[Changes of serum hepatocyte growth factor in coronary artery disease].

Hepatocyte growth factor (HGF) is an endothelial cell specific growth factor involved in the repair of endothelial cells and collateral formation, however, the role for coronary artery disease is still unknown. We measured serum HGF level in various coronary artery diseases to examine the clinical significance. Serum HGF level was measured using the enzyme-linked immunosorbent assay method in patients with stable effort angina pectoris (n = 26), old myocardial infarction (n = 18), unstable angina pectoris (UAP; n = 10) and acute myocardial infarction (AMI; n = 21). As a control group, we selected 11 patients with neurocirculatory asthenia. Blood samples from peripheral veins were collected at cardiac catheterization before heparin administration. In the AMI group, blood samples were also collected at 48, 72 hr, 1, 2, 3 and 4 weeks from the peripheral veins and 48 and 72 hr after reperfusion from the coronary sinus. Serum HGF level was significantly higher in the UAP (0.41 +/- 0.12 ng/ml, p < 0.001) and AMI groups (0.38 +/- 0.26 ng/ml, p < 0.05) compared to the control group (0.19 +/- 0.09 ng/ml). Serum HGF level peaked 48 hr after reperfusion in both the peripheral veins (0.42 +/- 0.16 ng/ml) and coronary sinus (0.58 +/- 0.23 ng/ml) in the AMI group, with a significantly higher level in the coronary sinus than the peripheral veins (p < 0.05). No significant correlation between peak HGF level in the peripheral veins and peak creatine kinase (CK), CK-MB, ejection fraction and cardiac index was observed. Serum HGF was elevated in acute coronary syndrome, indicating advanced endothelial cell damage. HGF is produced, at least partially, in the heart in patients with AMI. Serum HGF level may be useful to detect endothelial cell damage rather than myocardial cell damage.

[Clinicopathological study of left ventricular remodeling after first acute myocardial infarction].

The morphological characteristics of post-infarction ventricular remodeling were determined by comparison of infarct location and histological changes of noninfarcted myocardium at autopsy. A total of 94 cases of first acute myocardial infarction with clinical courses of 0 to 37 days were studied. Hearts were sliced on the short axis at the level of 1/3 of the distance from the atrioventricular ring to the apex. Wall thicknesses of the infarcted and noninfarcted areas, and the endocardial and epicardial perimeter lengths of the left ventricle were measured. Myocyte diameter and number of myocytes in the noninfarcted area were measured. Infarcts were classified into 3 groups based on infarct location (51 anterior, 22 posterior, and 21 nontransmural circumferential) and each group was further divided according to the clinical course of less than 72 hours or longer. Fifty two patients died within 72 hours. Cardiac rupture was the most common cause of death in the anterior group. Patients in the posterior group chiefly died due to cardiogenic shock and in the circumferential group chiefly died to pump failure. According to the number of stenosed coronary arteries, cardiac rupture was the most common cause of death in single-vessel disease in both anterior and posterior groups (62.1% and 55.6%, respectively). In double-vessel disease, the most common cause of death in the anterior group was still cardiac rupture (50.0%). On the other hand, 50.0% of the posterior group died of cardiogenic shock in double-vessel disease. Patients with triple-vessel disease mainly died due to heart failure in all groups. Wall thickness of the infarcted myocardium was decreased in the anterior group after 72 hours (11.8 +/- 3.5 vs 7.8 +/- 2.5 mm). Endocardial perimeter length was increased in the anterior and circumferential groups (83.6 +/- 25.6 vs 116.3 +/- 29.5 mm, 75.2 +/- 12.0 vs 117.6 +/- 3.1 mm, respectively). Endocardial/epicardial perimeter length ratio increased with longer clinical course in the anterior group. No specific change in wall thickness or perimeter length was found in the posterior group. Noninfarcted wall thickness was preserved in both the anterior and posterior groups. Myocyte diameter and number of myocytes in the noninfarcted area showed no significant difference after 72 hours. The nature of ventricular remodeling differs with infarct location. Ventricular dilation occurred during the clinical course in the anterior group. The transmural and adjacent areas are more important than the remote noninfarcted area in post-infarction remodeling within this period.

Morphological classification of atrial muscle in the atrioventricular junctional area--3-dimensional reconstruction of serial sections of the human heart.

To trace anatomical structures that might be associated with the dual atrioventricular (AV) nodal pathway and to investigate the morphologic characteristics of the cells that form these pathways, we examined serial sections of the AV junctional area with a light microscope and reconstructed them 3-dimensionally with a computer. Twelve hearts were obtained at autopsy from patients who had not shown AV conduction disturbances or supraventricular tachycardia before death. The method of Lev et al was used to prepare serial sections. Fascicles of atrial muscle contiguous with the AV node were examined with a light microscope and were classified into 3 groups, on the basis of morphologic characteristics and myocyte diameter. A computer was used to reconstruct 3-dimensionally the course of the fascicles and surrounding structures. At the border of the AV node and bundle of His relatively large myocytes extended directly into the AV bundle from the anterosuperior interatrial septum. Morphologically, the course was considered to be consistent with the fast pathway. In contrast, small cells that entered the AV node from the inferoposterior interatrial septum resembled sinus node cells with few myofibrils and a winding shape. These cells extended from the coronary sinus ostium to the tricuspid valve annulus and are thought to make up the slow pathway.

Cardiac sympathetic innervation in patients with dilated cardiomyopathy--immunohistochemical study using anti-tyrosine hydroxylase antibody.

Depletion of norepinephrine in the left ventricular myocardium in cases of dilated cardiomyopathy (DCM) has been suggested. However, there have been few histological studies of the sympathetic nerves, in which myocardial norepinephrine is believed to exist. We performed an immunohistological study of the density of tyrosine hydroxylase (TH, a marker of sympathetic nerves)-positive nerve fiber in endomyocardial biopsy specimens in cases of DCM using antibody against TH. TH-positive nerves were stained brown along with the myocardium, and they were more dense in the right ventricle than in the left ventricle in both the DCM and control groups. The density of TH-positive nerves in cases of DCM was significantly less than that in the control group in the subendocardial myocardium of the right and left ventricles, but especially in the left ventricle. A correlation was observed in the DCM group between the density of TH-positive nerves and the ejection fraction in the right ventricle, but not in the left ventricle. In the failing human heart, a decrease in subendocardial sympathetic nerve density may be one of the causes of myocardial norepinephrine depletion.