Takuya Kanehisa

Effect of chronic administration of propranolol on lipoprotein composition

Chronic effects of propranolol on plasma lipids and lipoprotein composition were examined in ten patients who had previous strokes and normal plasma lipids. Although plasma triglyceride and total cholesterol were not affected by propranolol, a slight decrease of free cholesterol and phospholipids and a significant increase of free fatty acids were observed in the eighth week of propranolol treatment. Reciprocal changes were observed in lipoprotein composition; these were an increase in lipids of very low-density lipoprotein and a decrease in lipids of both low-density and high-density lipoproteins. Postheparin lipolytic activity was significantly suppressed by the administration of propranolol. Inhibition of lipoprotein lipase by propranolol was considered to have played a role in the reciprocal changes of lipoprotein composition.

Diastolic bulging of the interventricular septum toward the left ventricle. An echocardiographic manifestation of negative interventricular pressure gradient between left and right ventricles during diastole.

Diastolic bulging of the interventricular septum (IVS) toward the left ventricle was observed by real-time cross-sectional echocardiography in three patients with primary pulmonary hypertension and one patient with secondary pulmonary hypertension after closure of an atrial septal defect. M-mode echocardiography showed a characteristic abnormal pattern of septal motion in diastole and in systole. In two patients, we attempted to correlate M-mode motion to the interventricular pressure gradient. During diastole, the interventricular pressure gradient between the left and right ventricles was negative and the pressure gradient curve was very similar to the M-mode echogram of the IVS. Banding studies in which acute right ventricular hypertension was produced in dogs showed similar shape changes, suggesting that the diastolic shape and motion of the septum are determined by the interventricular pressure gradient between the ventricles. Diastolic bulging of the IVS toward the left ventricle in our patients results from negative interventricular pressure gradient between the left and right ventricles during diastole.

Electrophysiological and histological abnormalities of the heart in myotonic dystrophy

Abstract For frequent complications of cardiac involvement, it is important to recognize exactly myotonic dystrophy from a cardiovascular standpoint. Electrophysiological and histological studies were performed in three patients. Analysis of the site of the conduction disturbances was revealed by His bundle electrography proximal to the His bundle in one patient and distal in two other patients. The histological examination for biopsied myocardium by light and electron microscopy disclosed replacement of large areas by fat and also showed varying degrees of cellular damage. The most striking abnormality of the heart muscles was found in the mitochondria in which a peculiar and granular substance bulged into the outer space. Both the conduction system and the myocardium were involved in our cases. The value of His bundle recordings and endomyocardial biopsy in evaluating cardiac abnormality in the disease were discussed.

Real-time cross-sectional echocardiographic evaluation of the interatrial septum by right atrium-interatrial septum-left atrium direction of ultrasound beam.

Real-time cross-sectional echocardiography was performed to record the interatrial septal echogram by right atrium-interatrial septum-left atrium (ASA) direction of the ultrasound beam by positioning the transducer to the right of the sternum. The configuration of the interatrial septum (IAS) and the change of the configuration through each cardiac cycle were studied in 10 normal subjects and 29 patients with left or right atrial overloading.In normal subjects the IAS was slightly convex toward the right atrium (RA) in end-systole and slightly convex toward the left atrium (LA) in end-diastole, respectively. In patients with mitral stenosis, the IAS protruded archwise toward the RA both in end-systole and in end-diastole, and showed only minimum difference through each cardiac cycle. In patients with acute mitral regurgitation, the IAS was markedly convex toward the RA in end-systole and slightly convex toward the LA in end-diastole; thus, the difference of the configuration of the IAS was increased. In patients with chronic mitral regurgitation, the IAS was moderately convex toward the RA in end systole and flat or slightly convex toward the RA in end-diastole. In patients with tricuspid regurgitation, the interatrial septal echogram showed several patterns. However, the change in the configuration of the IAS throughout the cardiac cycle showed a characteristic pattern, i.e., it was more convex toward the LA or less convex toward the RA in end-systole than in end-diastole.The observation of the change in the interatrial septal configuration may be useful in the diagnosis of right or left atrial overloading. The mechanism by which the configuration is altered seems to be the interatrial pressure gradient through each cardiac cycle.

Echocardiographic analysis of interatrial septal motion.

Abstract Interatrial septal motion was analyzed in 12 normal subjects and 19 patients with right or left atrial overloading using a new method for recording echograms of the mid portion of the interatrial septum through each cardiac cycle. In normal subjects, septal motion was characterized by eight distinct points that were identified and designated on the septal echogram. The septum showed gradual anterior motion (toward the right atrium) in mid and end systole and in early diastole. After reaching the most anterior point, it moved posteriorly (toward the left atrium). During mid diastole it showed very little motion. After the P wave of electrocardiogram it showed slight posterior and then anterior motion. In all eight patients with mitral stenosis, the motion of the interatrial septum was diminished. In all seven patients with mitral regurgitation due to chordal rupture, the septal motion was increased. Systolic fluttering of the septum was observed in four of seven patients. In two patients with Ebsteins anomaly, paradoxical motion of the interatrial septum (posterior motion in systole) was observed. In two patients with primary pulmonary hypertension, septal motion was very much decreased. Interatrial septal motion was thought to result from the interatrial pressure gradient through each cardiac cycle. This method of recording the motion of the interatrial septum seems to be useful for diagnosing right or left atrial overloading and for studying hemodynamic events in both atria.

Cardiac involvement in the Kugelberg-Welander syndrome

Two cases of the Kugelberg-Welander syndrome (juvenile form of progressive spinal muscular atrophy) associated with cardiomyopathy and cardiomegaly are presented. The first patient, a 24 year old man, had atrial flutter with complete atrioventricular (A-V) block due to A-H block. Echocardiography revealed an increase in the left atrial and right ventricular dimensions. The second patient was a 26 year old man whose electrocardiogram revealed an A-V junctional rhythm, deep Q wave in leads I, aVL and V5 to V6 and an RS pattern in lead V1. Histologic examination of the myocardium in Case 2 showed slight interstitial fibrosis. Review of previously reported cases shows that (1) the atrium, the ventricular myocardium and A-V conducting tissue may be involved, and (2) atrial arrhythmias, A-V conduction disturbances and congestive heart failure may occur in the Kugelberg-Welander syndrome.

Effect of intraventricular administration of noradrenaline and dopamine on the levels of corticosterone in rats and denervation hypersensitivity resulting from intraventricular administration of 6-hydroxydopamine.

Abstract The effects of intraventricular administration of noradrenaline (NA) on the resting levels, stress-induced rises and dexamethasone-induced decreases of plasma corticosterone (B) were studied in rats. The effect of pretreatment with intraventricular administration of 6-hydroxydopamine (6-OHDA) on the effects of NA or dopamine (DA), which was injected intraventricularly, was also examined. The results obtained were as follows: 1) Intraventricular administration of 1.0 μg of NA did not cause a decrease in concentrations of plasma B. 2) Ten μg of NA injected intraventricularly resulted in a rise of the levels of plasma B. 3) The stimulating action of centrally administered NA was more marked when the pre-injection concentrations of B were lower. 4) Pretreatment with intraventricular administration of 6-OHDA facilitated the action of intraventricularly administered NA in the regulation of pituitary-adrenocortical functions. The result suggests a development of denervation hypersensitivity caused by the pretreatment. 5) Intraventricular administration of NA did not block stress-induced rises of plasma B. 6) Intraventricular administration of NA counteracted dexamethasone-induced decrements of plasma B. 7) This counteraction was enhanced by pretreatment with intraventricular administration of 6-OHDA. This also suggests a development of denervation hypersensitivity resulting from intraventricular administration of 6-OHDA. 8) Intraventricular administration of 1.0 μg of DA caused no change in the concentrations of plasma B in either control or 6-OHDA treated animals.

Motion of the interatrial septum in acute mitral regurgitation. Clinical and experimental echocardiographic studies.

The interatrial septal echocardiograms from 15 patients with acute mitral regurgitation due to ruptured chordae tendineae were compared with those from 14 normal subjects. On the cross-sectional echocardiogram, the interatrial septal configuration in patients with chordal rupture showed a characteristic pattern in which the interatrial septum (IAS) was flat or slightly convex toward the left atrium at end-diastole and became markedly convex toward the right atrium at end-systole. On the M-mode echocardiogram, the interatrial septal amplitude was greater in patients with chordal rupture (12.4 ± 1.9 mm) than in normal subjects (9.4 ± 0.9 mm). Systolic fluttering of the IAS was found in five of 10 patients with rupture of the chordae attached to the posterior mitral leaflet. This finding was thought to be specific for acute mitral regurgitation due to ruptured chordae to the posterior mitral leaflet. After operation, the amplitude of the IAS became normal or diminished and systolic fluttering of the IAS disappeared. Animal experiments performed to clarify the mechanism of these findings showed that increased systolic motion of the IAS resulted from an increase in the systolic left atrial-to-right atrial pressure gradient due to acute mitral regurgitation. The systolic fluttering of the IAS was thought to represent a jet stream against the IAS due to rupture of the chordae tendineae to the lateral half of the posterior mitral leaflet. We conclude that the interatrial septal echocardiogram reflects the hemodynamic changes due to acute mitral regurgitation and direction of the regurgitant jet against the IAS. This finding may prove to be important in diagnosing acute mitral regurgitation secondary to ruptured chordae tendineae.

Paroxysmal hypertension in aortitis syndrome.

Three patients with aortitis syndrome ehibited paroxysmal hypertension which seemed to result from baroreceptor dysfunction. All of the patients had signs of active inflammation of aortitis syndrome and stenotic carotid and subclavian arteries. During the attacks, the blood pressure rose to at least 230 mm. Hg systolic and the heart rate exceeded 100. However, with prolonged administration of steroid hormones, the attacks ceased. In two patients with dilated thoracic aortas and aortic regurgitation, the attacks of paroxysmal hypertension occurred without apparent precipitating factors and were followed by anginal pain with marked ST depression. The sympathicotonic state resulting from the disturbance of the baroreceptors was considered to be responsible for the attacks. In another patient, the attacks occurred in the course of treatment with a steroid hormone and were provoked only by voluntary micturition. This post-micturition hypertension was presumed to be an expression of abnormal overshooting following a fall in blood pressure after voiding.

Hypobetalipoproteinemia with abnormal prebetalipoprotein

A 47-year-old man who had cerebellar ataxia and low plasma lipid and lipoprotein levels is reported. His tendon reflexes were hyperactive and the plantar responses were extensor. There was no acanthocytosis. Total lipids (380 mg/dl), total cholesterol (106 mg/dl), esterified cholesterol (74 mg/dl), triglyceride (58 mg/dl), phospholipids (124 mg/dl) and free fatty acids (303 muequiv./l) were generally decreased. A disturbance of lipid absorption due to a defect of chylomicron formation and hepatic steatosis were also disclosed. On lipoprotein electrophoresis, prebetalipoprotein was very faint and migrated more slowly than normal. Betalipoprotein and alphalipoprotein were moderately reduced in concentration but migrated normally. The concentration of isolated VLDL was only one-tenth of that in normal subjects and it migrated as slow prebetalipoprotein. Although the lipid composition of VLDL was similar to that of normal VLDL, the lack of minor components was disclosed by SDS-PAG electrophoresis. Incorporation of [1-14C]acetate into VLDL lipids was significantly reduced to a greater extent than that of LDL and HDL. From these findings, we discuss the possibility that hypobetalipoproteinemia results from impaired VLDL synthesis.