The ischemic threshold of protein synthesis and energy state was determined 1, 6, and 12 h after middle cerebral artery (MCA) occlusion in rats. Local blood flow and amino acid incorporation were measured by double tracer autoradiography, and local ATP content by substrate-induced bioluminescence. The various images were evaluated at the striatal level in cerebral cortex by scanning with a microdensitometer with 75 microns resolution. Each 75 x 75 microns digitized image pixel was then converted into the appropriate units of either protein synthesis, ATP content, or blood flow. The ischemic threshold was defined as the flow rate at which 50% of pixels exhibited complete metabolic suppression. One hour after MCA occlusion, the threshold of protein synthesis was 55.3 +/- 12.0 ml 100 g-1 min-1 and that of energy failure was 18.5 +/- 9.8 ml 100 g-1 min-1. After 6 and 12 h of MCA occlusion, the threshold of protein synthesis did not change (52.0 +/- 9.6 and 56.0 +/- 6.5 ml 100 g-1 min-1, respectively) but the threshold of energy failure increased significantly at 12 h following MCA occlusion to 31.9 +/- 9.7 ml 100 g-1 min-1 (p less than 0.05 compared to 1 h ATP threshold value; all values are mean +/- SD). In focal cerebral ischemia, therefore, the threshold of energy failure gradually approached that of protein synthesis. Our results suggest that with increasing duration of ischemia, survival of brain tissue is determined by the high threshold of persisting inhibition of protein synthesis and not by the much lower one of acute energy failure.(ABSTRACT TRUNCATED AT 250 WORDS)

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Hepatocyte growth factor (HGF) is a potent angiogenic factor. The efficacy and safety of intramuscular injection of a naked plasmid encoding human HGF gene (beperminogene perplasmid, Collategene) was investigated in patients with critical limb ischemia (CLI) in a multicenter, randomized, double-blind, placebo-controlled trial. The randomization ratio for plasmid to placebo was 2:1. Injection sites were selected in each patient limb based on angiographic findings. Placebo or plasmid was injected on days 0 and 28. Evaluation of efficacy was carried out after 12 weeks. The primary end point was the improvement of rest pain in patients without ulcers (Rutherford 4) or the reduction of ulcer size in patients with ulcer(s) (Rutherford 5).Secondary end points were ankle-brachial pressure index, amputation, and quality of life (QOL). Forty-four patients were treated, and we performed interim analysis of efficacy in 40 patients. The overall improvement rate of the primary end point was 70.4% (19/27) in HGF group and 30.8% (4/13) in placebo group, showing a significant difference (P ¼ 0.014). In Rutherford 5 patients, HGF achieved a significantly higher improvement rate (100% [11/11]) than placebo (40% [2/5]; P ¼ 0.018). HGF plasmid also improved QOL. There were no major safety problems. HGF gene therapy is safe and effective for CLI.

In recent years, endovascular repair with stent-grafts has made great advances as a minimally invasive alternative to conventional open surgery in the treatment of aortic aneurysm and dissection. Although many commercial endograft systems are now used worldwide for the treatment of these pathologies in the abdominal aorta, only a few dedicated stent-grafts have been developed for use in the thoracic aorta. However, these secondgeneration commercial endografts have almost identical specifications and performance profiles in terms of structure, function, and delivery mechanism as stent-graft systems employed in the abdominal aorta. Thus, endografts have been used in the thoracic aorta with little consideration to the morphological and hemodynamic characteristics specific to the aortic arch and the deployment techniques needed to navigate this curved region of the thoracic aorta. This review will survey the literature on aortic arch stent-graft repair and identify key elements critical to the successful design of an endograft to treat lesions in the aortic arch.

ulse wave velocity (PWV) is used in the management of atherosclerotic cardiovascular disease as a validated marker of disease severity and a predictor of future events. [1][2][3][4] Recently, the use of brachial -ankle PWV, which can be obtained by simply wrapping the 4 extremities with blood pressure cuffs, was validated 5-7 and the technique is quite simple it is thus useful for screening the general population; in addition, the ankle -brachial blood pressure index (ABI) can also be simultaneously obtained. [5][6][7] For accurate PWV measurement, a clear recording of the pulse waves is very important, but in cases of severe atherosclerosis, the stenosis of the arteries affects the recording and it is not sufficiently clear. 8,9 ABI is a simple marker of peripheral arterial stenosis 10-15 and can provide information about the prevalence of arterial stenosis in subjects who are undergoing a brachial -ankle PWV recording. However, the cut-off value for ABI at which the accuracy of brachial -ankle PWV measurements is diminished because of arterial stenosis has not been established. Therefore, we proposed and evaluated the following hypothesis. At the site of arterial stenosis, the serial changes in the waveform obscure the foot of the waveform and delay the calculated PWV. 9 The discrepancy in brachial -ankle PWV (abnormal difference) between the 2 sides of the Circulation Journal Vol.69, January 2005body reflects the lack of accuracy of the brachial -ankle PWV measurement on the delayed side because of arterial stenosis. Therefore, we examined the ABI on the side of the delayed brachial -ankle PWV as a marker of the lack of brachial -ankle PWV accuracy in patients with a discrepancy in their brachial -ankle PWV values (abnormal difference). Methods SubjectsOf the patients who visited the outpatient clinic of the Second Department of Internal Medicine of Tokyo Medical University Hospital or were admitted to the department for the diagnosis or treatment of cardiovascular disease between April 2001 and August 2003, patients who underwent a brachial -ankle PWV recording and gave their informed consent were enrolled in the study. Subjects with a plasma creatinine concentration of greater than 176.8 mol/L, with an aortic graft, and those with atrial fibrillation, were excluded. The total number of subjects was 1,361 (60±12 years old). Atherosclerotic cardiovascular diseases were classified according to the criteria of the International Classification of Diseases (10th version) for coronary heart disease, cerebrovascular disease, and peripheral arterial disease. Hypertension, dyslipidemia and diabetes mellitus were diagnosed according to the guidelines of the Japanese Society of Hypertension, 16 the Japan Atherosclerosis Society 17 and the Japan Diabetes Society. 18 The study's protocol was approved by the ethical committee of Tokyo Medical University. Background The present study was conducted to establish the cutoff value of the ankle -brachial pressure index (ABI) at which the accuracy of brachial -ankle pulse wave v...