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Biomedical subjects

K Kugiyama

Publications and source records attributed to K Kugiyama.

At least 127 records · Page 7Linked to original sources
PubMed1993

Transferable lipids in oxidized low-density lipoprotein stimulate plasminogen activator inhibitor-1 and inhibit tissue-type plasminogen activator release from endothelial cells.

Decreased fibrinolytic activity has been reported in atherosclerotic cardiovascular diseases. To determine whether oxidized low-density lipoprotein (Ox-LDL), which accumulates in atherosclerotic arteries, modulates the endothelial fibrinolytic system, cultures of human umbilical vein endothelial cells were incubated with low-density lipoproteins or lipids, and levels of plasminogen activator inhibitor-1 (PAI-1) and tissue-type plasminogen activator (t-PA) antigens in the conditioned medium were measured by enzyme-linked immunosorbent assay. Ox-LDL (30 micrograms protein/mL) and its extracted lipid (50 micrograms cholesterol/mL) stimulated PAI-1 release by 42 +/- 3% and 29 +/- 3% of control cultures, respectively, whereas Ox-LDL and its lipid inhibited t-PA release by 42 +/- 4% and 53 +/- 3% of control cultures, respectively. Native LDL and its lipid were inactive on their release. Ox-LDL depleted of hydrophilic lipids, which was prepared by the incubation with defatted albumin (an acceptor for hydrophilic lipids), lost both the stimulatory action on PAI-1 and the inhibitory action on t-PA. The extracted lipid from the incubated albumin, which has been found to accept the hydrophilic lipids from Ox-LDL, gained the stimulatory action on PAI-1 and the inhibitory action on t-PA. Ox-LDL depleted of lysophosphatidylcholine (LPC), which was prepared by the incubation with phospholipase B, lost the stimulatory effect on PAI-1, whereas the inhibitory effect on t-PA remained present in the Ox-LDL depleted of LPC. The incubation with synthetic palmitoyl LPC (10 microM) stimulated PAI-1 release by 85 +/- 7% of control.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Survival↗
PubMed1992

A study on coronary hemodynamics during acetylcholine-induced coronary spasm in patients with variant angina: endothelium-dependent dilation in the resistance vessels.

The epicardial coronary artery of patients with variant angina is hyperreactive to the constrictive effect of acetylcholine, but it is not known whether the coronary microvasculature also constricts in response to acetylcholine. Incremental doses of acetylcholine were injected into the left coronary artery of 57 patients with variant angina and with spasm in this artery. By measuring coronary sinus blood flow, coronary hemodynamic status just before angiographic documentation of spasm was examined. Acetylcholine induced spasm in the left coronary artery in all patients. It also decreased the diameter of the nonspasm artery by 36 +/- 19% from baseline. For all patients, coronary sinus blood flow was 89 +/- 38 ml/min at baseline and increased to 104 +/- 61 ml/min during an acetylcholine-induced anginal attack (p less than 0.01). In 10 patients with spasm in both the left anterior descending and left circumflex arteries (that is, multivessel spasm), coronary sinus blood flow decreased from 84 +/- 21 to 52 +/- 26 ml/min (p less than 0.01). In the other 47 patients with spasm in only one of these two arteries (that is, single-vessel spasm), coronary sinus blood flow increased from 90 +/- 41 to 115 +/- 61 ml/min (p less than 0.01) without change in the rate-pressure product. It is concluded that in patients with variant angina, acetylcholine induces spasm and constriction in the epicardial coronary artery, whereas it dilates the resistance vessels presumably through the release of the endothelium-dependent relaxing factor.

Acetylcholine↗
PubMed1992

Suppression of endothelin-1 secretion by lysophosphatidylcholine in oxidized low density lipoprotein in cultured vascular endothelial cells.

Oxidatively modified low density lipoprotein (oxidized LDL), an atherogenic lipoprotein that exists in the atherosclerotic arteries, has been shown to alter endothelial cell functions. In the present study, we examined the effects of oxidized LDL on the production of endothelin-1-like immunoreactivity (ET-1-LI) by the cultured vascular endothelial cells from porcine aorta and human umbilical vein. Incubation with oxidized LDL resulted in a dose-dependent suppression of ET-1-LI release by both endothelial cells. Oxidized LDL also inhibited thrombin-mediated stimulation of ET-1-LI secretion. However, native LDL had no effects on ET-1-LI secretion. A lipid extract from oxidized LDL, but not from native LDL, inhibited ET-1-LI secretion, indicating that the lipid component of oxidized LDL was required for the inhibition of ET-1-LI secretion. Oxidative modification of LDL was associated with degradation of a substantial amount of phosphatidylcholine to lysophosphatidylcholine (LPC). Pretreatment with defatted albumin, which is an acceptor for hydrophilic lipids including LPC, reduced LPC concentration in oxidized LDL to that in native LDL and simultaneously prevented the inhibitory effects of oxidized LDL on ET-1-LI secretion. Incubation with synthetic LPC (palmitoyl), but not with synthetic phosphatidylcholine (dipalmitoyl), suppressed ET-1-LI secretion by the endothelial cells. No cell death was observed during the incubations as judged by the trypan blue exclusion test, and protein synthesis of the endothelial cells was not affected by lipids or lipoproteins at a concentration at which suppression of ET-1-LI was observed. We concluded that LPC in oxidized LDL causes suppression of ET-1-LI release, which may counteract the vasoconstrictive properties of atherosclerotic arteries.

Animals↗
PubMed1992

Lysophosphatidylcholine inhibits surface receptor-mediated intracellular signals in endothelial cells by a pathway involving protein kinase C activation.

Lysophosphatidylcholine (lysoPC) transferred from oxidatively modified low density lipoprotein (Ox-LDL) to the endothelial surface membrane has been shown to produce a selective unresponsiveness to cell surface receptor-regulated endothelium-dependent relaxation (EDR) in the rabbit aorta. To determine its mechanism we examined the effects of lysoPC on endothelial surface receptor-mediated transmembrane signals. Incubation for 1 minute with palmitoyl lysoPC (5-10 microM) decreased thrombin (Th, 2 units/ml)- or histamine (His, 0.1 mM)-stimulated inositol 1,4,5-trisphosphate (IP3) production in primary cultures of human umbilical vein endothelial cells (HUVECs). LysoPC also decreased Th- or His-induced intracellular calcium ([Ca2+]i, fura 2) elevation. Pretreatment with protein kinase C (PKC) inhibitors staurosporine (100 nM) or H-7 (50 microM) prevented the inhibitory actions of lysoPC, but HA-1004 had no effect. Incubation for 5 minutes with phorbol 12-myristate 13-acetate (PMA, 100 nM) produced the inhibitory actions on the Th- or His-induced intracellular signals, which closely mimic those exhibited by lysoPC. However, the inhibitory effect of lysoPC was lost in cells that were depleted of PKC by pretreatment for 24 hours with 100 nM PMA. Furthermore, incubation of the cells for 1 minute with lysoPC stimulated PKC activity in the membrane fraction. In organ chamber experiments with porcine coronary artery rings, pretreatment with staurosporine (20 nM) attenuated lysoPC-induced impairment of EDR in response to Th. These results indicate that lysoPC, which accumulates in Ox-LDL and atherosclerotic arterial walls, inhibits the early transmembrane signaling pathway in endothelial cells, and PKC activation could at least partially be involved in the negative regulation by lysoPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Decreased perfusion in myocardial region of normal donor artery secondary to collateral development. Stress 201Tl myocardial emission CT performed in patients with single vessel exertional angina having collaterals.

Thirty-one patients suffering from single vessel exertional angina with collaterals (Group A) were evaluated by stress 201T1 myocardial emission CT (Tl-SPECT) with 16 controls of severely stenotic single vessel exertional angina without collaterals (Group B). Group A included 21 patients (68%) who showed an extensive perfusion defect in double artery myocardial regions, including the normal donor artery myocardial region (DMR). However, there were no such cases in Group B, giving a significant difference between these 2 groups (p less than 0.001). Four patients in Group A, having a perfusion defect both in DMR and in the collateral dependent myocardial region (CMR) underwent a successful percutaneous transluminal coronary angioplasty (PTCA) with disappearance of collaterals. Tl-SPECT findings after PTCA showed no perfusion defect either in CMR or in DMR. This has been explained on the basis that the coronary collaterals stole blood and produced perfusion defect in DMR.

Aged↗
PubMed1990

Magnesium deficiency detected by intravenous loading test in variant angina pectoris.

To study whether magnesium (Mg) deficiency is present in patients with variant angina, 24-hour Mg retention of low dose Mg (0.2 mEq/kg lean body weight) administered intravenously over 4 hours in 20 patients with variant angina was examined. No patient had received calcium antagonists before or during the study. All had attacks of chest pain associated with ST elevation on electrocardiograms. Twenty-one subjects without ischemic heart disease were studied as control subjects. Ten patients with variant angina were restudied 10 to 529 days (mean 235 +/- 30) after the treatment with calcium antagonists (diltiazem 120 to 240 or nifedipine 40 to 80 mg/day), which resulted in complete suppression of anginal attacks. The mean serum Mg concentrations in the patients with variant angina and the control subjects were 2.1 +/- 0.05 and 2.1 +/- 0.03 mg/dl, respectively (difference not significant). However, 24-hour Mg retention in the patients with variant angina was 60 +/- 5%, while that in the control subjects was 36 +/- 3% (p less than 0.001), suggesting that Mg deficiency is present in at least some patients with variant angina. The mean serum Mg concentrations before and after calcium antagonist treatment in 10 patients with variant angina were 2.1 +/- 0.09 and 2.1 +/- 0.07 mg/dl, respectively (difference not significant). However, 24-hour Mg retention decreased significantly (p less than 0.01) from 60 +/- 6 to 34 +/- 7% after the treatment. There is Mg deficiency in many patients with variant angina and it is corrected after treatment with calcium antagonists.

Adult↗
PubMed1990

Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins.

Atherosclerosis in animals and humans is associated with an unresponsiveness of arteries and arterioles to endothelium-dependent vasodilators--agents acting on smooth muscle indirectly by stimulating the release from endothelial cells of a vasodilator principle (endothelium-derived relaxing factor). Altered vasomotor regulation in atherosclerosis could partly reflect an injurious action of abnormal lipoproteins on endothelium. Recently, 'cell-modified' or 'oxidized' low-density lipoprotein (EC-LDL) has received increasing attention because of its potential cytotoxic and atherogenic properties. We report here that arteries exposed to EC-LDL in vitro show an endothelium-dependent vasoregulatory impairment closely resembling that of atherosclerotic arteries. Our results indicate that transfer of lysolecithin from EC-LDL to endothelial membranes produces a selective unresponsiveness to receptor-regulated endothelium-dependent vasodilators.

Acetylcholine↗
PubMed1988

Suppression of exercise-induced angina by magnesium sulfate in patients with variant angina.

The effects of intravenous magnesium on exercise-induced angina were examined in 15 patients with variant angina and in 13 patients with stable effort angina and were compared with those of placebo. Symptom-limited bicycle exercise and thallium-201 myocardial scintigraphy were performed after intravenous administration of 0.27 mmol/kg body weight of magnesium sulfate and after placebo on different days. In all patients, serum magnesium levels after administration of magnesium sulfate were about twofold higher than levels after placebo. Exercise-induced angina associated with transient ST segment elevation occurred in 11 patients with variant angina receiving placebo and in only 2 of these patients receiving magnesium (p less than 0.005). On the other hand, exercise-induced angina was not suppressed by magnesium in any patient with stable effort angina. In these patients there was no significant difference in exercise duration after administration of placebo versus after administration of magnesium. The size of the perfusion defect as measured by thallium-201 scintigraphy was significantly less in patients with variant angina receiving magnesium than that in those receiving placebo (p less than 0.001), whereas it was not significantly different in patients with stable effort angina receiving placebo versus magnesium. In conclusion, exercise-induced angina is suppressed by intravenous magnesium in patients with variant angina but not in patients with stable effort angina. This beneficial effect of magnesium in patients with variant angina is most likely due to improvement of regional myocardial blood flow by suppression of coronary artery spasm.

Adult↗
PubMed1988

Multivessel coronary spasm in patients with variant angina: a study with intracoronary injection of acetylcholine.

Multivessel coronary spasm has been described but its incidence in patients with variant angina still remains unclear. Thirty-three patients with variant angina were studied during coronary angiographic examination with selective intracoronary injection of acetylcholine (ACh). In all but three patients, the location of ischemia during attack was determined by the electrocardiographic findings, by exercise 201Tl myocardial scintigraphy, and by two-dimensional echocardiography during a hyperventilation test, and the coronary artery (or arteries) responsible for the attack was predicted before the study. ACh induced spasm of at least one coronary artery in all but one patient. ACh induced spasm of both the left and right coronary arteries (i.e., multivessel coronary spasm) in 24 patients: in two of the four patients who were predicted to have spasm of the left coronary artery, in six of the 11 predicted to have spasm of the right coronary artery, in 13 of the 15 predicted to have spasm of both the left and right coronary arteries, and in three of the three in whom coronary artery responsible for attack had not been predicted. This ACh-induced spasm of the left and right coronary arteries occurred separately and no patients showed hemodynamic instability during attack. In one patient in whom multivessel coronary spasm had been predicted and ACh failed to induice coronary spasm, ergonovine maleate (0.2 mg) induced spasm of both the left and right coronary arteries simultaneously, resulting in severe prolonged hypotension. Nineteen of the 25 patients in whom multivessel coronary spasm was documented showed angiographically normal or nearly normal coronary arteries after administration of nitroglycerin.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1987

Simultaneous multivessel coronary artery spasm demonstrated by quantitative analysis of thallium-201 single photon emission computed tomography.

Thallium-201 myocardial scintigraphy with quantitative analysis of emission computed tomography was performed during episodes of angina in 19 patients with variant angina and nearly normal coronary arteriographic findings. Eleven patients (group I) were shown by arteriography to have spasm in 2 or more large coronary arteries. Eight patients (group II) had spasm in only 1 coronary artery. In 7 patients in group I, significant diffuse perfusion defects simultaneously appeared in multiple coronary artery regions on the scintigram (group IA). The extent and severity of the perfusion defect as measured by thallium-201 tomography were significantly greater in group IA than in group II (p less than 0.001 and p less than 0.01, respectively). The duration of transient ST-segment elevation during the attack in group IA was significantly longer than in group II (p less than 0.001). The incidence of ventricular arrhythmias, including ventricular tachycardia, or complete atrioventricular block during the anginal attack was significantly higher (p less than 0.05) in group IA than in group II. In all study patients, neither attack nor scintigraphic perfusion defect appeared on the repeat test after oral administration of nifedipine. In conclusion, multivessel coronary artery spasm simultaneously appears and causes the attack in many patients with variant angina and nearly normal coronary arteriographic findings, and myocardial ischemia due to simultaneous multivessel coronary spasm is likely to be more extensive and severe, persist longer and have a higher frequency of potentially dangerous arrhythmias than that due to spasm of only 1 coronary artery.

Angina Pectoris, Variant↗
PubMed1986

Effects of propranolol and nifedipine on exercise-induced attack in patients variant angina: assessment by exercise thallium-201 myocardial scintigraphy with quantitative rotational tomography.

To examine the effects of propranolol and nifedipine on exercise-induced attack in patients with variant angina, exercise 201Tl myocardial scintigraphy with quantitative analysis by emission-computed tomography was performed in 20 patients with variant angina after oral propranolol (80 mg), nifedipine (20 mg), and placebo. Exercise-induced attack occurred in 11 patients on placebo, in 14 on propranolol, and in none on nifedipine. The exercise duration was significantly shorter in those on propranolol (p less than .05), but significantly longer in patients on nifedipine (p less than .05) than in those on placebo. The peak rate-pressure product was significantly lower in patients on propranolol (p less than .01), but did not change in those on nifedipine, as compared with that in patients on placebo. The size of the perfusion defect as measured by 201Tl tomography was significantly greater in patients on propranolol (p less than .05), but significantly less in those on nifedipine (p less than .01) than in those on placebo. In conclusion, propranolol does not suppress but rather may aggravate exercise-induced attack in patients with variant angina, while nifedipine suppresses it. This unfavorable effect of propranolol on exercise-induced attack in patients with variant angina is likely to be due to a reduction of regional myocardial blood flow.

Adult↗
PubMed1986

Induction of coronary artery spasm by acetylcholine in patients with variant angina: possible role of the parasympathetic nervous system in the pathogenesis of coronary artery spasm.

We injected acetylcholine (ACh), the neurotransmitter of the parasympathetic nervous system, into the coronary arteries of 28 patients with variant angina. Injection of 10 to 80 micrograms ACh into the coronary artery responsible for the attack induced spasm together with chest pain and ST segment elevation or depression on the electrocardiogram in 30 of the 32 arteries of the 25 of the 27 patients. The injection of 20 to 100 micrograms ACh into the coronary artery not responsible for the attack in 18 patients resulted in various degrees of constriction in most of them, but no spasm in any of them. After intravenous injection of 1.0 to 1.5 mg atropine sulfate, the injection of ACh into the coronary artery responsible for the attack did not induce spasm or attack in any of the nine coronary arteries injected in eight patients. We conclude that the intracoronary injection of ACh induces coronary spasm and attack in patients with variant angina and that the activity of the parasympathetic nervous system may play a role in the pathogenesis of coronary spasm. We also conclude that the intracoronary injection of ACh is a useful test for provocation of coronary spasm.

Acetylcholine↗
PubMed1984

Blocking effect of verapamil on conduction over a catecholamine-sensitive bypass tract in exercise-induced Wolff-Parkinson-White syndrome.

By intravenous administration of isoproterenol, 0.5 micrograms/min, a catecholamine-sensitive bypass tract was confirmed in two patients with exercise-induced Wolff-Parkinson-White syndrome. In a 24 year old woman, an intravenous bolus injection of 5 mg of verapamil suddenly blocked conduction over a catecholamine-sensitive bypass tract. In a 62 year old man, the exercise-induced Wolff-Parkinson-White syndrome disappeared after 3 days of oral administration of verapamil (120 mg/day). These observations suggest that a slow inward calcium current plays an important role in conduction over a catecholamine-sensitive bypass tract in exercise-induced Wolff-Parkinson-White syndrome.

Adult↗
PubMed1984

Electrophysiologic effects of atropine and isoproterenol on the cardiac conduction system in familial amyloid polyneuropathy.

In ten patients with familial amyloid polyneuropathy (FAP), the effects of atropine and isoproterenol on the cardiac conduction system were studied using surface electrocardiogram (ECG) and His bundle electrograms. Intravenous administration of atropine sulfate, 1 mg, prolonged the sinus cycle length ( SNCL ) in 6 of 8, sinus node recovery time (SNRT) in 3 of 6, automaticity recovery time of the atrioventricular (A-V) node in one, A-H interval in 4 of 7, effective refractory periods of the atrium and A-V node in 4 of 6 and in 3 of 7 patients, respectively. Continuous intravenous administration of isoproterenol, 0.5 micrograms/min, shortened the SNCL , SNRT, A-H interval and refractory periods of the atrium and A-V node in all patients. We conclude that the therapeutic doses of atropine may be useless or potentially detrimental for bradyarrhythmias or conduction blocks in some patients with FAP, but that isoproterenol may have beneficial effects on those arrhythmias in FAP.

Adult↗