Hiromichi Ohnishi

Greater than normal expression of the collagen-binding stress protein heat-shock protein-47 in the infarct zone in rats after experimentally-induced myocardial infarction.

BackgroundThe heat‐shock protein with relative molecular mass 47 000 (HSP47) can bind to procollagen molecules in the endoplasmic reticulum, and acts as a molecular chaperone during the processing and secretion of procollagen. ObjectiveTo test our hypothesis that HSP47 is expressed in the myocardial infarct zone. MethodsWe induced myocardial infarction in male Sprague–Dawley rats by ligation of left coronary artery. The expression of HSP47 was examined by Northern blotting, in‐situ hybridization, Western blotting and immunohistochemistry. The time‐dependent change in the distribution of HSP47 messenger RNA (mRNA) signal was compared with the changes in expression of α1(I) and α1(III) collagen mRNA by in‐situ hybridization. The hypoxic induction of HSP47 in cultured cardiac fibroblasts was examined by Northern‐blot analysis. ResultsNorthern blotting demonstrated that the expression of HSP47 mRNA had increased on day 2, reaching a maximum level around day 14 (induced 3.5‐fold compared with the preligation hearts) and was maintained at a high level up to day 28. In‐situ hybridization analysis revealed HSP47 mRNA signals in spindle‐shaped mesenchymal cells located between surviving myocytes in the infarcts peripheral zone 24 h after the ligation, and in the entire infarct zone on day 14. The sequential changes in distribution of HSP47 mRNA signal were identical to those of the α1(I) and α1(III) collagen mRNA. Western blotting demonstrated that expression of HSP47 protein in the infarct zone had increased. Immunofluorescent staining revealed positivity for HSP47 in the infarcts peripheral zone on day 2 and in the entire infarct zone on day 14. Northern blotting revealed that the expression of HSP47 mRNA in cultured cardiac fibroblasts in hypoxic cultures was greater than that in normoxic cultures. ConclusionThe present data demonstrated that an increase in expression of HSP47 is produced by spindle‐shaped mesenchymal cells in the infarct zone. Expression of HSP47 mRNA was concurrent with the expression of collagen mRNA of types I and III. Hypoxia is one of the factors which induces expression of HSP47.

Inverse Correlation Between Seasonal Changes in Home Blood Pressure and Atmospheric Temperature in Treated-Hypertensive Patients

We examined the relationships between home blood pressure (BP) and atmospheric temperature in 20 treated-hypertensive patients. A significant correlation between morning and evening BP and atmospheric temperature was found. For morning systolic blood pressure (SBP), the maximal seasonal difference was 13.2 mmHg with 25.5°C temperature difference. Morning SBP increased by approximately 0.41 mmHg with a 1°C decrease in atmospheric temperature. A similar but weaker correlation with temperature was observed for morning diastolic, evening systolic and diastolic blood pressure (DBP). The present study provides important information in respect to BP changes with atmospheric temperature that should be taken into account in the analysis and treatment of hypertension.

Double-Sector Lorenz Plot Scattering in an R-R Interval Analysis of Patients With Chronic Atrial Fibrillation Incidence and Characteristics of Vertices of the Double- Sector Scattering

Abstract Animal experiments have demonstrated that the minimum R-R interval during atrial fibrillation is proportional to the functional refractory period of the atrioventricular node. On Lorenz plots, atrial fibrillation is characterized by sector-shaped scattering; the vertex of the sector (ie, the minimum R-R interval) represents the functional refractory period. According to the atrioventricular nodal dual-pathway theory, it was hypothesized that the dual atrioventricular nodal pathways associated with chronic atrial fibrillation represent two vertices with two sectors. Detection of two-sector Lorenz plot scattering was attempted in 48 patients with chronic atrial fibrillation who underwent 24-hour ambulatory electrocardiography. Lorenz plot scattering was constructed by means of a computer. Two sectors, suggesting dual pathways, were detected in 19 (40%) of the 48 patients. The two vertices, located at 388 ± 61 ms (mean ± SD) and 580 ± 60 ms were considered to represent the functional refractory periods of the fast and slow pathways, respectively. The vertex indicating the fast pathway showed greater circadian variation than that indicating the slow pathway. In one patient with dual-sector Lorenz plot scattering, whose atrial fibrillation spontaneously converted to sinus rhythm, an electrophysiologic study demonstrated dual atrioventricular nodal pathways. Thus, the Lorenz plot analysis identified two sectors, indicating the dual pathways, in approximately 40% of the patients with chronic atrial fibrillation, and the characteristics of the functional refractory periods of both pathways were estimated from the characteristics of the vertices. Although this study did not provide direct evidence of the dual atrioventricular nodal pathways, the analysis of Lorenz plot scattering may be clinically useful for studying the effects of drugs and/or ablation on the ventricular response in patients with atrial fibrillation based on the dual atrioventricular nodal pathway theory.

Relationship between activin A level and infarct size in patients with acute myocardial infarction undergoing successful primary coronary intervention.

BACKGROUND Activin A, a member of the transforming growth factor-beta cytokine family, has been suggested to have a role in inflammation. We examined the serum level of activin A in patients with acute myocardial infarction (AMI) undergoing successful primary percutaneous coronary intervention (PCI). METHODS The subjects were 30 AMI patients, 20 stable angina pectoris (AP) patients and 20 normal subjects. The serum levels of activin A in AMI patients were measured before PCI and on days 1, 2, 7, and 14. RESULTS Activin A levels before PCI in AMI patients (557+/-255 pg/ml) showed a significantly higher value than those in AP patients (364+/-159 pg/ml) and control subjects (316+/-144 pg/ml). Increased serum activin A level before PCI was decreased on day 2, and then gradually re-elevated on days 7 and 14. The serum activin A level before PCI was correlated with log-transformed peak creatine kinase (CK) as a surrogate of infarct size (r=0.48, p=0.008). Stepwise multiple regression analysis demonstrated that the serum activin A level before PCI was an independent predictor of peak CK. CONCLUSIONS The serum activin A level, increased in AMI, was positively correlated with peak CK and CK-MB levels which are measures of infarction size.

Reperfusion accelerates the distribution of type I and III collagen messenger RNA expression after acute myocardial infarction: in situ hybridization in experimental infarction in rats.

BACKGROUND The effects of reperfusion on the time-dependent appearance and distribution of type I and III collagen messenger RNA (mRNA) expression had not hitherto been examined. OBJECTIVE To compare the sequential changes in the extent of distribution of type I and III collagen mRNA expression in reperfused infarct hearts of rats with those in unreperfused infarct hearts. METHODS Using an experimental rat model of infarction, we examined type I and III collagen mRNA expression with specific rat pro alpha 1 (I) and human pro alpha 1 (III) collagen riboprobes by in-situ hybridization. Reperfusion was established after a 2 h coronary ligation that produced complete necrosis of the myocytes. RESULTS Positive signals both for alpha 1 (I) and for alpha 1 (III) collagen mRNA appeared in the infarct peripheral zone 12 h after coronary ligation both of the reperfused and of unreperfused hearts. The spread of signal into the infarct central zone occurred 1-2 days earlier for the reperfused hearts than it did for the unreperfused hearts. The difference between the distributions of signals for the reperfused and unreperfused hearts became obscure on day 14. No notable difference between the extents of signal distribution for alpha 1 (I) and alpha 1 (III) collagen mRNA was obtained. We observed intense signals from spindle-shaped mesenchymal cells (myofibroblasts and fibroblasts) located between surviving myocytes in the marginal zone of the infarct. No myocyte exhibited signals both for alpha 1 (I) and for alpha 1 (III) collagen mRNA. CONCLUSION In the present study, using in-situ hybridization, we demonstrated that reperfusion accelerates the distribution of expression both of alpha 1 (I) and of alpha 1 (III) collagen mRNA in the infarct zone after acute myocardial infarction in rats.