Shuzo Matsuo

Programmed cell death induced by ischemia-reperfusion in rat intestinal mucosa

Apoptosis after ischemia-reperfusion (I/R) was characterized in rat small intestine. Under halothane anesthesia, the superior mesenteric artery in the rat was occluded for 15 or 60 min, followed by reperfusion. Ratios of fragmented DNA to total DNA, electrophoresis, and immunohistochemical staining were examined after I/R. Some rats were pretreated with alpha-difluoromethylornithine (DFMO) to examine the relationship between intestinal apoptosis and ornithine decarboxylase (ODC) activity. The percentage of fragmented DNA significantly increased just after ischemia and peaked at 1 h after reperfusion in the jejunum and ileum. These increases were significantly higher in the 60-min ischemia group compared with the 15-min ischemia group. This increase decreased 6 h after reperfusion. The results were corroborated by histological evaluations of the intestine under the same conditions. DFMO completely abolished elevation of ODC activity 6 h after reperfusion but did not change the percentage of fragmented DNA. Apoptosis in rat small intestine was induced by ischemia of the gut, and this process was exacerbated by reperfusion. The changes in apoptosis were independent of ODC activity.Apoptosis after ischemia-reperfusion (I/R) was characterized in rat small intestine. Under halothane anesthesia, the superior mesenteric artery in the rat was occluded for 15 or 60 min, followed by reperfusion. Ratios of fragmented DNA to total DNA, electrophoresis, and immunohistochemical staining were examined after I/R. Some rats were pretreated with α-difluoromethylornithine (DFMO) to examine the relationship between intestinal apoptosis and ornithine decarboxylase (ODC) activity. The percentage of fragmented DNA significantly increased just after ischemia and peaked at 1 h after reperfusion in the jejunum and ileum. These increases were significantly higher in the 60-min ischemia group compared with the 15-min ischemia group. This increase decreased 6 h after reperfusion. The results were corroborated by histological evaluations of the intestine under the same conditions. DFMO completely abolished elevation of ODC activity 6 h after reperfusion but did not change the percentage of fragmented DNA. Apoptosis in rat small intestine was induced by ischemia of the gut, and this process was exacerbated by reperfusion. The changes in apoptosis were independent of ODC activity.

Phasic coronary artery flow velocity determined by Doppler flowmeter catheter in aortic stenosis and aortic regurgitation

Phasic coronary artery flow velocity was recorded in 14 patients with aortic regurgitation (AR), 4 with aortic stenosis, 61 with other heart diseases and in 2 normal subjects by means of a bidirectional Doppler flowmeter catheter. The normal pattern of the phasic coronary artery flow velocity was characterized by a small forward flow during systole (S wave) and a large forward flow during diastole (D wave). The phasic coronary artery flow velocity in patients with AR showed increased S wave and decreased D wave. The area under the S-wave curve divided by the area under the D-wave curve (S/D ratio) in patients with AR increased (left coronary artery flow velocity 0.66 +/- 0.39, p less than 0.05; right coronary flow velocity 0.79 +/- 0.36, p less than 0.01) as compared with the S/D ratio in patients with other heart diseases (left coronary flow velocity 0.32 +/- 0.12; right coronary artery flow velocity 0.38 +/- 0.17). There was a tendency toward a relative positive correlation between S/D ratio values and AR cineangiographic grades. Decreased S/D ratios were observed in 4 patients with aortic stenosis. It is believed that no reports exist on phasic coronary flow velocity recorded in conscious patients who had aortic valve disease.

Mental stress test is an effective inducer of vasospastic angina pectoris: comparison with cold pressor, hyperventilation and master two-step exercise test

BACKGROUND Cold pressor, hyperventilation and exercise stress tests were usually used for inducing an angina attack in patients with vasospastic angina pectoris. We induced vasospastic angina attack using the mental calculation stress test, and compared the results with those using other stress tests. SUBJECTS AND METHODS Subjects were 29 patients with vasospastic angina pectoris. Their ages were 60.8+/-8.4 years. Coronary vasospasm was induced by an acetylcholine infusion test during coronary angiography. The mental stress test was performed as follows; after memorizing six digits numbers, they repeated these numbers in reverse for 5 min, and performed serial subtraction of 17 from 1000 for 5 min. Blood pressure, heart rate and ECG were recorded every 1-5 min during the mental stress test. The serum concentrations of epinephrine and norepinephrine were measured before and during the mental stress test. We compared these results with those obtained using cold pressor, hyperventilation and the Master two-step exercise stress test. RESULTS (1) Eight of the 29 patients (28%) showed ischemic ST-T change, which was caused by the mental stress test. (2) The increase in norepinephrine was greater in patients with an ST-T change than without an ST-T change (0.11+/-0.06 vs. 0.04+/-0.04 ng/ml, P<0.01). (3) The incidence of the ST-T change caused by the mental stress test (28%) was similar to the cold pressor test (27%) and greater than that caused by the hyperventilation test (13%). The incidence of ST-T change caused by the Master two-step test was 55%. CONCLUSIONS The mental stress test is an effective inducer of vasospastic angina attack, and attack may be induced by neurohumoral vasoconstrictive reflex and/or increased left ventricular afterload.

Effect of ticlopidine on exercise-induced Platelet aggregation and exercise tolerance time in patients with ischemic heart disease

Platelet aggregation is one of the most important mechanisms for acute myocardial infarction during exercise. We sought to evaluate the effect of ticlopidine (TP) on platelet aggregation (PA) during exercise in patients with ischemic heart disease (IHD). We studied 38 patients with IHD, 26 patients with effort angina pectoris, and 12 patients with a previous myocardial infarction. In protocol I, subjects were divided into two groups. Drugs altering platelet aggregation were withheld 2-4 weeks before the study in 25 patients (control group). TP (200 mg/day) was administered for 7 days in 13 patients (ticlopidine group). A symptom-limited modified Bruce protocol treadmill exercise test was performed. PA was measured at rest and after exercise by using optical densitometry induced by adenosine diphosphate (ADP). PA ratio (percentage of maximum) was compared. In protocol II, in 12 patients, treadmill exercise test and PA measurement were performed with and without TP. PA significantly increased after exercise in control (from 51.7+/-23.3% to 64.4+/-27.7%, p < 0.01) and ticlopidine (from 31.9+/-10.5% to 42.0+/-20.4%, p < .01) groups; however, its grade was lower in the ticlopidine group than in the control group. After exercise, PA was lower in the ticlopidine group than in control group (42.0+/-20.4% vs. 64.4+/-27.7%; p < 0.01). In the same patients, PA was lower with TP than without TP after exercise. Treadmill exercise-tolerance time was greater in the ticlopidine group than in the control group, but not statistically significant (762.3+/-139.2 vs. 711.6+/-169.6 s; NS). Exercise-tolerance time was significantly greater with TP than without TP in same patient (791.7+/-98.9 vs. 733.3+/-152.8 s; p < .05). TP suppressed the increase of PA during exercise and increased the exercise-tolerance time in patients with IHD.

Short- and long-term effects of nisoldipine on cardiac function and exercise tolerance in patients with hypertrophic cardiomyopathy

Nisoldipine is a second generation dihydropyridine calcium antagonist having characteristics of strong coronary artery dilating effect and less negative inotropic action. The purpose of this study was to evaluate the effect of nisoldipine on the cardiac function (systolic and diastolic) and the exercise tolerance in patients with hypertrophic cardiomyopathy (HCM).Subjects: Twenty-three patients with HCM were studied.Methods: We measured the following indices using M-mode and pulsed wave Doppler echocardiography before and after nisoldipine therapy; left ventricular fractional shortening (LVFS), isometric relaxation time (IRT), deceleration half-time (DHT) of early diastolic mitral (E) flow, late diastolic mitral (A) flow and A/E ratio. Symptomlimited treadmill exercise test was performed. Exercise tolerance (EX) time was measured. Nisoldipine of 10mg/day was orally administered. Same tests were repeated on day 14 and after 6 months.Results: 1) Short-term effects; LVFS did not change (55.9±5.9%→57.0±7.4%, NS) after 2 weeks. However, LV diastolic function significantly improved (IRT; 92.1±7.7 ms→85.2±11.6 ms, p<0.05, DHT; 70.7±16.2 ms→63.3±3.7 ms, p<0.05). EX time increased (8.9±2.6 min→ 10.0±3.3 min, p<0.05). 2) Long-term effects; LV diastolic function had a tendency toward improvement, but is statistically not significant (IRT; 91.1±7.6→83.8±11.6 ms, DHT; 73.1±23.4→61.0±11.4 ms, A/E; 1.26±0.29→1.11±0.36) after 6 months. EX time was significantly increased (9.4±1.7→ 10.1±1.7 min, p<0.05).Conclusions: Nisoldipine improved LV diastolic dysfunction and exercise tolerance in patients with HCM. These effects were similar to the first generation calcium antagonists. LV diastolic dysfunction may be improved due to the reduction of intracellular calcium concentration and the relief of myocardial ischemia by strong coronary artery dilating effect. However, nisoldipine did not affect the LV systolic function because of its less negative inotropic effect.

The effect of beta-adrenergic blockade in dilated cardiomyopathy--a questionnaire study in Japan.

SummaryThe effect of beta-blockade in dilated cardiomyopathy was studied by a questionnaire survey. Thirty-three cases were monitored in whom metoprolol (22 patients, 35.9 ± 20.4 mg, mean ± SD), propranolol (four patients, 26.3 ± 7.5 mg), or other beta-blockers (seven patients) were administered. Four patients died, but no direct relationship was found between administration of beta-blocker and death. The NYHA functional class improved significantly. The mean heart rate decreased from 96/min to 77/min (P < 0.01). The mean cardiothoracic ratio decreased from 55.6% to 52.1% (P < 0.01). The mean ejection fraction of the left ventricle measured by echocardiogram increased from 30.4% to 36.9% (P < 0.01). Exercise tolerance in the treadmill test improved significantly. There was no change in blood pressure, nor were there arrhythmias seen on Holter electrocardiograms. In two patients, congestive heart failure deteriorated after administration of beta-blockers. It is concluded that beta-adrenergic blockade has a beneficial effect in most of the patients with dilated cardiomyopathy.

LEFT ATRIAL MYXOMA MIMICKING A SYSTEMIC DISEASE

46才女子で,発熱,関節痛体重減少を主訴とし,貧血,血沈亢進, γ-globulinの増加など,多彩な全身症状および所見を呈した症例で,聴診所見,心音図,心尖拍動図所見などより,左房粘液腫を疑い,心臓カテーテル,心血管造影にてこれを確認し,手術に成功した1例を報告した.また,本例にみられた術前,術後の心音および心尖拍動図の所見ならびに免疫学的検査所見について若干の考察を行なつた.