurine-supplemented rats also showed higher nitric oxide secretion, evidenced by increased urinary excretion of nitrite. CONCLUSION: Taurine effectively improves metabolism in OLETF rats by decreasing serum cholesterol and triacylglycerol, presumably via increased secretion of cholesterol into bile acid and decreased production of cholesterol because of increased nitric oxide production.

Batista's operation with coronary artery bypass grafting and mitral valve plasty for ischemic dilated cardiomyopathy.

A 52-year-old male was admitted for angina pectoris and congestive heart failure classified as New York Heart Association class III. Coronary angiography showed 95% stenosis in the left anterior descending artery, 99% stenosis in the first diagonal branch, total occlusion in the left circumflex artery, and a hypoplastic right coronary artery. Left ventriculography showed a severely dilated left ventricle (ejection fraction 20%) and mild mitral regurgitation. In the myocardial scintigram using 99m-tetrofosmin, there was no viability in the posterolateral wall although the other wall was viable. Partial left ventriculectomy, which is called Batista's operation, coronary artery bypass grafting and Alfieri's mitral valve plasty were performed concomitantly. Postoperatively, the ejection fraction was improved to 39%, and all grafts were patent. The patient was discharged in New York Heart Association class I. We concluded that to succeed in partial left ventriculectomy for ischemic dilated cardiomyopathy, not only should there be no viability in the posterolateral wall to be resected for volume reduction, but the coronary artery which perfuses the residual myocardium with viability should be graftable.

Decreased food intake and body weight in pancreatic polypeptide-overexpressing mice.

BACKGROUND & AIMS: Pancreatic polypeptide (PP) is a 36-amino acid hormone produced by F cells within the pancreatic islets and the exocrine pancreas. The definitive function of PP in mammalian physiology remains to be determined. This study examined the effects of chronic overexpression of PP through the development of PP transgenic mice. METHODS: PP transgenic mice were created by using mouse PP complementary DNA under the control of the cytomegalovirus immediate early enhancer-chicken beta-actin hybrid promoter (pCAGGS expression vector). RESULTS: A unique line of transgenic mice was created that overexpresses PP in the pancreatic islets with low levels of expression in other tissues including the brain. Plasma PP concentrations were more than 20 times higher than those of control littermates. However, PP overproduction led to postnatal lethality in half of the pups because of markedly decreased milk intake. The remaining PP transgenic mice gained less weight with specifically reduced food intake and fat mass compared with controls, a result that was more evident in male than in female mice. The transgenic mice exhibited a reduced rate of gastric emptying of a solid meal but had normal oxygen consumption and fasting leptin levels. Immunoneutralization with anti-PP antiserum reversed the phenotypic changes of transgenic animals. CONCLUSIONS: PP could be involved in feeding and body weight regulation partly through regulation of gastric emptying.

[A case who needed additional Daggett's procedure for residual shunt after infarction exclusion technique for post-infarction ventricular septal perforation].

A 71-year-old woman had the surgical repair of post-infarction ventricular septal perforation with infarction exclusion technique. Three days after operation, residual shunt was observed by echocardiogram and she developed cardiac failure. Pulmonary to systemic flow ratio was 2.1, and pulmonary artery pressure was 42/23 (33) mmHg. Additional surgery for residual shunt was performed 22 days after the first operation. The part of Xenomedica patch was found loosely floating in the LV cavity. The infarcted myocardium was firm enough to closed directly, so a double Hemashield cardiovascular fabric was sutured on the left side of the perforated septum around VSP (Daggett's Procedure). The ventriculotomy was closed including the fabric with two felt strips. The postoperative course was uneventful. Though infarction exclusion technique has the advantage in many cases, much attention must be paid to prevent residual shunt.

[Emergency coronary artery bypass grafting for acute coronary syndrome].

Emergency CABG for acute coronary syndrome (ACS) was studied. Sixty patients had CABG for medically refractory UAP, 78 patients for AMI and 8 patients for post-infarction angina (PIA). In UAP group 7 patients (12%) died postoperatively, mainly due to perioperative myocardial infarction (PMI) and operative complications. In AMI group, 26 patients (33%) died, 14 of them due to myocardial failure. The operative mortality was extremely high in shock-state patients group (48%) and cardiac pulmonary arrest state patients group (85%). Operative result was poor in those patients whose infarct-related artery was not recanalized preoperatively. Operative mortality was 13% in PIA group. It was concluded that the reduction of mortality of those patients required much refined myocardial preservation technique and powerful mechanical assist system to support the postoperative myocardial failure.

Plasma endothelin-1 elevation associated with alcohol-induced variant angina.

Vasospastic angina as a result of alcohol ingestion has been reported, but the mechanism of alcohol-induced coronary artery spasm is presently unknown. This report presents 2 cases of alcohol-induced variant angina (VA) with elevated levels of plasma endothelin-1 after alcohol ingestion. In case 1, the plasma endothelin-1 concentration was 3.15 pg/ml before drinking (normal <2.30 pg/ml) and increased to 4.09 pg/ml when measured 5 h after alcohol ingestion. After 2 months of abstinence, the plasma endothelin-1 concentration was 2.88 pg/ml and 6 months after abstinence, it decreased to 2.03 pg/ml (normal range). In case 2, the plasma endothelin-1 concentration was 2.44 pg/ml before drinking and increased to 4.36 pg/ml when measured 5 h after alcohol ingestion. After 2 months of abstinence, the plasma endothelin-1 concentration was 3.04 pg/ml and 6 months after abstinence, it decreased to 2.09 pg/ml (normal range). These 2 cases suggest that a relationship may exist between alcohol-induced VA and elevation in the plasma endothelin-1 concentration after alcohol ingestion.

Effects of troglitazone on frequency of coronary vasospastic-induced angina pectoris in patients with diabetes mellitus.

This study investigates the effects of troglitazone, an insulin sensitizer, on the clinical manifestation of coronary vasospastic angina pectoris in patients with diabetes mellitus. Troglitazone reduces frequency of angina pectoris and improves endothelial function.

Evaluation of coronary artery bypass grafts using helical scan computed tomography.

The patency of coronary artery bypass grafts was evaluated by helical computed tomographic (CT) scan. One hundred forty patients who received an enhanced chest CT scan and a coronary angiography after bypass surgery were studied before discharge at the Fukui Cardiovascular Center. Among them was a total of 398 grafts and 436 anastomoses. For the evaluation of 248 vein grafts, the CT scan showed a 99.5% correct positive ratio and an overall accuracy of 96.4%. In 122 internal thoracic arteries tested, an overall accuracy of 64.7% was obtained. In gastroepiploic artery tests the overall accuracy was 33.3% and in radial artery tests it was 45.5%. Thirty-seven venous sequential anastomoses in 34 grafts and 1 internal thoracic artery sequential anastomosis were also evaluated. In the venous sequential anastomosis, the CT scan showed a 73.0% of accuracy overall. This study showed that the helical CT scan was useful to evaluate graft patency following bypass surgery.

[Coronary artery bypass surgery in octogenarian].

Between May 1992 and December 1997, 14 parents aged 80 or older underwent CABG with cardiopulmonary bypass. (Group A: mean age 82.1 +/- 1.73). This group was compared with 127 patients aged 70s. (Group B: mean 73.3 +/- 0.70). Left main trunk stenosis was more frequent in group A (p < 0.05), and number of patient who had old myocardial infarction was also frequent (p < 0.05). Emergency operation and preoperative use of intra aortic balloon pump was frequent in group A (p < 0.05). While there was no significant change in the number of graft per patient and used number of internal thoracic artery between the two groups, postoperative complications such as atrial arrhythmia and respiratory failure was appeared more frequently in group A (p < 0.05). The hospital mortality did not differ between the groups (21.4% for group A and 14.2% for group B). In group A, 11 patients are alive without recurrence of angina. In conclusion, while there is many problems pre and post operative term, CABG in over 80 years patients of age was satisfactory result, so we should not exclude octogenarian because of age alone.