A possible involvement of oxygen free radicals in the development of myocardial acidosis during coronary occlusion in dogs

Summary The present study was designed to examine whether free radical scavengers attenuate myocardial acidosis induced by partial occlusion of the coronary artery in dogs. The myocardial pH was determined by a micro glass pH electrode inserted in the endocardial layers of the left ventricular wall perfused by the left anterior descending coronary artery. The left anterior'descending coronary artery was occluded for 90 min incompletely so that the flow would be 1/2–1/3 the original flow. The myocardial pH before partial occlusion was 7.54–7.55. Partial occlusion decreased the flow in the left anterior descending coronary artery by 49.3–64.9% and the myocardial pH by 0.71–0.76, and increased the ST segment (surface electrocardiogram) by 6.3–9.3 mV. Saline (0.5 ml/kg), recombinant human superoxide dismutase (70,000 or 210,000 U/kg), or catalase (55,000 or 165,000 U/kg) was injected intravenously 30 min after partial occlusion. The injection of recombinant human superoxide dismutase or catalase alone did not restore the myocardial pH that had been decreased by coronary occlusion. The combined injection of recombinant human superoxide dismutase (70,000 U/kg) + catalase (55,000 U/kg), however, restored the myocardial pH without restoration of ST segment. In conclusion, recombinant human superoxide dismutase + catalase attenuated myocardial acidosis during ischaemia, suggesting a possible involvement of oxygen free radicals in the development of myocardial acidosis (especially in the endocardial layers) during ischaemia. Send offprint requests to Y. Abiko at the above adress     

Strong antibody reaction against glycosphingolipids injected in liposome-embedded forms in beta3GN-T5 knockout mice

It is known that mutant mice of the beta-1,3-N-acetylglucosaminyltransferase gene (beta3Gn-T5) respond well to T-cell dependent and independent antigens. Here, we examined the effectiveness of anti-ganglioside antibody generation by immunization of beta3Gn-T5 mutant mice with liposome-embedded glycosphingolipids such as GD1a and GT1b. Consequently, the mutant mice showed a more efficient generation of anti-GD1a or anti-GT1b antibodies than wild-type mice in an enzyme-linked immunosorbent assay using sera during immunization. Thus, the beta3Gn-T5 deficient mutant mice proved more responsive than wild-type mice to not only protein antigens, but also to carbohydrates in glycolipids. Furthermore, about 50% of monoclonal antibodies generated using splenocytes of the immunized mutant mice were of the IgG class. Besides general high responsiveness to proteins and glycolipids, it could be expected that the mutant mice of beta3Gn-T5 would be useful in the generation of monoclonal antibodies towards lacto-/neolacto-series glycolipids, since these mutants lack lacto-/neolacto-series glycolipids. In fact, they showed a good serum response in immuno-fluorescence assay with cultured living cells when immunized by glycolipids extracted from ovarian cancer cell lines. These results suggested that beta3Gn-T5 mutant mice are useful for the generation of anti-glycolipid antigens with lacto-/neolacto-core structures expressed in cancer cells.     

Cardiac β-adrenergic receptor density and myocardial systolic function in the remote noninfarcted region after prior myocardial infarction with left ventricular remodelling

Purpose

After myocardial infarction (MI), left ventricular (LV) remodelling is observed in noninfarcted LV myocardium. LV remodelling is closely associated with systolic heart failure. Since myocardial dysfunction is related to the downregulation of cardiac postsynaptic beta-adrenergic receptors (β-AR), we hypothesized that a reduction in β-AR density may be manifested in the remote noninfarcted region and such reduction may be related to myocardial systolic dysfunction. Accordingly, we assessed β-AR density with a focus on the remote noninfarcted region.

Methods

Cardiac PET was performed in 15 patients with a prior MI and 10 age-matched healthy controls using ¹¹C-CGP 12177, a radioligand for β-receptors. The maximum number of available specific ¹¹C-CGP 12177 binding sites per gram of tissue was calculated in regions of interest using an established graphical method. LV regional systolic function was assessed based on peak systolic myocardial strain on the LV wall in the longitudinal direction using two-dimensional ultrasound speckle tracking imaging. LV volumes and LV ejection fraction (EF) were also measured.

Results

The LV end-diastolic volume index was significantly larger in patients than in controls (67.8?±?16.9 vs. 49.1?±?12.3?ml/m², p?p?p?Conclusion In the remote noninfarcted region in patients, β-AR downregulation was observed, which was related to deterioration of local myocardial systolic function.     

Congenital coronary artery fistula draining into the superior vena cava with giant saccular aneurysm--report of a case

A 42-year-old woman who had a coronary artery fistula, associated with a giant coronary saccular aneurysm was reported. The coronary artery fistula originated from the proximal portion of the right coronary artery drained into the superior vena cava. The chief complaint was heart murmur which was detected at the 2nd intercostal space of the right sternal border. No other symptoms were present. The aneurysm was approximately 5 X 7 cm in size. In the operation using cardiopulmonary bypass, the proximal and distal portions of the coronary artery fistula were ligated successfully without aneurysmorrhaphy. The postoperative conditions was even without any complications. Congenital coronary artery fistulas with a giant saccular aneurysm should be surgically treated as soon as possible because of potential risk of aneurysmal rupture.     

Experimental intraocular lens implantation in the rabbit eye and in the mouse peritoneal space. Part III: Giant cell formation on the implanted lens surface

Among the cell components appearing on an implanted intraocular lens (IOL), the macrophage is the most active participant in the foreign-body response. The morphological stages of the macrophage in the response include not only an activated form and a flat epithelioid cell, but also a giant cell observed in the later stage of the response. The giant cells on the IOLs implanted in the rabbit eye and in the mouse peritoneal space were investigated by means of Wolter's implant cytology staining and scanning and transmission electron microscopic observation. Differences in the two biological environments as the site of IOL implantation are discussed.     

Analysis of the interaction of reserpine with actin by the photoaffinity labelling method.

The interaction of reserpine with one of the cytoskeletal proteins, actin, was analyzed by the photoaffinity labelling method using [3H]reserpine. Reserpine bound sufficiently to G- or oligomeric actin, but hardly to F-actin under the same experimental conditions. This result could be explained if reserpine binds to a specific region of the G-actin molecule that is responsible for actin-actin interactions. It is concordant with this idea that [3H]reserpine bound only to specific proteolytic fragments of actin. When reserpine was mixed with crude extracts of two kinds of tissues, chicken gizzard smooth muscle and bovine adrenal medulla, it bound to the 42 kDa protein of sodium dodecyl sulfate-polyacrylamide gel electrophoresis in both cases. Its molecular size and abundance suggest strongly that this 42 kDa protein is actin. The binding of reserpine to actin was inhibited by dopamine in a dose-dependent manner. These results suggest that actin could be one of the target molecules of reserpine.     

Ictal alteration of 99mTc ECD SPECT imaging in a patient with secondary paroxysmal kinesigenic dyskinesia caused by hyperglycemia.

We described a 61-year-old man with diabetes mellitus who presented with hyperglycemia related paroxysmal kinesigenic dyskinesia (PKD) with sudden development of paroxysmal unilateral involuntary movements (IMs) of his neck and the left extremities. Ictal 99mTc-ethylcysteinate dimer SPECT (ECD-SPECT) revealed a hyperperfusion over the contralateral frontal cortex and a hypoperfusion over the contralateral basal ganglia. Immediate correction of hyperglycemia after admission resulted in a marked improvement of IMs and a return to normal cerebral blood flow on interictal ECD-SPECT imaging. These findings suggest that dysfunction of the indirect pathway through the basal ganglia lead to an imbalance of the cortico-striato-thalamo-cortical circuit and may have contributed to the cause of PKD in this case.     

Deposition of extracellular matrix on intraocular lenses in rabbits: An immunohistochemical and transmission electron microscopic study

Background: We examined by transmission electron microscopy the accumulation of extracellular matrix on intraocular lenses (IOLs) implanted experimentally into rabbit eyes, and evaluated the immunolocalization of such extracellular matrix components as collagen types I, III, and IV, and cellular fibronectin on these IOLs. Methods: Phacoemulsification and aspiration of the crystalline lens were performed and an IOL was implanted into the capsular bag of each eye of each of 16 adult albino rabbits under general anesthesia. After up to 12 weeks, the animals were killed and the IOLs were removed. Specimens were processed for transmission electron microscopy or for immunohistochemical detection collagen types I, III, and IV, and cellular fibronectin. Results: Transmission electron microscopy revealed an accumulation of extracellular matrix between the residual anterior lens capsule and the surface of an IOL explanted 4 weeks after surgery. Collagen types I and III and cellular fibronectin were detected immunohistochemically on each IOL in association with cellular deposits. Type IV collagen-immunoreactive matrix was not seen on the optic portion, but was detected on the haptic portion of one of six IOLs examined. Conclusion: Each component of the extracellular matrix that is deposited on the IOL supplies scaffolding for the adhesion and proliferation of cells. These components are considered to be produced by cells such as lens epithelial cells and macrophages that adhere to the IOL surface.Presented in part at the Annual Meeting of the Association for Research in Vision and Ophthalmology at Fort Lauderdale, Florida, USA on 15 May 1995 at the Quintessence of Ophthalmology Meeting in Sopron, Hungary, on 6 October 1995