[Juxta renal aortic occlusion].
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Biomedical subjects
Publications and source records attributed to K Kosuga.
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BACKGROUND: Oxidized LDL and lysophosphatidylcholine (LPC) have been reported to inhibit the endothelium-dependent relaxation (EDR) mediated by nitric oxide. Recently, a new vasorelaxing factor, endothelium-derived hyperpolarizing factor (EDHF), which hyperpolarizes and relaxes the porcine coronary artery in the presence of N omega-nitro-L-arginine (NNA) and indomethacin (IM), has been reported. We examined whether LPC also inhibits both the EDHF-mediated relaxation and membrane hyperpolarization of the porcine coronary artery. METHODS AND RESULTS: EDHF was evaluated as the bradykinin- or A23187-induced relaxation of the porcine coronary artery contracted by prostaglandin F2 alpha in the presence of NNA and IM. We also directly measured the membrane potential of the porcine coronary artery. The effects of LPC on both relaxation and membrane hyperpolarization were investigated. At concentrations of 0 to 20 mumol/L, LPC dose-dependently inhibited the NNA/IM-resistant EDR induced by bradykinin and A23187, and the relaxation was reversible after the absorption of LPC with albumin. LPC also inhibited the bradykinin- and A23187-induced hyperpolarization of the porcine coronary artery. CONCLUSIONS: In the present study, LPC was found to inhibit not only nitric oxide-mediated but also EDHF-mediated relaxation of the porcine coronary artery. Our findings suggest a new regulatory mechanism in the atherosclerotic coronary artery.
A full-length cDNA encoding mouse squalene epoxidase was isolated by screening a mouse liver cDNA library with the rat squalene epoxidase gene as a probe. The cDNA had an open reading frame for a 572 amino acid polypeptide with a calculated molecular mass of 63.8 kDa. The predicted amino acid sequence of the mouse enzyme contained an FAD-binding motif, and was 93% identical to that of the rat enzyme. The former is one amino acid shorter than the latter. Blotting analyses showed that the mRNA is 2.8 kb in size and that a single copy of the gene is present in the mouse genome.
Hepatocyte nuclear factor 4 (HNF-4) is a liver-enriched transcription factor involved in the expression of many liver-specific genes. In the preceding communication (Hata, S., Tsukamoto, T. and Osumi, T. (1992) Biochim. Biophys. Acta 1131, 211-213), we reported the presence of two isoforms of mRNA for HNF-4 in rat liver and kidney. The longer isoform contained a segment of 30 bases which was not present in the shorter one. As an initial step to determine whether or not other mammals have these mRNA isoforms, we isolated a cDNA for mouse HNF-4 using the rat HNF-4 gene as a probe. The cDNA had an open reading frame for a 465 amino acid polypeptide. The deduced amino acid sequence was remarkably conserved between mouse HNF-4 and rat HNF-4 (99.6% identical). Moreover, like the cDNA for the larger rat isoform, the mouse cDNA contained an extra segment of 30 bp in the coding region near the C-terminus. Blotting analyses showed that the mRNA is about 3.7 kb in size and that a single copy of the gene is present in the mouse genome. Next we carried out the polymerase chain reaction (PCR) using primers located just upstream and downstream of the extra segment. Two PCR products were amplified from a mouse liver cDNA library. Determination of their nucleotide sequences proved that they exactly corresponded to the two rat isoforms. Finally, we amplified a DNA fragment (1.1 kb in size) from mouse genomic DNA using the same PCR primers as above. Its nucleotide sequence unequivocally confirmed that different splice donor sites were used to generate the two isoforms.
The inhibitory effect of ongoing rejection and the changes that occurred in mononuclear cell subpopulations were compared between four groups of rats treated with FK506 or steroids. Group 1 was given no immunosuppressive drugs, group 2 was given FK506 from the day of grafting, group 3 was commenced on FK506 on the 4th day after grafting, and group 4 was commenced on methylprednisolone (MP) on the 4th day after grafting. The graft survival times in groups 2 and 3 were significantly longer than those in groups 1 and 4, and there were fewer CD3+ and CD4+ T lymphocytes in the peripheral blood in the groups treated with immunosuppressive drugs than in group 1. In group 4, the levels in both the peripheral blood and thymus were significantly lower than those in the groups treated with FK506 despite the fact that graft rejection occurred soon after the discontinuation of steroid administration. Moreover, the levels of interleukin-2 receptors and macrophages in groups 2, 3, and 4 were significantly lower than that in group 1 postoperatively; however, the number of macrophages in groups 2 and 3 was significantly lower than that in group 4 on the 10th day after transplantation. The findings of this study demonstrated that FK506, even if administered after rejection has begun, might inhibit the subsequent extensive allograft rejection more specifically and effectively than steroids, and that the measurement of a marker for macrophages in the peripheral blood could be useful for the detection of rejection following allograft transplantation in rats.
In order to clarify the relationship between the patency of the infarcted arteries and subsequent long-term prognosis after thrombolytic therapy, we evaluated 116 patients with acute myocardial infarction treated with intracoronary (112 patients) or intravenous (four patients) urokinase. Patients treated with angioplasty after thrombolysis were excluded. The infarcted vessel was recanalized in 52 patients (patent group) and was not in the remaining 64 patients (occluded group). Five-year and 8-year follow up was conducted in 91% and 81% of the patients, respectively. The 1-, 5- and 8-year survival rate for the patent and occluded group was 91.8 and 80.9%, 80.8 and 79.2%, and 75.9 and 75.6%, respectively. The survival rate in the patent group tended to be higher than that in the occluded group up to 4 years. However, after 5 years, both groups showed similar survival rates. Therefore, reopening of the infarcted arteries with thrombolysis was not an independent predictor for late cardiac death (Cox regression analysis).
The durability of mitral valve repaired with reconstructive techniques is variable. If the durability continues to be good, mitral valve repair may be the procedure of choice in many patients with mitral regurgitation. Between December 1970 and June 1993, 54 patients had mitral valve repair for non-rheumatic mitral regurgitation. There were 38 men and 16 women with a mean age of 46.8 (range 19-68) years. The pathology which required surgical treatment was torn chordae in 38 patients, elongation of the chordae in five, valve prolapse without elongation or rupture of the chordae in six, infective endocarditis in three, and annular dilatation in two. Forty-four patients had triangular or quadrangular resection of the mitral leaflet, and seven had annuloplasty alone. Choral reconstruction was performed on three patients. There were no operative deaths. Five patients (9%) died late after operation. The actuarial survival rate and the valve-related death-free rate at 10 years were 83.9% and 90.0%, respectively. Seven patients (13%) required reoperation. Freedom from reoperation at 10 years was 84.5%. Improper evaluation of residual regurgitation during operation and suture dehiscence were the principal causes of reoperation. It was concluded that mitral valve repair for non-rheumatic mitral regurgitation showed low operative mortality and stable long-term results. It is suggested that intraoperative transoesophageal colour Doppler echocardiography provides accurate assessment of mitral valve competence and may be helpful in reducing the need for reoperation.
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A 58-year-old Japanese woman who had a history of aortic valve replacement for congenital bicuspid valve, was admitted for investigation of facial edema and of pulselessness of the right leg. Physical examination disclosed the patient suffering from a superior vena cava syndrome. On auscultation, a continuous murmur was heard at the left lower sternal border. Computed tomographic scans revealed aortic dissection extending from the ascending aorta to the bifurcation. Echocardiography showed an intimal flap in the dilated ascending aorta, but not abnormal blood flow from the aorta to the right atrium was detected. Cardiac catheterization and aortography, however, allowed a correct diagnosis of aortic dissection with fistula to the right atrium and with obstruction of the right common iliac artery. The patient received emergency aortic root replacement and reconstruction of the coronary arteries and then recovered uneventfully.
A 64-year-old woman without manifestations of Marfan syndrome was referred for the close investigation of a pulsatile abdominal mass. Computed tomographic scans and magnetic resonance images revealed aneurysmal dilatation of the entire aorta, including the ascending aorta and extending to the bifurcation of the aorta, as well as tortuousness of the thoracoabdominal and abdominal aorta. Digital subtraction angiography also showed aneurysmal dilatation of the entire aorta and trivial aortic regurgitation. However, aortic annular dilatation was not found by echocardiography or aortography. The entire aorta was replaced in two stages. First, graft replacement of the ascending aorta, except for the sinus segment, and the aortic arch was performed using an elephant trunk technique under hypothermic cardiopulmonary bypass with selective cerebral perfusion. Twelve weeks later, the remaining aorta, including the descending aorta and extending to the common iliac artery on the right side, and to the common femoral artery on the left side, was replaced with a partial cardiopulmonary bypass using femoral artery and vein cannulation. We believe that patients with mega aorta syndrome are best treated by total aortic replacement. The results in the present case indicate that the elephant trunk technique is useful for extensive aortic replacement in stages, and greatly facilitates the second stage operative procedures.
Myocardial injury after heart storage has been known to contribute to an increase in myocardial calcium content or oxygen free radical production. The present experiment was designed to determine the inhibitory effect of steroid in the preservation solution on myocardial injury during simple immersion of isolated rat hearts. The experimental group was divided into 5 sub-groups according to the concentration of steroid added to the solution. Group I was stored in preservation solution containing no steroid. Groups II to V were stored in preservation solutions containing methylprednisolone in concentrations of 50 mg/L, 100 mg/L, 150 mg/L, and 200 mg/L, respectively. After the rat hearts were isolated, crystalloid cardioplegic solution at 4 degrees C was used for cardiac arrest, and the hearts were immersed in 4 degrees C Euro-Collins solution for 8 h. Hearts were then maintained under ischemic conditions at 25 degrees C for 15 min. After 60 min of reperfusion at 37 degrees C, cardiac function was measured and biochemical analyses of coronary effluent and myocardium were performed. The cardiac outputs in groups IV and V were significantly higher than those in groups I and II (p < 0.01). Creatine kinase-MB in coronary effluent in groups IV and V were significantly lower than those in groups I and II at 15, 30 and 60 min after reperfusion (p < 0.05). The level of arachidonic acid at 1 and 5 min, and the level of malondialdehyde at 5 min, after reperfusion in groups III, IV and V were significantly lower than those in groups I and II. Myocardial adenosine triphosphate was most preserved in group IV, and myocardial arachidonic acid, malondialdehyde, and calcium levels and water content in groups IV and V were lower than those in groups I and II. Ultrastructural observations also showed that myofilaments and mitochondria were well preserved in groups III, IV and V at 15 min after reperfusion compared with those in groups I and II. These results indicate that the addition of steroid to preservation solution might be effective in preventing myocardial injury during preservation of rat hearts, and the optimal concentration appears to range from 150 mg/L to 200 mg/L.
A 57-year-old man with manifestations of Marfan syndrome was referred for detail examination of cardiac murmur to our hospital. Cardioangiography showed moderate aortic valve regurgitation (2/4), and severe mitral valve regurgitation (3/4), in addition to aneurysmal dilatation of the aortic root. Moderate tricuspid valve regurgitation (2/4) was also detected by Doppler echocardiography. Aortic root replacement with the Cabrol technique, mitral valve replacement with a St. Jude Medical valve, and repair of the tricuspid valve with the bicuspidalization technique were simultaneously performed in this patient. His postoperative recovery was uneventful. In this study, we discuss about the indications of simultaneous aortic root replacement and mitral valve replacement in a patient with Marfan syndrome.
Between December, 1967, and July, 1994, 96 patients underwent repair of the mitral valve for acquired mitral valve regurgitation. According to Carpentier's classification, mitral valve pathology resulting in valve regurgitation was classified into three types; 4 patients assigned to type I, 63 type II, and 29 type III. The operative mortality rate was 1.0%. Follow-up data were available in 95 patients from 0.5 year to 25.3 years (mean average 8.8 years). The late mortality rate were not different between patients with valve pathology of type I, II and those with valve pathology of type III. Thromboembolism occurred on three patients for an embolic rate of 0.4% per patient-years. Twenty-eight patients required reoperation for residual MR and dehiscence of suture lines (type II; 10 cases, reoperation-free rate at 20 years, 83.2%) or recurrent MR due to progression of valve deformity (type III, 18 cases, reoperation-free rate at 20 years, 14.8%). These results demonstrate that patients with type I and II valve are good candidates for MVP, and that high incidence of reoperation for recurrent MR may limit the application of MVP to selected patients with type III valve.
The usefulness of the free inferior epigastric artery (IEA) as a coronary bypass graft was studied. Among 149 patients for coronary bypass grafting (CABG) between October 1992 and December 1994, the free IEA was used in 12 patients. The mean number of distal anastomosis was 3.7 per patient. The mean distal size of the IEA was 1.3 mm in diameter and the mean length was 9.4 cm. The IEA graft was anastomosed to the obtuse marginal branch in 5, to the diagonal branch in 4, and the right ventricular branch in 3. The proximal anastomosis of the IEA was constructed to the ascending aorta in three and to the saphenous vein (SVG) or to the internal thoracic artery (ITA) in 4 or 5, respectively. Postoperative angiogram demonstrated patent graft in ten and occluded graft in two in whom the size of IEA was less than 1.0 mm in distal diameter and the IEA was anastomosed to the aorta or to the SVG. The IEA was considered to be useful alternative arterial graft when it was used as "interposed graft" of which proximal anastomosis was made to the ITA and size-matching of the graft to the coronary artery was appropriate. The long-term patency of the graft can determine the true efficacy of the IEA for CABG.
Aortic valve repair was performed in 61 patients having aortic regurgitation (AR) associated with ventricular septal defect (VSD). Preoperative regurgitation was classified according to the Sellers' classification and grade I was in 3 patients, grade II in 19, grade III in 34, and grade IV in 5 patients. Forty-six patients underwent only plication of aortic valve, and in 15 patients the commissuroplasty was added to reinforce the free edge of the cusp. Furthermore, aortoplasty (aortic annuloplasty) was performed in 11. Actuarial survival rate and freedom from reoperation rate were 91.6% and 87.2%, respectively at 10 years after the initial repair. The rate of freedom from deterioration for 22 patients showing grade I or II of AR before the initial operation was 86.4% at 1 year, 76.7% at 5 and 10 years, while the rate for 36 patients with grade III or more severe AR was 91.7% at 1 year, 77.4% at 5 years and 63.9% at 10 years. The rate at 10 years after operation between the two groups was different significantly (p < 0.05). Twenty among 22 patients having grade I or II of AR before operation were in NYHA class I, while 23 of 30 survivors with grade III or IV of AR were in class I, 6 in class II, and 1 in class III. Eight patients received reoperation and four of them underwent repeated conservative aortic valve repair, and one received aortic valve replacement at reoperation. Five of 7 survivors with reoperation improved in NYHA class I and 2 in class II. These results suggested that careful follow-up was required especially for the first 10 years after the initial operation in patients showing preoperative severe AR and receiving aortic repair.
Ebselen, 2-phenyl-1,2-benzisoselenazole-3(2H)-one can preferentially inhibit the activity of inducible nitric oxide (NO) synthase with little inhibition of endothelial constitutive NO synthase within a certain concentration range. This suggests that ebselen deserves further in vivo studies to examine its possible application to the therapy of septic shock where inducible NO synthase is responsible for vasodilation.
A study was conducted on 20 patients who underwent tricuspid valve replacement (TVR) with the St. Jude Medical (SJM) valve. Isolated TVR was performed on 9 patients, and additional mitral, or mitral and aortic valve replacements were performed on 11 patients. Four patients (20%) died in the early postoperative period, but there were no deaths related to the SJM valve in the tricuspid position. The mean follow-up period of the 16 survivors was 74.4 months, and there have been no deaths during the follow-up period. The postoperative actuarial survival rate was 80%, 10 years after surgery. Three patients, representing 0.25%/patient-months, developed valve thrombosis, the valve thrombosis-free rate being 72.8%, 10 years after surgery, while entrapment of a leaflet by endothelial pannus was found in one patient, representing 0.08%/patient-months. Thus, the incidence of all prosthetic valve-related complications was 0.34%/patient-months, and the postoperative complication-free rate was 65.3%, 10 years after surgery. The medium-term follow-up study of TVR with the SJM valve revealed no prosthetic valve-related deaths and a relatively low incidence of prosthetic valve-related complications. However, as with other mechanical valves, valve thrombosis was a major risk posed by the SJM valve in the tricuspid position.