Hitoshi Koito

Clinical Significance of S-T Segment Elevation in Lead aVR in Anterior Myocardial Infarction

The significance of exercise-induced S-T elevation in aVR was studied in 57 patients with recent anterior infarction and single-vessel disease. S-T elevation in aVR was found at peak exercise in 24 patients. Although the initial defect area was similar in the groups with and without S-T elevation in aVR, the redistribution area was larger in the former group (p < 0.01). When three electrocardiographic criteria were used in the multivariate analysis, S-T elevation in aVR was the significant variable related to redistribution in the anterior wall. Thus, S-T elevation in aVR may indicate ischemia of the anterior wall.

An improved computer method to prepare 3D magnetic resonance images of thoracic structures

The mediastinal and cardiovascular anatomy is complex. We have developed a three-dimensional (3D) reconstruction system for the major mediastinal structures using magnetic resonance imaging data on a NeXT workstation. The program uses a combination of automatic and manual procedures to determine the contours of the cardiac structures. The geometric centers of the contours are connected by a 3D space curve, and the central axis of each cardiac structures is determined. The contours are projected on the perpendicular plane to the central axis and semiautomatically processed until the contours of one pixel are obtained. Then the surface rendering with transparency is performed. Compositing combines two images so that both appear in the composite, superimposed on each other. Demonstration of the various mediastinal lines and cardiovascular diseases by the composits of the partly transparent 3D images has promoted a better understanding of the complex mediastinal and cardiovascular anatomy and diseases.

Small-Vessel Vasculopathy Due to Aberrant Autophagy in LAMP-2 Deficiency

Lysosomal associated membrane protein 2 (LAMP2) is physiologically implicated in autophagy. A genetic LAMP2 defect causes Danon disease, which consists of two major phenotypes of myopathy and cardiomyopathy. In addition, arteriopathy may manifest on rare occasions but the pathological basis remains unknown. We encountered two Danon families that developed small-vessel vasculopathy in the coronary or cerebral arteries. To investigate the underlying mechanisms, we characterized the biological features of LAMP-2–deficient mice and cultured cells. LAMP-2–deficient mice at 9–24 months of age showed medial thickening with luminal stenosis due to proliferation of vascular smooth muscle cells (VSMC) in muscular arteries. Ultrastructural analysis of VSMC revealed various autophagic vacuoles scattered throughout the cytoplasm, suggesting impaired autophagy of long-lived metabolites and degraded organelles (i.e., mitochondria). The VSMC in Lamp2 null mice expressed more vimentin but less α-smooth muscle actin (α-SMA), indicating a switch from contractile to synthetic phenotype. Silencing of LAMP2 in cultured human brain VSMC showed the same phenotypic transition with mitochondrial fragmentation, enhanced mitochondrial respiration, and overproduction of reactive oxygen species (ROS). These findings indicate that LAMP-2 deficiency leads to arterial medial hypertrophy with the phenotypic conversion of VSMC, resulting from age-dependent accumulation of cellular waste generated by aberrant autophagy.