The purpose of the present study was to examine the pathogenesis of diabetic cardiomyopathy of the human diabetic heart from the standpoint of the microvascular structure.For this purpose, four diabetic and three control hearts were used.All of the materials were obtained at autopsy performed within 3 hours after death.No complications of heart disease were found in any of the cases. Vascular casts were prepared by means of injection of methylmethacrylate from the coronary artery after flushing and fixing with osmotically adjusted phosphate buffer containing heparin and 2.0% glutaraldehyde. The perfusion and plastic injection were carried out at a pressure of 90 to 100 mmHg. Subsequently, the plastic injected cardiac tissues were cut from the anterior wall of the left ventricle. The vascular casts were obtained after immersion of the tissue in diluted sodium hypochloride, followed by carbon and gold coating for increasing the electron conductivity.The specimens were then observed under a scanning electron microscope (Hitachi S510). In a general survey of the control hearts, the vascular beds were demonstrated as a rather regular and compact capillary network, the majority of which ran parallel to the muscle fibers while showing well developed anastomoses with each other between neighboring capillaries.The size of the individual capillary casts (e.g.capillary lumen) was uniform.On the other hand, the diabetic hearts revealed marked irregular narrowing of the capillary lumen and diminishment and/or disappearance of capillaries and anastomoses.These findings were found to be well reflected in a decreasing of the capillary density and the area ratio of the capillary bed per unit volume. The above results were also supported by a morphornetric study of ordinary histopathological sections of corresponding areas. In addition, focal twisting, spiralling, and unusual straightening of the capillaries were found.Interestingly, focal cystic and/or saccular dilatation of the capillary lumen was recognized scattered in the diabetic hearts with a suggestion of microaneurysm formation. The above findings were thought to be meaningful and to be responsible for the development of diabetic cardiomyopathy, although it remains unknown whether the observed vascular changes were primary or not in the disease process.
Recently, a particular allele of C4 (C4So) was reported to be associated with IDDM in Basques. However, since this association could be due to differences in ethnic background, we examined the C4 polymorphism in Japanese patients with IDDM using high voltage agarose gel electrophoresis and immunofixation.This investigation was important not only to clarify the differences among ethnic groups, but also to understand the pathogenesis of IDDM, since C4 is linked to the HLA-B or D/R locus and plays an important role in inflammation and neutralization of viruses.The present data revealed no association between IDDM and the C4So allele.The findings suggest that a C4 independent mechanism plays an important role in the pathogenesis of IDDM.