Clinical evaluation of 123I-MIBG for assessment of the sympathetic nervous system in the heart (multi-center clinical trial)

Multi-center clinical trial of 123I-metaiodobenzylguanidine (123I-MIBG) was carried out to assess its utility as a scintigraphic imaging agent reflecting sympathetic neuronal function in cardiovascular field. Studies were performed on patients with heart diseases of three categories, myocardial infarction, angina pectoris and cardiomyopathy. Scintigraphic images, reflecting sympathetic neuronal function were obtained with 123I-MIBG from all of those categories of patients and the efficacy of the imaging was revealed in 781 (95.0%) out of 822 patients. In some patients abnormality was suggested in sympathetic neuronal function with 123I-MIBG imaging, in spite of normal findings with myocardial perfusion scintigraphy by 201TlCl. In all 981 patients studied with 123I-MIBG, there have been no severe adverse reactions, except complaints of burning on injection site of the agent or nausea, etc. from 4 patients. We conclude that 123I-MIBG imaging is one of the effective tools for diagnostic use reflecting topical sympathetic neuronal function in the heart, judging from its safety and efficacy.     

Morphological observations of the apical surface of chick retinal pigment epithelium

Chick embryonic retina was examined in order to investigate morphological changes of the apical portion of retinal pigment epithelial (RPE) cells. Whole retina and RPE sheets were observed by fluorescence microscopy (rhodamine-phalloidin preparation) and transmission electron microscopy. Photoreceptor cells had no inner and outer segments on the 8th day in ovo. The inner segments have been formed on the 15th day and the outer segments on the 19th day. RPE sheets had short and blunt apical processes on the 8th day, elongated and slender ones on the 15th day, and well-developed and melanin-containing processes on the 19th day. RPE of the 19th day had numerous bundles of actin filaments associated with melanin pigments in the basal portion of the apical processes and in the apical cytoplasm. In rhodamine-phalloidin preparations, intense fluorescence was localized in the RPE apical processes and cytoplasm on the 19th day. We concluded that RPE apical processes develop in accordance with the photoreceptor development.     

CCU network as primary care of acute myocardial infarction

The early pre-hospital care of patients with acute myocardial infarction (AMI) is critical because of high mortality during acute phase of AMI. A CCU network has been established by the Metropolitan Tokyo CCU Communication Society and the help of the Ambulance Units through the Control Room of the Tokyo Fire Department, performing ECG telephone line transmission and telephone consultation. Out of 1439 patients admitted by means of CCU network during the 8-month period (Jan. 1982-Aug. 1982), 505 (30.3 percent) had AMI as a final cardiac diagnosis. Many patients were admitted directly to the CCU by ambulance from the place where the patient was located, with the shortest overall time of 7 hours 25 minutes. Fifty-three percent of patients with AMI were admitted within 6 hours after the onset of symptoms. The mean patients' decision time was 9 hours 48 minutes, which comprised one half of the overall period as well as physician delay of 6 hours 36 minutes on the average. Thus, community oriented educational programs to more fully inform the population and individual hospital evaluations to hospitalize patients with chest discomfort are needed in order to shorten the decision time and physician delay expediting the care of these patients.     

Improved myocardial ischemia and left ventricular function during exercise after successful percutaneous transluminal coronary angioplasty

Percutaneous transluminal coronary angioplasty (PTCA) was performed in 42 patients with effort angina, 28 (67%) of them underwent successful angioplasty. Treadmill exercise testing, thallium-201 myocardial scintigraphy and radionuclide ventriculography were performed before and after PTCA for evaluation of the improvement of myocardial ischemia and left ventricular function at rest and during exercise. The average exercise duration by treadmill testing in 14 successful cases increased from 14 +/- 4 (mean +/- S.D.) to 16 +/- 2 minutes (p less than 0.05). Sixteen of 28 the patients were studied by thallium-201 myocardial scintigraphy. Before PTCA, regions of decreased thallium-201 uptake after exercise were observed in 12 of the 16 patients. After angioplasty, no distinct defects were recognizable in 9 of the 12 patients, and in the remaining three, a significant decrease in defects was recognized. Fifteen of the 28 patients were studied by radionuclide ventriculography. The mean ejection fraction was 61 +/- 5% at rest and 56 +/- 11% during exercise (N.S.) before PTCA. After angioplasty, the ejection fraction was unchanged at rest (61 +/- 5 to 62 +/- 4%), but increased significantly during exercise (62 +/- 4 to 74 +/- 4%, p less than 0.001). In conclusion, left ventricular function was improved by successful PTCA due to improvement of myocardial ischemia. The long term results require further study.     

Non-viral in vivo thrombomodulin gene transfer prevents early loss of thromboresistance of grafted veins.

OBJECTIVE: Immediate loss of thrombomodulin activity in the endothelium of vein grafts has been demonstrated during 90 min exposure to arterial circulation; this loss of activity is ascribed as an important cause of early thrombosis. Conventional ex vivo gene transfection after vein harvest cannot cover this acute period immediately after implantation. We have established a highly efficient non-viral gene therapy protocol utilizing modified transferrin receptor-facilitated gene transfer. Using this technique, we examined whether in vivo thrombomodulin gene therapy, directed to the endothelium of rat veins 2 days prior to grafting, may prevent thromboresistance impairment of vein grafts under simulated arterial circulation. METHODS: Abdomen of SD rat was opened and cationic liposome:transferrin:thrombomodulin gene complexes or the vector without DNAs were applied to the inferior vena cava of rats while blood flow was reduced by proximal and distal clamping. After 2 days, the transfected veins were harvested and thrombomodulin expression and thromboresistance properties determined before and after exposure to an artificial circuit. RESULTS: The trial of gene transfection using variable doses of DNAs confirmed that 7.5 microg of total DNAs was the most efficient quantity for thrombomodulin gene transfection to IVCs, although accompanying an increase of gene expression in other downstream organs. By transfection of the thrombomodulin gene in IVCs, the generation capacity of activated protein C in venous endothelium increased three-fold compared with veins treated with vector alone (P<0.01). Under simulated arterial circulation, perfusion of veins treated with vector alone decreased thrombomodulin activity to 36% of preperfused levels (P<0.01), whereas transfected grafts preserved the activity at normal vein endothelium levels even after perfusion. Consequently, the increase in endothelial thrombin activity induced by simulated arterial circulation was markedly attenuated in transfected veins (P<0.01), while immunohistochemistry confirmed the preservation of endothelial lining. CONCLUSIONS: Transferrin receptor-facilitated in vivo gene transfer to the inferior vena cava resulted in sufficient thrombomodulin gene expression immediately after graft implantation and subsequent maintenance of thromboresistance even after exposure to arterial pressure. Although further studies are needed, the present results suggest the possibility of gene therapy targeting acute phases of vein graft disease.