Clinical characteristics and possible mechanism of paroxysmal atrial fibrillation induced by intracoronary injection of acetylcholine.
Explore the source record for details and available documents.
Acetylcholine↗
Biomedical subjects
N Ochi
Publications and source records attributed to N Ochi.
Ser-59 is the major phosphorylation site in alphaB-crystallin accumulated in the brains of patients with Alexander's disease.
The phosphorylation state of alphaB-crystallin accumulated in the brains of two patients with Alexander's disease (one infantile and one juvenile type) was determined by means of SDS-PAGE or isoelectric focusing of soluble and insoluble fractions of brain extracts and subsequent western blot analysis with specific antibodies against alphaB-crystallin and each of three phosphorylated serine residues. The level of mammalian small heat shock protein of 25-28 kDa (Hsp27) in the same fraction was also estimated by western blot analysis. The majority of alphaB-crystallin was detected in the insoluble fraction of brain homogenates and phosphorylation was preferentially observed at Ser-59 in both cases. A significant level of phosphorylation at Ser-45 but not Ser-19 was also detected. Hsp27 was found at considerable levels in the insoluble fractions. alphaB-crystallin and phosphorylated forms were detected in the cerebrospinal fluid of patient with the juvenile type. AlphaB-crystallin and phosphorylated forms were also detectable at considerable levels in the insoluble fraction of brain homogenates from patients with Alzheimer's disease and aged controls. The phosphorylation site was mostly at Ser-59 in all cases. Immunohistochemically, alphaB-crystallin was stained in Rosenthal fibers in brains of patients with Alexander's disease and their peripheral portions were immunostained with antibodies recognizing phosphorylated Ser-59. These results indicate that the major phosphorylation site in alphaB-crystallin in brains of patients with Alexander's disease or Alzheimer's disease as well as in aged controls is Ser-59.
Adult↗
New non-invasive protocol for detection of coronary spastic angina with significant organic stenosis.
OBJECTIVES: This study sought to determine whether a newly-combined test, accelerated exercise following mild hyperventilation (HV) is more beneficial to detect ischaemic evidence in patients with pharmacology-induced coronary artery spasm (CAS) and luminal narrowing of > 75% than classic methods. METHODS AND RESULTS: Forty consecutive patients who all had luminal narrowing of > 75% but < 90% and pharmacology-induced coronary vasospasms of fixed lesions were involved in this study. In these patients, initial HV test, followed by treadmill (TM) exercise test and lastly the newly combined test were performed on three consecutive days. Of the 40 patients, firstly six, secondarily 16 and lastly 32 had positive responses to the HV test, TM exercise test, and newly combined test, respectively. The remaining six patients (15%) had negative results, although the triple sequential tests were performed. Thus, sensitivity of the HV test, the TM exercise test, and the newly combined test was 15% (6/40), 40% (16/40), and 84% (32/38), respectively. Specificity of the three tests were all 100% (46/46). Non-sustained ventricular tachycardia and hypotension were observed in two (5%) patients. However, no serious or irreversible complications were encountered in this study. CONCLUSIONS: We recommend the newly combined protocol rather than the classic tests for the detection of ischaemic evidence in patients with coronary spastic angina and fixed stenosis.
Acetylcholine↗
Usefulness of accelerated exercise following mild hyperventilation for the induction of coronary artery spasm : comparison with an acetylcholine Test.
STUDY OBJECTIVES: This study was performed to compare the results of accelerated exercise following mild hyperventilation and a standard acetylcholine (ACh) test for the induction of coronary artery spasm in patients with drug-induced coronary artery spasm. METHODS AND RESULTS: The subjects were 74 patients with angiographically confirmed coronary artery spasm who were examined using accelerated exercise (ie, exercise that was accelerated every minute according to the protocol of Bruce and Horsten) following mild hyperventilation and who were not receiving any medication. ACh was injected in incremental doses of 20 microg and 50 microg into the right coronary artery and incremental doses of 20 microg, 50 microg, and 100 microg into the left coronary artery. Positive coronary spasm was defined as > or =99% luminal narrowing. Accelerated exercise following a mild hyperventilation test was as useful for detecting evidence of ischemia as was an ACh test (48 patients [64.9%] vs 49 patients [66.2%], respectively; not significant). No difference was observed between ischemic changes on ECG as a result of the newly combined method and the occurrence of ACh-induced spasm. ACh-induced coronary vasospasm occurred in 61 patients (82.4%). In the remaining 13 patients, intracoronary administration of ergonovine provoked coronary spasms. No serious irreversible complications were detected as a result of this newly combined method. CONCLUSIONS: The effectiveness of our newly combined procedure is equivalent to that of an ACh test to diagnose patients with coronary artery spasm.
Acetylcholine↗
Comparative results of coronary intervention in patients with variant angina versus those with non-variant angina.
Coronary angioplasty is reported to be feasible and safe in patients with coronary spasm and fixed stenosis. However, the long-term results are not positive. We compared the results of coronary angioplasty in 20 patients with variant angina versus 17 patients with non-variant angina among 231 consecutive patients with vasospastic angina. Coronary angioplasty was performed successfully in all 37 patients without any complications. Stenting for coronary dissection or recoil was performed in 8 patients, directional coronary atherectomy was selected for ostial lesion of left anterior descending coronary artery stenosis in 2 patients, and standard balloon angioplasty was performed in 27 patients. There were no clinical differences between the two groups. The restensois rate in patients with variant angina was similar to that in patients with non-variant angina (30% vs 29%, ns). There was no relationship between the provoked spasm and restenosis. During the follow-up period, no major complications were observed in patients with variant angina or those with non-variant angina. In conclusion, full medication with calcium channel antagonists and isosorbide dinitrate, and treatment by coronary angioplasty including the use of new devices, were useful treatments for patients with coronary vasospasm and significant organic stenosis. There was no difference concerning the results of coronary intervention between the patients with variant angina and those with non-variant angina.
Aged↗
[Central nervous system involvements in Duchenne/Becker muscular dystrophy].
Duchenne/Becker muscular dystrophy (DMD/BMD) are the most common inherited muscular diseases caused by mutations in the dystrophin gene. The identification of novel dystrophins in the brain has recently implicated its absence or malfunction etiologically in mental retardation (MR). We therefore examined the relationship between molecular abnormalities and clinical phenotypes. Deletions of the dystrophin gene were analyzed in a total of 137 DMD/BMD patients (DMD 94, BMD 43) to determine central nervous system (CNS) symptoms. The mental capacity was assessed and patients with IQs below 70 were defined as mentally retarded. Thirty-nine percent of DMD boys and 12% of BMD patients were classified as mentally retarded. Eight DMD and 2 BMD patients were diagnosed as having autism. Forty-four percent of DMD and 79% of BMD patients had deletions in the dystrophin gene. All the DMD/BMD patients with deletions upstream of the 5' end of the gene were mentally normal. All of DMD/BMD patients with MR and/or autism had deletions containing the 3' end, although some patients with similar deletions were mentally normal. Our data suggest that Dp140, Dp71 and/or Dp116, the C-terminal translational products of dystrophin, may be related to MR and/or autism in DMD/BMD. However, there was an exception in our series. Three of eight sibling pairs in our cases had different phenotypes, although they had the same mutations in the dystrophin gene. Thus the CNS phenotypes were not determined by the mutations of dystrophin gene alone, and the interaction of dystrophin with other nuclear genes may play important roles.
Adolescent↗
Major complications during spasm provocation tests with an intracoronary injection of acetylcholine.
This study sought to clarify major complications associated with acetylcholine testing. Serious major complications, such as sustained ventricular tachycardia, shock, and cardiac tamponade were determined in 4 of 715 patients (0.56%), but no cases of death or irreversible complications occurred. The spasm provocation test using acetylcholine should be performed carefully, although it is considered a safe and reliable method.
Acetylcholine↗
Clinical characteristics of female patients with coronary spastic angina: comparison with male patients.
There are many patients with vasospastic angina who have minor atherosclerosis, and in Japan the majority of them are male. No data exist concerning sex differences in patients with coronary spastic angina, so the present study sought to clarify the clinical characteristics between male and female patients with vasospastic angina. Between April 1991 and June 1998, 204 consecutive patients were diagnosed with vasospastic angina and of these, 26 (12.7%) were female. An acetylcholine test was performed with incremental doses of 20, 50, and 80 microg injected into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Ergonovine was injected in a total dose of 40 microg into the right coronary artery and 64 microg into the left coronary artery. Coronary spasm was defined as 99% or more luminal narrowing accompanied by ischemic changes on ECG. Compared with male patients, female patients had less organic stenosis (12 vs 33%, p<0.05), less history of smoking (15 vs 85%, p<0.01), and fewer focal spasms (31 vs 64%, p<0.01). There were no other differences between the 2 groups. In conclusion, Japanese female patients with vasospastic angina had the characteristics of diffuse provoked spasm, less organic stenosis, and less history of smoking, but only 1 in 10 of all patients with vasospastic angina are female.
Aged↗
New combined spasm provocation test in patients with rest angina: intracoronary injection of acetylcholine after intracoronary administration of ergonovine.
The incidence of provoked coronary spasm with the standard single spasm provocation test has been relatively low in patients with rest angina. The present study examined the clinical usefulness of a newly designed spasm provocation test, an intracoronary injection of acetylcholine (ACh) following an ergonovine (ER) test, in patients with rest angina who demonstrated low disease activity and atypical chest pain. Triple sequential spasm provocation tests were performed in 24 patients with atypical chest pain who had no ischemia and in 40 patients with rest angina who had distinct ischemia. Initially, an ACh test (20-100 microg) and then an ER test (40-64 microg) were performed and then, if no spasm was provoked, an intracoronary injection of ACh was given after the ER test to evaluate coronary spasm. Coronary spasm was defined as total or subtotal occlusion. In the 24 patients with atypical chest pain, no spasm was provoked by intracoronary injection of either ACh or ER, but coronary spasms were induced in 2 patients using the new method, with the remaining 22 not experiencing spasm (specificity of new method, 92%). In the 40 patients with rest angina, intracoronary injection of ACh induced coronary spasm in 22 patients (group I) and 6 (group II) demonstrated spasm with intracoronary injection of ER. Coronary spasm was not induced by either the ACh test or the ER test in 12 patients (group III). The intracoronary administration of ACh after the ER test provoked spasm in 11 of 12 patients. Diffuse spasms were provoked in 10 of 11 patients. In patients with rest angina, the frequency of chest pain attacks in 1 month experienced by patients in group III (0.8+/-0.8) was significantly lower than that of patients in group I (7.0+/-5.3, p<0.01) or II (3.5+/-2.3, p<0.05). No serious or irreversible complications related to this new combined method were observed. In conclusion, this method was safe and reliable for the induction of coronary spasm in patients with rest angina who may have low disease activity.
Acetylcholine↗
Genetic analysis of Japanese patients with persistent hyperinsulinemic hypoglycemia of infancy: nucleotide-binding fold-2 mutation impairs cooperative binding of adenine nucleotides to sulfonylurea receptor 1.
To elucidate the genetic etiology of persistent hyperinsulinemic hypoglycemia of infancy (PHHI) in the Japanese population, we conducted a polymerase chain reaction-single-strand conformation polymorphism analysis of the sulfonylurea receptor 1 (SUR1) and Kir6.2 genes in 17 Japanese PHHI patients, including a pair of siblings from a consanguineous family. We also analyzed the glutamate dehydrogenase gene for the exons encoding an allosteric regulatory domain of the enzyme. In the SUR1 gene, we identified one frameshift (I446fsdelT) and two missense (R1420C, R1436Q) mutations. None of these mutations were found in control Japanese subjects. Siblings homozygous for the R1420C mutation had a mild form, whereas two patients heterozygous for the I446fsdelT and R1436Q mutations, respectively, exhibited a severe form of PHHI. Functional consequences of these mutations on K(ATP) function were evaluated using 86Rb+ efflux studies in COS-7 cells. SUR1-446fsdelT and SUR1-1436Q did not form a functional K(ATP). Western blot analysis after transient expression in COS-7 cells revealed the expression of SUR1-1436Q protein to be markedly reduced, suggesting SUR1-1436Q to be unstable in these cells. K(ATP)(SUR1-1420C) showed reduced responses to metabolic inhibition by oligomycin and 2-deoxyglucose. K(ATP) channels are under complex regulation by intracellular ATP and ADP. ATP both inhibits and activates these channels. The inhibition is probably mediated through direct ATP interaction with a pore-forming subunit Kir6.2, whereas the activation is likely to be through a regulatory subunit SUR1. There is a cooperative regulation of ATP and ADP binding to SUR1, and this cooperativity may be involved in regulating the K(ATP) channel. In SUR1-1420C, high-affinity binding of ATP to the nucleotide-binding fold (NBF)-1 was indistinguishable from that of wild-type SUR1. However, stabilization of ATP binding to NBF-1 by MgATP or MgADP was impaired, suggesting that this defect may account for impaired K(ATP)(SUR1-1420C) function. This is the first direct biochemical evidence that the cooperativity of nucleotide binding to SUR1 is impaired in a SUR1 mutant causing PHHI. No mutations were identified in the Kir6.2 and glutamate dehydrogenase genes. The genetic etiology of PHHI appears to be heterogeneous. SUR1 mutations may account for no more than 20% of PHHI cases in Japanese patients. Mutations of Kir6.2 and glutamate dehydrogenase genes are likely to be even less common.
ATP-Binding Cassette Transporters↗
Positron emission tomography in juvenile Alexander disease.
A 13-year-old boy with cervical kyphosis was diagnosed as having juvenile Alexander disease because of the typical MRI findings, abnormally elevated alphaB-crystallin and heat shock protein 27 in the cerebrospinal fluid. Positron emission tomography with 18F-fluorodeoxyglucose demonstrated hypometabolism in the frontal white matter corresponding to the areas with leukodystrophy. However, the overlying gray matter preserved normal glucose metabolism.
Adolescent↗
Frequency of provoked coronary vasospasm in patients undergoing coronary arteriography with spasm provocation test of acetylcholine.
This study examines the incidence of spasm by intracoronary injection of acetylcholine in Japanese patients who underwent coronary angiography. The subjects were 685 consecutive patients (477 men, mean age 63.2 +/- 7.5 years) who were studied with an acetylcholine test. Acetylcholine was injected in incremental doses of 20, 50, and 80 microg into the right coronary artery and 20, 50, and 100 microg into the left coronary artery. Spasm was defined as total or subtotal occlusion. Coronary vasospasm was determined in 221 patients (32.3%). Spasm occurred often during effort and rest in patients with angina (25 of 51, 49.0%), exertional angina (25 of 74, 33.8%), recent myocardial infarction (30 of 80, 37.5%), healed myocardial infarction (14 of 37, 37.8%), and especially in patients with rest angina (83 of 124, 66.9%), whereas spasm was relatively uncommon in patients with nonischemic heart disease (23 of 252, 9.1%). Spasm was superimposed on significant atherosclerotic lesions in 35.9% of patients as well as on nonfixed atherosclerotic lesions in 30.8% of patients. We conclude that >9% of Japanese patients may have coronary vasospasm with intracoronary injection of acetylcholine and recommend the provocation test for evaluating coronary vasospasm if coronary angiography is undertaken.
Acetylcholine↗
Investigation of the most effective provocation test for patients with coronary spastic angina: usefulness of accelerated exercise following hyperventilation.
This study sought to compare the clinical usefulness of the hyperventilation plus cold stress test or the hyperventilation combined with accelerated exercise test with other single tests in patients with coronary spastic angina. The study examined 24 patients (23 men, mean age 66 years) with angiographically confirmed coronary spastic angina and less than 50% stenosis. Moreover, none had spontaneous ST segment elevation before the study. Under no medication for at least 24 h prior, 4 procedures were performed from 09.00 h to 11.00 h: (i) a hyperventilation test for 5 min (HV(5)); (ii) HV(5) combined with a cold stress test for the last 2 min (HV(5)+CS(2)); (iii) a treadmill exercise test based on Bruce's protocol (TM(3)); and (iv) a treadmill exercise test accelerated at 1 min intervals according to Bruce's protocol immediately after HV(5) (HV(5)+TM(1)). The rate of appearance of chest pain and ischemia-induced ECG changes due to HV(5)+TM(1) were significantly higher than the other 3 tests. HV(5)+CS(2) was not superior to HV(5) alone. The incidence of provoked ST segment elevation due to HV(5)+TM(1) was higher than with the other 3 procedures. Thus, in patients with coronary spastic angina, no spontaneous ST segment elevation and near normal coronary arteries, HV(5)+CS(2) was no more useful than HV(5) alone. It is recommended that the newly designed HV(5)+TM(1) combination test be used for documenting evidence of ischemia in patients with coronary spastic angina, low disease activity and near normal coronary arteries.
Acetylcholine↗
Limited efficacy of magnesium for the treatment of variant angina.
Some patients with variant angina show both ST segment elevation at rest and exercise-induced ST segment elevation. Magnesium deficiency has also been observed in patients with variant angina. This study investigated the correlation between the degree of magnesium deficiency and the efficacy of intravenous administration of magnesium in patients with variant angina. Fifteen patients with angiographically confirmed variant angina were assessed for magnesium deficiency and whether intravenous administration of magnesium (19.2 mEq/l) suppressed exercise-induced ST segment elevation. All 15 patients were studied with a magnesium retention test (0.2 mEq/kg over 4 hr) to analyze magnesium deficiency. In our study, magnesium retention rate in patients with variant angina was not higher than that of controls (57 +/- 24% vs 45 +/- 10%, NS). All 15 patients had anginal attacks during accelerated exercise combined with hyperventilation after placebo infusion, whereas only 8 patients had anginal attacks after magnesium administration. ST segment elevation occurred in 14 patients after placebo infusion, but in only 4 patients after magnesium administration. There were no correlations between disease activity, degree of magnesium deficiency or failure of suppression of ST elevation by the intravenous administration of magnesium. Intravenous administration of magnesium can suppress exercise-induced coronary spasms in some patients with variant angina, but the degree of magnesium deficiency did not correlate with the suppressions of exercise-induced ST elevation after magnesium administration. Intravenous administration of magnesium had limited efficacy in patients with variant angina and exercise-induced ST segment elevation.
Acetylcholine↗
A case of variant angina pectoris with similar findings on both rest and matched exercise thallium-201 studies.
A patient with variant angina showed similar findings on both the rest and matched exercise 201Thallium (201Tl) myocardial perfusion scintigrams. The 65-year old man was admitted to hospital because of rest angina. His electrocardiogram during the attack disclosed ST segment elevation on inferior leads. However, emergency coronary arteriogram showed no fixed stenosis. Intracoronary injection of acetylcholine induced a spasm on the distal right coronary artery, but not in the left coronary artery. In the rest 201Tl study, septal perfusion was low on the early image, although partial redistribution of this site was observed on the delayed image without the appearance of chest pain or electrocardiographic ischemic change. Similary, in the 201Tl exercise study undergone 2 weeks later, septal redistribution was diagnosed because the early image had decreased septal perfusion. Both the exercise 123I-metaiodobenzylguanidine study and the rest 123I-betamethyl-p-iodophenyl-pentadecanoic acid study showed inferior abnormalities on the early and delayed images. Although a coronary spasm was not induced in the left anterior descending artery with the acetylcholine test, septal redistribution was observed on the delayed image of both the rest and exercise 201Tl studies. The mechanism of the redistribution on the rest 201Tl study was unclear.
Aged↗
[Usefulness of intracoronary injection of acetylcholine and ergonovine in patients with variant angina].
The correlation was examined between the angina-producing arteries predicted to be responsible for the sites of ST segment elevation during spontaneous ischemic attacks and the arteries in which spasm was induced by intracoronary injection of either acetylcholine or ergonovine in patients with variant angina. From 1991 January to 1996 June, 42 patients with variant angina, 40 men and 2 women with a mean age of 61.6 years old, underwent the acetylcholine provocation test within 2 weeks of observation of the last ST segment elevation. After discontinuation of antianginal agents for at least 24 hours, a bolus of acetylcholine was injected in incremental doses of 20, 50 micrograms (occasionally 80 micrograms) into the right coronary artery and of 20, 50 and 100 micrograms incrementally into the left coronary artery to provoke coronary spasm. Intracoronary injection of ergonovine was added in nine patients, in whom intracoronary injection of acetylcholine failed to document coronary spasm on the arteries predicted to be responsible for the sites of ST segment elevation during anginal attacks. Ergonovine was injected in total doses of 40 micrograms into the right coronary artery and of 64 micrograms into the left coronary artery. Positive spasm was defined as induction of more than 99% reversible stenosis. The correlation between the arteries predicted to be responsible for the sites of ST segment elevation during attacks and the vessels in which spasm was induced by acetylcholine test was 78.6% for all patients and 80.0% for all sites of ST segment elevation. By adding the ergonovine test after the acetylcholine test, the correlation increased to 95.2% for all patients and 95.6% for all sites of ST segment elevation. The correlation observed agrees with previous studies in which the ergonovine test was performed in patients without induced spasm by intracoronary injection of acetylcholine and that the super-imposed ergonovine test is useful for diagnosing patients with variant angina.
Acetylcholine↗
[Usefulness of thallium-201 myocardial scintigraphy during hyperventilation and accelerated exercise test in patients with vasospastic angina and nearly normal coronary artery].
The usefulness of thallium-201 (201Tl) myocardial scintigraphy was studied in 109 patients with vasospastic angina who had nearly normal coronary arteries (degree of stenosis < 50%). Coronary spasm was confirmed by pharmacologic agents in all 109 patients from January 1991 to June 1996. The appearance rate of visual redistribution on 201Tl myocardial scintigraphy was compared between four groups, 34 patients performing graded bicycle ergometer exercise starting at a work load of 50 W with increments of 25 W every 3 min [Ergo (3) group], 14 patients performing hyperventilation for 5 min [HV (5) group], 31 patients performing bicycle ergometer exercise with increments of 25 W every 1 min after 5 min hyperventilation [HV (5) + Ergo (1) group], and 30 patients at rest (Rest group). The value of the visual redistribution rate on 201Tl myocardial scintigrams in the HV(5) + Ergo (1) group (65%) was higher than that in the patients of other groups [Ergo (3) 41%, HV (5) 43%, Rest 33%]. However, there were no significant differences between the four groups. Stress 201Tl imaging after hyperventilation and accelerated exercise is useful to disclose ischemic evidence in about two thirds of patients with vasospastic angina and nearly normal coronary arteries, whereas about 40% of patients had visual redistribution on 201Tl myocardial scintigrams by performing standard procedures.
Acetylcholine↗
[Characteristics of spasm-induced vessels in patients with vasospastic angina and a history of syncope].
One hundred and eighty-seven consecutive patients with vasospastic angina and coronary spasm provoked by intracoronary injection of acetylcholine and/or ergonovine were treated from January 1991 to June 1997. Fifteen of these patients, 14 men and one woman (mean age of 63 years old), had a history of syncope. There were no significant differences in the distribution of induced spasm vessels, single spasm vs multiple spasms, variant angina pectoris and organic stenosis (< 75%) between patients with and without a history of syncope. There were no significant differences concerning the distribution of the sites of induced spasm in the circumflex artery and left anterior descending artery between the two groups. However, coronary spasm in the proximal portion of the right coronary artery (segment 1 or 2 according to the functional classification of American Heart Association) occurred more frequently in patients with a history of syncope [80.0% (12/15) vs 45.3% (78/172); p < 0.05]. Twelve of the 96 patients with coronary spasm in the proximal portion of the right coronary artery had a history of syncope, so these patients require careful management.
Acetylcholine↗