Norihiko Sugihara

Quantitative approach to the histopathology of the biopsied right ventricular myocardium in patients with diabetes mellitus

SummaryFor the purpose of studying the clinicopathology of the biopsied myocardium in patients with diabetes mellitus, the diameter of right ventricular myocardial cells and diffuse perimysial fibrosis of biopsied myocardium were measured quantitatively. Seven healthy controls and nine diabetic patients without hypertension or coronary arterial disease were subjected to this study. The degree of diabetic complications was mild to moderate. The diameter of myocardial cells was measured and the degree of diffuse perimysial fibrosis was assessed by the point-counting method using a square grid, in which the distance between the points was 10 µm. Over 2000 points which lay on the longitudinally cut myocardial cells and on the interstitial fibrosis stained by the Mallory-Azan method were measured. Percentage fibrosis was calculated according to the formula: percentage fibrosis=(points lying on the interstitial fibrosis)/[(points lying on the myocardial cell)+(points lying on the interstitial fibrosis)] × 100. The results were as follows. The mean diameter of right ventricular myocardial cells in patients with diabetes mellitus was significantly larger than that of controls (P<0.01). The percentage fibrosis of diabetic patients was significantly higher than that of controls (P<0.01). There was no significant correlation between the histopathological measurements and clinical features. It is concluded that hypertrophy of myocardial cells and interstitial fibrosis of the myocardium exist even in mild diabetes mellitus.

Assessment of autonomic nervous activity by heart rate spectral analysis in patients with variant angina

The purpose of this study was to assess the role of the autonomic nervous system in the pathogenesis of coronary artery spasm in patients with variant angina. We evaluated cardiac sympathetic and parasympathetic activity from the power (logarithmic scale) of the low-frequency (approximately 0.04 to 0.12 Hz) and the high-frequency (approximately 0.22 to 0.32 Hz) spectral components of heart rate variability with Holter monitoring in seven patients with nocturnal variant angina and in 11 healthy men who served as control subjects. None of the patients had organic coronary artery stenosis as determined by angiography. Low-frequency and high-frequency logarithmic values were calculated for each 5-minute period from 30 minutes before to immediately before each angina attack. The logarithmic low-frequency value during the 5-to-0-minute period was greater than the low-frequency values during most of the other periods (p < 0.05 - p < 0.01). The logarithmic high-frequency values during the 10-to-5-minute and 5-to-0-minute periods were greater than those during the 30-to-25-minute period (p < 0.05 and p < 0.01, respectively). These data indicate that parasympathetic activity increased during the 10 minutes before attacks of nocturnal variant angina, whereas sympathetic activity with vagal modulation increased during the 5 minutes before such attacks. The same pattern of changes in heart rate variability was found in the absence of ST-segment elevation in patients and in control subjects. So this phenomenon was not just associated with coronary spasm and variant angina. It is suggested that circadian variation in disease activity is also associated with spontaneous attacks.

Cardiac characteristics and postoperative courses in Cushing's syndrome

To assess the cardiac characteristics and postoperative courses in patients with Cushings syndrome, electrocardiography and echocardiography were performed to study 12 consecutive, unselected patients, and results were compared with those of essential hypertension and primary aldosteronism. Eleven patients had hypertension and 7 had diabetes mellitus. Before adrenalectomy, common electrocardiographic abnormalities consisted of high-voltage QRS complexes (10 patients) and negative T waves (7 patients). Echocardiograms showed left ventricular hypertrophy in 9 patients, and all the patients had evidence of asymmetric septal hypertrophy. In patients with left ventricular hypertrophy, the thickness of the interventricular septum ranged from 16 to 32 mm, whereas the ratio of the thickness of interventricular septum to that of the posterior wall ranged from 1.33 to 2.67. The interventricular septum in Cushings syndrome was extremely thicker and asymmetric septal hypertrophy occurred more often than essential hypertension and primary aldosteronism. Nine patients could be followed up after operation. In these patients abnormal electrocardiographic findings had normalized, the thickness of interventricular septum had decreased and asymmetric septal hypertrophy had disappeared except in 1 patient. The reason why left ventricular hypertrophy in Cushings syndrome is severe is still unknown. Because left ventricular hypertrophy is more severe and the frequency of asymmetric septal hypertrophy much greater in Cushings syndrome than in essential and other secondary hypertension, it is thought that not only increased aortic pressure but excessive plasma cortisol may be etiologic factors in the progression of left ventricular hypertrophy in Cushings syndrome.

Left Atrial Afterload Mismatch in Hypertrophic Cardiomyopathy

To investigate left atrial (LA) booster pump function in hypertrophic cardiomyopathy (HC), LA and left ventricular pressure-volume loops were estimated in 5 control subjects, 6 patients with essential hypertension and 11 patients with HC. Investigation of LA preload revealed that LA pressure and volume immediately before LA contraction were both increased in patients with hypertension (10 +/- 5 mm Hg, 71 +/- 19 ml/m2) compared with control subjects (7 +/- 1 mm Hg, 59 +/- 6 ml/m2), and even more increased in patients with HC (16 +/- 7 mm Hg, 81 +/- 25 ml/m2). Investigation of LA afterload revealed that the left ventricular chamber stiffness constant was higher in patients with hypertension (0.035 +/- 0.015) than in control subjects (0.028 +/- 0.009), and even more increased in patients with HC (0.056 +/- 0.017). LA stroke work index was higher in patients with hypertension (116 +/- 34 mm Hg.ml) and HC (115 +/- 19 mm Hg.ml) than in control subjects (87 +/- 23 mm Hg.ml). Investigation of LA ejection revealed that LA stroke index was higher in patients with hypertension (24 +/- 5 ml/m2) than in control subjects (18 +/- 4 ml/m2) and patients with HC (18 +/- 2 ml/m2), and LA ejection fraction was lower in patients with HC (23 +/- 6%) than in control subjects (32 +/- 7%) and patients with hypertension (34 +/- 8%). In patients with HC, LA function curve showed a shift to the lower right, and LA stroke index was inversely correlated (r = -0.76) with LA afterload. This study suggests that LA booster pump failure due to LA afterload mismatch exists in HC.

Correlation between histopathological changes and mechanical dysfunction in diabetic rat hearts

Recent clinical and experimental studies have suggested that diabetic patients may develop myocardial dysfunction in the absence of coronary heart disease and hypertension. In this study, the correlation between histopathological changes and myocardial dysfunction was studied in experimental diabetic rat hearts. Male Wistar rats were made diabetic at 9 weeks of age with a single intravenous injection of streptozotocin 50 mg/kg. The diabetic rats were studied along with age-matched control and insulin-treated rats at 4, 8, 12 and 24 weeks after the induction of diabetes to investigate isolated papillary muscle contraction and the histopathological picture simultaneously. In the isometric contractions, resting and developed tensions were similar. Time to peak tension and time to 1/2 relaxation were prolonged and the peak rate of tension rise and tension fall was depressed. On histological examination of left ventricular walls, diameters of myocytes were similar at all disease durations. Interstitial fibrosis and disarrangement of myocytes after 12 weeks were slightly increased in the diabetic hearts. Mechanical parameters did not worsen in parallel with the duration of diabetes and histological changes, but correlated with the blood glucose level. These data suggest that short-term mechanical defects in the experimental diabetic rat heart result from the metabolic disorder itself, with histopathological changes occurring later.

Coronary angiographic characteristics in Japanese patients with heterozygous familial hypercholesterolemia

Coronary angiographic findings were analyzed in 51 consecutive patients (36 males and 15 females) with heterozygous familial hypercholesterolemia (FH) and 279 consecutive patients (216 males and 63 females) without FH (non-FH). The coronary stenosis index and over 75% stenosis vessel subset were almost three times as high in the FH group. The incidence of myocardial infarction was almost twice as high in the FH group. Levels of total cholesterol and its lipoprotein fractions, except HDL-cholesterol, were almost twice as high in the FH group. In the FH group aged under 50 years, the two parameters of coronary angiogram and the incidence of myocardial infarction were significantly higher in males than in females. However, in the group aged over 50 years, all three parameters were not significantly different between those in males and females. The level of HDL-cholesterol was significantly lower in males than in females. A significantly higher incidence (18%) of coronary ectasia was observed in the FH group compared with the incidence (2%) in non-FH. All patients with coronary ectasia were males, except one female with FH. On comparison of the males among the FH patients with those among the non-FH patients matched for total cholesterol, age and other risk factors, the FH patients were associated with a significantly higher degree of coronary atherosclerosis and lower level of HDL-cholesterol. Seven FH patients with a normal coronary angiogram were observed. However, any factors as regards age, total cholesterol, HDL-cholesterol and Achilles tendon thickness failed to distinguish between the FH patients with a normal coronary angiogram and those without.(ABSTRACT TRUNCATED AT 250 WORDS)

Abdominal Aortic Aneurysms in Familial Hypercholesterolemia—Case Reports

Familial hypercholesterolemia (FH) is a genetic disease characterized by high serum cholesterol levels and premature coronary atherosclerosis. Hyper cholesterolemia is one of the factors promoting the arteriosclerotic process and is a major cause of aortic aneurysm. Few data are available, however, about abdominal aortic aneurysms (AAAs) in patients with FH. In this study, the clini cal and angiographic characteristics of AAAs found in patients with FH were investigated. Thirty-one cases (23 men, 8 women, aged fifty ± fourteen years) were examined by coronary angiography, thoracic and abdominal aortography, and clinical data. Abdominal aortography detected abdominal aneurysms in 8 cases (26%), all of whom were men, including 4 cases (50%) that were compli cated by diabetes mellitus. The abdominal aneurysm patients manifested severe coronary atherosclerosis, severe abdominal aortic irregularity, and higher blood pressure than the nonaneurysm FH patients. These findings suggest that AAAs are an important and prevalent feature in FH, especially in men with diabetes mellitus and high blood pressure.

Effects of preload reduction on left atrial pump pump function in hypertrophic cardiomyopathy and myocardial infarction

To characterize the preload dependence of augmented left-atrial pump function in left-ventricular dysfunction, the changes in the transmitral flow velocity pattern induced by a lower-body negative pressure (LBNP) of −20 and −40 mm Hg were investigated in 19 ,patients with hypertrophic cardiomyopathy, 17 patients with myocardial infarction and 19 control subjects. The maximal early diastolic flow velocity and early diastolic flow velocity integral decreased with −20 mm Hg LBNP, with even greater decreases occuring with −40 mm Hg LBNP in all groups

Early Diastolic Dysfunction of Left Ventricle and its Relation to Pathologic Finding in Patients with Diabetes Mellitus

In diabetes mellitus, the development of myocardial injury secondary to hypertension and coronary arteriosclerosis poses a major clinical problem. In addition, this issue has been the focus of great interest and it has been demonstrated that the existence of myocardial injury is not attributable to hypertension or coronary arteriosclerosis. It has also been reported in various pathological studies that even in the diabetic heart without hypertension and coronary artery lesions, various histological changes such as myocyte hypertrophy, perivascular fibrosis, and interstitial fibrosis are present (1–3). On the other hand, the existence of functional abnormalities such as left ventricular systolic and diastolic dysfunction has also been reported (4–12). It is, however, not yet clear which pathological changes account for these functional disturbances in the diabetic heart. To clarify this point we investigated the relation between systolic and diastolic function and the myocardial histological findings in diabetic patients.