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[Tryptase levels are elevated during spontaneous ischemic episodes in unstable angina but not after the ergonovine test in variant angina].

Activated mast cells are present in human coronary atheromas, as well as in the adventitia of patients with variant angina, and may play an important role in plaque rupture and coronary vasomotion. To assess whether or not activation of mast cells is a primary event, we measured serum levels of tryptase, a specific marker of mast cell activation, in 8 patients with unstable angina during a spontaneous ischemic episode (Group 1) and in 5 patients with variant angina (Group 2) during ergonovine-induced coronary spasm. Blood samples were collected as soon as possible after the onset of pain and ECG changes (0 min), and after 5, 15 and 60 min. Tryptase levels in Group 1 were 0.13 U/l (range 0.017-0.44) at the onset of pain and significantly raised to 0.75 U/l (range 0.05-2.49) at 5 min, decreasing to 0.076 U/l (range 0.018-0.16) at 15 min and to 0.085 U/l (range 0.01-0.25) at 60 min (p = 0.035). Conversely, tryptase levels in Group 2 were 0.09 U/l (range 0.07-0.13) at 0 min, 0.11 U/l (range 0.07-0.22) at 5 min, 0.10 U/l (range 0.07-0.18) at 15 min, 0.11 U/l (range 0.07-0.17) at 60 min (NS). In conclusion, tryptase levels raise during spontaneous ischemic episodes in unstable angina, but not after ergonovine-provoked ischemia in variant angina, suggesting that a primary, yet unknown stimulus, may activate mast cells during some ischemic episodes in unstable angina.

Aged↗

Lack of effect of methyl-ergonovine on postpartum lactation.

There is little information about the action of ergot derivatives other than bromocriptine (CB 154) on plasma prolactin and milk secretion in human beings. In a recent report it has been suggested that ergonovine might interfere with lactation when administered post partum. The present study shows that methyl-ergonovine (Methergine), a closely related compound, has no action on prolactin or milk secretion as measured in a group of 10 breast feeding mothers in comparison with another 10 untreated puerperas.

Female↗

Acute myocardial infarction with "normal" coronary arteries: clinical and angiographic profiles, with ergonovine testing.

Among 528 patients consecutively undergoing selective coronary angiography after acute myocardial infarction, ten cases (1.9%) with angiographically normal coronary arteries were identified. Eight of these ten patients were 45 years of age or younger and comprised 11% of those studied in this age group, with higher prevalence in females (five of 18 [28%]) versus males, (three of 57 [5%]). Common features besides the young age of patients included predominance of female sex, smoking as a risk factor, and the lack of preinfarction symptoms. An ergonovine test was carried out in seven of these patients, and all tested patients failed to show any evidence of focal coronary spasm. Three patients had recanalization of the infarct-related vessel by intracoronary streptokinase. The lack of a history of variant angina in nine patients, the negative response to ergonovine provocation in seven, and documented thrombolysis after intracoronary streptokinase in three seem to indicate that a thrombotic process is a leading factor in myocardial infarction in such cases. Angiographic studies of this young subset of patients would enhance their identification and might reveal the pathophysiologic mechanisms involved with potentially significant clinical implications. Long-term follow-up of such cases will be needed to determine their ultimate prognosis.

Journal Article↗

Noninvasive ergonovine maleate provocative testing for coronary artery spasm: the need for routine thallium-201 imaging.

We administered ergonovine and used both electrocardiographic monitoring and thallium-201 [201Tl] imaging to detect reversible ischemia in 100 patients. Patients already established as having coronary artery spasm and those with nonbypassed, proximal, high-grade coronary artery stenosis were excluded. No complication occurred in any patient. The use of thallium imaging in addition to electrocardiographic monitoring resulted in a higher degree of sensitivity than did ECG monitoring alone. Fourteen patients demonstrated evidence of coronary artery spasm as documented by 201Tl imaging but of the 14, significant ECG changes occurred in only 50%, and classic ST segment elevation in 21%. Thus, in carefully selected patients the noninvasive provocation of coronary spasm can be accomplished safely, but ECG monitoring must be combined with thallium-201 imaging to achieve an acceptable degree of sensitivity.

Adult↗

Ergonovine provocative testing: description of a "double catheter technique".

Since coronary arteries should be immediately accessible during ergonovine provocative testing (EPT), a double catheter technique is described. Using the catheter sheath technique from the right and left femoral arteries, right and left Judkins' catheters are introduced into each femoral artery. Selective coronary cineangiography during EPT is thus rapidly performed without the delay of exchanging catheters. Should coronary arterial spasm occur during the test, nitroglycerin can be administered into the coronary artery without delay.

Cardiac Catheterization↗

Effects of intracoronary injection of ergonovine on angiographic normal coronary arteries: study of 108 consecutive patients.

To assess the local and systemic intracoronary (IC) ergonovine maleate (EM), single or repeated 25 micrograms bolus injections were administered to 108 consecutive patients with chest pain and normal coronary arteriograms. Coronary artery spasm (CAS) was induced in 17 (15.7%) patients. None of these patients developed ST-segment depression, and ST-segment elevation appeared in only 6 (35.3%). In 59 of the 91 patients without CAS, both the IC and the intravenous (IV) EM arteriographic and hemodynamic effects were compared. The mean diameter of the vessels was reduced by 15% (p less than 0.001) after two single 25 micrograms ICEM injections. Only insignificant changes were induced in the heart rate (baseline 80 +/- 15; after ICEM 79 +/- 15 beats/min; p = NS) and systolic aortic pressure (baseline 147 +/- 27; after ICEM 149 +/- 28 mmHG; p = NS). Following 350 micrograms of cumulative IVEM, the mean coronary diameter decreased by 20% (p less than 0.01 vs. ICEM dose) and the heart rate diminished slightly (76 +/- 12 beats/min, p less than 0.01). However, the systolic aortic pressures did increase by 16% (171 +/- 28 mmHg; p less than 0.001). No major complications were observed. Thus, to induce CAS the IC delivery route appears to be safe, allows for more accurate titration, and adverse systemic effects, such as hypertension, are avoided.

Adult↗

Ergonovine-induced esophageal spasm in patients with chest pain resembling angina pectoris.

We studied the effect of ergonovine maleate (EM) on esophageal motor activity in 18 consecutive patients with angina-like chest pain. Significant coronary artery disease was excluded in each patient by cardiac catheterization studies. Baseline esophageal motility was abnormal in 12 patients (66%). After injection of EM, ten patients developed their typical chest pain at the onset of repetitive contractions. Thus, chest pain and esophageal dysfunction were clearly linked. Compared with saline injection, only the repetitive contractions were significantly increased after AM in these patients (P less than 0.01). Amplitude and duration of contractions were increased after EM, but not significantly. Due to potentially serious adverse effects, however, EM cannot be recommended for routine use as a provocative agent.

Adult↗

Selective ergonovine-induced coronary artery spasm and ST-segment alternans after blunt thoracic trauma.

A 24-year-old man was found to have angiographically normal coronary arteries shortly after suffering blunt thoracic trauma. Selective ergonovine administration into the left coronary artery induced total occlusion of the left anterior descending branch and electrical alternans of the ST-segment. This case demonstrates coronary artery spasm as a possible mechanism of coronary occlusion after blunt thoracic trauma.

Adult↗

Location of focal vasospasm provoked by ergonovine maleate within coronary arteries in patients with vasospastic angina pectoris.

This study examined whether coronary focal vasospasm occurs in a nonuniform distribution within the coronary tree and whether a longitudinal plaque distribution pattern is present in patients with vasospastic angina using 3-dimensional intravascular ultrasound analysis. Of 121 patients with clinically suspected angina without fixed stenosis in the coronary arteries, vasospasm was provoked in 82 patients with 92 lesions (42 focal, 50 diffuse) by intravenous ergonovine maleate injection. Most focal vasospasms occurred in the proximal third of the coronary arteries (proximal 28, mid 8, distal 6, p <0.01), corresponding to the historical high-risk zones for acute coronary occlusion. More plaque burden also existed in the proximal third of the coronary arteries in patients with focal vasospasm.

Angina Pectoris↗

ST-segment elevation and ventricular fibrillation without coronary spasm by intracoronary injection of acetylcholine and/or ergonovine maleate in patients with Brugada syndrome.

OBJECTIVES: The study examined whether patients with Brugada syndrome are sensitive to vagal stimulation or ischemia. BACKGROUND: Experimental studies have suggested that a prominent transient outward current (I(to))-mediated action potential notch and a subsequent loss of the action potential dome in the epicardium, but not in the endocardium, give rise to ST-segment elevation and subsequent ventricular fibrillation (VF). METHODS: We evaluated the frequency of coronary spasm, augmentation (> or =0.1 mV) of ST-segment elevation in leads V(1) to V(3), and induction of VF by intracoronary injection of acetylcholine (ACh) and/or ergonovine maleate (EM) in 27 symptomatic patients with Brugada syndrome and 30 control subjects. RESULTS: The coronary spasm was induced in 3 (11%) of the 27 patients with Brugada syndrome and in 13 (43%) of the 30 control subjects. ST-segment elevation was augmented by 11 (33%) of the 33 right coronary injections (ACh: 6/11 [55%]; EM: 5/22 [23%]), without coronary spasm, but not by any of the left coronary injections in patients with Brugada syndrome. Ventricular fibrillation was induced by 3 (9%) of the 33 right coronary injections (ACh: 2/11 [18%]; EM: 1/22 [5%]), but not by any of the left coronary injections. In contrast, neither ST-segment elevation nor VF was observed in any of the control subjects. CONCLUSIONS: Our results support the hypothesis that mild ischemia and vagal influences act additively or synergistically with the substrate responsible for the Brugada syndrome to elevate the ST-segment and precipitate VF. These observations suggest that Brugada patients may be at a higher risk for ischemia-related sudden death.

Acetylcholine↗

Prognostic implication of ergonovine echocardiography in patients with near normal coronary angiogram or negative stress test for significant fixed stenosis.

OBJECTIVES: The goal of this study was to assess the prognostic value of ergonovine echocardiography (Erg Echo) for diagnosis of coronary vasospasm (CVS) in patients without significant fixed coronary stenosis. MATERIAL AND METHODS: Medical records of 650 patients who underwent Erg Echo were reviewed. Before Erg Echo, absence of significant fixed coronary stenosis was confirmed by invasive coronary angiography (CAG) in 316 patients (49%) or by noninvasive confirmation of negative treadmill or normal myocardial perfusion scan in 334 patients (51%). The cardiac events after Erg Echo were tabulated and these included cardiac death, myocardial infarction (MI), readmission due to intractable chest pain. RESULTS: The average age was 54 +/- 10 years, with 223 women and 427 men. Erg Echo was positive in 237 patients (36%), for whom long-acting calcium channel blocker and nitrates were prescribed. During follow-up (46 +/- 23 months), cardiac events developed in 13% (30 of 237) of the positive Erg Echo group and 3% (14 of 413) of the negative Erg Echo group (P <.001). Incidence of cardiac death was higher in the positive Erg Echo group (3.4% vs 0.7%, P =.022). The 5-year survival rate (93% +/- 3% vs 99% +/- 1%, P =.013) and event-free survival rate (94% +/- 2% vs 77% +/- 6%, P <.001) were significantly lower in the positive Erg Echo group. Smoking (hazards ratio 6.3; 95% CI 1.7-23.5) and multivessel spasm (hazards ratio 37.2, 95% CI, 8.1 to 170.4) were independent factors associated with cardiac death and/or MI. CONCLUSION: Erg Echo for noninvasive diagnosis of CVS in the differential diagnosis of chest pain provides useful prognostic information for patients without significant fixed coronary stenosis and can play a role as a cost-effective diagnostic strategy in these selected patients.

Adult↗

Hyperventilation and ergonovine tests in Prinzmetal's variant angina: comparative sensitivity and relation with the activity of the disease.

Hyperventilation (HV) and ergonovine (E) tests were carried out in a group of 32 patients with variant angina to compare their sensitivity and to correlate the results with the activity of the disease. The HV test was positive in 84% of the patients and E in 94% of them; the percentage of positive responses to HV was similar to that to E (96% vs 100%) in the patients with daily attacks, while it was lower (55% vs 77%) in those with sporadic attacks. All 27 patients with a positive HV also had a positive response to E, while of the five patients with a negative HV, two also had a negative response to E and the other three had a positive E at a higher dose than that of the patients with daily attacks. The incidence of chest pain and of ST-segment elevation or depression or T-wave positivization was similar during the two tests; however, spontaneous remission of ischaemia was more frequent after HV than after E and ventricular arrhythmias less frequent during the HV test. At the onset of myocardial ischaemia pH was significantly higher compared with basal values (7.51 +/- 0.07 vs 7.38 +/- 0.05, P less than 0.001), while double product was not significantly different compared with basal (10.0 +/- 2.4 vs 9.2 +/- 2.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Angina Pectoris, Variant↗

Efficacy of isosorbide-5-mononitrate versus nifedipine in preventing spontaneous and ergonovine-induced myocardial ischaemia. A double-blind, placebo-controlled study.

This study was designed to assess the efficacy of oral nifedipine as compared to oral isosorbide-5-mononitrate in the prevention of spontaneous and induced vasospastic myocardial ischaemia. Twenty-one patients admitted to the Coronary Care Unit as a result of angina at rest underwent both Holter monitoring and an echo-ergonovine test during placebo and following either isosorbide-5-mononitrate or nifedipine according to a double-blind randomized trial. Both drugs caused a statistically significant reduction in spontaneous (87% and 95%, respectively) and induced ischaemic attacks (66% and 75%, respectively). No significant difference was found between the two drugs.

Administration, Oral↗

Induction of coronary artery spasm by two pharmacological agents: comparison between intracoronary injection of acetylcholine and ergonovine.

BACKGROUND AND OBJECTIVES: There have been few studies comparing the clinical usefulness for the induction of coronary artery spasm (CAS) between acetylcholine (ACh) and ergonovine (ER). This study is designed: (1) to examine the duration of effect after intracoronary injection of ACh on the responsible vessels using a 0.014 inch, 15 MHz Doppler guide wire, and (2) to evaluate the efficacy of two pharmacological agents, ACh and ER, for the induction of CAS in patients with <50% stenosis in the cardiac laboratory. METHODS: Phasic coronary flow velocity patterns were recorded at rest and during ACh tests in 22 patients with normal or near-normal coronary arteries. The tip of the guide wire was placed on the proximal right coronary artery (RCA) and mid-left anterior descending artery. We measured the time required to baseline level of average peak velocity after intracoronary injection of ACh. We performed selective intracoronary administration of both ER and ACh in the same 171 patients (106 men, 65 women, mean age of 62+/-10 years) with <50% stenosis. Under no medication, ACh was injected first in incremental doses of 20, 50, and 80 microg into the RCA and of 20, 50, and 100 microg into the left coronary artery (LCA). Ten minutes later, ER was administered at 10 microg/min for four minutes for a maximal dose of 40 microg on the RCA and at 16 microg/min over four minutes for a total dose of 64 microg on the LCA. Positive spasm was defined as > or =99% luminal narrowing. RESULTS: The time-averaged peak velocity returned to baseline after intracoronary injection of ACh within 10 minutes in all 120 procedures, consisted of 19 with positive spasm (RCA (n=10): 245+/-33 s; LCA (n=9): 351+/-187 s) and 101 with negative spasm (RCA (n=48): 155+/-62 s, LCA (n=53): 248+/-106 s). In the overall results, there was no difference concerning the incidence of provoked spasm between the two pharmacological agents (ACh: 33% versus ER: 32%, NS). Coronary spasms were induced by either pharmacological agent in 134 vessels. Concordance in this study was 94% in all vessels, whereas the remaining 6% of vessels were different from each other. The non-concordance rate of the right coronary artery was significantly higher than that of the left coronary artery (10% versus 4%, p<0.01). However, ER provoked more focal spasms, whereas ACh provoked more diffuse and distal spasms, compared with each other. Seventy-four (55%) of the 134 vessels had coronary spasms in the same coronary arteries. Concordance of both provoked spasm sites and spasm configurations in the same coronary artery was observed in only 18 (13%) vessels. No serious or irreversible complications were observed during the two sequential tests. CONCLUSIONS: As a spasm provocation test, there were no differences between ACh and ER. We recommend the supplementary use of these two pharmacological agents for the induction of CAS in the cardiac laboratory, if available.

Acetylcholine↗

Clinical impact of selective spasm provocation tests: comparisons between acetylcholine and ergonovine in 1508 examinations.

BACKGROUND: There are few reports regarding the concordance of coronary arterial response between acetylcholine (ACh) and ergonovine (ER) spasm provocation tests. OBJECTIVES: We attempted to perform selective spasm provocation tests to examine the incidence of provoked spasm in patients who had undergone first coronary angiography as much as possible and we compared the coronary arterial response and clinical usefulness between selective intracoronary injection of ACh and intracoronary administration of ER. METHODS: We performed 1508 selective spasm provocation tests, consisting of 873 ACh tests and 635 ER tests, from 1991 to 2002. We examined the frequency of provoked spasms of each agent retrospectively. ACh 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. ER was administered as 10 microg/min over 4 min for a maximal dose of 40 microg in the right coronary artery and as 16 microg/min over 4 min for a total dose of 64 microg in the left coronary artery. Coronary spasm was defined as transient >99% luminal narrowing. RESULTS: Intracoronary ACh provoked spasms in 36.0% of patients and intracoronary ER induced spasms in 29.8% of patients. In patients with ischemic heart disease, the incidence of provoked spasms was not different between ACh tests (50.9%) and ER tests (43.8%). In contrast, the frequency of provoked spasms with ACh tests was significantly higher than that with ER tests (11.0% compared with 6.4%, P<0.05) in patients without ischemic heart disease. Moreover, ACh provoked more spasms in patients without fixed stenosis than ER (36.2% compared with 25.5%, P<0.01) and multiple spasms were frequently observed when performing ACh tests (40.0% compared with 27.0%, P<0.01). Major complications were observed in 1.4% of patients with ACh tests and in 0.2% of patients with ER tests. The need for intracoronary administration of isosorbide dinitrate to relieve coronary spasms during ER testing before performing another coronary artery test was more frequently observed in ACh tests (5.04% compared with 1.49%, P<0.01). However, no serious irreversible complications, such as death or acute myocardial infarction, were observed in this study. There was a significant difference in sex, history of smoking and hyperlipidemia between patients with and without spasms for both tests, whereas no difference in age or hypertension was observed in either test. CONCLUSION: Thus, both selective ACh and ER tests were useful as spasm provocation tests.

Acetylcholine↗

Coronary artery spasm: use of ergonovine in diagnosis.

Ergonovine maleate was administered to 69 patients with chest pain but without significant coronary artery disease (less than 10% luminal diameter obstruction) to determine whether coronary artery spasm could be provoked. Coronary artery spasm was seen at angiography, or inferred from ECG or thallium myocardial perfusion scan changes. The test was positive in 16 patients: all five patients with documented variant angina (Group A); ten of the 19 patients with suspected variant angina (Group B); one of the 11 patients with exercise-induced chest pain (Group C); and none of the 34 patients with atypical chest pain (Group D). Patients with a positive test usually smoked, complained of recurrent nocturnal or early morning chest pain, showed ST changes during spontaneous chest pain and had minot degrees of fixed coronary obstruction (30--70%), when compared to those with a negative test. The only major side effect of the test was transient ventricular tachycardia which occurred in three patients and was reverted by sublingual and parenteral nitroglycerine.

Aged↗

Frequency of provoked coronary spasms in patients undergoing coronary arteriography using a spasm provocation test via intracoronary administration of ergonovine.

There are no data concerning the incidence of provoked coronary arterial spasms via intracoronary administration of ergonovine (ER). This study sought to establish the incidence of spasms due to intracoronary injection of ER in Japanese patients who underwent coronary angiography. The subjects were 596 consecutive patients (369 men, mean age 64.2 +/- 10.3 years) who were studied with a selective ER test. ER was administered in total doses of 40 microg into the right coronary artery and 64 microg into the left coronary artery. A positive spasm was defined as a total or subtotal occlusion. Coronary vasospasms were determined in 173 patients (29.0%). Spasms occurred often in patients with ischemic heart disease (43.3%); during effort and rest in patients with angina (46.3%), exertional angina (27.7%), recent myocardial infarction (36.7%), healed myocardial infarction (34.1%), and especially in patients with rest angina (55.5%), but were relatively uncommon in patients with nonischemic heart disease (3.7%). The incidence of provoked coronary spasms in this study was 2.2-2.6 times higher than in previous reports with intravenous ER administration. More spasms were superimposed on significant atherosclerotic lesions than on nonfixed atherosclerotic lesions (42.8% vs 24.0%, p < 0.01). No serious or irreversible complications were observed in this study. In conclusion, intracoronary administration of ER was a safe and reliable test. Compared with Caucasian patients, in Japanese patients, coronary arterial spasms occurred 2-3 times more frequently with various cardiac disorders.

Aged↗