Kenji Noma

Pathology of the Liver in “Idiopathic Portal Hypertension” Associated with Autoimmune Disease

The histopathology of the liver in idiopathic portal hypertension (IPH) associated with autoimmune disease (15 cases), was examined and compared with that of IPH without autoimmune disease (31 cases). It was found that hepatic histopathology was heterogeneous in the cases with autoimmune disease. That is, the hepatic histopathology in 7 cases was similar to that of classic IPH without autoimmune disease, and the remaining 8 cases disclosed unusual lesions such as focal non suppurative cholangitis, nodular parenchymal hyperplasia, moderate portal inflammation, and intrahepatic ductopenia. These unusual lesions, which frequently coexisted in the same case, were not typical ones for making other diagnoses such as primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. These findings suggest that unusual histologic lesions in the livers of IPH patients with autoimmune disease may represent an accentuated immunologic reaction inherent in IPH, or that such cases may be an abortive or incomplete form of primary biliary cirrhosis or nodular regenerative hyperplasia of the liver. Acta Pathol Jpn 39: 586‐592, 1989.

Mitochondrial DNA deletion in human myocardium

Mutation of myocardial mitochondrial DNA was investigated in human left ventricles obtained at autopsy using the polymerase chain reaction (PCR). Seventeen autopsy cases were examined, including patients with diabetes mellitus, myocardial infarction, cardiomyopathy, cancer, and other diseases. Two cases of diabetes mellitus, 2 of myocardial infarction, and 1 of pulmonary fibrosis showed a 7.4 kb deletion of myocardial mitochondrial DNA. Primer shift PCR confirmed that an amplified DNA fragment had not been obtained by misannealing of the primers. It is unclear how much these findings are related to the severity or prognosis of the various diseases, but they indicate that mutation of myocardial mitochondrial DNA can occur in other diseases besides cardiomyopathy, although the influence of aging could not be excluded.

Beneficial effect of ACE inhibitor in congestive heart failure

The effects of captopril, an angiotensin-converting enzyme inhibitor, on congestive heart failure (CHF) were investigated in animal and clinical studies. Congestive heart failure was induced in rats by a combination of pressure and volume overload. Cardiac pressure overload was induced by constricting one renal artery (Goldblatt rat) and volume overload was induced by aorto-caval fistula. Captopril (100 mg/kg/day) was then administered for 14 weeks. Isometric contraction was assessed using isolated left ventricular papillary muscles. The maximum developed tension and the maximum rate of increase in tension (dT/dtmax) were decreased in untreated rats with CHF and improved in captopriltreated rats. The left ventricular myosin isoenzyme pattern was shifted towards V3 in untreated rats with CHF, and was shifted back towards V1 in the captopril-treated rats. In the clinical study, captopril (37.5–75 mg/day) was administered to patients with cardiomyopathy for 12 months. There was no effect on left ventricular mass in hypertrophic cardiomyopathy, although systolic anterior motion of the mitral valve disappeared in one patient. In dilated cardiomyopathy, however, left ventricular mass tended to decrease. These results indicate that captopril has a beneficial effect in congestive heart failure.

Various routes of septal propagation in common atrial flutter.

AbstractIntroduction: Although in the treatment of common atrial flutter, the isthmus between the tricuspid valve annulus and the eustachian ridge is often chosen as the site for conduction block by radiofrequency ablation, the precise path of the flutter circuit remains unknown. We therefore investigated the propagation of the atrial flutter wave front around the coronary sinus ostium and how its path is altered by application of radiofrequency current. Methods and Results: To assess activation pattern, activation in the region surrounding the coronary sinus ostium was mapped using a deflectable decapolar catheter under basal conditions and while applying radiofrequency current to the septal isthmus, between the tricuspid valve annulus and the eustachian ridge. In five of eleven patients studied, the eustachian ridge side, below the coronary sinus ostium, was activated earlier, and the flutter wave exited from either the tricuspid valve annulus side or the eustachian ridge side, above the coronary sinus ostium. In four patients, a partial line of block created by applying radiofrequency current between the tricuspid valve annulus and the coronary sinus ostium or between the coronary sinus ostium and the eustachian ridge led to a shift in the direction of propagation of the flutter wave front from anterior to posterior or from posterior to anterior of the coronary sinus ostium, and prolongation of the cycle length. Conclusion: Application of radiofrequency current to the septal isthmus, between the tricuspid valve annulus and the eustachian ridge, can shift both the anterior and posterior propagation of flutter around the coronary sinus ostium.

The Influence of Diabetes on Myocardial Contractility and Energetics in Spontaneously Hypertensive Rats

Diabetic patients with hypertension show a high incidence of the development of heart failure. The mechanisms involved in heart failure at the myocardial cellular level remain unclear. To elucidate the myocardial alterations occurring in hypertension associated with diabetes, we examined myocardial contractility and ventricular myosin isoenzymes in diabetic spontaneously hypertensive rats (SHR). Myocardial contractility was assessed by measuring the isometric tension developed in isolated left ventricular papillary muscles, and ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis.

Influences of a Long-Term Treatment with Antihypertensive Drugs on Left Ventricular Myosin Isoenzyme Pattern in Spontaneously Hypertensive Rats

Rat’s left ventricular myosin is separated into three isoenzymes by pyrophosphate gel electrophoresis (1–3),i.e. VM-1,2,3, which have greater electrophoretic mobility and ATPase activity in order. Thyroid hormone’s administration and endurance swimming training can induce the shift of ventricular myosin isoenzyme pattern towards VM-1. Aging, chronic pressure overload and thyreostatic treatment, on the other hand, can shift the pattern towards VM-3 (4–12). The shift of myosin isoenzyme pattern towards VM-3 in pressure overloaded myocardium is thought to be an adaptational process to keep force development efficient with low oxygen and energy utilization (13,14). In spontaneously hypertensive rats (SHR) the concentration of VM-3 isomyosin in left ventricle is higher than that of age-matched normotensive rats. The aim of the present study is to examine to what extent alters myosin isoenzyme pattern with some antihypertensive drugs.

Structural and enzymatic alterations of cardiac contractile proteins under chronic pressure overload

Heart muscles obtained from human left ventricles at autopsies and from hypertrophied hearts of SHR were homogenized in Weber’s solution and the crude actomyosin was extracted. Crude extract was designed as sample I. Natural actomyosin (sample II) was purified from sample I.